Sample records for background translocation frequencies

  1. BCL2 Translocation Frequency Rises with Age in Humans

    Microsoft Academic Search

    Yafei Liu; Antonio M. Hernandez; Darryl Shibata; Gino A. Cortopassi

    1994-01-01

    The background frequency of t(14;18) (q32;q21) chromosomal translocations at the locus associated with B-cell leukemia\\/lymphoma-2 (BCL2) was determined from a survey of the peripheral blood lymphocytes (PBLs) of 53 living individuals and from tissues of 31 autopsies by using a nested PCR assay. The translocation was detected in 55% of PBLs and 35% of autopsied spleens with a frequency of

  2. Increased frequency of chromosome translocations in airline pilots with long-term flying experience

    PubMed Central

    Yong, L C; Sigurdson, A J; Ward, E M; Waters, M A; Whelan, E A; Petersen, M R; Bhatti, P; Ramsey, M J; Ron, E; Tucker, J D

    2008-01-01

    Background Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. Methods We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromo-some painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. Results There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). Conclusions This data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk. PMID:19074211

  3. High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots1234

    PubMed Central

    Petersen, Martin R; Sigurdson, Alice J; Sampson, Laura A; Ward, Elizabeth M

    2009-01-01

    Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, ?-carotene, ?-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, ?-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for ?median compared with

  4. Retrospective biodosimetry using translocation frequency in a stable cell of occupationally exposed to ionizing radiation

    PubMed Central

    Cho, Min Su; Lee, Jin Kyung; Bae, Keum Seok; Han, Eun-Ae; Jang, Seong Jae; Ha, Wi-Ho; Lee, Seung-Sook; Barquinero, Joan Francesc; Kim, Wan Tae

    2015-01-01

    Two cases of hematological malignancies were reported in an industrial radiography company over a year, which were reasonably suspected of being consequences of prolonged exposure to ionizing radiation because of the higher incidence than expected in the general population. We analyzed chromosomal aberrations in the peripheral blood lymphocytes from the other workers who had been working under similar circumstances as the patients in the company. Among the subjects tested, 10 workers who belonged to the highest band were followed up periodically for 1.5 years since the first analysis. The aim of this study was to clarify pertinence of translocation analysis to an industrial set-up where chronic exposure was commonly expected. To be a useful tool for a retrospective biodosimetry, the aberrations need to be persistent for a decade or longer. Therefore we calculated the decline rates and half-lives of frequency for both a reciprocal translocation and a dicentric chromosome and compared them. In this study, while the frequency of reciprocal translocations was maintained at the initial level, dicentric chromosomes were decreased to 46.9% (31.0–76.5) of the initial frequency over the follow-up period. Our results support the long-term stability of reciprocal translocation through the cell cycle and validate the usefulness of translocation analysis as a retrospective biodosimetry for cases of occupational exposure. PMID:25922373

  5. Retrospective biodosimetry using translocation frequency in a stable cell of occupationally exposed to ionizing radiation.

    PubMed

    Cho, Min Su; Lee, Jin Kyung; Bae, Keum Seok; Han, Eun-Ae; Jang, Seong Jae; Ha, Wi-Ho; Lee, Seung-Sook; Barquinero, Joan Francesc; Kim, Wan Tae

    2015-07-01

    Two cases of hematological malignancies were reported in an industrial radiography company over a year, which were reasonably suspected of being consequences of prolonged exposure to ionizing radiation because of the higher incidence than expected in the general population. We analyzed chromosomal aberrations in the peripheral blood lymphocytes from the other workers who had been working under similar circumstances as the patients in the company. Among the subjects tested, 10 workers who belonged to the highest band were followed up periodically for 1.5 years since the first analysis. The aim of this study was to clarify pertinence of translocation analysis to an industrial set-up where chronic exposure was commonly expected. To be a useful tool for a retrospective biodosimetry, the aberrations need to be persistent for a decade or longer. Therefore we calculated the decline rates and half-lives of frequency for both a reciprocal translocation and a dicentric chromosome and compared them. In this study, while the frequency of reciprocal translocations was maintained at the initial level, dicentric chromosomes were decreased to 46.9% (31.0-76.5) of the initial frequency over the follow-up period. Our results support the long-term stability of reciprocal translocation through the cell cycle and validate the usefulness of translocation analysis as a retrospective biodosimetry for cases of occupational exposure. PMID:25922373

  6. Chromosome translocation frequencies measured in interphase lymphocytes of A-bomb survivors

    SciTech Connect

    Cantu, A.; Richards, C.; Burroughs, F.; Lucas, J.N. (Lawrence Livermore National Lab., CA (United States))

    1993-01-01

    The authors have compared metaphase chromosome translocation frequencies with interphase chromosome aberration frequencies measured in lymphocytes of A-bomb survivors using FISH. Whole chromosome probes for chromosomes 1, 2, and 4 were used to measure metaphase translocations, and a repetitive probe that binds to the paracentromeric 1q12 locus of chromosome 1 (pUC1.77) was used to measure interphase chromosome aberrations. Doses for the individuals studied ranged from 0 to 4 Gy. The interphase hybridization pattern appeared as one or two distinct spots in normal interphase cells, and as three distinct spots in cells carrying a translocation. Although pUC1.77 is small ([approximately]1% of genome), the increased speed in scoring interphase cells (a factor of 50 faster than scoring metaphase cells) compensates for the small size of the probe. A linear correlation was found between interphase and metaphase aberration frequencies. The data suggest that aberration frequencies may be obtained from interphase cells of individuals exposed decades previously, where dicentrics have decayed. Detection of interphase chromosome aberrations should facilitate automation of chromosome aberration scoring.

  7. High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots.

    PubMed

    Yong, Lee C; Petersen, Martin R

    2011-02-01

    Experimental studies suggest that B vitamins such as niacin, folate, riboflavin, vitamin B6 and vitamin B12 may protect against DNA damage induced by ionising radiation (IR). However, to date, data from IR-exposed human populations are not available. We examined the intakes of these B vitamins and their food sources in relation to the frequency of chromosome translocations as a biomarker of cumulative DNA damage, in eighty-two male airline pilots. Dietary intakes were estimated by using a self-administered semi-quantitative FFQ. Translocations in peripheral blood lymphocytes were scored by using fluorescence in situ hybridisation whole-chromosome painting. Negative binomial regression was used to estimate rate ratios and 95 % CI, adjusted for age and occupational and lifestyle factors. We observed a significant inverse association between translocation frequency and dietary intake of niacin (P = 0·02): adjusted rate ratio for subjects in the highest tertile compared with the lowest tertile was 0·58 (95 % CI 0·40, 0·83). Translocation frequency was not associated with total niacin intake from food and supplements as well as dietary or total intake of folate, riboflavin or vitamin B6 or B12. However, the adjusted rate ratios were significant for subjects with ? median compared with < median intake of whole grains (P = 0·03) and red and processed meat (P = 0·01): 0·69 (95 % CI 0·50, 0·96) and 1·56 (95 % CI 1·13, 2·16), respectively. Our data suggest that a high intake of niacin from food or a diet high in whole grains but low in red and processed meat may protect against cumulative DNA damage in IR-exposed persons. PMID:20932352

  8. Genetic background of HSH in three Polish families and a patient with an X;9 translocation

    Microsoft Academic Search

    Reetta Jalkanen; Ewa Pronicka; Henna Tyynismaa; Andre Hanauer; Roxanne Walder; Tiina Alitalo

    2006-01-01

    Hypomagnesemia with secondary hypocalcemia (HSH) is a rare inherited disease, characterised by neurological symptoms, such as tetany, muscle spasms and seizures, due to hypocalcemia. It has been suggested that HSH is genetically heterogeneous, but only one causative gene, TRPM6, on chromosome 9 has so far been isolated. We have now studied the genetic background of HSH in four Polish patients

  9. Reciprocal translocations

    SciTech Connect

    NONE

    1993-12-31

    Chapter 26, describes reciprocal translocations of chromosomes: their occurrence, breakpoints, and multiple rearrangements. In addition, phenotypes of balanced and unbalanced translocation carriers and fetal death are discussed. Examples of translocation families are given. Meiosis and genetic risk in translocation carriers is presented. Finally, sperm chromosomes in meiotic segregation analysis is mentioned. 39 refs., 3 figs., 1 tab.

  10. Mode of ATM-dependent suppression of chromosome translocation

    Microsoft Academic Search

    Motohiro Yamauchi; Keiji Suzuki; Yasuyoshi Oka; Masatoshi Suzuki; Hisayoshi Kondo; Shunichi Yamashita

    It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere\\/telomere FISH and

  11. Scattering of cold-atom coherences by hot atoms: frequency shifts from background-gas collisions.

    PubMed

    Gibble, Kurt

    2013-05-01

    Frequency shifts from background-gas collisions currently contribute significantly to the inaccuracy of atomic clocks. Because nearly all collisions with room-temperature background gases that transfer momentum eject the cold atoms from the clock, the interference between the scattered and unscattered waves in the forward direction dominates these frequency shifts. We show they are ? 10 times smaller than in room-temperature clocks and that van der Waals interactions produce the cold-atom background-gas shift. General considerations allow the loss of the Ramsey fringe amplitude to bound this frequency shift. PMID:23683186

  12. Efficient induction of Wheat-agropyron cristatum 6P translocation lines and GISH detection.

    PubMed

    Song, Liqiang; Jiang, Lili; Han, Haiming; Gao, Ainong; Yang, Xinming; Li, Lihui; Liu, Weihua

    2013-01-01

    The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome) carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by (60)Co-?irradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes. PMID:23874966

  13. Efficient Induction of Wheat-Agropyron cristatum 6P Translocation Lines and GISH Detection

    PubMed Central

    Song, Liqiang; Jiang, Lili; Han, Haiming; Gao, Ainong; Yang, Xinming; Li, Lihui; Liu, Weihua

    2013-01-01

    The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome) carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by 60Co-?irradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes. PMID:23874966

  14. Modifications to the cosmic 21-cm background frequency spectrum by scattering via electrons in galaxy clusters

    SciTech Connect

    Cooray, Asantha [Department of Physics and Astronomy, 4186 Frederick Reines Hall, University of California, Irvine, California 92697 (United States)

    2006-05-15

    The cosmic 21-cm background frequency spectrum related to the spin-flip transition of neutral hydrogen present during and before the era of reionization is rich in features associated with physical processes that govern transitions between the two spin states. The intervening electrons in foreground galaxy clusters inversely Compton scatter the 21-cm background spectrum and modify it just as the cosmic microwave background (CMB) spectrum is modified by inverse-Compton scattering. Towards typical galaxy clusters at low redshifts, the resulting modification is a few tenths milli-Kelvin correction to the few tens milli-Kelvin temperature of 21-cm signal relative to that of the cosmic microwave background blackbody spectrum. The modifications are mostly associated with sharp changes in the cosmic 21-cm background spectrum such as due to the onset of a Lyman-{alpha} radiation field or heating of neutral gas. Though low-frequency radio interferometers that are now planned for 21-cm anisotropy measurements are insensitive to the mean 21-cm spectrum, differential observations of galaxy clusters with these interferometers can be utilized to indirectly establish global features in the 21-cm frequency spectrum. We discuss the feasibility to detect the spectrum modified by clusters and find that, for upcoming interferometers, while a detection towards an individual cluster is challenging, one can average signals over a number of clusters, selected based on the strength of the Sunyave-Zel'dovich effect at high radio frequencies involving CMB scattering alone, to establish the mean 21-cm spectrum.

  15. Cosmological constraints on the very low frequency gravitational-wave background

    SciTech Connect

    Seto, Naoki [Theoretical Astrophysics, California Institute of Technology, MC 130-33, Pasadena, California 91125 (United States); Department of Physics and Astronomy, University of California, 4186 Frederick Reines Hall, Irvine, California 92697 (United States); Cooray, Asantha [Department of Physics and Astronomy, University of California, 4186 Frederick Reines Hall, Irvine, California 92697 (United States)

    2006-01-15

    The curl modes of cosmic microwave background polarization allow one to indirectly constrain the primordial background of gravitational waves with frequencies around 10{sup -18} to 10{sup -16} Hz. The proposed high precision timing observations of a large sample of millisecond pulsars with the pulsar timing array or with the square kilometer array can either detect or constrain the stochastic gravitational-wave background at frequencies greater than roughly 0.1 yr{sup -1}. While existing techniques are limited to either observe or constrain the gravitational-wave background across six or more orders of magnitude between 10{sup -16} and 10{sup -10} Hz, we suggest that the anisotropy pattern of time variation of the redshift related to a sample of high-redshift objects can be used to study the background around a frequency of 10{sup -12} Hz. Useful observations to detect an anisotropy signal in the global redshift change include spectroscopic observations of the Ly-{alpha} forest in absorption towards a sample of quasars, redshifted 21 cm line observations either in absorption or emission towards a sample of neutral HI regions before or during reionization, and high-frequency (0.1 to 1 Hz) gravitational-wave analysis of a sample of neutron star-neutron star binaries detected with gravitational-wave instruments such as the Decihertz Interferometer Gravitational Wave Observatory (DECIGO). For reasonable observations expected in the future involving extragalactic sources, we find limits at the level of {omega}{sub GW}<10{sup -6} at a frequency around 10{sup -12} Hz while the ultimate limit is likely to be around {omega}{sub GW}<10{sup -11}. On the other hand, if there is a background of gravitational waves at 10{sup -12} Hz with an amplitude larger than this limit, its presence will be visible as a measurable anisotropy in the time-evolving redshift of extragalactic sources.

  16. Production and identification of wheat-Agropyron cristatum 6P translocation lines.

    PubMed

    Luan, Yang; Wang, Xiaoguang; Liu, Weihua; Li, Chunye; Zhang, Jinpeng; Gao, Ainong; Wang, Yandong; Yang, Xinming; Li, Lihui

    2010-07-01

    The narrow genetic background of wheat is the primary factor that has restricted the improvement of crop yield in recent years. The kernel number per spike is the most important factor of the many potential characteristics that determine wheat yield. Agropyron cristatum (L.) Gaertn., a wild relative of wheat, has the characteristics of superior numbers of florets and kernels per spike, which are controlled by chromosome 6P. In this study, the wheat-A. cristatum disomic addition and substitution lines were used as bridge materials to produce wheat-A. cristatum 6P translocation lines induced by gametocidal chromosomes and irradiation. The results of genomic in situ hybridization showed that the frequency of translocation induced by gametocidal chromosomes was 5.08%, which was higher than the frequency of irradiated hybrids (2.78%) and irradiated pollen (2.12%). The fluorescence in situ hybridization results of the translocation lines showed that A. cristatum chromosome 6P could be translocated to wheat ABD genome, and the recombination frequency was A genome > B genome > D genome. The alien A. cristatum chromosome 6P was translocated to wheat homoeologous groups 1, 2, 3, 5 and 6. We obtained abundant translocation lines that possessed whole-arm, terminal, segmental and intercalary translocations. Three 6PS-specific and four 6PL-specific markers will be useful to rapidly identify and trace the translocated fragments. The different wheat-A. cristatum 6P translocation lines obtained in this study can provide basic materials for analyzing the alien genes carried by chromosome 6P. The translocation line WAT33-1-3 and introgression lines WAI37-2 and WAI41-1, which had significant characteristics of multikernel (high numbers of kernels per spike), could be utilized as novel germplasms for high-yield wheat breeding. PMID:20490543

  17. Background

    Cancer.gov

    Extensive evidence has demonstrated that 24-hour dietary recalls provide the highest quality, least biased dietary data. Traditional 24-hour recalls, however, are expensive and impractical for large-scale research because they rely on trained interviewers and multiple administrations to estimate usual intakes. As a result, researchers often make use of food frequency questionnaires, which are less expensive but contain substantial error.

  18. Efficient mid-infrared single-photon frequency upconversion detection with ultra-low background counts

    NASA Astrophysics Data System (ADS)

    Gu, Xiaorong; Huang, Kun; Pan, Haifeng; Wu, E.; Zeng, Heping

    2013-05-01

    We demonstrate an efficient mid-infrared single-photon detection system with ultra-low background counts based on the frequency upconversion detection technique. The signal photons of 3.39 ?m came from a He–Ne laser and the pump beam was provided by a mode-locked ytterbium-doped fiber laser. Taking into account the pulsed pumping and continuous-wave signaling scheme, the peak conversion efficiency of 64% was achieved at an average pump power of 28.3 mW. The corresponding detection efficiency was inferred to be 6.1% with ultra-low background counts of 400 s?1.

  19. The temperature of the cosmic microwave background radiation at a frequency of 10 GHz

    Microsoft Academic Search

    A. Kogut; M. Bersanelli; G. de Amici; S. D. Friedman; M. Griffith; B. Grossan; S. Levin; G. F. Smoot; C. Witebsky

    1988-01-01

    We have measured the temperature of the cosmic microwave background radiation (CMBR) at a frequency of 10 GHz (wavelength 3.0 cm) as part of a larger effort to determine the spectrum of the CMBR in the Rayleigh-Jeans region. The instrument used is a superheterodyne Dicke-switched radiometer. We have repeated the measurement over four summers with successively improved techniques and equipment.

  20. Position and frequency shifts induced by massive modes of the gravitational wave background in alternative gravity

    SciTech Connect

    Bellucci, Stefano [INFN Laboratori Nazionali di Frascati, Via Enrico Fermi 40, I-00044 Frascati (Italy); Capozziello, Salvatore; De Laurentis, Mariafelicia [Dip. di Scienze Fisiche, Universita di Napoli 'Federico II' and INFN Sez. di Napoli, Compl. Universitario Monte S. Angelo, Ed. N, Via Cinthia, I-80126 Napoli (Italy); Faraoni, Valerio [Physics Department, Bishop's University, Sherbrooke, Quebec, Canada J1M 1Z7 (Canada)

    2009-05-15

    Alternative theories of gravity predict the presence of massive scalar, vector, and tensor gravitational wave modes in addition to the standard massless spin 2 graviton of general relativity. The deflection and frequency shift effects on light from distant sources propagating through a stochastic background of gravitational waves, containing such modes, differ from their counterparts in general relativity. Such effects are considered as a possible signature for alternative gravity in attempts to detect deviations from Einstein's gravity by astrophysical means.

  1. Phase unwrapping algorithm based on double-frequency fringe projection and fringe background

    NASA Astrophysics Data System (ADS)

    Zhao, Hong; Zhang, Chunwei

    2015-02-01

    A phase unwrapping algorithm specially designed for phase-shifting fringe projection profilometry (FPP) is proposed. This algorithm is based on a principle that combines a refined double-frequency fringe projection algorithm and a fringe background based quality guided phase unwrapping algorithm (QGPUA). The phase demodulated from high-frequency fringe images are partially unwrapped by that from the low-frequency ones. This would help to avoid phase order ambiguity in the eventual phase unwrapping while guarantee the phase resolution. The fringe background based QGPUA is adopted to completely unwrap the partially unwrapped phase. The quality map utilized during the phase unwrapping is generated from the fringe background and divided into different subregions. Further unwrapping for the partially unwrapped phase goes on in the order from phase in the highest quality subregion to that in the lowest one gradually. Partially unwrapped phase in each subregion is unwrapped with flood-fill algorithm. Therefore the phase unwrapping speed can be improved. The proposed method can make the phase unwrapping for phase-shifting FPP more robust and faster. Experiment result confirms the effectiveness of the proposed method.

  2. NANOGrav: prospects for the detection of a stochastic background of low-frequency gravitational waves

    NASA Astrophysics Data System (ADS)

    Siemens, Xavier

    2014-03-01

    For the better part of the last decade, the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has been using the Green Bank and Arecibo radio telescopes to monitor millisecond pulsars. NANOGrav aims to directly detect low-frequency gravitational waves which cause small changes to the times of arrival of radio pulses. In this talk I will discuss the work of the NANOGrav collaboration and recent progress made toward realistic simulations of our sensitivity to a stochastic background of gravitational waves. I will show that a detection is possible as early as 2017.

  3. Towards a High Temporal Frequency Grass Canopy Thermal IR Model for Background Signatures

    NASA Technical Reports Server (NTRS)

    Ballard, Jerrell R., Jr.; Smith, James A.; Koenig, George G.

    2004-01-01

    In this paper, we present our first results towards understanding high temporal frequency thermal infrared response from a dense plant canopy and compare the application of our model, driven both by slowly varying, time-averaged meteorological conditions and by high frequency measurements of local and within canopy profiles of relative humidity and wind speed, to high frequency thermal infrared observations. Previously, we have employed three-dimensional ray tracing to compute the intercepted and scattered radiation fluxes and for final scene rendering. For the turbulent fluxes, we employed simple resistance models for latent and sensible heat with one-dimensional profiles of relative humidity and wind speed. Our modeling approach has proven successful in capturing the directional and diurnal variation in background thermal infrared signatures. We hypothesize that at these scales, where the model is typically driven by time-averaged, local meteorological conditions, the primary source of thermal variance arises from the spatial distribution of sunlit and shaded foliage elements within the canopy and the associated radiative interactions. In recent experiments, we have begun to focus on the high temporal frequency response of plant canopies in the thermal infrared at 1 second to 5 minute intervals. At these scales, we hypothesize turbulent mixing plays a more dominant role. Our results indicate that in the high frequency domain, the vertical profile of temperature change is tightly coupled to the within canopy wind speed In the results reported here, the canopy cools from the top down with increased wind velocities and heats from the bottom up at low wind velocities. .

  4. Robertsonian translocations

    SciTech Connect

    NONE

    1993-12-31

    Chapter 27, describes the occurrence of Robertsonian translocations (RTs), which refer to the recombination of whole chromosome arms, in both monocentric and dicentric chromosomes. The nonrandom participation of acrocentric chromosomes in RTs is documented by various methods, including unbiased ascertainment and ascertainment through trisomy, infertility, unspecified mental retardation, and Prader-Willi syndrome. Causes of nonrandom participation of chromosomes in RTs is presented, as are the following topics: segregation in carriers of RTs and segregation in sperm cells of RT carriers, interchromosomal effects and conclusions. 48 refs., 3 figs., 2 tabs.

  5. Microbiology of bacterial translocation in humans

    Microsoft Academic Search

    C J O’Boyle; J MacFie; C J Mitchell; D Johnstone; P M Sagar; P C Sedman

    1998-01-01

    Background—Gut translocation of bacteria has been shown in both animal and human studies. Evidence from animal studies that links bacterial translocation to the development of postoperative sepsis and multiple organ failure has yet to be confirmed in humans.Aims—To examine the spectrum of bacteria involved in translocation in surgical patients undergoing laparotomy and to determine the relation between nodal migration of

  6. Burst, background, and triggered low-frequency earthquakes and non-volcanic tremors

    NASA Astrophysics Data System (ADS)

    Shapiro, N.; Frank, W.; Kostoglodov, V.; Husker, A. L.; Daub, E. G.; Radiguet, M.; Wu, C.; Guyer, R. A.; Nadeau, R. M.; Campillo, M.; Payero, J. S.; Prieto, G. A.; Shelly, D. R.; Johnson, P. A.

    2013-12-01

    Since the first observations of slow-slip events (SSEs), non-volcanic tremor (NVT), and low-frequency earthquakes (LFEs), strong links have been identified between the three slow earthquake phenomena, such as increased NVT and LFE activity during large SSEs and the burst-like, or episodic, behavior of both NVT and LFEs. We focus here on the latter observation, exploring this distinct characteristic of LFEs and NVT. Analysis of the LFE and NVT catalogs from Guerrero, Mexico and Parkfield, California reveals a steady background event rate underlying a non-periodic burst-like behavior. We develop a simple algorithm to generate a catalog of bursts for both LFEs and NVTs, separating the events that occur within bursts from the background rate. We observe that just as LFEs and NVTs occur on two different time scales (from seconds to minutes or hours), their bursts occur on similarly different time scales (from minutes or hours to days). Using these decomposed background and burst event rates, we then attempt to model different potential triggering mechanisms such as slow-slip events with a brittle ductile friction model (Daub et al. [2011]) that could potentially reproduce the observed behavior.

  7. Low-dose ionizing radiation and chromosome translocations: a review of the major considerations for human biological dosimetry.

    PubMed

    Tucker, James D

    2008-01-01

    Chromosome translocations are a molecular signature of ionizing radiation exposure. Translocations persist significantly longer after exposure than other types of chromosome exchanges such as dicentrics. This persistence makes translocations the preferred aberration type for performing radiation dosimetry under conditions of protracted exposure or when exposure assessments are temporally delayed. Low doses of radiation are inherently difficult to quantify because the frequency of induced events is low and the background level of translocations among unexposed subjects can show considerable variability. Analyses of translocation frequencies can be confounded by several factors, including age of the subject, lifestyle choices such as cigarette smoking, the presence of clones of abnormal cells, and possibly genotypic variability among subjects. No significant effects of gender or race have been observed, but racial differences have not been completely ruled out. Translocation analyses may be complicated by the presence of different types of exchanges, i.e., reciprocal or non-reciprocal, and because translocations sometimes occur as a component of complex exchanges that include other forms of chromosome rearrangements. Rates of radiation exposure, ranging from acute to chronic, are known to influence the accumulation of translocations and may also affect their persistence. The influences on translocation frequencies of low-dose radiation hypersensitivity as well as the bystander effect and the adaptive response remain poorly characterized. Thus, quantifying the relationship between radiation dose and the frequency of translocations in any given subject requires attention to multiple issues. Part of the solution to understanding the in vivo dose-response relationship is to have accurate estimates of the baseline levels of translocations in healthy unexposed subjects, and some work in this area has been accomplished. Long-term cytogenetic follow-up of exposed subjects is needed to characterize translocation persistence, which is especially relevant for risk analyses. More work also needs to be done in the area of quantifying the role of known confounders. Characterizing the role of genotype will be especially important. Improvements in the ability to use translocation frequencies for low-dose biological dosimetry will require scoring very large numbers of cells per subject, which may be accomplished by developing a rapid automated image analysis system. This work would enhance our comprehension of the effects of low-dose radiation exposure and could lead to significant improvements in understanding the relationship between chromosome damage and human health. PMID:18485804

  8. An evaluation of the frequency shift caused by collisions with background gas in the primary frequency standard NPL-CsF2.

    PubMed

    Szymaniec, Krzysztof; Lea, Stephen; Liu, Kun

    2014-01-01

    Collisions between cold cesium atoms and background gas atoms at ambient temperature reduce the cold atom signal in a fountain clock and at the same time produce a shift in the measured clock frequency. We evaluate the shift in the NPL-CsF2 cesium fountain primary frequency standard based on measurements of the fractional loss of cold atoms from the atomic cloud during the interrogation time combined with a model by Gibble that quantifies the relationship between the loss and the frequency shift. PMID:24402908

  9. The signal photon flux, background photons and shot noise in electromagnetic response of high-frequency relic gravitational waves

    Microsoft Academic Search

    Jin Li; Kai Lin; Fangyu Li; Yuanhong Zhong

    2011-01-01

    On the basis of the electromagnetic response of high frequency relic gravitational waves (HFRGWs), we research on more accurate\\u000a calculation of signal (i.e. transverse perturbative photon flux (PPF)) and background photons flux (BPF) in the sycro-resonance\\u000a electromagnetic system, which consists of Gaussian beam (GB), a static magnetic field and fractal membranes. According to\\u000a the relationship between frequency of gravitational waves

  10. Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes

    PubMed Central

    Howarth, KD; Blood, KA; Ng, BL; Beavis, JC; Chua, Y; Cooke, SL; Raby, S; Ichimura, K; Collins, VP; Carter, NP; Edwards, PAW

    2008-01-01

    Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. A total of 200 breakpoints were identified and all were mapped to 1Mb resolution on BAC arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2kb resolution using oligonucleotide arrays. Many more of the translocations were balanced at 1Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Secondly, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300, and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer. PMID:18084325

  11. Phase unwrapping algorithm based on multi-frequency fringe projection and fringe background for fringe projection profilometry

    NASA Astrophysics Data System (ADS)

    Zhang, Chunwei; Zhao, Hong; Gu, Feifei; Ma, Yueyang

    2015-04-01

    A phase unwrapping algorithm specially designed for the phase-shifting fringe projection profilometry (FPP) is proposed. It combines a revised dual-frequency fringe projectionalgorithm and a proposed fringe background based quality guided phase unwrapping algorithm (FB-QGPUA). Phase demodulated from the high-frequency fringe patterns is partially unwrapped by that demodulated from the low-frequency ones. Then FB-QGPUA is adopted to further unwrap the partially unwrapped phase. Influences of the phase error on the measurement are researched. Strategy to select the fringe pitch is given. Experiments demonstrate that the proposed method is very robust and efficient.

  12. Translocation Renal Cell Carcinomas in Adults: A Single Institution Experience

    PubMed Central

    Zhong, Minghao; De Angelo, Patricia; Osborne, Lisa; Mondolfi, Paniz; Geller, Matthew; Yang, Youfeng; Linehan, W. Marston; Merino, Maria J.; Cordon-Cardo, Carlos; Cai, Dongming

    2012-01-01

    Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20–40% of pediatric RCCs with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathological features of adult translocation RCC from a single institution. Utilizing tissue microarray (TMA), immunohistochemistry, cytogenetic examination, and FISH, we identified 6 (~5%) cases of TFE3 translocation RCC and 1 (<1%) case of TFEB translocation RCC in 121 consecutive adult renal cell carcinoma cases between 2001 and 2009. Our results suggest that weak TFE3 staining of a significant proportion of RCC cases may due to expression of the full length TFE3 protein rather than the chimeric fusion protein resulting from chromosomal translocation. PMID:22446944

  13. Production and identification of wheat - Agropyron cristatum (1.4P) alien translocation lines.

    PubMed

    Liu, Wei-Hua; Luan, Yang; Wang, Jing-Chang; Wang, Xiao-Guang; Su, Jun-Ji; Zhang, Jin-Peng; Yang, Xin-Ming; Gao, Ai-Nong; Li, Li-Hui

    2010-06-01

    The P genome of Agropyron Gaertn., a wild relative of wheat, contains an abundance of desirable genes that can be utilized as genetic resources to improve wheat. In this study, wheat - Aegilops cylindrica Host gametocidal chromosome 2C addition lines were crossed with wheat - Agropyron cristatum (L.) Gaertn. disomic addition line accession II-21 with alien recombinant chromosome (1.4)P. We successfully induced wheat - A. cristatum alien chromosomal translocations for the first time. The frequency of translocation in the progeny was 3.75%, which was detected by molecular markers and genomic in situ hybridization (GISH). The translocation chromosomes were identified by dual-color GISH /fluorescence in situ hybridization (FISH). The P genomic DNA was used as probe to detect the (1.4)P chromosome fragment, and pHvG39, pAs1, or pSc119.2 repeated sequences were used as probes to identify wheat translocated chromosomes. The results showed that six types of translocations were identified in the three wheat - A. cristatum alien translocation lines, including the whole arm or terminal portion of a (1.4)P chromosome. The (1.4)P chromosome fragments were translocated to wheat chromosomes 1B, 2B, 5B, and 3D. The breakpoints were located at the centromeres of 1B and 2B, the pericentric locations of 5BS, and the terminals of 5BL and 3DS. In addition, we obtained 12 addition-deletion lines that contained alien A. cristatum chromosome (1.4)P in wheat background. All of these wheat - A. cristatum alien translocation lines and addition-deletion lines would be valuable for identifying A. cristatum chromosome (1.4)P-related genes and providing genetic resources and new germplasm accessions for the genetic improvement of wheat. The specific molecular markers of A. cristatum (1.4)P chromosome have been developed and used to track the (1.4)P chromatin. PMID:20555436

  14. Background radio-frequency radiation and its impact on radio astronomy Michelle C. Storey, Bruce MacA Thomas and John M. Sarkissian

    E-print Network

    Sarkissian, John M.

    1 Background radio-frequency radiation and its impact on radio astronomy Michelle C. Storey, Bruce 1710 Email:mstorey@atnf.csiro.au Abstract: The use of radio-frequency telecommunications equipment is dramatically increasing, and one consequence is that background levels of radio-frequency radiation

  15. Mode of ATM-dependent suppression of chromosome translocation

    SciTech Connect

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)] [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  16. Low-Frequency Measurments of the Cosmic Background RadiationSpectrum

    SciTech Connect

    Smoot, G.F.; De Amici, G.; Friedman, S.D.; Witebsky, C.; Sironi,G.; Bonelli, G.; Mandolesi, N.; Cortiglioni, S.; Morigi, G.; Partridge,R.B.; Danese, L.; De Zotti, G.

    1984-11-01

    The long-wavelength spectrum of the cosmic background radiation has been measured at five wavelengths (0.33, 0.9, 3.0, 6.3, and 12.0 cm). These measurements represent a continuation of the work reported by Smoot et al. (1983). The combine results have a weighted average of 2.73 {+-} 0.05 K and are consistent with past measurements. They limit the possible Compton distortion of the Cosmic Background Radiation spectrum to less than 8%.

  17. Low Frequency measurment of the Spectrum of the Cosmic BackgroundRadiation

    SciTech Connect

    Smoot, G.F.; De Amici, G.; Friedman, S.D.; Witebsky, C.; Mandolesi, N.; Partridge, R.b.; Sironi, G.; Danese, L.; De Zotti, G.

    1983-06-01

    We have made measurements of the cosmic background radiation spectrum at 5 wavelengths (0.33, 0.9, 3, 6.3, and 12 cm) using radiometers with wavelength-scaled corrugated horn antennas having very low sidelobes. A single large-mouth (0.7 m diameter) liquid-helium-cooled absolute reference load was used for all five radiometers. The results of the observations are consistent with previous measurements and represent a significant improvement in accuracy.

  18. Frequency multiplexed superconducting quantum interference device readout of large bolometer arrays for cosmic microwave background measurements.

    PubMed

    Dobbs, M A; Lueker, M; Aird, K A; Bender, A N; Benson, B A; Bleem, L E; Carlstrom, J E; Chang, C L; Cho, H-M; Clarke, J; Crawford, T M; Crites, A T; Flanigan, D I; de Haan, T; George, E M; Halverson, N W; Holzapfel, W L; Hrubes, J D; Johnson, B R; Joseph, J; Keisler, R; Kennedy, J; Kermish, Z; Lanting, T M; Lee, A T; Leitch, E M; Luong-Van, D; McMahon, J J; Mehl, J; Meyer, S S; Montroy, T E; Padin, S; Plagge, T; Pryke, C; Richards, P L; Ruhl, J E; Schaffer, K K; Schwan, D; Shirokoff, E; Spieler, H G; Staniszewski, Z; Stark, A A; Vanderlinde, K; Vieira, J D; Vu, C; Westbrook, B; Williamson, R

    2012-07-01

    A technological milestone for experiments employing transition edge sensor bolometers operating at sub-Kelvin temperature is the deployment of detector arrays with 100s-1000s of bolometers. One key technology for such arrays is readout multiplexing: the ability to read out many sensors simultaneously on the same set of wires. This paper describes a frequency-domain multiplexed readout system which has been developed for and deployed on the APEX-SZ and South Pole Telescope millimeter wavelength receivers. In this system, the detector array is divided into modules of seven detectors, and each bolometer within the module is biased with a unique ?MHz sinusoidal carrier such that the individual bolometer signals are well separated in frequency space. The currents from all bolometers in a module are summed together and pre-amplified with superconducting quantum interference devices operating at 4 K. Room temperature electronics demodulate the carriers to recover the bolometer signals, which are digitized separately and stored to disk. This readout system contributes little noise relative to the detectors themselves, is remarkably insensitive to unwanted microphonic excitations, and provides a technology pathway to multiplexing larger numbers of sensors. PMID:22852677

  19. Effect of selective suppression of spatial frequency domain noise on visual detection of a sample object in an inhomogeneous background

    NASA Astrophysics Data System (ADS)

    Pietrzyk, Mariusz W.; McDonald, J. Scott; Brennan, Patrick C.; Bourne, Roger M.

    2012-02-01

    This study aims to investigate the effect of selective suppression of spatial frequency (SF) domain Gaussian white noise on visibility of a sample object in inhomogeneous backgrounds. SF-specific variation in signal-to-noise ratio due to selective signal averaging in the SF domain is a consequence of some of MRI acquisition methods. This study models the potential effect on visibility of an object in a complex image. A single disc was randomly positioned in 25 of 50 synthetic clustered lumpy background images. Neutral, low mid and high frequency suppressed Gaussian white noise was added in the frequency domain to simulate SF-weighted MRI signal averaging. Twelve readers performed visual searching and localization tasks on ordered sets. Subjects were asked to detect and locate discs and to rank confidence level. Sensitivity, specificity and ROC analyses were performed. Readers achieved significantly higher ROC AUC - Azscores - (p<0.001) and case-based sensitivity (p<0.001) and target-based sensitivity (p<0.001) with images in which low SF noise was suppressed. Also, significant higher cased-based sensitivity (p=0.005), target-based sensitivity (p=0.022) and Az-values (p=0.01) were scored under mid SF noise filtration. No significant differences were observed when images with SF-neutral noise suppression were compared with high SF noise suppression. In conclusion, increase of low and also mid SF signal signal-to-noise ratio significantly improves human performance in visual detection of simple targets in inhomogeneous backgrounds and suggests that a low SF bias in MRI signal averaging may enhance diagnostic quality.

  20. Chromosome translocations: a biomarker for retrospective biodosimetry.

    PubMed Central

    Lucas, J N

    1997-01-01

    We discuss here the results from our studies demonstrating that simple translocations detected by chromosome painting can be used to reconstruct radiation doses for workers exposed within the dose limits and for individuals with past exposure. To be useful, a biomarker for exposure and risk assessment should employ an end point that is highly quantitative, stable over time, and relevant to human risk. Recent advances in chromosome staining using fluorescence in situ hybridization facilitate fast and reliable measurement of simple translocations, a type of DNA damage linked both to prior clastogenic exposure and to risk. In contrast to other biomarkers available, the frequency of simple translocations in individuals exposed to whole-body radiation is stable over time postexposure, has little interindividual variability, and can be measured accurately at low frequencies. PMID:9467057

  1. Translocating Laysan Teal

    USGS Multimedia Gallery

    John Klavitter of the US Fish and Wildlife Service, left, and USGS biologist Michelle Reynolds attach transmitters to critically endangered Laysan teal that were translocated from Laysan to Midway Island to expand the species' population and range. ...

  2. Fluctuations in polymer translocation

    NASA Astrophysics Data System (ADS)

    Krapivsky, P. L.; Mallick, K.

    2010-07-01

    We investigate a model of chaperone-assisted polymer translocation through a nanopore in a membrane. Translocation is driven by irreversible random sequential absorption of chaperone proteins that bind to the polymer on one side of the membrane. The proteins are larger than the pore and hence the backward motion of the polymer is inhibited. This mechanism rectifies Brownian fluctuations and results in an effective force that drags the polymer in a preferred direction. The translocated polymer undergoes an effective biased random walk and we compute the corresponding diffusion constant. Our methods allow us to determine the large deviation function which, in addition to velocity and diffusion constant, contains the entire statistics of the translocated length.

  3. A Measurement of the Temperature of the Cosmic MicrowaveBackground at a Frequency of 7.5 GHz

    SciTech Connect

    Kogut, A.; Bensadoun, M.; De Amici, Giovanni; Levin, S.; Smoot,George F.; Witebsky, C.

    1989-06-01

    We have measured the intensity of the cosmic microwave background (CMB) at a frequency of 7.5 GHz (wavelength 4.0 cm) using a ground-based, total power radiometer calibrated at the horn aperture by an external cryogenic reference target. The radiometer measured the difference in antenna temperature between the reference target and the zenith sky from a dry, high-altitude site. Subtraction of foreground signals (primarily atmospheric and galactic emission) measured with the same instrument leaves the CMB as the residual. The radiometer measured the atmospheric antenna temperature by correlating the signal change with the airmass in the beam during tip scans. The small galactic signal was subtracted based on extrapolation from lower frequencies, and was checked by differential drift scans. The limiting uncertainty in the CMB measurement was the effect of ground radiation in the antenna sidelobes during atmospheric measurements. The thermodynamic temperature of the CMB at 7.5 GHz is 2.59 {+-} 0.07 K (68% confidence level).

  4. Multi-frequency measurements of the NVSS foreground sources in the cosmic background imager fields. I. Data release

    NASA Astrophysics Data System (ADS)

    Angelakis, E.; Kraus, A.; Readhead, A. C. S.; Zensus, J. A.; Bustos, R.; Krichbaum, T. P.; Witzel, A.; Pearson, T. J.

    2009-07-01

    Context: We present the results of the flux density measurements at 4.85 GHz and 10.45 GHz of a sample of 5998 NVSS radio sources with the Effelsberg 100 m telescope. Aims: The initial motivation was the need to identify the NVSS radio sources that could potentially contribute significant contaminating flux in the frequency range at which the Cosmic Background Imager experiment operated. Methods: An efficient way to achieve this challenging goal has been to compute the high frequency flux density of those sources by extrapolating their radio spectrum. This is determined by the three-point spectral index measured on the basis of the NVSS entry at 1.4 GHz and the measurements at 4.85 GHz and 10.45 GHz carried out with the 100 m Effelsberg telescope. Results: These measurements are important since the targeted sample probes the weak part of the flux density distribution, hence the decision to make the data available. Conclusions: We present the table with flux density measurements of 3434 sources that showed no confusion allowing reliable measurements, their detection rates, their spectral index distribution and an interpretation which explains satisfactorily the observed uncertainties. Full Table 8 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/501/801

  5. Chromosomal translocations and palindromic AT-rich repeats.

    PubMed

    Kato, Takema; Kurahashi, Hiroki; Emanuel, Beverly S

    2012-06-01

    Repetitive DNA sequences constitute 30% of the human genome, and are often sites of genomic rearrangement. Recently, it has been found that several constitutional translocations, especially those that involve chromosome 22, take place utilizing palindromic sequences on 22q11 and on the partner chromosome. Analysis of translocation junction fragments shows that the breakpoints of such palindrome-mediated translocations are localized at the center of palindromic AT-rich repeats (PATRRs). The presence of PATRRs at the breakpoints indicates a palindrome-mediated mechanism involved in the generation of these constitutional translocations. Identification of these PATRR-mediated translocations suggests a universal pathway for gross chromosomal rearrangement in the human genome. De novo occurrences of PATRR-mediated translocations can be detected by PCR in normal sperm samples but not somatic cells. Polymorphisms of various PATRRs influence their propensity for adopting a secondary structure, which in turn affects de novo translocation frequency. We propose that the PATRRs form an unstable secondary structure, which leads to double-strand breaks at the center of the PATRR. The double-strand breaks appear to be followed by a non-homologous end-joining repair pathway, ultimately leading to the translocations. This review considers recent findings concerning the mechanism of meiosis-specific, PATRR-mediated translocations. PMID:22402448

  6. Signal Photon Flux and Background Noise in a Coupling Electromagnetic Detecting System for High Frequency Gravitational Waves

    E-print Network

    F. Y. Li; N. Yang; Z. Y. Fang; R. M. L. Baker Jr.; G. V. Stephenson; H. Wen

    2010-06-17

    A coupling system between Gaussian type-microwave photon flux, static magnetic field and fractal membranes (or other equivalent microwave lenses) can be used to detect high-frequency gravitational waves (HFGWs) in the microwave band. We study the signal photon flux, background photon flux and the requisite minimal accumulation time of the signal in the coupling system. Unlike pure inverse Gertsenshtein effect (G-effect) caused by the HFGWs in the GHz band, the the electromagnetic (EM) detecting scheme (EDS) proposed by China and the US HFGW groups is based on the composite effect of the synchro-resonance effect and the inverse G-effect. Key parameters in the scheme include first-order perturbative photon flux (PPF) and not the second-order PPF; the distinguishable signal is the transverse first-order PPF and not the longitudinal PPF; the photon flux focused by the fractal membranes or other equivalent microwave lenses is not only the transverse first-order PPF but the total transverse photon flux, and these photon fluxes have different signal-to-noise ratios at the different receiving surfaces. Theoretical analysis and numerical estimation show that the requisite minimal accumulation time of the signal at the special receiving surfaces and in the background noise fluctuation would be $\\sim10^3-10^5$ seconds for the typical laboratory condition and parameters of $h_{r.m.s.}\\sim10^{-26}-10^{-30}$ at 5GHz with bandwidth $\\sim$1Hz. In addition, we review the inverse G-effect in the EM detection of the HFGWs, and it is shown that the EM detecting scheme based only on the pure inverse G-effect in the laboratory condition would not be useful to detect HFGWs in the microwave band.

  7. Phosphate translocator and adenylate translocator in chromoplast membranes

    Microsoft Academic Search

    Bodo Liedvogel; Hans Kleinig

    1980-01-01

    It is shown by the criteria of saturation kinetics, specificity, and inhibition experiments that chromoplast membranes from the daffodil flower contain a phosphate translocator for the counter-exchange of phosphate, and 3-phosphoglycerate, as well as phosphoenolpyruvate; they also contain an adenylate translocator. This is the first report on the occurrence of these translocators in non-green plastids. Both translocators exhibit certain dissimilar

  8. Temperature dependence of DNA translocations through solid-state nanopores

    NASA Astrophysics Data System (ADS)

    Verschueren, Daniel V.; Jonsson, Magnus P.; Dekker, Cees

    2015-06-01

    In order to gain a better physical understanding of DNA translocations through solid-state nanopores, we study the temperature dependence of ?-DNA translocations through 10 nm diameter silicon nitride nanopores, both experimentally and theoretically. The measured ionic conductance G, the DNA-induced ionic-conductance blockades ? G and the event frequency ? all increase with increasing temperature while the DNA translocation time ? decreases. G and ? G are accurately described when bulk and surface conductances of the nanopore are considered and access resistance is incorporated appropriately. Viscous drag on the untranslocated part of the DNA coil is found to dominate the temperature dependence of the translocation times and the event rate is well described by a balance between diffusion and electrophoretic motion. The good fit between modeled and measured properties of DNA translocations through solid-state nanopores in this first comprehensive temperature study, suggest that our model captures the relevant physics of the process.

  9. Temperature dependence of DNA translocations through solid-state nanopores.

    PubMed

    Verschueren, Daniel V; Jonsson, Magnus P; Dekker, Cees

    2015-06-12

    In order to gain a better physical understanding of DNA translocations through solid-state nanopores, we study the temperature dependence of ?-DNA translocations through 10 nm diameter silicon nitride nanopores, both experimentally and theoretically. The measured ionic conductance G, the DNA-induced ionic-conductance blockades [Formula: see text] and the event frequency ? all increase with increasing temperature while the DNA translocation time ? decreases. G and [Formula: see text] are accurately described when bulk and surface conductances of the nanopore are considered and access resistance is incorporated appropriately. Viscous drag on the untranslocated part of the DNA coil is found to dominate the temperature dependence of the translocation times and the event rate is well described by a balance between diffusion and electrophoretic motion. The good fit between modeled and measured properties of DNA translocations through solid-state nanopores in this first comprehensive temperature study, suggest that our model captures the relevant physics of the process. PMID:25994084

  10. Simulations of Polymer Translocation

    NASA Astrophysics Data System (ADS)

    Vocks, H.

    2008-07-01

    Transport of molecules across membranes is an essential mechanism for life processes. These molecules are often long, and the pores in the membranes are too narrow for the molecules to pass through as a single unit. In such circumstances, the molecules have to squeeze -- i.e., translocate -- themselves through the pores. DNA, RNA and proteins are such naturally occuring long molecules in a variety of biological processes. Understandably, the process of translocation has been an active topic of current research: not only because it is a cornerstone of many biological processes, but also due to its relevance for practical applications. Translocation is a complicated process in living organisms -- the presence of chaperone molecules, pH, chemical potential gradients, and assisting molecular motors strongly influence its dynamics. Consequently, the translocation process has been empirically studied in great variety in biological literature. Study of translocation as a biophysical process is more recent. Herein, the polymer is simplified to a sequentially connected string of N monomers as it passes through a narrow pore on a membrane. The quantities of interest are the typical time scale for the polymer to leave a confining cell (the ``escape of a polymer from a vesicle'' time scale), and the typical time scale the polymer spends in the pore (the ``dwell'' time scale) as a function of N and other parameters like membrane thickness, membrane adsorption, electrochemical potential gradient, etc. Our research is focused on computer simulations of translocation. Since our main interest is in the scaling properties, we use a highly simplified description of the translocation process. The polymer is described as a self-avoiding walk on a lattice, and its dynamics consists of single-monomer jumps from one lattice site to another neighboring one. Since we have a very efficient program to simulate such polymer dynamics, which we decribe in Chapter 2, we can perform long simulations in which long polymers creep through tiny pores. In Chapter 3 we study pore blockage times for a translocating polymer of length N, driven by a field E across te pore. In three dimensions we find that the typical time the pore remains blocked during a translocation event scales as N^{1.37}/E We show that the scaling behavior stems from the polymer dynamics at the immediate vicinity of the pore -- in particular, the memory effects in the polymer chain tension imbalance across the pore. Chapter 4 studies the unbiased translocation of a polymer with length N, surrounded by equally long polymers, through a narrow pore in a membrane. We show that in dense polymeric systems a relaxation time exists that scales as N^{2.65}, much longer than the Rouse time N^2. If the polymers are well entangled, we find that the mean dwell times scales as N^{3.3}, while for shorter, less entangled polymers, we measure dwell times scaling as N^{2.7}. In Chapter 5 we study the translocation of an RNA molecule, pulled through a nanopore by an optical tweezer, as a method to determine its secondary structure. The resolution with which the elements of the secondary structure can be determined is limited by thermal fluctuations, ruling out single-nucleotide resolution under normal experimental conditions.

  11. The frequency of precocious segregation of sister chromatids in mouse female meiosis I is affected by genetic background.

    PubMed

    Danylevska, Anna; Kovacovicova, Kristina; Awadova, Thuraya; Anger, Martin

    2014-09-01

    Mammalian female gametes frequently suffer from numerical chromosomal aberrations, the main cause of miscarriages and severe developmental defects. The underlying mechanisms responsible for the development of aneuploidy in oocytes are still not completely understood and remain a subject of extensive research. From studies focused on prevalence of aneuploidy in mouse oocytes, it has become obvious that reported rates of aneuploidy are strongly dependent on the method used for chromosome counting. In addition, it seems likely that differences between mouse strains could influence the frequency of aneuploidy as well; however, up till now, such a comparison has not been available. Therefore, in our study, we measured the levels of aneuploidy which has resulted from missegregation in meiosis I, in oocytes of three commonly used mouse strains-CD-1, C3H/HeJ, and C57BL/6. Our results revealed that, although the overall chromosomal numerical aberration rates were similar in all three strains, a different number of oocytes in each strain contained prematurely segregated sister chromatids (PSSC). This indicates that a predisposition for this type of chromosome segregation error in oocyte meiosis I is dependent on genetic background. PMID:24935618

  12. The origins of ALK translocations.

    PubMed

    Roukos, Vassilis; Mathas, Stephan

    2015-01-01

    Translocations involving the anaplastic lymphoma kinase (ALK) gene locus on chromosome 2p23 were first described in anaplastic large cell lymphoma (ALCL). Although most commonly fused to the nucleophosmin (NPM1) gene on chromosome 5q35, which results in the t(2;5)(p23;q35)/NPM1-ALK translocation, several other ALK translocation partners have meanwhile been identified. Furthermore, apart from ALCL, ALK-involving translocations have been described in other hematopoietic and non-hematopoietic cancers. However, despite a rapid increase in literature on the nature and tissue distribution of ALK-translocations, much less is known about the mechanisms of formation of these translocations. The emergence of translocations has been linked to the transcriptional activity of the respective genome regions, reorganization of the chromatin and activation of the DNA repair machinery. In this review we discuss mechanisms and implications of formation of ALK-translocations. PMID:25961701

  13. Mode of ATM-dependent suppression of chromosome translocation.

    PubMed

    Yamauchi, Motohiro; Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi

    2011-12-01

    It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs. PMID:22093823

  14. The persistence of chromosome translocations in a radiation worker accidentally exposed to tritium

    Microsoft Academic Search

    J. N. Lucas; M. Poggensee; T. Straume

    1992-01-01

    The chromosome translocation frequency in lymphocytes of an individual accidentally exposed to tritium six years previously was measured using chromosome painting, Comparisons with results from cytogenetic studies shortly after the accident indicate that the translocation frequency has remained unaltered in this individual for six years.Copyright © 1992 S. Karger AG, Basel

  15. Effect of the genetic background on recombination frequency in the cn-vg region of the second chromosome of natural populations of Drosophila melanogaster.

    PubMed

    Hofmanová, J

    1975-01-01

    Newly established test stocks made it possible to follow the effect of three different defined genetic backgrounds (first and third chromosomes) on recombination frequency in the cn-vg region of the second chromosomes isolated from four natural populations of Drosophila melanogaster. One background was composed of the chromosomes with inversions obtained from the stock (see article) and another two backgrounds were of the standard type consisting one-half of the original chromosomes from the natural population and one-half of the chromosomes of the stocks Oregon R or Samarkand. Using the analysis of variance significant differences in RF values were found between and within populations and especially between the different backgrounds. Some simple and double interactions between the above factors played a role. The highest RF values were obtained on the background [corrected] with inversions. The effect of the different genetic backgrounds [corrected] by the action of the genetic modifiers of RF. The different genetic backgrounds affected the variations in RF values in individual populations and the different populations reacted differentially to the changed genetic background. The design of the experiment permitted an estimation of the causal compoenents of variance and heritability of RF from the sib analysis. The additive component of variance was present in only two of the populations under test; the respective estimates of heritability were very low. PMID:804421

  16. Acrylamide: induction of heritable translocations in male mice

    SciTech Connect

    Shelby, M.D.; Cain, K.T.; Cornett, C.V.; Generoso, W.M.

    1987-01-01

    Acrylamide (AA), known to induce dominant lethals in male rodents, was studied in the mouse heritable translocation test by using intraperitoneal injections on 5 consecutive days. Matings on days 7-10 following the last injection yielded a high frequency of translocation carriers in the F/sub 1/ male population, which demonstrated that acrylamide is an effective inducer of translocations in postmeiotic germ cells. As an inducer of both dominant lethals and heritable translocations in late spermatids and early spermatozoa, AA is similar to alkylating agents such as ethylmethanesulfonate and ethylene oxide. However, AA's chemical structure, the nature of adducts formed with DNA, and its lack of mutagenicity in bacteria suggest a different mechanism as the basis for AA's germ cell mutagenicity.

  17. Translocations in epithelial cancers

    PubMed Central

    Chad Brenner, J.; Chinnaiyan, Arul M.

    2009-01-01

    Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

  18. Within-Range Translocations and Their Consequences in European Larch

    PubMed Central

    Wagner, Stefanie; Liepelt, Sascha; Gerber, Sophie; Petit, Rémy J.

    2015-01-01

    In contrast to biological invasions, translocations of individuals within a species range are understudied, due to difficulties in systematically detecting them. This results in limited knowledge about the corresponding processes and uncertainties regarding the status of extant populations. European larch, a forest tree whose fragmented native distribution is restricted to the Alps and to other Central European mountains, has been massively planted for at least 300 years. Here we focus on the genetic characterization of translocations having taken place within its native range. Microsatellite variation at 13 nuclear loci and sequence data of two mitochondrial DNA fragments were analyzed on the basis of a comprehensive range-wide population sample. Two complementary methods (Geneclass and Structure) were used to infer translocation events based on nuclear data whereas mitochondrial data were used for validation of these inferences. Using Geneclass, we found translocation events in a majority of populations. Additional cases of translocation and many instances of admixture were identified using Structure, thanks to the clear-cut ancestral genetic structure detected in this species. In particular, a strong divide between Alpine and Central European populations, also apparent at mitochondrial markers, helped uncover details on translocation events and related processes. Translocations and associated admixture events were found to be heterogeneously distributed across the species range, with a particularly high frequency in Central Europe. Furthermore, translocations frequently involved multiple geographic sources, some of which were over-represented. Our study illustrates the importance of range-wide investigations for tracing translocations back to their origins and for revealing some of their consequences. It provides some first clues for developing suitable conservation and management strategies. PMID:26000791

  19. Fluorescence in situ hybridization analysis using PAX8- and PPARG-specific probes reveals the presence of PAX8-PPARG translocation and 3p25 aneusomy in follicular thyroid neoplasms.

    PubMed

    Chia, Wai Kit; Sharifah, Noor Akmal; Reena, Rahayu Md Zin; Zubaidah, Zakaria; Clarence-Ko, Ching Huat; Rohaizak, Muhammad; Naqiyah, Ibrahim; Srijit, Das; Hisham, Abdullah Nor; Asmiati, Arbi; Rafie, Md Kaslan

    2010-01-01

    At the present time, the differentiation between follicular thyroid carcinoma (FTC) and adenoma can be made only postoperatively and is based on the presence of capsular or vascular invasion. The ability to differentiate preoperatively between the malignant and benign forms of follicular thyroid tumors assumes greater importance in any clinical setting. The PAX8-PPARG translocation has been reported to occur in the majority of FTC. In this study, a group of 60 follicular thyroid neoplasms [18 FTC, 1 Hurthle cell carcinoma (HCC), 24 follicular thyroid adenomas (FTA), 5 Hurthle cell adenomas (HCA), and 12 follicular variants of papillary thyroid carcinomas (FV-PTC)] were analyzed to determine the prevalence of the PAX8-PPARG translocation by fluorescence in situ hybridization. The PAX8-PPARG translocation was detected in 2/18 FTC (11.1%). In addition, 2/18 (11.1%) FTC and 1/5 (20%) HCA showed 3p25 aneusomy only. The frequency of the translocation detected in the study was lower compared to the earlier studies conducted in Western countries. This might be attributed to the ethnic background and geographic location. Detection of either the PAX8-PPARG translocation or the 3p25 aneusomy in FTC indicates that these are independent genetic events. It is hereby concluded that 3p25 aneusomy or PAX8-PPARG translocation may play an important role in the molecular pathogenesis of follicular thyroid tumors. PMID:19963130

  20. Frequency of EGFR and KRAS Mutations in Patients with Non Small Cell Lung Cancer by Racial Background: Do Disparities exist?

    PubMed Central

    Bauml, Joshua; Mick, Rosemarie; Zhang, Yu; Watt, Christopher D.; Vachani, Anil; Aggarwal, Charu; Evans, Tracey; Langer, Corey

    2013-01-01

    Introduction Mutations in EGFR and KRAS can impact treatment decisions for patients with NSCLC. The incidence of these mutations varies, and it is unclear whether there is a decreased frequency among African Americans (AfAs). Methods We performed a retrospective chart review of 513 NSCLC patients undergoing EGFR and KRAS mutational analysis at the Hospital of the University of Pennsylvania between May 2008 and November 2011. Clinical and pathologic data were abstracted from the patients’ electronic medical record. Results Of 497 patients with informative EGFR mutation analyses, the frequency of EGFR mutation was 13.9%. The frequency of EGFR mutations was associated with race (p<0.001) and was lower in AfA patients compared to Caucasian (C) patients but did not reach statistical significance (4.8% vs 13.7%, p=0.06). Mean Charlson Comorbidity Index and number of cigarette pack years were significantly lower in patients with EGFR mutations (p=0.01 and p<0.001, respectively). Multivariable logistic regression analysis showed a significant association between race and EGFR mutation (p=0.01), even after adjusting for smoking status (p<0.001) and gender (p=0.03). KRAS mutation (study frequency 28.1%) was not associated with race (p=0.08; p=0.51 for Afa vs C patients), but was more common among smokers (p<0.001) and females (p=0.01). Conclusions Based on multivariable analysis, even after adjusting for smoking status and gender, we found that race was statistically significantly associated with EGFR mutation, but not KRAS mutational status. To our knowledge, this is the largest single institution series to date evaluating racial differences in EGFR and KRAS mutational status among patients with NSCLC. PMID:23806795

  1. Heritable translocation test in mice.

    PubMed

    Generoso, W M; Bishop, J B; Gosslee, D G; Newell, G W; Sheu, C J; von Halle, E

    1980-09-01

    The status of the heritable-translocation test in mice with respect to its usefulness in practical testing was evaluated by using information available in the open literature. A total of 47 reports were evaluated; 29 were judged to contain adequate information to classify whether or not a given chemical induced heritable translocations. Heritable-translocation data were available for 32 compounds; data were not adequate for 15 compounds. Of the remaining 17 compounds, clear-cut determination of positive or negative effects was made for 14 compounds, while data for 3 compounds were only suggestive of either negative or positive effects. 10 chemicals have been shown to induce heritable translocations. These chemicals are either direct or indirect alkylating agents. The heritable-translocation test needs to be improved before it can be used in wide-scale practical testing. The most important question is whether or not historical controls can be used in tests for significance; the cost of concurrent controls is prohibitive. There is a need to standardize methods used in testing laboratories with respect to the size of error involved in classifying translocation heterozygotes and the power of the test. There is also a need to study in the effectiveness of non-alkylating clastogens in inducing heritable translocations in mice. PMID:7453713

  2. Theoretical background for continental- and global-scale full-waveform inversion in the time-frequency domain

    NASA Astrophysics Data System (ADS)

    Fichtner, Andreas; Kennett, Brian L. N.; Igel, Heiner; Bunge, Hans-Peter

    2008-11-01

    We propose a new approach to full seismic waveform inversion on continental and global scales. This is based on the time-frequency transform of both data and synthetic seismograms with the use of time- and frequency-dependent phase and envelope misfits. These misfits allow us to provide a complete quantification of the differences between data and synthetics while separating phase and amplitude information. The result is an efficient exploitation of waveform information that is robust and quasi-linearly related to Earth's structure. Thus, the phase and envelope misfits are usable for continental- and global-scale tomography, that is, in a scenario where the seismic wavefield is spatially undersampled and where a 3-D reference model is usually unavailable. Body waves, surface waves and interfering phases are naturally included in the analysis. We discuss and illustrate technical details of phase measurements such as the treatment of phase jumps and instability in the case of small amplitudes. The Fréchet kernels for phase and envelope misfits can be expressed in terms of their corresponding adjoint wavefields and the forward wavefield. The adjoint wavefields are uniquely determined by their respective adjoint-source time functions. We derive the adjoint-source time functions for phase and envelope misfits. The adjoint sources can be expressed as inverse time-frequency transforms of a weighted phase difference or a weighted envelope difference. In a comparative study, we establish connections between the phase and envelope misfits and the following widely used measures of seismic waveform differences: (1) cross-correlation time-shifts; (2) relative rms amplitude differences; (3) generalized seismological data functionals and (4) the L2 distance between data and synthetics used in time-domain full-waveform inversion. We illustrate the computation of Fréchet kernels for phase and envelope misfits with data from an event in the West Irian region of Indonesia, recorded on the Australian continent. The synthetic seismograms are computed for a heterogeneous 3-D velocity model of the Australian upper mantle, with a spectral-element method. The examples include P body waves, Rayleigh waves and S waves, interfering with higher-mode surface waves. All the kernels differ from the more familar kernels for cross-correlation time-shifts or relative rms amplitude differences. The differences arise from interference effects, 3-D Earth's structure and waveform dissimilarities that are due to waveform dispersion in the heterogeneous Earth.

  3. Persistence of radiation-induced translocations in human peripheral blood determined by chromosome painting.

    PubMed

    Matsumoto, K; Ramsey, M J; Nelson, D O; Tucker, J D

    1998-06-01

    We have investigated the persistence of translocations and other types of chromosome damage with time using human peripheral blood acutely exposed in vitro to 137Cs gamma rays at doses ranging from 0.5 to 4 Gy. Freshly drawn blood from one donor was irradiated and metaphase chromosomes were prepared 2 to 7 days after exposure. Chromosomes 1, 2 and 4 were painted red-orange and chromosomes 3, 5 and 6 were painted green by fluorescence in situ hybridization (FISH) using "semi-directly" labeled whole-chromosome painting probes. This type of labeling combines direct and indirect labeling and showed significant advantages over both these other methods. All types of structural chromosome aberrations were classified by the Protocol for Aberration Identification and Nomenclature Terminology (PAINT) system. The yields of dicentric chromosomes, acentric fragments and ring chromosomes diminished with time as expected. Translocations exhibited greater persistence but showed a clear and statistically significant reduction in frequency at all doses. The mathematical model suggested that the translocation frequencies would reach a plateau of approximately 4, 15, 51, 106 and 179 translocations per 100 cell equivalents after irradiation with 0.5, 1, 2, 3 and 4 Gy, respectively. When translocations were classified by the conventional system, an analysis of the distribution of translocations and dicentrics per cell indicated that both types of exchanges were Poisson-distributed 48 h postirradiation. However, cells bearing translocations have a higher possibility of having dicentrics than cells without translocations. These findings suggest that dicentrics may contribute to a decline of translocation frequencies with time, and that some translocations are not completely persistent. The results obtained here using human blood exposed in vitro may influence the use of translocations as a retrospective biodosimeter of exposure to ionizing radiation in humans. PMID:9611099

  4. Polymer translocation induced by adsorption

    E-print Network

    Pyeong Jun Park; Wokyung Sung

    1998-02-10

    We study the translocation of a flexible polymer through a pore in a membrane induced by its adsorption on \\trans side of the membrane. When temperature $T$ is higher than $T_c$, the adsorption-desorption transition temperature, attractive interaction between polymer and membrane plays little role in affecting polymer conformation, leading to translocation time that scales as $\\tau\\sim L^3$ where $L$ is the polymer contour length. When $T < T_c$, however, the translocation time undergoes a sharp crossover to $\\tau\\sim L^2$ for sufficiently long polymers, following the second order conformational (adsorption) transition. The translocation time is found to exhibit the crossover around $T=T_c'$, which is lower than $T_c$ for polymers shorter than a critical length($N

  5. Mechanism of helicase translocation along nucleic acid

    E-print Network

    Zhang, Yunxin

    2012-01-01

    In cells, helicase translocation along nucleic acid is essential for many biological processes. However, so far, the mechanism of this translocation is not fully understood. Recent studies show that helicase might translocate through two processes, active process and passive process, with different translocation rate. In this study, a model including such two processes is presented. In which, each of these two processes consists of two sub-processes, chemical sub-process in which needed translocation factors are attached, and mechanochemical sub-process in which helicase makes a forward translocation step. Helicase can switch stochastically between these two processes with external force dependent rates. By this model, ribosome translocation along message RNA is detailed discussed. We found that, with the increase of external force, the mean translocation rate of ribosome increases from one lower limit to one upper limit, and both of these two limits increase with concentrations of the translocation factors. ...

  6. Partners with reciprocal translocations: genetic counseling for the 'double translocation'.

    PubMed

    Cook, L; Hartsfield, J K; Vance, G H

    1998-05-01

    SV at age 2 years presented with multiple congenital anomalies including an absent left kidney, anal stenosis, vertebral abnormalities, partial sacral agenesis, microcephaly, dysmorphic facial features, growth deficiency, and developmental delay. She was found to have a complex chromosomal rearrangement derived from balanced translocations in each parent. PMID:9660061

  7. Translocation bactérienne : mythe ou réalité ?

    Microsoft Academic Search

    G. Plantefève; G. Bleichner

    2001-01-01

    Bacterial translocation is defined as the passage of viable enteric bacteria across the intestinal mucosal barrier to the mesenteric lymph nodes and distant organs. Three mechanisms have been suggested to explain the phenomenon: altered intestinal barrier function, bacterial overgrowth, and impaired host defense. In experimental approach, reduced blood flow in the gut, trauma, chronic inflammation or immunosuppression are conditions that

  8. Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate

    Microsoft Academic Search

    E C Clark; S D Patel; P R Chadwick; G Warhurst; A Curry; G L Carlson

    2003-01-01

    Background and aims: Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes.Methods: The effect of tumour necrosis factor ? (TNF-?) on translocation of Escherichia coli C25

  9. Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model

    Microsoft Academic Search

    Barbara Rothen-Rutishauser; Christian Mühlfeld; Fabian Blank; Claudia Musso; Peter Gehr

    2007-01-01

    BACKGROUND: Experimental studies provide evidence that inhaled nanoparticles may translocate over the airspace epithelium and cause increased cellular inflammation. Little is known, however, about the dependence of particle size or material on translocation characteristics, inflammatory response and intracellular localization. RESULTS: Using a triple cell co-culture model of the human airway wall composed of epithelial cells, macrophages and dendritic cells we

  10. Disease dynamics during wildlife translocations: disruptions to the host population and potential consequences for transmission in desert tortoise contact networks

    USGS Publications Warehouse

    Aiello, Christina M.; Nussear, Kenneth E.; Walde, Andrew D.; Esque, Todd C.; Emblidge, Patrick G.; Sah, Pratha; Bansal, S.; Hudson, Peter J.

    2014-01-01

    Wildlife managers consider animal translocation a means of increasing the viability of a local population. However, augmentation may disrupt existing resident disease dynamics and initiate an outbreak that would effectively offset any advantages the translocation may have achieved. This paper examines fundamental concepts of disease ecology and identifies the conditions that will increase the likelihood of a disease outbreak following translocation. We highlight the importance of susceptibility to infection, population size and population connectivity – a characteristic likely affected by translocation but not often considered in risk assessments – in estimating outbreak risk due to translocation. We then explore these features in a species of conservation concern often translocated in the presence of infectious disease, the Mojave Desert tortoise, and use data from experimental tortoise translocations to detect changes in population connectivity that may influence pathogen transmission. Preliminary analyses comparing contact networks inferred from spatial data at control and translocation plots and infection simulation results through these networks suggest increased outbreak risk following translocation due to dispersal-driven changes in contact frequency and network structure. We outline future research goals to test these concepts and aid managers in designing effective risk assessment and intervention strategies that will improve translocation success.

  11. Acute myeloid leukemia with 11q23 translocations: myelomonocytic immunophenotype by multiparameter flow cytometry

    Microsoft Academic Search

    Baer; CC Stewart; D Lawrence; DC Arthur; K Mrózek; MP Strout; FR Davey; CA Schiffer; CD Bloomfield

    1998-01-01

    11q23 translocations (t(11q23)) are recurring cytogenetic abnormalities in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia, involving the same gene, ALL1 (or MLL). Mixed lineage antigen expression has been reported in these leukemias, but its frequency and clinical significance are unknown. We immunophenotyped leukemia cells from 19 adult de novo AML patients with t(11q23) by multiparameter flow cytometry. Translocations

  12. Dynamics of polymer translocation through kinked nanopores

    NASA Astrophysics Data System (ADS)

    Wang, Junfang; Wang, Yilin; Luo, Kaifu

    2015-02-01

    Polymer translocation through nanopore has potential technological applications for DNA sequencing, where one challenge problem is to slow down translocation speed. Inspired by experimental findings that kinked nanopores exhibit a large reduction in translocation velocity compared with their straight counterparts, we investigate the dynamics of polymer translocation through kinked nanopores in two dimensions under an applied external field. With increasing the tortuosity of an array of nanopores, our analytical results show that the translocation probability decreases. Langevin dynamics simulation results support this prediction and further indicate that with increasing the tortuosity, translocation time shows a slow increase followed by a rapid increase after a critical tortuosity. This behavior demonstrates that kinked nanopores can effectively reduce translocation speed. These results are interpreted by the roles of the tortuosity for decreasing the effective nanopore diameter, increasing effective nanopore length, and greatly increasing the DNA-pore friction.

  13. Facilitated translocation of polypeptides through a single nanopore

    NASA Astrophysics Data System (ADS)

    Bikwemu, Robert; Wolfe, Aaron J.; Xing, Xiangjun; Movileanu, Liviu

    2010-11-01

    The transport of polypeptides through nanopores is a key process in biology and medical biotechnology. Despite its critical importance, the underlying kinetics of polypeptide translocation through protein nanopores is not yet comprehensively understood. Here, we present a simple two-barrier, one-well kinetic model for the translocation of short positively charged polypeptides through a single transmembrane protein nanopore that is equipped with negatively charged rings, simply called traps. We demonstrate that the presence of these traps within the interior of the nanopore dramatically alters the free energy landscape for the partitioning of the polypeptide into the nanopore interior, as revealed by significant modifications in the activation free energies required for the transitions of the polypeptide from one state to the other. Our kinetic model permits the calculation of the relative and absolute exit frequencies of the short cationic polypeptides through either opening of the nanopore. Moreover, this approach enabled quantitative assessment of the kinetics of translocation of the polypeptides through a protein nanopore, which is strongly dependent on several factors, including the nature of the translocating polypeptide, the position of the traps, the strength of the polypeptide-attractive trap interactions and the applied transmembrane voltage.

  14. Facilitated Translocation of Polypeptides Through A Single Nanopore

    PubMed Central

    Bikwemu, Robert; Wolfe, Aaron J.; Xing, Xiangjun; Movileanu, Liviu

    2011-01-01

    The transport of polypeptides through nanopores is a key process in biology and medical biotechnology. Despite its critical importance, the underlying kinetics of polypeptide translocation through protein nanopores is not yet comprehensively understood. Here, we present a simple two-barrier, one-well kinetic model for the translocation of short positively charged polypeptides through a single transmembrane protein nanopore that is equiped with negatively charged rings, simply called traps. We demonstrate that the presence of these traps within the interior of the nanopore dramatically alters the free energy landscape for the partitioning of the polypeptide into the nanopore interior, as revealed by significant modifications in the activation free energies required for the transitions of the polypeptide from one state to other. Our kinetic model permits the calculation of the relative and absolute exit frequencies of the short cationic polypeptides through either opening of the nanopore. Moreover, this approach enabled quantitative assessment of the kinetics of translocation of the polypeptides through a protein nanopore, which is strongly dependent on several factors, including the nature of the translocating polypeptide, the position of the traps, the strength of the polypeptide-attractive trap interactions and the applied transmembrane voltage. PMID:21339604

  15. DNA translocation through graphene nanopores.

    PubMed

    Schneider, Grégory F; Kowalczyk, Stefan W; Calado, Victor E; Pandraud, Grégory; Zandbergen, Henny W; Vandersypen, Lieven M K; Dekker, Cees

    2010-08-11

    Nanopores--nanosized holes that can transport ions and molecules--are very promising devices for genomic screening, in particular DNA sequencing. Solid-state nanopores currently suffer from the drawback, however, that the channel constituting the pore is long, approximately 100 times the distance between two bases in a DNA molecule (0.5 nm for single-stranded DNA). This paper provides proof of concept that it is possible to realize and use ultrathin nanopores fabricated in graphene monolayers for single-molecule DNA translocation. The pores are obtained by placing a graphene flake over a microsize hole in a silicon nitride membrane and drilling a nanosize hole in the graphene using an electron beam. As individual DNA molecules translocate through the pore, characteristic temporary conductance changes are observed in the ionic current through the nanopore, setting the stage for future single-molecule genomic screening devices. PMID:20608744

  16. Campylobacter jejuni induces transcellular translocation of commensal bacteria via lipid rafts

    PubMed Central

    Kalischuk, Lisa D; Inglis, G Douglas; Buret, Andre G

    2009-01-01

    Background Campylobacter enteritis represents a risk factor for the development of inflammatory bowel disease (IBD) via unknown mechanisms. As IBD patients exhibit inflammatory responses to their commensal intestinal microflora, factors that induce translocation of commensal bacteria across the intestinal epithelium may contribute to IBD pathogenesis. This study sought to determine whether Campylobacter induces translocation of non-invasive intestinal bacteria, and characterize underlying mechanisms. Methods Mice were infected with C. jejuni and translocation of intestinal bacteria was assessed by quantitative bacterial culture of mesenteric lymph nodes (MLNs), liver, and spleen. To examine mechanisms of Campylobacter-induced bacterial translocation, transwell-grown T84 monolayers were inoculated with non-invasive Escherichia coli HB101 ± wild-type Campylobacter or invasion-defective mutants, and bacterial internalization and translocation were measured. Epithelial permeability was assessed by measuring flux of a 3 kDa dextran probe. The role of lipid rafts was assessed by cholesterol depletion and caveolin co-localization. Results C. jejuni 81–176 induced translocation of commensal intestinal bacteria to the MLNs, liver, and spleen of infected mice. In T84 monolayers, Campylobacter-induced internalization and translocation of E. coli occurred via a transcellular pathway, without increasing epithelial permeability, and was blocked by depletion of epithelial plasma membrane cholesterol. Invasion-defective mutants and Campylobacter-conditioned cell culture medium also induced E. coli translocation, indicating that C. jejuni does not directly 'shuttle' bacteria into enterocytes. In C. jejuni-treated monolayers, translocating E. coli associated with lipid rafts, and this phenomenon was blocked by cholesterol depletion. Conclusion Campylobacter, regardless of its own invasiveness, promotes the translocation of non-invasive bacteria across the intestinal epithelium via a lipid raft-mediated transcellular process. PMID:19338680

  17. Direct and Acclimatory Responses of Dark Respiration and Translocation to Temperature

    PubMed Central

    Bunce, James A.

    2007-01-01

    Background and Aims Accounting for the acclimation of respiration of plants to temperature remains a major problem in analysis of carbon balances of plants and ecosystems. Translocation of carbohydrates out of leaves in the dark requires energy from respiration. In this study relationships between the responses of leaf respiration and translocation to temperature are examined. Methods Direct and acclimatory responses to temperature of respiration and translocation in the dark were investigated in mature leaves of soybean and amaranth. In some cases translocation from leaves was prevented by heat-girdling the phloem in the leaf petiole, or photosynthesis during the previous day was altered. Key Results In both species short-term increases in temperature early in the dark period led to exponential increases in rates of respiration. However, respiration rates decreased toward the end of the dark period at higher temperatures. Stopping translocation largely prevented this decrease in respiration, suggesting that the decrease in respiration was due to low availability of substrates. In soybean, translocation also increased with temperature, and both respiration and translocation fully acclimated to temperature. In amaranth, translocation in the dark was independent of temperature, and respiration did not acclimate to temperature. Respiration and translocation rates both decreased with lower photosynthesis during the previous day in the two species. Conclusions Substrate supply limited total night-time respiration in both species at high temperatures and following days with low photosynthesis. This resulted in an apparent acclimation of respiration to high temperatures within one night in both species. However, after long-term exposure to different temperatures there was no evidence that lack of substrates limited respiration in either species. In amaranth, respiration did not limit translocation rates over the temperature range of 20–35 °C. PMID:17483153

  18. Membrane translocation by anthrax toxin.

    PubMed

    Collier, R John

    2009-12-01

    Much attention has been focused on anthrax toxin recently, both because of its central role in the pathogenesis of Bacillus anthracis and because it has proven to be one of the most tractable toxins for studying how enzymic moieties of intracellularly acting toxins traverse membranes. The Protective Antigen (PA) moiety of the toxin, after being proteolytically activated at the cell surface, self-associates to form a heptameric pore precursor (prepore). The prepore binds up to three molecules of Edema Factor (EF), Lethal Factor (LF), or both, forming a series of complexes that are then endocytosed. Under the influence of acidic pH within the endosome, the prepore undergoes a conformational transition to a mushroom-shaped pore, with a globular cap and 100A-long stem that spans the membrane. Electrophysiological studies in planar bilayers indicate that EF and LF translocate through the pore in unfolded form and in the N- to C-terminal direction. The pore serves as an active transporter, which translocates its proteinaceous cargo across the endosomal membrane in response to DeltapH and perhaps, to a degree, Deltapsi. A ring of seven Phe residues (Phe427) in the lumen of the pore forms a seal around the translocating polypeptide and blocks the passage of ions, presumably preserving the pH gradient. A charge state-dependent Brownian ratchet mechanism has been proposed to explain how the pore translocates EF and LF. This transport mechanism of the pore may function in concert with molecular chaperonins to effect delivery of effector proteins in catalytically active form to the cytosolic compartment of host cells. PMID:19563824

  19. Problems with mitigation translocation of herpetofauna.

    PubMed

    Sullivan, Brian K; Nowak, Erika M; Kwiatkowski, Matthew A

    2015-02-01

    Mitigation translocation of nuisance animals is a commonly used management practice aimed at resolution of human-animal conflict by removal and release of an individual animal. Long considered a reasonable undertaking, especially by the general public, it is now known that translocated subjects are negatively affected by the practice. Mitigation translocation is typically undertaken with individual adult organisms and has a much lower success rate than the more widely practiced conservation translocation of threatened and endangered species. Nonetheless, the public and many conservation practitioners believe that because population-level conservation translocations have been successful that mitigation translocation can be satisfactorily applied to a wide variety of human-wildlife conflict situations. We reviewed mitigation translocations of reptiles, including our own work with 3 long-lived species (Gila monsters [Heloderma suspectum], Sonoran desert tortoises [Gopherus morafkai], and western diamond-backed rattlesnakes [Crotalus atrox]). Overall, mitigation translocation had a low success rate when judged either by effects on individuals (in all studies reviewed they exhibited increased movement or increased mortality) or by the success of the resolution of the human-animal conflict (translocated individuals often returned to the capture site). Careful planning and identification of knowledge gaps are critical to increasing success rates in mitigation translocations in the face of increasing pressure to find solutions for species threatened by diverse anthropogenic factors, including climate change and exurban and energy development. PMID:25040040

  20. Persistence of radiation-induced translocations in rat peripheral blood determined by chromosome painting

    SciTech Connect

    Tucker, J.D.; Briner, J.F.; Eveleth, G.G. [Lawrence Livermore National Lab., CA (United States)] [and others] [Lawrence Livermore National Lab., CA (United States); and others

    1997-12-31

    In this article, we address the issue of persistence of chromosome exchanges following acute in vitro exposure of rat peripheral blood to {sup 137}Cs. Irradiation occurred 24 hr after culture initiation, and metaphase chromosomes were prepared 2, 3, 4, and 5 days later. Chromosomes 1, 2, and 4 were painted in unique colors and scored for structural aberrations. Dicentric chromosomes an acentric fragments diminished rapidly with time, as expected. Translocations exhibited greater persistence, but still showed a reduction in frequency, reaching a plateau of approximately 65 and 55% of their initial values, 4 days after exposure to 1 and 2 Gy, respectively. An exponentially declining model was fit to the combined dicentric, acentric fragment, and translocation frequencies, which showed that all three aberration types declined at equivalent rates. The frequencies of dicentrics and fragments declined to a plateau of zero, while translocations reached a plateau at frequencies significantly greater than zero. The decline in translocations with time is inconsistent with prevailing theoretical expectations, but is consistent with a model where some translocations are fully stable (persistent) and some are unstable (not persistent) through cell division. These results may have implications for radiation biodosimetry in humans.

  1. What Drives the Translocation of Proteins?

    Microsoft Academic Search

    S ANFORD SIMON; C HARLES PESKIN; GEORGE OSTER

    1992-01-01

    We propose that protein translocation across lipid bilayers is driven by biased random thermalmotion. This "Brownian Ratchet" mechanism rests on the assumption that there is a chemicalasymmetry between the cis and trans sides of the membrane. Several mechanism couldcontribute to rectifying the thermal reptation of the protein, including binding anddissociation of chaperonins to the translocating chain, a pore-associated ATPase, pH

  2. Translocation in the nonpolytrichaceous moss grimmia laevigata

    Microsoft Academic Search

    Peter Alpert

    1989-01-01

    A superficially rhizomatous habit suggested that the moss Grimmia laevigata might function as a clonal, rhizomatous plant and translocate photoassimilates to below ground organs, even though the species is outside the order Polytrichales, which includes the only mosses known to posses sieve cells. Labelling with ¹⁴COâ indicated that at least 10% of newly assimilated carbon was translocated out of leafy

  3. Origins of chromosome translocations in childhood leukaemia

    Microsoft Academic Search

    Joe Wiemels; Mel F. Greaves

    2003-01-01

    Chromosome translocations are often early or initiating events in leukaemogenesis, occurring prenatally in most cases of childhood leukaemia. Although these genetic changes are necessary, they are usually not sufficient to cause leukaemia. How, when and where do translocations arise? And can these insights aid our understanding of the natural history, pathogenesis and causes of leukaemia?

  4. Haloarchaeal Protein Translocation via the Twin Arginine Translocation Pathway

    SciTech Connect

    Pohlschroder Mechthild

    2009-02-03

    Protein transport across hydrophobic membranes that partition cellular compartments is essential in all cells. The twin arginine translocation (Tat) pathway transports proteins across the prokaryotic cytoplasmic membranes. Distinct from the universally conserved Sec pathway, which secretes unfolded proteins, the Tat machinery is unique in that it secretes proteins in a folded conformation, making it an attractive pathway for the transport and secretion of heterologously expressed proteins that are Sec-incompatible. During the past 7 years, the DOE-supported project has focused on the characterization of the diversity of bacterial and archaeal Tat substrates as well as on the characterization of the Tat pathway of a model archaeon, Haloferax volcanii, a member of the haloarchaea. We have demonstrated that H. volcanii uses this pathway to transport most of its secretome.

  5. The unfolding story of anthrax toxin translocation.

    PubMed

    Thoren, Katie L; Krantz, Bryan A

    2011-05-01

    The essential cellular functions of secretion and protein degradation require a molecular machine to unfold and translocate proteins either across a membrane or into a proteolytic complex. Protein translocation is also critical for microbial pathogenesis, namely bacteria can use translocase channels to deliver toxic proteins into a target cell. Anthrax toxin (Atx), a key virulence factor secreted by Bacillus anthracis, provides a robust biophysical model to characterize transmembrane protein translocation. Atx is comprised of three proteins: the translocase component, protective antigen (PA) and two enzyme components, lethal factor (LF) and oedema factor (OF). Atx forms an active holotoxin complex containing a ring-shaped PA oligomer bound to multiple copies of LF and OF. These complexes are endocytosed into mammalian host cells, where PA forms a protein-conducting translocase channel. The proton motive force unfolds and translocates LF and OF through the channel. Recent structure and function studies have shown that LF unfolds during translocation in a force-dependent manner via a series of metastable intermediates. Polypeptide-binding clamps located throughout the PA channel catalyse substrate unfolding and translocation by stabilizing unfolding intermediates through the formation of a series of interactions with various chemical groups and ?-helical structure presented by the unfolding polypeptide during translocation. PMID:21443527

  6. Mechanochemical aspects of axonemal dynein activity studied by in vitro microtubule translocation.

    PubMed

    Hamasaki, T; Holwill, M E; Barkalow, K; Satir, P

    1995-12-01

    We have determined the relationship between microtubule length and translocation velocity from recordings of bovine brain microtubules translocating over a Paramecium 22S dynein substratum in an in vitro assay chamber. For comparison with untreated samples, the 22S dynein has been subjected to detergent and/or to pretreatments that induce phosphorylation of an associated 29 kDa light chain. Control and treated dyneins have been used at the same densities in the translocation assays. In any given condition, translocation velocity (v) shows an initial increase with microtubule length (L) and then reaches a plateau. This situation may be represented by a hyperbola of the general form v = aL/(L+b), which is formally analogous to the Briggs-Haldane relationship, which we have used to interpret our data. The results indicate that the maximum translocation velocity Vo(= a) is increased by pretreatment, whereas the length constant KL(= b), which corresponds to Km, does not change with pretreatment, implying that the mechanochemical properties of the pretreated dyneins differ from those of control dyneins. The conclusion that KL is constant for defined in vitro assays rules out the possibility that the velocity changes seen are caused by changes in geometry in the translocation assays or by the numbers of dyneins or dynein heads needed to produce maximal translocational velocity. From our analysis, we determine that f, the fraction of cycle time during which the dynein is in the force-generating state, is small--roughly 0.01, comparable to the f determined previously for heavy meromyosin. The practical limits of these mechanochemical changes imply that the maximum possible ciliary beat frequency is about 120 Hz, and that in the physiological range of 5-60 Hz, beat frequency could be controlled by varying the numbers of phosphorylated outer arm dyneins along an axonemal microtubule. PMID:8599664

  7. Polymer Translocation througha Pore in a Membrane

    E-print Network

    W. Sung; P. J. Park

    1998-02-10

    We construct a new statistical physical model of polymer translocation through a pore in a membrane treated as the diffusion process across a free energy barrier. We determine the translocation time in terms of chain flexibility yielding an entropic barrier, as well as in terms of the driving mechanisms such as transmembrane chemical potential difference and Brownian ratchets. It turns out that, while the chemical potential differences induce pronounced effects on translocation due to the long-chain nature of the polymer, the ratchets suppress this effect and chain flexibility.

  8. Polymer translocation induced by bad solvent

    NASA Astrophysics Data System (ADS)

    Lorscher, Christopher; Bhattacharya, Aniket; Ala-Nissila, Tapio

    2009-03-01

    We report Langevin dynamics simulation studies of a translocating homopolymer through a nano pore induced by different existing solvent conditions at the cis and trans compartments of the pore. Specifically, we study the mean first passage time as a function of the chain length N and determine the scaling exponent ˜N^?. We also look at the mean force experienced by the chain and its conformations as a function of the translocated segments. Our studies also reveal detail picture of the translocation process which may provide insights relevant for the entry of a DNA into a host cell.

  9. K(+) , Na(+) , and Mg(2+) on DNA translocation in silicon nitride nanopores.

    PubMed

    Uplinger, James; Thomas, Brian; Rollings, Ryan; Fologea, Daniel; McNabb, David; Li, Jiali

    2012-12-01

    In this work, we report on how salt concentration and cation species affect DNA translocation in voltage-biased silicon nitride nanopores. The translocation of dsDNA in linear, circular, and supercoiled forms was measured in salt solutions containing KCl, NaCl, and MgCl(2) . As the KCl concentrations were decreased from 1 to 0.1 M, the time taken by a DNA molecule to pass through a nanopore was shorter and the frequency of the translocation in a folded configuration was reduced, suggesting an increase in DNA electrophoretic mobility and DNA persistence length. When the salt concentration was kept at 1 M, but replacing K(+) with Na(+) , longer DNA translocation times (t(d) ) were observed. The addition of low concentrations of MgCl(2) with 1.6 M KCl resulted in longer t(d) and an increased frequency of supercoiled DNA molecules in a branched form. These observations were consistent with the greater counterion charge screening ability of Na(+) and Mg(2+) as compared to K(+) . In addition, we demonstrated that dsDNA molecules indeed translocated through a ?10 nm nanopore by PCR amplification and gel electrophoresis. We also compared the dependence of DNA mobility and conformation on KCl concentration and cation species measured at single molecule level by silicon nitride nanopores with existing bulk-based experimental results and theoretical predictions. PMID:23147752

  10. K+, Na+, and Mg2+on DNA Translocation in Silicon Nitride Nanopores

    PubMed Central

    Uplinger, James; Thomas, Brian; Rollings, Ryan; Fologea, Daniel; McNabb, David; Li, Jiali

    2012-01-01

    In this work we report on how salt concentration and cation species affect DNA translocation in voltage-biased silicon nitride nanopores. The translocation of double-stranded DNA (dsDNA) in linear, circular, and supercoiled forms was measured in salt solutions containing KCl, NaCl, and MgCl2. As the KCl concentrations were decreased from 1M to 0.1M, the time taken by a DNA molecule to pass through a nanopore was shorter and the frequency of the translocation in a folded configuration was reduced, suggesting an increase in DNA electrophoretic mobility and DNA persistence length. When the salt concentration was kept at 1M, but replacing K+ with Na+, longer DNA translocation times (td) were observed. The addition of low concentrations of MgCl2 with 1.6M KCl resulted in longer td and an increased frequency of supercoiled DNA molecules in a branched form. These observations were consistent with the greater counterion charge screening ability of Na+ and Mg2+ as compared to K+. In addition, we demonstrated that dsDNA molecules indeed translocated through a ~10 nm nanopore by PCR amplification and gel electrophoresis. We also compared the dependence of DNA mobility and conformation on KCl concentration and cation species measured at single molecule level by silicon nitride nanopores with existing bulk-based experimental results and theoretical predictions. PMID:23147752

  11. Background-limited operation of 4K-cryocooled THz photoconductive detector system with a wide frequency range of 0.8 to 4THz

    Microsoft Academic Search

    Makoto Aoki; Kento Mochizuki; Saroj Raman Tripathi; Kentaroh Watanabe; Hiroshi Murakami; Moriaki Wakaki; Norihisa Hiromoto

    2009-01-01

    We have demonstrated a terahertz (THz) detector system which employs three terahertz photoconductive semiconductor detectors to realize a response to a wide frequency range of 0.8 to 4 THz and a mechanical 4 K GM refrigerator instead of a liquid helium container to perform practical and convenient use. Optical and electrical performance of the THz detector system was evaluated at

  12. Translocation of ?-Synuclein Expressed in Escherichia coli?

    PubMed Central

    Ren, Guoping; Wang, Xi; Hao, Shufeng; Hu, Hongyu; Wang, Chih-chen

    2007-01-01

    ?-Synuclein is a major component of Lewy bodies in Parkinson's disease. Although no signal sequence is apparent, ?-synuclein expressed in Escherichia coli is mostly located in the periplasm. The possibilities that ?-synuclein translocated into the periplasm across the inner membrane by the SecA or the Tat targeting route identified in bacteria and that ?-synuclein was released through MscL were excluded. The signal recognition particle-dependent pathway is involved in the translocation of ?-synuclein. The C-terminal 99-to-140 portion of the ?-synuclein molecule plays a signal-like role for its translocation into the periplasm, cooperating with the central 61-to-95 section. The N-terminal 1-to-60 region is not required for this translocation. PMID:17277073

  13. Stress and translocation: alterations in the stress physiology of translocated birds

    PubMed Central

    Dickens, Molly J.; Delehanty, David J.; Romero, L. Michael

    2009-01-01

    Translocation and reintroduction have become major conservation actions in attempts to create self-sustaining wild populations of threatened species. However, avian translocations have a high failure rate and causes for failure are poorly understood. While ‘stress’ is often cited as an important factor in translocation failure, empirical evidence of physiological stress is lacking. Here we show that experimental translocation leads to changes in the physiological stress response in chukar partridge, Alectoris chukar. We found that capture alone significantly decreased the acute glucocorticoid (corticosterone, CORT) response, but adding exposure to captivity and transport further altered the stress response axis (the hypothalamic–pituitary–adrenal axis) as evident from a decreased sensitivity of the negative feedback system. Animals that were exposed to the entire translocation procedure, in addition to the reduced acute stress response and disrupted negative feedback, had significantly lower baseline CORT concentrations and significantly reduced body weight. These data indicate that translocation alters stress physiology and that chronic stress is potentially a major factor in translocation failure. Under current practices, the restoration of threatened species through translocation may unwittingly depend on the success of chronically stressed individuals. This conclusion emphasizes the need for understanding and alleviating translocation-induced chronic stress in order to use most effectively this important conservation tool. PMID:19324794

  14. THE GENETIC ANALYSIS OF A RECIPROCAL TRANSLOCATION

    Microsoft Academic Search

    RAJA E. ROSENBLUTH; DAVID L. BAILLIE

    The Caenorhabditis elegans mutation e873, which results in a recessive un- coordinated phenotype (formerly named Unc-72) and which had been isolated after 32P treatment (BRENNER 1974), has now been found to act as a crossover suppressor and to be associated with a translocation between linkage groups (LGs) 111 and V. The translocation has been named, eTl(ZI1; V); eT1 acts as

  15. Human chromosome variation with two Robertsonian translocations

    Microsoft Academic Search

    Rodman Morgan; Helen Bixenman; Frederick Hecht

    1985-01-01

    A woman was found to have 42 autosomes due to engagement of both chromosomes 14 in Robertsonian rearrangements, one with a chromosome 21 and the other with a chromosome 22: t(14q21q) and t(14q22q). The two translocations appear monocentric and by silver staining have no rRNA activity. The t(14q21q) translocation is familial and was ascertained through a nephew with Down syndrome,

  16. Translocation of polymers in a lattice model.

    PubMed

    Zurek, S; Ko?mider, M; Drzewi?ski, A; van Leeuwen, J M J

    2012-06-01

    Voltage-driven polymer translocation is studied by means of a stochastic lattice model. The model incorporates voltage drop over the membrane as a bias in the hopping rate through the pore and exhibits the two main ingredients of the translocation process: driven motion through the pore and diffusive supply of chain length towards the pore on the cis-side and the drift away from the pore on the trans-side. The translocation time is either bias limited or diffusion limited. In the bias-limited regime the translocation time is inversely proportional to the voltage drop over the membrane. In the diffusion-limited regime the translocation time is independent of the applied voltage, but it is rather sensitive to the motion rules of the model. We find that the whole regime is well described by a single curve determined by the initial slope and the saturation value. The dependence of these parameters on the length of the chain, the motion rules and the repton statistics are established. Repulsion of reptons as well as the increase of chain length decrease the throughput of the polymer through the pore. As for free polymers, the inclusion of a mechanism for hernia creations/annihilations leads to the cross-over from Rouse-like behaviour to reptation. For the experimentally most relevant case (Rouse dynamics) the bimodal power law dependence of the translocation time on the chain length is found. PMID:22699389

  17. Driven Polymer Translocation into a Crosslinked Gel

    NASA Astrophysics Data System (ADS)

    Sean, David; Slater, Gary

    2015-03-01

    In a typical polymer translocation setup, a thin membrane is used to separate two chambers and a polyelectrolyte is driven by an electric field to translocate from one side of the membrane to the other via a small nanopore. However, the high translocation rate that results from the forces required to drive this process makes optical and/or electrical analysis of the translocating polymer challenging. Using coarse-grained Langevin Dynamics simulations we investigate how the translocation process can be slowed down by placing a crosslinked gel on the trans-side of the membrane. Since the driving electric field is localized in the neighborhood of the nanopore, electrophoretic migration is only achieved by a ``pushing'' action from the polymer segment residing in the nanopore. For the case of a flexible polymer we find that the polymer fills the gel pores via multiple ``herniation'' processes, whereas for a semi-flexible chain in a tight gel there are no hernias and the polymer follows a smooth curvilinear path. Moreover, for the case of a semi-flexible polymer the gel makes the translocation process more uniform by reducing the acceleration at the end of the process.

  18. Ratcheting up protein translocation with anthrax toxin

    PubMed Central

    Feld, Geoffrey K; Brown, Michael J; Krantz, Bryan A

    2012-01-01

    Energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. They are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton-gradient-driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order-to-disorder mechanism (akin to a heat-engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton-gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation. PMID:22374876

  19. Ratcheting up protein translocation with anthrax toxin.

    PubMed

    Feld, Geoffrey K; Brown, Michael J; Krantz, Bryan A

    2012-05-01

    Energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. They are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton-gradient-driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order-to-disorder mechanism (akin to a heat-engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton-gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation. PMID:22374876

  20. A Theory of Resistive Hose Instability in Intense Charged Particle Beams Propagating Through Background Plasma With Low Electron Collision-Frequency

    Microsoft Academic Search

    Han S. Uhm; Ronald C. Davidson

    2005-01-01

    Stability properties of the resistive hose instability is investigated for a rounded current-density profile of a charged particle beam propagating through a background plasma where the electron collision time$(1\\/nu_c)$is comparable to or longer than the magnetic decay time$(tau_d)$. The eigenvalue equation is derived based on the energy group model, including the stabilizing influence of a finite magnetic decay time. The

  1. [Synapsis and chiasma distribution in mice heterozygous for translocations in chromosomes 16 and 17].

    PubMed

    Borodin, P M; Gorlov, I P; Agul'nik, A I; Agul'nik, S I; Rubinski?, A O

    1991-02-01

    Electron microscopic analysis of synaptonemal complexes and analysis of chiasmata distribution in male mice heterozygous for Robertsonian translocation T(16; 17)7Bnr - (Rb7), for synaptonemal reciprocal translocation T(16;17)43H - (T43), in double heterozygotes for these translocations and in males with partial trisomy of the proximal region of chromosome 17 was carried out. Synaptic disturbances around the breakpoints of the translocations, such as asynapsis of homologous regions of partners and non-homologous synapsis of centromeric regions of acrocentric chromosomes, were revealed. Synaptic regularity in the proximal part of the chromosome 17 appeared to be affected by no t12 haplotype. Good coincidence between sizes of mitotic chromosomes and corresponding lateral elements of synaptonemal complexes was found for all chromosomes, with the exception of Rb7 in trisomics. In the latter karyotype, the proximal part of chromosome 17 involved in Robertsonian fusion seems to be shortened in the course of zygotene and never synapted with homologous segment of neither the acrocentric chromosome 17 nor large product of reciprocal translocation. Drastic increase in chiasmata frequency in the proximal part of chromosome 17 was revealed in heterozygotes for T43H and in trisomics, as compared with the double heterozygotes Rb7/T43. The latter finding was explained by the existence of two independent pairing segments in the former karyotypes. PMID:1874435

  2. Dynamics of translocation and substrate binding in individual complexes formed with active site mutants of {phi}29 DNA polymerase.

    PubMed

    Dahl, Joseph M; Wang, Hongyun; Lázaro, José M; Salas, Margarita; Lieberman, Kate R

    2014-03-01

    The ?29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual ?29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the ?29 DNAP-DNA binary complex and the ?29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation. Here, we have examined the dynamics of translocation and substrate binding in complexes formed with the Y226F and Y390F mutants. The Y226F mutation diminished the forward and reverse rates of translocation, increased the affinity for dNTP in the post-translocation state by decreasing the dNTP dissociation rate, and increased the affinity for pyrophosphate in the pre-translocation state. The Y390F mutation significantly decreased the affinity for dNTP in the post-translocation state by decreasing the association rate ?2-fold and increasing the dissociation rate ?10-fold, implicating this as a mechanism by which this mutation impedes DNA synthesis. The Y390F dissociation rate increase is suppressed when complexes are examined in the presence of Mn(2+) rather than Mg(2+). The same effects of the Y226F or Y390F mutations were observed in the background of the D12A/D66A mutations, located in the exonuclease active site, ?30 ? from the polymerase active site. Although translocation rates were unaffected in the D12A/D66A mutant, these exonuclease site mutations caused a decrease in the dNTP dissociation rate, suggesting that they perturb ?29 DNAP interdomain architecture. PMID:24464581

  3. Cosmic microwave background radiation

    Microsoft Academic Search

    Lyman Page; David Wilkinson

    1999-01-01

    The cosmic microwave background radiation (CMBR) is widely interpreted as the thermal afterglow of a hot big bang. Measurements of the CMBR intensity as a function of frequency constrain the history of cosmic energetics. Measurements of the anisotropy in the CMBR temperature provide a snapshot of the distribution of fluctuations in the gravitational potential at the earliest stages of cosmic

  4. Familial translocation t(9;16).

    PubMed Central

    Dowman, C; Lockwood, D; Allanson, J

    1989-01-01

    We report a female with a deletion of 9p and concomitant duplication of 16q [46,XX,-9,+der(9),t(9;16)(p24;q13)]. Parental chromosome analysis showed a balanced maternal translocation [46,XX,t(9;16)(p24;q13)]. Three other cases of translocations involving chromosomes 9 and 16 have been reported, one of them with identical breakpoints. A review of published reports of deletion 9p and duplication 16q is presented, and a comparison is made with previously described cases. Images PMID:2671373

  5. Polymer Translocation out of Planar Confinements

    E-print Network

    Debabrata Panja; Gerard T. Barkema; Robin C. Ball

    2007-11-19

    Polymer translocation in three dimensions out of planar confinements is studied in this paper. Three membranes are located at $z=-h$, $z=0$ and $z=h_1$. These membranes are impenetrable, except for the middle one at $z=0$, which has a narrow pore. A polymer with length $N$ is initially sandwiched between the membranes placed at $z=-h$ and $z=0$ and translocates through this pore. We consider strong confinement (small $h$), where the polymer is essentially reduced to a two-dimensional polymer, with a radius of gyration scaling as $R^{\\tinytext{(2D)}}_g \\sim N^{\

  6. Effect of fundamental-frequency and sentence-onset differences on speech-identification performance of young and older adults in a competing-talker background.

    PubMed

    Lee, Jae Hee; Humes, Larry E

    2012-09-01

    This study investigated the benefits of differences between sentences in fundamental frequency (F0) and temporal onset for sentence pairs among listener groups differing in age and hearing sensitivity. Two experiments were completed with the primary difference between experiments being the way in which the stimuli were presented. Experiment 1 used blocked stimulus presentation, which ultimately provided redundant acoustic cues to mark the target sentence in each pair, whereas Experiment 2 sampled a slightly more restricted stimulus space, but in a completely randomized presentation order. For both experiments, listeners were required to detect a cue word ("Baron") for the target sentence in each pair and to then identify the target words (color, number) that appeared later in the target sentence. Results of Experiment 1 showed that F0 or onset separation cues were beneficial to both cue-word detection and color-number identification performance. There were no significant differences across groups in the ability to detect the cue word, but groups differed in their ability to identify the correct color-number words. Elderly adults with impaired hearing had the greatest difficulty with the identification task despite the application of spectral shaping to restore the audibility of the speech stimuli. For the most part, the primary results of Experiment 1 were replicated in Experiment 2, although, in the latter experiment, all older adults, whether they had normal or impaired hearing, performed worse than young adults with normal hearing. From Experiment 2, the benefits received for a difference in F0 between talkers of 6 semitones were equivalent to those received for an onset asynchrony of 300 ms between sentences and, for such conditions, the combination of both sound-segregation cues resulted in an additive benefit. PMID:22978898

  7. Underground statistical measurements of the world-wide magnetic-background level in the millihertz frequency range with the [SQUID]2 magnetometer

    NASA Astrophysics Data System (ADS)

    Pozzo di Borgo, E.; Marfaing, J.; Waysand, G.

    2012-04-01

    The passive ground sensor system [SQUID]2 (SQUID with Shielding QUalified for Ionosphere Detection) is a three-axis cryogenically cooled magnetometer installed within the LSBB (Laboratoire Souterrain à Bas Bruit) in the South-East of France. This permanent operating device is sheltered by a unique underground shielded cell buried under 518m of karstic rock in a low noise environment, leading to a noise level lower than 3 fT/?Hz above 40Hz. Various phenomena, mainly linked to earthquakes contributions, have been identified at the local scale through a magneto-hydrodynamic correlation or at the global ones, resulting from the Earth-ionosphere coupling. As standing waves altering the surface of the Earth, free oscillations of Earth consecutive to earthquake events can also contribute to the magnetic field variation. Because the ionosphere is a complex and nonlinear system affected by a large number of independent parameters, it appears obvious to constrain the number of sources. Investigation of the ULF magnetic pulsations detected by [SQUID]2 over very quiet seismic and ionospheric conditions allows to defined a first experimental baseline of ionosphere magnetic noise [Marfaing et al. 2009]. Here, the analysis is performed to a set of 24 magnetically quiet days in order to establish a statistical baseline for the "global minimal magnetic level" in the site. The mean magnetic spectrum obtained in the millihertz range is characterized by several pulsations of noticeable amplitude above the flicker noise. An attempt of discrimination of the seismogenic contribution has been proposed through the polarization analysis proposed by Hayakawa et al. [2007]. Some frequencies coincide with the Earth's eigenmodes with less than 1% deviation; this includes the possibility of the superposition of several interplaying signals in the spectra of ionospheric or Earth's origin, assumed by the weak turbulence theory. These results provide complementary analysis to validate the various theoretical models of the free oscillations of Earth and extend the knowledge of the Earth-ionosphere coupling.

  8. Nanopore arrays in a silicon membrane for parallel single-molecule detection: DNA translocation.

    PubMed

    Zhang, Miao; Schmidt, Torsten; Jemt, Anders; Sahlén, Pelin; Sychugov, Ilya; Lundeberg, Joakim; Linnros, Jan

    2015-08-01

    Optical nanopore sensing offers great potential in single-molecule detection, genotyping, or DNA sequencing for high-throughput applications. However, one of the bottle-necks for fluorophore-based biomolecule sensing is the lack of an optically optimized membrane with a large array of nanopores, which has large pore-to-pore distance, small variation in pore size and low background photoluminescence (PL). Here, we demonstrate parallel detection of single-fluorophore-labeled DNA strands (450 bps) translocating through an array of silicon nanopores that fulfills the above-mentioned requirements for optical sensing. The nanopore array was fabricated using electron beam lithography and anisotropic etching followed by electrochemical etching resulting in pore diameters down to ?7 nm. The DNA translocation measurements were performed in a conventional wide-field microscope tailored for effective background PL control. The individual nanopore diameter was found to have a substantial effect on the translocation velocity, where smaller openings slow the translocation enough for the event to be clearly detectable in the fluorescence. Our results demonstrate that a uniform silicon nanopore array combined with wide-field optical detection is a promising alternative with which to realize massively-parallel single-molecule detection. PMID:26180050

  9. Post-Release Dispersal in Animal Translocations: Social Attraction and the “Vacuum Effect”

    PubMed Central

    Mihoub, Jean-Baptiste; Robert, Alexandre; Le Gouar, Pascaline; Sarrazin, François

    2011-01-01

    Animal translocations are human-induced colonizations that can represent opportunities to contribute to the knowledge on the behavioral and demographic processes involved in the establishment of animal populations. Habitat selection behaviors, such as social cueing, have strong implications on dispersal and affect the establishment success of translocations. Using modeling simulations with a two-population network model (a translocated population and a remnant population), we investigated the consequences of four habitat selection strategies on post-translocation establishment probabilities in short- and long-lived species. Two dispersal strategies using social cues (conspecific attraction and habitat copying) were compared to random and quality-based strategies. We measured the sensitivity of local extinctions to dispersal strategies, life cycles, release frequencies, remnant population and release group sizes, the proportion of breeders and the connectivity between populations. Our results indicate that social behaviors can compromise establishment as a result of post-release dispersal, particularly in long-lived species. This behavioral mechanism, the “vacuum effect”, arises from increased emigration in populations that are small relative to neighboring populations, reducing their rate of population growth. The vacuum effect can drive small remnant populations to extinction when a translocated group is large. In addition, the magnitude of the vacuum effect varies non-linearly with connectivity. The vacuum effect represents a novel form of the behaviorally mediated Allee effect that can cause unexpected establishment failures or population extinctions in response to social cueing. Accounting for establishment probabilities as a conditional step to the persistence of populations would improve the accuracy of predicting the fates of translocated or natural (meta)populations. PMID:22194784

  10. Translocating turtles: trials, tribulations and triumphs

    Microsoft Academic Search

    N. M ROSOVSKY

    ABSTRACT This paper reviews attempts to translocate sea turtle eggs or hatchlings from their normal natal beaches to currently unoccupied potential nesting beaches, in the hope of establishing colonies in those places. Among topics considered are sex ratio, imprint- ing, headstarting, and the use of living tags. The trouble is nobody knows how a new resident colony is formed.

  11. A new Robertsonian translocation, 8/23, in cattle

    E-print Network

    Paris-Sud XI, Université de

    Note A new Robertsonian translocation, 8/23, in cattle L Biltueva, S Sharshova, A Sharshov was performed using electron microscopy. cattle / chromosome / Robertsonian translocation Résumé - Une nouvelle-eight different centric fusion translocations are known in cattle of which 12 have been described with the method

  12. Secreted Listeria adhesion protein (Lap) influences Lap-mediated Listeria monocytogenes paracellular translocation through epithelial barrier

    PubMed Central

    2013-01-01

    Background Listeria adhesion protein (Lap), an alcohol acetaldehyde dehydrogenase (lmo1634) promotes bacterial paracellular translocation through epithelial cell junctions during gastrointestinal phase of infection. Secreted Lap is critical for pathogenesis and is mediated by SecA2 system; however, if strain dependent variation in Lap secretion would affect L. monocytogenes paracellular translocation through epithelial barrier is unknown. Methods Amounts of Lap secretion were examined in clinical isolates of L. monocytogenes by cell fractionation analysis using Western blot. Quantitative reverse transcriptase PCR (qRT-PCR) was used to verify protein expression profiles. Adhesion and invasion of isolates were analyzed by in vitro Caco-2 cell culture model and paracellular translocation was determined using a trans-well model pre-seeded with Caco-2 cells. Results Western blot revealed that expression of Lap in whole cell preparation of isolates was very similar; however, cell fractionation analysis indicated variable Lap secretion among isolates. The strains showing high Lap secretion in supernatant exhibited significantly higher adhesion (3.4 - 4.8% vs 1.5 - 2.3%, P?translocation in Caco-2 cells than the low secreting isolates. In cell wall fraction, Lap level was mostly uniform for both groups, while Lap accumulated in cytosol in low secreting strains indicating that Lap distribution in cellular compartments is a strain-dependent phenomenon, which may be controlled by the protein transport system, SecA2. ?secA2 mutants showed significantly reduced paracellular translocation through epithelial barrier (0.48?±?0.01 vs 0.24?±?0.02, P?translocation through paracellular route and may serve as an indicator for pathogenic potential of an isolate. PMID:23799938

  13. Stiff filamentous virus translocations through solid-state nanopores

    NASA Astrophysics Data System (ADS)

    McMullen, Angus; de Haan, Hendrick W.; Tang, Jay X.; Stein, Derek

    2014-06-01

    The ionic conductance through a nanometer-sized pore in a membrane changes when a biopolymer slides through it, making nanopores sensitive to single molecules in solution. Their possible use for sequencing has motivated numerous studies on how DNA, a semi-flexible polymer, translocates nanopores. Here we study voltage-driven dynamics of the stiff filamentous virus fd with experiments and simulations to investigate the basic physics of polymer translocations. We find that the electric field distribution aligns an approaching fd with the nanopore, promoting its capture, but it also pulls fd sideways against the membrane after failed translocation attempts until thermal fluctuations reorient the virus for translocation. fd is too stiff to translocate in folded configurations. It therefore translocates linearly, exhibiting a voltage-independent mobility and obeying first-passage-time statistics. Surprisingly, lengthwise Brownian motion only partially accounts for the translocation velocity fluctuations. We also observe a voltage-dependent contribution whose origin is only partially determined.

  14. Translocation and encapsulation of siRNA inside carbon nanotubes.

    PubMed

    Mogurampelly, Santosh; Maiti, Prabal K

    2013-01-21

    We report spontaneous translocation of small interfering RNA (siRNA) inside carbon nanotubes (CNTs) of various diameters and chirality using all atom molecular dynamics simulations with explicit solvent. We use umbrella sampling method to calculate the free energy landscape of the siRNA entry and translocation event. Free energy profiles show that siRNA gains free energy while translocating inside CNT, and barrier for siRNA exit from CNT ranges from 40 to 110 kcal/mol depending on CNT chirality and salt concentration. The translocation time ? decreases with the increase of CNT diameter with a critical diameter of 24 A? for the translocation. In contrast, double strand DNA of the same sequence does not translocate inside CNT due to large free energy barrier for the translocation. This study helps in understanding the nucleic acid transport through nanopores at microscopic level and may help designing carbon nanotube based sensor for siRNA. PMID:23343299

  15. Expression pattern of a nuclear encoded mitochondrial arginine-ornithine translocator gene from Arabidopsis

    Microsoft Academic Search

    Elisabetta Catoni; Marcelo Desimone; Melanie Hilpert; Daniel Wipf; Reinhard Kunze; Anja Schneider; U. I. Flugge; Karin Schumacher; Wolf B Frommer

    2003-01-01

    BACKGROUND: Arginine and citrulline serve as nitrogen storage forms, but are also involved in biosynthetic and catabolic pathways. Metabolism of arginine, citrulline and ornithine is distributed between mitochondria and cytosol. For the shuttle of intermediates between cytosol and mitochondria transporters present on the inner mitochondrial membrane are required. Yeast contains a mitochondrial translocator for ornithine and arginine, Ort1p\\/Arg11p. Ort1p\\/Arg11p is

  16. Breakpoint Mapping and Array CGH in Translocations: Comparison of a Phenotypically Normal and an Abnormal Cohort

    PubMed Central

    Baptista, Julia; Mercer, Catherine; Prigmore, Elena; Gribble, Susan M.; Carter, Nigel P.; Maloney, Viv; Thomas, N. Simon; Jacobs, Patricia A.; Crolla, John A.

    2008-01-01

    We report the analyses of breakpoints in 31 phenotypically normal and 14 abnormal carriers of balanced translocations. Our study assesses the differences between balanced translocations in normal carriers and those in abnormal carriers, focusing on the presence of genomic imbalances at the breakpoints or elsewhere in the genome, presence of cryptic chromosome rearrangements, and gene disruption. Our hypothesis is that all four features will be associated with phenotypic abnormalities and absent or much less frequent in a normal population. In the normal cohort, we identified neither genomic imbalances at the breakpoints or elsewhere in the genome nor cryptic chromosome rearrangements. In contrast, we identified candidate disease-causing imbalances in 4/14 abnormal patients. These were three breakpoint associated deletions and three deletions unrelated to the breakpoints. All six de novo deletions originated on the paternally inherited chromosome. Additional complexity was also present in one of these cases. Gene disruption by the breakpoints was present in 16/31 phenotypically normal individuals and in 5/14 phenotypically abnormal patients. Our results show that translocations in phenotypically abnormal patients are molecularly distinct from those in normal individuals: the former are more likely to be associated with genomic imbalances at the breakpoints or elsewhere and with chromosomal complexity, whereas the frequency of gene disruption is similar in both normal and abnormal translocation carriers. PMID:18371933

  17. Financial Costs of Large Carnivore Translocations – Accounting for Conservation

    PubMed Central

    Weise, Florian J.; Stratford, Ken J.; van Vuuren, Rudolf J.

    2014-01-01

    Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars). Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n?=?23), and $2,108 per leopard (n?=?6). One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%), followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4%) of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards (66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%) with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC) and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis. PMID:25126849

  18. Tasmanian low frequency Galactic background surveys

    NASA Technical Reports Server (NTRS)

    Cane, H. V.

    1987-01-01

    The results of LF (2-20-MHz) radio-astronomy observations obtained in Tasmania during solar-minimum winters since 1956 are briefly summarized. The low ionospheric f0F2 values (near 1 MHz) occurring in Tasmania in these periods are noted; the 2000-ft-diameter Llanherne array used for Galactic mapping at 2-20 MHz is described; the techniques employed are discussed; and sample maps are shown.

  19. Development of Triticum aestivum-Leymus racemosus translocation lines using gametocidal chromosomes.

    PubMed

    Yuan, Jianhua; Chen, Peidu; Liu, Dajun

    2003-10-01

    Specific chromosomes of certain Aegilops species introduced into wheat genome background may often facilitate chromosome breakage and refusion, and finally result in a variety of chromosome restructuring. Such a phenomenon is commonly called gametocidal effect of the chromosomes. The chromosome 2C of Ae. cylindrica is one of such chromosomes. In the present study, scab resistant wheat-L. racemosus addition lines involving chromosomes Lr.2 and Lr.7 were crossed to wheat-Ae. cylindrica disomic addition line Add2C. Then F(1) hybrids were subsequently backcrossed with wheat cv "Chinese Spring". BC(1) plants with chromosome structural aberration were identified by C-banding. In the self-pollinated progenies of these plants, three translocation lines were developed and characterized by mitotic and meiotic analysis combined with C-banding and fluorescent in situ hybridization (FISH) using biotin-labeled genomic DNA of L. racemosus as probe. Some other putative translocation lines to be further characterized were also found. The practicability and efficiency of the translocation between wheat and alien chromosomes induced by gametocidal chromosomes, as well as the potential use of the developed alien translocation lines were also discussed. PMID:19448992

  20. Cosmic Microwave Background Theory

    Microsoft Academic Search

    J. Richard Bond

    1998-01-01

    A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in ell -space are consistent with a Delta T flat in frequency and broadly follow inflation-based expectations. That the

  1. Pore formation and translocation of melittin.

    PubMed Central

    Matsuzaki, K; Yoneyama, S; Miyajima, K

    1997-01-01

    Melittin, a bee venom, is a basic amphiphilic peptide, which mainly acts on the lipid matrix of membranes, lysing various cells. To elucidate the molecular mechanism, we investigated its interactions with phospholipid vesicles. The peptide formed a pore with a short lifetime in the membrane, as revealed by the release of an anionic fluorescent dye, calcein, from the liposomes. Our new double-labeling method clarified that the pore size increased with the peptide-to-lipid ratio. Upon the disintegration of the pore, a fraction of the peptides translocated across the bilayer. The pore formation was coupled with the translocation, which was proved by three fluorescence experiments recently developed by our laboratory. A novel model for the melittin pore formation was discussed in comparison with other pore-forming peptides. PMID:9251799

  2. Translocation of coyote rabies--Florida, 1994.

    PubMed

    1995-08-11

    Translocation of a rabies variant from one area to another has been identified increasingly in the United States. During November and December 1994, rabies was diagnosed in five dogs from two associated kennels in Florida; in addition, two other dogs being kept at one of the kennels died with suspected, but unconfirmed, rabies. Rabies virus recovered from the five dogs was identified as a variant not previously found in Florida but endemic in coyotes (Canis latrans) in south Texas. The suspected source of infection was translocation of infected coyotes from Texas to Florida. This report summarizes the findings of an investigation of these cases by the Alachua County Public Health Unit, the Florida Department of Health and Rehabilitative Services, and CDC. PMID:7623760

  3. Translocation in the nonpolytrichaceous moss grimmia laevigata

    SciTech Connect

    Alpert, P. (Univ. of Massachusetts, Amherst (USA))

    1989-10-01

    A superficially rhizomatous habit suggested that the moss Grimmia laevigata might function as a clonal, rhizomatous plant and translocate photoassimilates to below ground organs, even though the species is outside the order Polytrichales, which includes the only mosses known to posses sieve cells. Labelling with {sup 14}CO{sub 2} indicated that at least 10% of newly assimilated carbon was translocated out of leafy shoot portions within 26 hr. Of this carbon, approximately 75% was apparently moved into leafless, basal shoot portions and 25% into below ground stems. Infrared gas analysis of net CO{sup 2} flux was used to check that labelling gave a realistic measure of photosynthesis. Physiological integration and clonal spread may account for the unusual ability of this moss to colonize extremely xeric microsites.

  4. Commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor 4

    Microsoft Academic Search

    Lee-Wei Chen; Wei-Jung Chang; Pei-Hsuan Chen; Ching-Mei Hsu

    2010-01-01

    BACKGROUND: Major burn is associated with decreased gut barrier function and increased bacterial translocation (BT). This study is to investigate whether commensal microflora induce host defense and decrease BT in burn mice. METHODS: First, we treated Wild type (WT) mice with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented

  5. Formation of Complex and Unstable Chromosomal Translocations in Yeast

    PubMed Central

    Schmidt, Kristina H.; Viebranz, Emilie; Doerfler, Lillian; Lester, Christina; Rubenstein, Aaron

    2010-01-01

    Genome instability, associated with chromosome breakage syndromes and most human cancers, is still poorly understood. In the yeast Saccharomyces cerevisiae, numerous genes with roles in the preservation of genome integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that lack Sgs1, a RecQ-like DNA helicase related to the human Bloom's-syndrome-associated helicase BLM, show an increased rate of genome instability, and we have previously shown that they accumulate recurring chromosomal translocations between three similar genes, CAN1, LYP1 and ALP1. Here, the chromosomal location, copy number and sequence similarity of the translocation targets ALP1 and LYP1 were altered to gain insight into the formation of complex translocations. Among 844 clones with chromosomal rearrangements, 93 with various types of simple and complex translocations involving CAN1, LYP1 and ALP1 were identified. Breakpoint sequencing and mapping showed that the formation of complex translocation types is strictly dependent on the location of the initiating DNA break and revealed that complex translocations arise via a combination of interchromosomal translocation and template-switching, as well as from unstable dicentric intermediates. Template-switching occurred between sequences on the same chromosome, but was inhibited if the genes were transferred to different chromosomes. Unstable dicentric translocations continuously gave rise to clones with multiple translocations in various combinations, reminiscent of intratumor heterogeneity in human cancers. Base substitutions and evidence of DNA slippage near rearrangement breakpoints revealed that translocation formation can be accompanied by point mutations, and their presence in different translocation types within the same clone provides evidence that some of the different translocation types are derived from each other rather than being formed de novo. These findings provide insight into eukaryotic genome instability, especially the formation of translocations and the sources of intraclonal heterogeneity, both of which are often associated with human cancers. PMID:20711256

  6. Metallic oxide nanoparticle translocation across the human bronchial epithelial barrier

    NASA Astrophysics Data System (ADS)

    George, Isabelle; Naudin, Grégoire; Boland, Sonja; Mornet, Stéphane; Contremoulins, Vincent; Beugnon, Karine; Martinon, Laurent; Lambert, Olivier; Baeza-Squiban, Armelle

    2015-02-01

    Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to quantify the translocation of different metallic NPs across human bronchial epithelial cells and to determine the factors influencing this translocation. Calu-3 cells forming a tight epithelial barrier when grown on a porous membrane in a two compartment chamber were exposed to fluorescently labelled NPs to quantify the NP translocation. NP translocation and uptake by cells were also studied by confocal and transmission electron microscopy. Translocation was characterized according to NP size (16, 50, or 100 nm), surface charge (negative or positive SiO2), composition (SiO2 or TiO2), presence of proteins or phospholipids and in an inflammatory context. Our results showed that NPs can translocate through the Calu-3 monolayer whatever their composition (SiO2 or TiO2), but this translocation was increased for the smallest and negatively charged NPs. Translocation was not associated with an alteration of the integrity of the epithelial monolayer, suggesting a transcytosis of the internalized NPs. By modifying the NP corona, the ability of NPs to cross the epithelial barrier differed depending on their intrinsic properties, making positively charged NPs more prone to translocate. NP translocation can be amplified by using agents known to open tight junctions and to allow paracellular passage. NP translocation was also modulated when mimicking an inflammatory context frequently found in the lungs, altering the epithelial integrity and inducing transient tight junction opening. This in vitro evaluation of NP translocation could be extended to other inhaled NPs to predict their biodistribution.Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to quantify the translocation of different metallic NPs across human bronchial epithelial cells and to determine the factors influencing this translocation. Calu-3 cells forming a tight epithelial barrier when grown on a porous membrane in a two compartment chamber were exposed to fluorescently labelled NPs to quantify the NP translocation. NP translocation and uptake by cells were also studied by confocal and transmission electron microscopy. Translocation was characterized according to NP size (16, 50, or 100 nm), surface charge (negative or positive SiO2), composition (SiO2 or TiO2), presence of proteins or phospholipids and in an inflammatory context. Our results showed that NPs can translocate through the Calu-3 monolayer whatever their composition (SiO2 or TiO2), but this translocation was increased for the smallest and negatively charged NPs. Translocation was not associated with an alteration of the integrity of the epithelial monolayer, suggesting a transcytosis of the internalized NPs. By modifying the NP corona, the ability of NPs to cross the epithelial barrier differed depending on their intrinsic properties, making positively charged NPs more prone to translocate. NP translocation can be amplified by using agents known to open tight junctions and to allow paracellular passage. NP translocation was also modulated when mimicking an inflammatory context frequently found in the lungs, altering the epithelial integrity and inducing transient tight junction opening. This in vitro evaluation of NP translocation could be extended to other inhaled NPs to predict their biodistribution. Electronic supplementary information (ESI) available: 1. NP synthesis. 2. NP characterization. 3. NP cytotoxicity and pro-inflammatory response. 4. Modulation of cellular permeability after NP treatment and NP retention inside the Calu-3 monolayer after 1 week of exposure. 5. NP translocation through TF in the absence of cells as a function of NP concentration, composition or corona. 6. Confocal microscopy observations of NCI-H292 cells exposed to fresh and conditioned media. 7. Quantification of NP internalization by Calu-3 cells by flow cytometry. See DOI: 10.1039/c4nr07079h

  7. Distribution and Translocation of 141Ce (III) in Horseradish

    PubMed Central

    Guo, Xiaoshan; Zhou, Qing; Lu, Tianhong; Fang, Min; Huang, Xiaohua

    2007-01-01

    Background and Aims Rare earth elements (REEs) are used in agriculture and a large amount of them contaminate the environment and enter foods. The distribution and translocation of 141Ce (III) in horseradish was investigated in order to help understand the biochemical behaviour and toxic mechanism of REEs in plants. Method The distribution and translocation of 141Ce (III) in horseradish were investigated using autoradiography, liquid scintillation counting (LSC) and electron microscopic autoradiography (EMARG) techniques. The contents of 141Ce (III) and nutrient elements were analysed using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). Results The results from autoradiography and LSC indicated that 141Ce (III) could be absorbed by horseradish and transferred from the leaf to the leaf-stalk and then to the root. The content of 141Ce (III) in different parts of horseradish was as follows: root > leaf-stalk > leaf. The uptake rates of 141Ce (III) in horseradish changed with the different organs and time. The content of 141Ce (III) in developing leaves was greater than that in mature leaves. The results from EMARG indicated that 141Ce (III) could penetrate through the cell membrane and enter the mesophyll cells, being present in both extra- and intra-cellular deposits. The contents of macronutrients in horseradish were decreased by 141Ce (III) treatment. Conclusions 141Ce (III) can be absorbed and transferred between organs of horseradish with time, and the distribution was found to be different at different growth stages. 141Ce (III) can enter the mesophyll cells via apoplast and symplast channels or via plasmodesmata. 141Ce (III) can disturb the metabolism of macronutrients in horseradish. PMID:17921527

  8. Association between simple sequence repeat-rich chromosome regions and intergenomic translocation breakpoints in natural populations of allopolyploid wild wheats

    PubMed Central

    Molnár, István; Cifuentes, Marta; Schneider, Annamária; Benavente, Elena; Molnár-Láng, Márta

    2011-01-01

    Background and Aims Repetitive DNA sequences are thought to be involved in the formation of chromosomal rearrangements. The aim of this study was to analyse the distribution of microsatellite clusters in Aegilops biuncialis and Aegilops geniculata, and its relationship with the intergenomic translocations in these allotetraploid species, wild genetic resources for wheat improvement. Methods The chromosomal localization of (ACG)n and (GAA)n microsatellite sequences in Ae. biuncialis and Ae. geniculata and in their diploid progenitors Aegilops comosa and Aegilops umbellulata was investigated by sequential in situ hybridization with simple sequence repeat (SSR) probes and repeated DNA probes (pSc119·2, Afa family and pTa71) and by dual-colour genomic in situ hybridization (GISH). Thirty-two Ae. biuncialis and 19 Ae. geniculata accessions were screened by GISH for intergenomic translocations, which were further characterized by fluorescence in situ hybridization and GISH. Key Results Single pericentromeric (ACG)n signals were localized on most U and on some M genome chromosomes, whereas strong pericentromeric and several intercalary and telomeric (GAA)n sites were observed on the Aegilops chromosomes. Three Ae. biuncialis accessions carried 7Ub–7Mb reciprocal translocations and one had a 7Ub–1Mb rearrangement, while two Ae. geniculata accessions carried 7Ug–1Mg or 5Ug–5Mg translocations. Conspicuous (ACG)n and/or (GAA)n clusters were located near the translocation breakpoints in eight of the ten translocated chromosomes analysed, SSR bands and breakpoints being statistically located at the same chromosomal site in six of them. Conclusions Intergenomic translocation breakpoints are frequently mapped to SSR-rich chromosomal regions in the allopolyploid species examined, suggesting that microsatellite repeated DNA sequences might facilitate the formation of those chromosomal rearrangements. The (ACG)n and (GAA)n SSR motifs serve as additional chromosome markers for the karyotypic analysis of UM genome Aegilops species. PMID:21036694

  9. Geographic Translocation of Bats: Known and Potential Problems

    PubMed Central

    2003-01-01

    Natural, accidental, and intentional translocation of bats, both intra- and intercontinentally, has been documented. Some bats have been translocated while incubating infectious diseases, including rabies or related lyssavirus infections; others have escaped confinement en route to or at their destinations, while others have been released deliberately. Known events and potential consequences of bat translocation are reviewed, including a proposed solution to the attendant problems. PMID:12533276

  10. DAX-1 Expression in Pediatric Rhabdomyosarcomas: Another Immunohistochemical Marker Useful in the Diagnosis of Translocation Positive Alveolar Rhabdomyosarcoma

    PubMed Central

    Virgone, Calogero; Lalli, Enzo; Bisogno, Gianni; Lazzari, Elena; Roma, Josep; Zin, Angelica; Poli, Elena; Cecchetto, Giovanni; Dall’Igna, Patrizia; Alaggio, Rita

    2015-01-01

    Objectives The aim of this study was to investigate the expression of DAX-1 in a series of pediatric rhabdomyosarcomas (RMS) with known translocation and compare it to Ap2?, known to be selectively expressed in ARMS. Design We revised a series of 71 alveolar rhabdomyosarcomas (ARMS), enrolled in the Italian Protocols RMS 79 and 96, and 23 embryonal rhabdomyosarcomas (ERMS) as controls. Before investigating Ap2? and DAX-1, ARMS were reviewed and reclassified as 48 ARMS and 23 non-ARMS. Results Translocation positive ARMS showed a characteristic Ap2?/DAX-1+ staining pattern in 78% of cases, while 76% of classic ERMS were negative for both. Ap2? alone was positive in 3.9% of RMS lacking translocation, whereas DAX-1 alone was positive in 25.4%. Conversely, 9% and 6% of translocation positive ARMS were positive only for DAX-1 or Ap2?, respectively. The 23 non-ARMS shared the same phenotype as ERMS but had a higher frequency of DAX-1 expression. Conclusions DAX-1 is less specific than Ap2?, however it is a sensitive marker for translocation positive ARMS and can be helpful in their diagnosis if used in combination with Ap2?. PMID:26168243

  11. Chromosome translocations measured by fluorescence in-situ hybridization: A promising biomarker

    SciTech Connect

    Lucas, J.N.; Straume, T.

    1995-10-01

    A biomarker for exposure and risk assessment would be most useful if it employs an endpoint that is highly quantitative, is stable with time, and is relevant to human risk. Recent advances in chromosome staining using fluorescence in situ hybridization (FISH) facilitate fast and reliable measurement of reciprocal translocations, a kind of DNA damage linked to both prior exposure and risk. In contrast to other biomarkers available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time post exposure, has a rather small inter-individual variability, and can be measured accurately at the low levels. Here, the authors discuss results from their studies demonstrating that chromosome painting can be used to reconstruct radiation dose for workers exposed within the dose limits, for individuals exposed a long time ago, and even for those who have been diagnosed with leukemia but not yet undergone therapy.

  12. The twin-arginine protein translocation pathway.

    PubMed

    Berks, Ben C

    2015-06-01

    The twin-arginine translocation (Tat) system, found in prokaryotes, chloroplasts, and some mitochondria, allows folded proteins to be moved across membranes. How this transport is achieved without significant ion leakage is an intriguing mechanistic question. Tat transport is mediated by complexes formed from small integral membrane proteins from just two protein families. Atomic-resolution structures have recently been determined for representatives of both these protein families, providing the first molecular-level glimpse of the Tat machinery. I review our current understanding of the mechanism of Tat transport in light of these new structural data. PMID:25494301

  13. Multistep protein unfolding during nanopore translocation

    NASA Astrophysics Data System (ADS)

    Rodriguez-Larrea, David; Bayley, Hagan

    2013-04-01

    Cells are divided into compartments and separated from the environment by lipid bilayer membranes. Essential molecules are transported back and forth across the membranes. We have investigated how folded proteins use narrow transmembrane pores to move between compartments. During this process, the proteins must unfold. To examine co-translocational unfolding of individual molecules, we tagged protein substrates with oligonucleotides to enable potential-driven unidirectional movement through a model protein nanopore, a process that differs fundamentally from extension during force spectroscopy measurements. Our findings support a four-step translocation mechanism for model thioredoxin substrates. First, the DNA tag is captured by the pore. Second, the oligonucleotide is pulled through the pore, causing local unfolding of the C terminus of the thioredoxin adjacent to the pore entrance. Third, the remainder of the protein unfolds spontaneously. Finally, the unfolded polypeptide diffuses through the pore into the recipient compartment. The unfolding pathway elucidated here differs from those revealed by denaturation experiments in solution, for which two-state mechanisms have been proposed.

  14. Specific Nucleoporin Requirement for Smad Nuclear Translocation ?

    PubMed Central

    Chen, Xiaochu; Xu, Lan

    2010-01-01

    Cytoplasm-to-nucleus translocation of Smad is a fundamental step in transforming growth factor ? (TGF-?) signal transduction. Here we identify a subset of nucleoporins that, in conjunction with Msk (Drosophila Imp7/8), specifically mediate activation-induced nuclear translocation of MAD (Drosophila Smad1) but not the constitutive import of proteins harboring a classic nuclear localization signal (cNLS) or the spontaneous nuclear import of Medea (Drosophila Smad4). Surprisingly, many of these nucleoporins, including Sec13, Nup75, Nup93, and Nup205, are scaffold nucleoporins considered important for the overall integrity of the nuclear pore complex (NPC) but not known to have cargo-specific functions. We demonstrate that the roles of these nucleoporins in supporting Smad nuclear import are separate from their previously assigned functions in NPC assembly. Furthermore, we uncovered novel pathway-specific functions of Sec13 and Nup93; both Sec13 and Nup93 are able to preferentially interact with the phosphorylated/activated form of MAD, and Nup93 acts to recruit the importin Msk to the nuclear periphery. These findings, together with the observation that Sec13 and Nup93 could interact directly with Msk, suggest their direct involvement in the nuclear import of MAD. Thus, we have delineated the nucleoporin requirement of MAD nuclear import, reflecting a unique trans-NPC mechanism. PMID:20547758

  15. The Tat-dependent protein translocation pathway.

    PubMed

    Hou, Bo; Brüser, Thomas

    2011-12-01

    The twin-arginine translocation (Tat) pathway is found in bacteria, archaea, and plant chloroplasts, where it is dedicated to the transmembrane transport of fully folded proteins. These proteins contain N-terminal signal peptides with a specific Tat-system binding motif that is recognized by the transport machinery. In contrast to other protein transport systems, the Tat system consists of multiple copies of only two or three usually small (?8-30 kDa) membrane proteins that oligomerize to two large complexes that transiently interact during translocation. Only one of these complexes includes a polytopic membrane protein, TatC. The other complex consists of TatA. Tat systems of plants, proteobacteria, and several other phyla contain a third component, TatB. TatB is evolutionarily and structurally related to TatA and usually forms tight complexes with TatC. Minimal two-component Tat systems lacking TatB are found in many bacterial and archaeal phyla. They consist of a 'bifunctional' TatA that also covers TatB functionalities, and a TatC. Recent insights into the structure and interactions of the Tat proteins have various important implications. PMID:25962051

  16. DNA Translocation in Nanometer Thick Silicon Nanopores.

    PubMed

    Rodríguez-Manzo, Julio A; Puster, Matthew; Nicolaï, Adrien; Meunier, Vincent; Drndi?, Marija

    2015-06-23

    Solid-state nanopores are single-molecule sensors that detect changes in ionic conductance (?G) when individual molecules pass through them. Producing high signal-to-noise ratio for the measurement of molecular structure in applications such as DNA sequencing requires low noise and large ?G. The latter is achieved by reducing the nanopore diameter and membrane thickness. While the minimum diameter is limited by the molecule size, the membrane thickness is constrained by material properties. We use molecular dynamics simulations to determine the theoretical thickness limit of amorphous Si membranes to be ?1 nm, and we designed an electron-irradiation-based thinning method to reach that limit and drill nanopores in the thinned regions. Double-stranded DNA translocations through these nanopores (down to 1.4 nm in thickness and 2.5 nm in diameter) provide the intrinsic ionic conductance detection limit in Si-based nanopores. In this regime, where the access resistance is comparable to the nanopore resistance, we observe the appearance of two conductance levels during molecule translocation. Considering the overall performance of Si-based nanopores, our work highlights their potential as a leading material for sequencing applications. PMID:26035079

  17. Translocation of red howler monkeys ( Alouatta seniculus) in French Guiana

    Microsoft Academic Search

    Cécile Richard-Hansen; J.-Christophe Vié

    2000-01-01

    A wide translocation program was conducted on neotropical fauna in French Guiana during the filling of a hydroelectric reservoir. Red howler monkeys (Alouatta seniculus) were studied because available data on their behavior in undisturbed conditions provided the basis for behavioral comparison with translocated animals. A resident howler population was present in the selected release area, but population densities were severely

  18. Transient accumulation of elastic energy in proton translocating ATP synthase

    E-print Network

    Steinhoff, Heinz-Jürgen

    Hypothesis Transient accumulation of elastic energy in proton translocating ATP synthase Dmitry A,18^20]. We analyzed the transient elastic storage of energy derived from four proton-translocation steps between FH and FI (see Fig. 1) gives a clue to how the elastic energy storage might function. The proton

  19. Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

    PubMed Central

    Tincati, Camilla; Silvestri, Guido

    2013-01-01

    In pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections, the translocation of microbial products from the gastrointestinal (GI) tract to portal and systemic circulation has been proposed as a major driver of the chronic immune activation that is associated with disease progression. Consistently, microbial translocation is not present in nonpathogenic SIV infections of natural host species. In vivo studies demonstrated that HIV/SIV-associated microbial translocation results from a series of immunopathological events occurring at the GI mucosa: (i) early and severe mucosal CD4+ depletion, (ii) mucosal immune hyperactivation/persistent inflammation; (iii) damage to the integrity of the intestinal epithelium with enterocyte apoptosis and tight junction disruption; and (iv) subverted the gut microbiome, with a predominance of opportunistic bacteria. Direct in situ evidence of microbial translocation has been provided for SIV-infected rhesus macaques showing translocated microbial products in the intestinal lamina propria and distant sites. While the mechanisms by which microbial translocation causes immune activation remain controversial, a key pathogenic event appears to be innate immunity activation via Toll-like receptors and other pathogen recognition receptors. Accumulating clinical observations suggest that microbial translocation might affect HIV disease progression, response to therapy, and non-AIDS comorbidities. Given its detrimental effect on overall immunity, several interventions to prevent/block microbial translocation are currently under investigation as novel therapeutic agents for HIV/AIDS. PMID:23297256

  20. MasterProof DNA Translocation Governed by Interactions with

    E-print Network

    MasterProof DNA Translocation Governed by Interactions with Solid-State Nanopores Meni Wanunu-driven translocation dynamics of individual DNA molecules through solid-state nanopores in the diameter range 3­5 nm with DNA length by two power laws: for short DNA molecules, in the range 150­3500 bp, we find an exponent

  1. Translocation events in a single walled carbon nanotube

    PubMed Central

    He, Jin; Liu, Hao; Pang, Pei; Cao, Di; Lindsay, Stuart

    2010-01-01

    Translocation of DNA oligomers through a single walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that introduction of a nucleotide alone, guanosine triphosphate into the input reservoir of a carbon nanotube nanofluidic also gives giant current pulses. Taken together with data on oligomer translocation, theses new results suggest that pulse width has a non-linear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of bias reversal. PMID:21179393

  2. Multistep Current Signal in Protein Translocation through Graphene Nanopores.

    PubMed

    Bonome, Emma Letizia; Lepore, Rosalba; Raimondo, Domenico; Cecconi, Fabio; Tramontano, Anna; Chinappi, Mauro

    2015-05-01

    In nanopore sensing experiments, the properties of molecules are probed by the variation of ionic currents flowing through the nanopore. In this context, the electronic properties and the single-layer thickness of graphene constitute a major advantage for molecule characterization. Here we analyze the translocation pathway of the thioredoxin protein across a graphene nanopore, and the related ionic currents, by integrating two nonequilibrium molecular dynamics methods with a bioinformatic structural analysis. To obtain a qualitative picture of the translocation process and to identify salient features we performed unsupervised structural clustering on translocation conformations. This allowed us to identify some specific and robust translocation intermediates, characterized by significantly different ionic current flows. We found that the ion current strictly anticorrelates with the amount of pore occupancy by thioredoxin residues, providing a putative explanation of the multilevel current scenario observed in recently published translocation experiments. PMID:25866995

  3. Interaction prolonged DNA translocation through solid-state nanopores.

    PubMed

    Liang, Zexi; Tang, Zhipeng; Li, Ji; Hu, Rui; Yu, Dapeng; Zhao, Qing

    2015-06-28

    An interesting smooth blocked nanopore and corresponding "current ladder" phenomenon was observed in DNA translocation experiments through solid-state nanopores. The ionic current shows several drop steps (current levels in the current ladder) with an identical drop interval, which corresponds to an individual unfolded DNA translocation event. This indicates that multiple anchored DNA molecules have one end inside the nanopore to cause such a current ladder. On each current level, normal DNA translocation events were detected. The event duration time increases as the level number increases, which means DNA translocates more slowly when more DNA molecules are inside the nanopore due to DNA-DNA interactions. The Langevin dynamic model was used to explain the experimental observations. This finding strongly suggests that DNA-DNA interactions greatly impact the translocation dynamics when DNA passes through the nanopores. PMID:26035070

  4. Absorption and Translocation of Sodium in Beans and Cotton 1

    PubMed Central

    Pearson, George A.

    1967-01-01

    At the end of a 4 hour absorption period approximately 95% of the sodium absorbed by bean plants was retained in the secondary roots. The sodium translocated to the shoot was retained in the stem. 2,4-Dinitrophenol decreased the amount retained in the secondary roots of bean plants and increased the amount translocated to the shoot. The stem retained most of the translocated sodium. Bean plants without roots absorbed considerably more sodium than plants with roots and translocated a greater proportion of the sodium to the petioles and blades. 2,4-Dinitrophenol reduced the amount of sodium in the stem and petioles and increased the amount in the blades. 2,4-Dinitrophenol reduced the amount of sodium retained by the secondary roots of cotton plants but did not appreciably affect the amounts translocated to the shoot. PMID:16656635

  5. Range-wide success of red-cockaded woodpecker translocations.

    SciTech Connect

    Edwards, John W.; Costa, Ralph

    2004-12-31

    Edwards, John W.; Costa, Ralph. 2004. Range-wide success of red-cockaded woodpecker translocations. In: Red-cockaded woodpecker; Road to Recovery. Proceedings of the 4th Red-cockaded woodpecker Symposium. Ralph Costa and Susan J. Daniels, eds. Savannah, Georgia. January, 2003. Chapter 6. Translocation. Pp 307-311. Abstract: Red-cockaded woodpeckers (Picoides borealis) have declined range-wide during the past century, suffering from habitat loss and the effects of fire exclusion in older southern pine forests. Red-cockaded woodpecker translocations are a potentially important tool in conservation efforts to reestablish red-cockaded woodpeckers in areas from which they have been extirpated. Currently, translocations are critical in ongoing efforts to save and restore the many existing small populations. We examined the effects of demographic and environmental factors on the range-wide success of translocations between 1989 and 1995.

  6. Strandwise translocation of a DNA glycosylase on undamaged DNA

    SciTech Connect

    Qi, Yan; Nam, Kwangho; Spong, Marie C.; Banerjee, Anirban; Sung, Rou-Jia; Zhang, Michael; Karplus, Martin; Verdine, Gregory L. (Harvard)

    2012-05-14

    Base excision repair of genotoxic nucleobase lesions in the genome is critically dependent upon the ability of DNA glycosylases to locate rare sites of damage embedded in a vast excess of undamaged DNA, using only thermal energy to fuel the search process. Considerable interest surrounds the question of how DNA glycosylases translocate efficiently along DNA while maintaining their vigilance for target damaged sites. Here, we report the observation of strandwise translocation of 8-oxoguanine DNA glycosylase, MutM, along undamaged DNA. In these complexes, the protein is observed to translocate by one nucleotide on one strand while remaining untranslocated on the complementary strand. We further report that alterations of single base-pairs or a single amino acid substitution (R112A) can induce strandwise translocation. Molecular dynamics simulations confirm that MutM can translocate along DNA in a strandwise fashion. These observations reveal a previously unobserved mode of movement for a DNA-binding protein along the surface of DNA.

  7. Bacterial translocation motors investigated by single molecule techniques.

    PubMed

    Allemand, Jean-Francois; Maier, Berenike

    2009-05-01

    Translocation of DNA and protein fibers through narrow constrictions is a ubiquitous and crucial activity of bacterial cells. Bacteria use specialized machines to support macromolecular movement. A very important step toward a mechanistic understanding of these translocation machines is the characterization of their physical properties at the single molecule level. Recently, four bacterial transport processes have been characterized by nanomanipulation at the single molecule level, DNA translocation by FtsK and SpoIIIE, DNA import during transformation, and the related process of a type IV pilus retraction. With all four processes, the translocation rates, processivity, and stalling forces were remarkably high as compared with single molecule experiments with other molecular motors. Although substrates of all four processes proceed along a preferential direction of translocation, directionality has been shown to be controlled by distinct mechanisms. PMID:19243443

  8. Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis.

    PubMed

    Weckselblatt, Brooke; Hermetz, Karen E; Rudd, M Katharine

    2015-07-01

    Unbalanced translocations are a relatively common type of copy number variation and a major contributor to neurodevelopmental disorders. We analyzed the breakpoints of 57 unique unbalanced translocations to investigate the mechanisms of how they form. Fifty-one are simple unbalanced translocations between two different chromosome ends, and six rearrangements have more than three breakpoints involving two to five chromosomes. Sequencing 37 breakpoint junctions revealed that simple translocations have between 0 and 4 base pairs (bp) of microhomology (n = 26), short inserted sequences (n = 8), or paralogous repeats (n = 3) at the junctions, indicating that translocations do not arise primarily from nonallelic homologous recombination but instead form most often via nonhomologous end joining or microhomology-mediated break-induced replication. Three simple translocations fuse genes that are predicted to produce in-frame transcripts of SIRPG-WWOX, SMOC2-PROX1, and PIEZO2-MTA1, which may lead to gain of function. Three complex translocations have inversions, insertions, and multiple breakpoint junctions between only two chromosomes. Whole-genome sequencing and fluorescence in situ hybridization analysis of two de novo translocations revealed at least 18 and 33 breakpoints involving five different chromosomes. Breakpoint sequencing of one maternally inherited translocation involving four chromosomes uncovered multiple breakpoints with inversions and insertions. All of these breakpoint junctions had 0-4 bp of microhomology consistent with chromothripsis, and both de novo events occurred on paternal alleles. Together with other studies, these data suggest that germline chromothripsis arises in the paternal genome and may be transmitted maternally. Breakpoint sequencing of our large collection of chromosome rearrangements provides a comprehensive analysis of the molecular mechanisms behind translocation formation. PMID:26070663

  9. Interaction prolonged DNA translocation through solid-state nanopores

    NASA Astrophysics Data System (ADS)

    Liang, Zexi; Tang, Zhipeng; Li, Ji; Hu, Rui; Yu, Dapeng; Zhao, Qing

    2015-06-01

    An interesting smooth blocked nanopore and corresponding ``current ladder'' phenomenon was observed in DNA translocation experiments through solid-state nanopores. The ionic current shows several drop steps (current levels in the current ladder) with an identical drop interval, which corresponds to an individual unfolded DNA translocation event. This indicates that multiple anchored DNA molecules have one end inside the nanopore to cause such a current ladder. On each current level, normal DNA translocation events were detected. The event duration time increases as the level number increases, which means DNA translocates more slowly when more DNA molecules are inside the nanopore due to DNA-DNA interactions. The Langevin dynamic model was used to explain the experimental observations. This finding strongly suggests that DNA-DNA interactions greatly impact the translocation dynamics when DNA passes through the nanopores.An interesting smooth blocked nanopore and corresponding ``current ladder'' phenomenon was observed in DNA translocation experiments through solid-state nanopores. The ionic current shows several drop steps (current levels in the current ladder) with an identical drop interval, which corresponds to an individual unfolded DNA translocation event. This indicates that multiple anchored DNA molecules have one end inside the nanopore to cause such a current ladder. On each current level, normal DNA translocation events were detected. The event duration time increases as the level number increases, which means DNA translocates more slowly when more DNA molecules are inside the nanopore due to DNA-DNA interactions. The Langevin dynamic model was used to explain the experimental observations. This finding strongly suggests that DNA-DNA interactions greatly impact the translocation dynamics when DNA passes through the nanopores. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01954k

  10. Minimizing the cost of translocation failure with decision-tree models that predict species' behavioral response in translocation sites.

    PubMed

    Ebrahimi, Mehregan; Ebrahimie, Esmaeil; Bull, C Michael

    2015-08-01

    The high number of failures is one reason why translocation is often not recommended. Considering how behavior changes during translocations may improve translocation success. To derive decision-tree models for species' translocation, we used data on the short-term responses of an endangered Australian skink in 5 simulated translocations with different release conditions. We used 4 different decision-tree algorithms (decision tree, decision-tree parallel, decision stump, and random forest) with 4 different criteria (gain ratio, information gain, gini index, and accuracy) to investigate how environmental and behavioral parameters may affect the success of a translocation. We assumed behavioral changes that increased dispersal away from a release site would reduce translocation success. The trees became more complex when we included all behavioral parameters as attributes, but these trees yielded more detailed information about why and how dispersal occurred. According to these complex trees, there were positive associations between some behavioral parameters, such as fight and dispersal, that showed there was a higher chance, for example, of dispersal among lizards that fought than among those that did not fight. Decision trees based on parameters related to release conditions were easier to understand and could be used by managers to make translocation decisions under different circumstances. Minimizar el Costo del Fracaso de la Reubicación con Modelos de Árboles de Decisión que Predigan la Respuesta Conductual de la Especie en los Sitios de Reubicación. PMID:25737134

  11. ?-PCR, A Simple Method to Detect Translocations and Insertion/Deletion Mutations

    PubMed Central

    Lin, Ming-Tseh; Tseng, Li-Hui; Rich, Roy G.; Hafez, Michael J.; Harada, Shuko; Murphy, Kathleen M.; Eshleman, James R.; Gocke, Christopher D.

    2011-01-01

    PCR detection of chromosomal translocations and small insertion/deletion mutations is challenging when potential amplicon size varies greatly. Molecular diagnostic laboratories face such difficulties with the BCL2-IGH translocation in follicular lymphoma and with internal tandem duplication mutation of the FLT3 gene in leukemia, where breakpoints are widely distributed, mutations may be multiple, signal strength is low, and background noise is elevated. We developed a strategy, called ?-PCR, that ensures PCR specificity and identifies individual breakpoints. ?-PCR uses two forward primers (external and internal) and a reverse primer simultaneously. The internal primer functions as a probe with a defined distance ? from the external primer. For follicular lymphoma, we prepared upstream, BCL2-specific primers for potential breakpoints to pair with a common, downstream VLJH primer. Multiplexed PCR amplicons are sized by capillary electrophoresis. Each of the upstream pairs has a defined interval separating them that uniquely identifies the breakpoint. The presence of two amplicons with a defined size difference confirms validity of the rearrangement and identity of the specific breakpoint, even if signal strength is low. By testing 40 follicular lymphoma and 12 control specimens from formalin-fixed, paraffin-embedded (FFPE) blocks, we showed that multiplex ?-PCR is a simple, sensitive strategy to identify translocations with multiple breakpoints or partners. The strategy was also applied to detect minor leukemic clones with internal tandem duplication mutations and could have broader applications for other insertion/deletion and duplication mutations. PMID:21227398

  12. Absence of Anaplastic Lymphoma Kinase Translocations in Signet Ring Cell Carcinomas of the Upper Gastrointestinal Tract

    PubMed Central

    Miller, Jill; Peng, Zhihua; Wilcox, Rebecca; Evans, Mark; Ades, Steven

    2014-01-01

    ABSTRACT BACKGROUND: Anaplastic lymphoma kinase (ALK) fusion oncogenes are present in multiple cancer types. The inversion of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes on chromosome 2 is present in a subset of patients with non-small-cell lung cancer (NSCLC). ALK-rearranged lung cancers demonstrate a significantly higher incidence of signet ring cell histology than do ALK-negative tumors. Based on the histologic similarities of ALK-rearranged NSCLC and signet ring cell carcinomas (SRCCs) of the gastrointestinal tract, we hypothesized that SRCC of the upper gastrointestinal (GI) tract may also harbor ALK translocations. METHODS: Thirty-five formalin-fixed, paraffin-embedded (FFPE) diagnostic tissue specimens of SRCC or poorly differentiated adenocarcinoma with greater than 10% signet ring cell features originating from the upper GI tract were obtained and confirmed by a board-certified, GI pathologist. SRCC specimens were analyzed by fluorescence in situ hybridization (FISH) analysis, with an ALK (2p23) break-apart probe. RESULTS: The FISH analysis revealed no evidence of ALK translocation. All 35 (100%) SRCC specimens showed intact ALK FISH signals. CONCLUSIONS: These data indicate that, despite histologic similarities between SRCC of the upper GI tract and ALK-positive NSCLC, ALK translocations are unlikely to be a significant contributor to the molecular etiology of SRCC. Further genomic investigations are ongoing. PMID:24799969

  13. Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia

    PubMed Central

    2014-01-01

    Background TiO2 particles are commonly used as dietary supplements and may contain up to 36% of nano-sized particles (TiO2-NPs). Still impact and translocation of NPs through the gut epithelium is poorly documented. Results We show that, in vivo and ex vivo, agglomerates of TiO2-NPs cross both the regular ileum epithelium and the follicle-associated epithelium (FAE) and alter the paracellular permeability of the ileum and colon epithelia. In vitro, they accumulate in M-cells and mucus-secreting cells, much less in enterocytes. They do not cause overt cytotoxicity or apoptosis. They translocate through a model of FAE only, but induce tight junctions remodeling in the regular ileum epithelium, which is a sign of integrity alteration and suggests paracellular passage of NPs. Finally we prove that TiO2-NPs do not dissolve when sequestered up to 24 h in gut cells. Conclusions Taken together these data prove that TiO2-NPs would possibly translocate through both the regular epithelium lining the ileum and through Peyer’s patches, would induce epithelium impairment, and would persist in gut cells where they would possibly induce chronic damage. PMID:24666995

  14. IGFBP-5 Promotes Fibrosis Independently of Its Translocation to the Nucleus and Its Interaction with Nucleolin and IGF

    PubMed Central

    Su, Yunyun; Nishimoto, Tetsuya; Feghali-Bostwick, Carol

    2015-01-01

    Background Insulin-like growth factor binding protein (IGFBP)-5 levels are increased in systemic sclerosis (SSc) skin and lung. We previously reported that IGFBP-5 is a pro-fibrotic factor that induces extracellular matrix (ECM) production and deposition. Since IGFBP-5 contains a nuclear localization signal (NLS) that facilitates its nuclear translocation, we sought to examine the role of nuclear translocation on the fibrotic activity of IGFBP-5 and identify IGFBP-5 binding partners relevant for its nuclear compartmentalization. Methods We generated functional wild type IGFBP-5 and IGFBP-5 with a mutated NLS or a mutated IGF binding site. Abrogation of nuclear translocation in the NLS mutant was confirmed using immunofluorescence and immunoblotting of nuclear and cytoplasmic cellular extracts. Abrogation of IGF binding was confirmed using western ligand blot. The fibrotic activity of wild type and mutant IGFBP-5 was examined in vitro in primary human fibroblasts and ex vivo in human skin. We identified IGFBP-5 binding partners using immunoprecipitation and mass spectrometry. We examined the effect of nucleolin on IGFBP-5 localization and function via sequence-specific silencing in primary human fibroblasts. Results Our results show that IGFBP-5-induced ECM production in vitro in primary human fibroblasts is independent of its nuclear translocation. The NLS-mutant also induced fibrosis ex vivo in human skin, thus confirming and extending the in vitro findings. Similar findings were obtained with the IGF-binding mutant. Nucleolin, a nucleolar protein that can serve as a nuclear receptor, was identified as an IGFBP-5 binding partner. Silencing nucleolin reduced IGFBP-5 translocation to the nucleus but did not block the ability of IGFBP-5 to induce ECM production and a fibrotic phenotype. Conclusions IGFBP-5 transport to the nucleus requires an intact NLS and nucleolin. However, nuclear translocation is not necessary for IGFBP-5 fibrotic activity; neither is IGF binding. Our data provide further insights into the role of cellular compartmentalization in IGFBP-5-induced fibrosis. PMID:26103640

  15. Chromosome pairing and recombination in mice heterozygous for different translocations in chromosomes 16 and 17.

    PubMed

    Borodin, P M; Gorlov, I P; Agulnik, A I; Agulnik, S I; Ruvinsky, A O

    1991-12-01

    In order to clarify the relationship between meiotic pairing and recombination, an electron microscopic (EM) study of synaptonemal complexes (SC) and an analysis of chiasma frequency and distribution were made in male mice singly and doubly heterozygous for Robertsonian [Rb(16.17)7Bnr] and reciprocal [T(16:17)43H] translocations and also in tertiary trisomics for the proximal region of chromosome 17. In all these genotypes an extensive zone of asynapsis/desynapsis around the breakpoints was revealed. At the same time a high frequency of non-homologous pairing was observed in precentromeric regions of acrocentric chromosomes. The presence in the proximal region of chromosome 17 of the t haplotype did not affect the synaptic behaviour of this region. Chiasma frequency in the proximal region of chromosome 17 in the T(16:17)43H heterozygotes and trisomics was increased when compared with that in Robertsonian heterozygotes. PMID:1773663

  16. Does translocation influence physiological stress in the desert tortoise?

    USGS Publications Warehouse

    Drake, K.K.; Nussear, K.E.; Esque, T.C.; Barber, A.M.; Vittum, K.M.; Medica, P.A.; Tracy, C.R.; Hunter, K.W.

    2012-01-01

    Wildlife translocation is increasingly used to mitigate disturbances to animals or habitat due to human activities, yet little is known about the extent to which translocating animals causes stress. To understand the relationship between physiological stress and translocation, we conducted a multiyear study (2007–2009) using a population of desert tortoises (Gopherus agassizii) near Fort Irwin, California. Blood samples were collected from adult tortoises in three treatment groups (resident, translocated and control) for 1 year prior to and 2 years after translocation. Samples were analyzed by radioimmunoassay for plasma total corticosterone (CORT), a glucocorticoid hormone commonly associated with stress responses in reptiles. CORT values were analyzed in relation to potential covariates (animal sex, date, behavior, treatment, handling time, air temperature, home-range size, precipitation and annual plant production) among seasons and years. CORT values in males were higher than in females, and values for both varied monthly throughout the activity season and among years. Year and sex were strong predictors of CORT, and translocation explained little in terms of CORT. Based on these results, we conclude that translocation does not elicit a physiological stress response in desert tortoises.

  17. Slowing DNA Translocation through a Nanopore Using a Functionalized Electrode

    PubMed Central

    Krishnakumar, Padmini; Gyarfas, Brett; Song, Weisi; Sen, Suman; Zhang, Peiming; Krsti?, Predrag; Lindsay, Stuart

    2013-01-01

    Nanopores were fabricated with an integrated microscale Pd electrode coated with either a hydrogen-bonding, or hydrophobic monolayer. Bare pores, or those coated with octane thiol, translocated single-stranded DNA with times of a few microseconds per base. Pores functionalized with 4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide slowed average translocation times, calculated as the duration of the event divided by the number of bases translocated, to about 100 microseconds per base at biases in the range of 50 to 80 mV. PMID:24161197

  18. Dose dependency of FISH-detected translocations in stable and unstable cells after Cs gamma irradiation of human lymphocytes in vitro.

    PubMed

    Romm, H; Stephan, G

    2004-01-01

    Human peripheral lymphocytes were exposed to 137Cs gamma-rays (0-4.3 Gy) in order to check the impact of unstable cells on the dose-response curve for translocations. Chromosomes 2, 4 and 8 were FISH-painted. 17,720 first dividing cells were analysed. For the discrimination between stable and unstable cells the painted and the counter-stained chromosomes were analysed at doses of 1 Gy and higher. The cell distribution of translocations follows a Poisson distribution. The data were fitted to the linear-quadratic function, y = c + alphaD + betaD2. As expected, the alpha coefficients of the dose-response curves for translocations in stable cells or in total cells do not differ. However, at doses >1 Gy, the frequency of all translocations in stable cells seems to be lower than the frequency in total cells. For the establishment of calibration curves for past dose assessment purposes, only complete translocations should be scored, in order to estimate reliable doses. PMID:15162031

  19. [The effect of Lr19-translocation on in vitro androgenesis and inheritance of leaf-rust resistance in DH3 lines and F2 hybrids of common wheat].

    PubMed

    Sibikeeva, Iu E; Sibikeev, S N; Krupnov, V A

    2004-09-01

    Leaf-rust resistance and androgenesis were studied in the anther cultures of Triticum aestivum L., which included Saratovskaya 29 cultivar, the isogenic line Ps29, and three F1 hybrids (L503/S55, L504/S58, ATS7/L1063) with 7DS-7DL-7Ae#1L translocation of Lr19 gene (Lr19 translocation) from Agropyron elongatum (Host) P.B. The Lr19 translocation was shown to affect the induction of embryogenesis and green plant regeneration. The frequencies of Lr19 translocation differed in F2 hybrids obtained by traditional hybridization and in sets of DH lines obtained in F1 anther cultures derived from the same combinations of T. aestivum parental forms. The number of leaf-rust resistant genotypes tended to decrease. The frequency of Lr19 translocation in the set of DH3 lines derived from F1 L504/S58 was significantly lower than in other sets of DH3 lines and F2 hybrid populations. PMID:15559150

  20. The evolutionary history of Drosophila buzzatii. IX. High frequencies of new chromosome rearrangements induced by introgressive hybridization.

    PubMed

    Naveira, H; Fontdevila, A

    1985-01-01

    Introgression of a chromosome segment from Drosophila serido into the genome of its sibling D. buzzatii brought about the release of mutator potential in the hybrids. Mutator activity was determined by examining the frequency of new chromosomal rearrangements, that appeared only in the progeny of hybrid individuals. Mutation frequency was 30 times greater in the progeny of hybrid males than in that of hybrid females. There was a remarkable influence of the D. buzzatii genetic background on the frequency of production of these new rearrangements. The appearance of a new rearrangement did not depend on the genotype of the larva that bore it, but only on that of its hybrid progenitor. Among the new rearrangements there were inversions, translocations, and duplications. The number of translocations was significantly lower than that of inversions or duplications; this last type was the most frequently recorded. The distribution of the aberrations among the four major autosomes seemed to be homogeneous, although the total number of breakpoints was significantly greater in chromosome 4 than in the others. No rearrangement was found on the X chromosome. Breakpoints within three of the four affected autosomes were not randomly distributed. PMID:3987443

  1. A rare Robertsonian translocation rob(14;22) carrier with azoospermia, meiotic defects, and testicular sperm aneuploidy.

    PubMed

    Sobotka, Vladimir; Vozdova, Miluse; Heracek, Jiri; Rubes, Jiri

    2015-08-01

    Male infertility is a serious problem in an increasing number of couples. We report an infertile man with non-obstructive azoospermia and karyotype 45,XY,rob(14;22). The immunofluorescence analysis of his testicular tissue using antibodies to SYCP1, SYCP3, HORMAD2, MLH1, and centromeres showed delayed synapsis of the chromosomes involved in the translocation, a varying extent of trivalent asynapsis and its association with sex chromosomes. The mean frequency of meiotic recombination per cell was within the range of normal values. Fluorescence in situ hybridization (FISH) with probes for chromosomes 14 and 22 revealed 5.83% of chromosomally abnormal testicular spermatozoa. FISH with probes for chromosomes X, Y, and 21 showed frequencies of disomic and diploid testicular spermatozoa increased when compared to ejaculated sperm of healthy donors, but comparable with published results for azoospermic patients. PGD by FISH for the translocation and aneuploidy of chromosomes X, Y, 13, 18, and 21 showed a normal chromosomal complement in one out of three analyzed embryos. A healthy carrier girl was born after the embryo transfer. This study shows the benefits of preimplantation genetic diagnosis in a case of a rare Robertsonian translocation carrier with azoospermia and a relatively low frequency of chromosomally unbalanced testicular spermatozoa. PMID:26043179

  2. Gut Microbiota Dysbiosis Is Associated with Inflammation and Bacterial Translocation in Mice with CCl4Induced Fibrosis

    Microsoft Academic Search

    Isabel Gómez-Hurtado; Arlette Santacruz; Gloria Peiró; Pedro Zapater; Ana Gutiérrez; Miguel Pérez-Mateo; Yolanda Sanz; Rubén Francés

    2011-01-01

    BackgroundGut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate.Hypothesis and AimsWe hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response.Animals and MethodsProgressive liver damage was induced in Balb\\/c mice

  3. Background, an important factor in visual search.

    PubMed

    De Vries, Jelmer P; Hooge, Ignace T C; Wertheim, Alexander H; Verstraten, Frans A J

    2013-06-28

    The ability to detect an object depends on the contrast between the object and its background. Despite this, many models of visual search rely solely on the properties of target and distractors, and do not take the background into account. Yet, both target and distractors have their individual contrasts with the background. These contrasts generally differ, because the target and distractors are different in at least one feature. Therefore, background is likely to play an important role in visual search. In three experiments we manipulated the properties of the background (luminance, orientation and spatial frequency, respectively) while keeping the target and distractors constant. In the first experiment, in which target and distractors had a different luminance, changing the background luminance had an extensive effect on search times. When background luminance was in between that of the target and distractors, search times were always short. Interestingly, when the background was darker than both the target and the distractors, search times were much longer than when the background was lighter. Manipulating orientation and spatial frequency of the background, on the other hand, resulted in search times that were longest for small target-background differences. Thus, background plays an important role in search. This role depends on the individual contrast of both target and distractors with the background and the type of feature contrast (luminance, orientation or spatial frequency). PMID:23623804

  4. A Robertsonian translocation in swine M. SCHWERIN, D. GOLISCH E. RITTER

    E-print Network

    Paris-Sud XI, Université de

    A Robertsonian translocation in swine M. SCHWERIN, D. GOLISCH E. RITTER Research Centre of Animal). The results obtained are discussed. Key words :Fusion translocation, swine. Résumé Une translocation or other types of Robertsonian translocation have been found in many cattle breeds. In contrast, in swine

  5. Using survival analysis to study translocation success in the Gila topminnow (Poeciliopsis occidentalis).

    PubMed

    Sheller, Frances J; Fagan, William F; Unmack, Peter J

    2006-10-01

    Translocation, the intentional release of captive-propagated and/or wild-caught animals into the wild in an attempt to establish, reestablish, or augment a population, is a commonly used approach to species conservation. Despite the frequent mention of translocation as an aid in threatened or endangered species recovery plans, translocations have resulted in the establishment of few sustainable populations. To improve the effectiveness of translocation efforts, it is essential to identify and adopt features that contribute to successful translocations. This study analyzed 148 translocations of the endangered Gila topminnow (Poeciliopsis occidentalis) to identify various factors that have significantly influenced translocation success. We quantified success as the "persistence time" of translocated populations and used survival analysis to interpret the role of several factors. The following factors affected persistence times of translocated populations: season in which the fish were translocated, habitat type of the translocation site, and genetic origin of the fish stocked. In general, factors associated with stocking, the population stocked, and the site of translocation can significantly affect the persistence of translocated populations and thus increase the probability of translocation success. For Gila topminnow, future translocations should be undertaken in late summer or fall (not early summer), should occur into ponds (not streams, wells, or tanks), and should generally utilize individuals from genetic lineages other than Monkey Spring. For other species, a key lesson emerging from this work is that life history attributes for each translocated species need to be considered carefully. PMID:17069370

  6. Contributed Paper The Role of Translocation in Recovery of Woodland

    E-print Network

    Hebblewhite, Mark

    (Rangifer tarandus caribou) were extirpated recently from Banff National Park, Canada, and translocations, conservation reliant species, protected area, PVA, Rangifer tarandus, recovery plan, reintroduction tarandus caribou) fue extirpado recientemente del Parque Nacional Banff, Canad´a, y se ha estado

  7. Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies.

    PubMed

    Bhatti, Parveen; Yong, Lee C; Doody, Michele M; Preston, Dale L; Kampa, Diane M; Ramsey, Marilyn J; Ward, Elizabeth M; Edwards, Alan A; Ron, Elaine; Tucker, James D; Sigurdson, Alice J

    2010-11-01

    Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects. PMID:20602108

  8. The Preprotein Translocation Channel of the Outer Membrane of Mitochondria

    Microsoft Academic Search

    Klaus-Peter Künkele; Susanne Heins; Markus Dembowski; Frank E Nargang; Roland Benz; Michel Thieffry; Jochen Walz; Roland Lill; Stephan Nussberger; Walter Neupert

    1998-01-01

    The preprotein translocase of the outer membrane of mitochondria (TOM complex) facilitates the recognition, insertion, and translocation of nuclear-encoded mitochondrial preproteins. We have purified the TOM complex from Neurospora crassa and analyzed its composition and functional properties. The TOM complex contains a cation-selective high-conductance channel. Upon reconstitution into liposomes, it mediates integration of proteins into and translocation across the lipid

  9. Driven translocation of a polymer: Fluctuations at work

    NASA Astrophysics Data System (ADS)

    Dubbeldam, J. L. A.; Rostiashvili, V. G.; Milchev, A.; Vilgis, T. A.

    2013-03-01

    The impact of thermal fluctuations on the translocation dynamics of a polymer chain driven through a narrow pore has been investigated theoretically and by means of extensive molecular dynamics (MD) simulation. The theoretical consideration is based on the so-called velocity Langevin (V-Langevin) equation which determines the progress of the translocation in terms of the number of polymer segments, s(t), that have passed through the pore at time t due to a driving force f. The formalism is based only on the assumption that, due to thermal fluctuations, the translocation velocity v=?(t) is a Gaussian random process as suggested by our MD data. With this in mind we have derived the corresponding Fokker-Planck equation (FPE) which has a nonlinear drift term and diffusion term with a time-dependent diffusion coefficient D(t). Our MD simulation reveals that the driven translocation process follows a super diffusive law with a running diffusion coefficient D(t)?t? where ?<1. This finding is then used in the numerical solution of the FPE which yields an important result: For comparatively small driving forces fluctuations facilitate the translocation dynamics. As a consequence, the exponent ? which describes the scaling of the mean translocation time with the length N of the polymer, ?N? is found to diminish. Thus, taking thermal fluctuations into account, one can explain the systematic discrepancy between theoretically predicted duration of a driven translocation process, considered usually as a deterministic event, and measurements in computer simulations. In the nondriven case, f=0, the translocation is slightly subdiffusive and can be treated within the framework of fractional Brownian motion (fBm).

  10. Molecular studies of translocations and trisomy involving chromosome 13

    SciTech Connect

    Robinson, W.P.; Bernasconi, F.; Dutly, F.; Schinzel, A.A. [Univ. of British Columbia, Vancouver (Canada)] [and others] [Univ. of British Columbia, Vancouver (Canada); and others

    1996-01-11

    Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13)(p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy. The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45, -13, -13, +t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy. 30 refs., 1 fig., 2 tabs.

  11. Controlled translocation of DNA segments through nanoelectrode gaps

    SciTech Connect

    Zhao, Xiongce [ORNL; Payne, Christina M [Vanderbilt University; Cummings, Peter T [ORNL

    2008-01-01

    Molecular dynamics simulations show that electrophoresis of DNA segments through a nanoscale electrode gap can be controlled by applying appropriate biased voltages in the transmembrane direction. The translocation velocities are dependent on both the DNA molecular weight and nucleotide structure. Application of alternating driving fields results in oscillatory motion of DNA inside the gap. Interruption of the driving field can effectively pause the translocation of DNA segments. Results from this work are useful for designing novel sequencing devices.

  12. Structure of the translocator domain of a bacterial autotransporter

    Microsoft Academic Search

    Clasien J Oomen; Peter van Ulsen; Patrick Van Gelder; Maya Feijen; J. P. M. Tommassen; Piet Gros

    2004-01-01

    Autotransporters are virulence-related proteins of Gram- negative bacteria that are secreted via an outer- membrane-based C-terminal extension, the translocator domain. This domain supposedly is sufficient for the transport of the N-terminal passenger domain across the outer membrane. We present here the crystal structure of the in vitro-folded translocator domain of the autotran- sporter NalP from Neisseria meningitidis, which reveals a

  13. Chromosome 3 translocations and familial renal cell cancer

    Microsoft Academic Search

    Anita C. M. Bonne; Danielle Bodmer; Eric F. P. M. Schoenmakers; C. M. A. van Ravenswaaij-Arts; N. Hoogerbrugge-van der Linden

    2004-01-01

    Renal cell carcinomas (RCCs) occur in both sporadic and familial forms. In a subset of families the occurrence of RCCs co-segregates with the presence of constitutional chromosome 3 translocations. Previously, such co-segregation phenomena have been widely employed to identify candidate genes in various hereditary (cancer) syndromes. Here we survey the translocation 3-positive RCC families that have been reported to date

  14. Evaluation of collared peccary translocations in the Texas Hill Country 

    E-print Network

    Porter, Brad Alan

    2007-09-17

    of collared peccaries, however, has not been evaluated. 1 Translocations have been used in the restoration of mid- to large-sized mammal populations in many areas of the United States (Nielsen 1988). For example, use of translocations for Sitka black-tailed... partitioning in sympatric populations of collared peccaries and feral hogs in southern Texas. Journal of Mammalogy 76: 784-799. Lee, D. J., and M. R. Vaughan. 2004. Black bear family breakup in western Virginia. Northeastern Naturalist 11: 111...

  15. What drives the translocation of stiff chains?

    PubMed Central

    Zandi, Roya; Reguera, David; Rudnick, Joseph; Gelbart, William M.

    2003-01-01

    We study the dynamics of the passage of a stiff chain through a pore into a cell containing particles that bind reversibly to it. Using Brownian molecular dynamics simulations we investigate the mean first-passage time as a function of the length of the chain inside for different concentrations of binding particles. As a consequence of the interactions with these particles, the chain experiences a net force along its length whose calculated value from the simulations accounts for the velocity at which it enters the cell. This force can in turn be obtained from the solution of a generalized diffusion equation incorporating an effective Langmuir adsorption free energy for the chain plus binding particles. These results suggest a role of binding particles in the translocation process that is in general quite different from that of a Brownian ratchet. Furthermore, nonequilibrium effects contribute significantly to the dynamics; e.g., the chain often enters the cell faster than particle binding can be saturated, resulting in a force several times smaller than the equilibrium value. PMID:12851462

  16. Multiscale model of platelet translocation and collision.

    PubMed

    Wang, Weiwei; Mody, Nipa A; King, Michael R

    2013-07-01

    The tethering of platelets on the injured vessel surface mediated by glycoprotein Ib? (GPIb?) - Von Willebrand factor (vWF) bonds, as well as the interaction between flowing platelets and adherent platelets, are two key events that take place immediately following blood vessel injury. This early-stage platelet deposition and accumulation triggers the initiation of hemostasis, a self-defensive mechanism to prevent the body from excessive blood loss. To understand and predict this complex process, one must integrate experimentally determined information on the mechanics and biochemical kinetics of participating receptors over very small time frames (1-1000 µs) and length scales (10-100 nm), to collective phenomena occurring over seconds and tens of microns. In the present study, a unique three dimensional multiscale computational model, platelet adhesive dynamics (PAD), was applied to elucidate the unique physics of (i) a non-spherical, disk-shaped platelet interacting and tethering onto the damaged vessel wall followed by (ii) collisional interactions between a flowing platelet with a downstream adherent platelet. By analyzing numerous simulations under different physiological conditions, we conclude that the platelet's unique spheroid-shape provides heterogeneous, orientation-dependent translocation (rolling) behavior which enhances cell-wall interactions. We also conclude that platelet-platelet near field interactions are critical for cell-cell communication during the initiation of microthrombi. The PAD model described here helps to identify the physical factors that control the initial stages of platelet capture during this process. PMID:23853387

  17. Surface modification of graphene nanopores for protein translocation.

    PubMed

    Shan, Y P; Tiwari, P B; Krishnakumar, P; Vlassiouk, I; Li, W Z; Wang, X W; Darici, Y; Lindsay, S M; Wang, H D; Smirnov, S; He, J

    2013-12-13

    Studies of DNA translocation through graphene nanopores have revealed their potential for DNA sequencing. Here we report a study of protein translocation through chemically modified graphene nanopores. A transmission electron microscope (TEM) was used to cut nanopores with diameters between 5 and 20 nm in multilayer graphene prepared by chemical vapor deposition (CVD). After oxygen plasma treatment, the dependence of the measured ionic current on salt concentration and pH was consistent with a small surface charge induced by the formation of carboxyl groups. While translocation of gold nanoparticles (10 nm) was readily detected through such treated pores of a larger diameter, translocation of the protein ferritin was not observed either for oxygen plasma treated pores, or for pores modified with mercaptohexadecanoic acid. Ferritin translocation events were reliably observed after the pores were modified with the phospholipid-PEG (DPPE-PEG750) amphiphile. The ion current signature of translocation events was complex, suggesting that a series of interactions between the protein and pores occurs during the process. PMID:24231385

  18. Dermatoglyphs in carriers of a balanced 15;21 translocation.

    PubMed

    Rodewald, A; Zankl, M; Zankl, H; Zang, K D

    1980-08-01

    Cytogenetic and dermatoglyphic features were studied in a large family with an inherited 15;21 translocation. Of 35 healthy members of the family, 21 carried the translocation chromosome and 14 were chromosomally normal. There were six members with Down's syndrome who had the translocation. Dermatoglyphic studies showed that carriers of this balanced translocation had the following peculiarities significantly more often than the general population. On the hands, they had ulnar loops on the fingertips, symmetrical high terminations of the A line, symmetrical ulnar loops on the hypothenar areas, distal loops in the 3rd interdigital areas, open fields in the 4th interdigital areas, axial triradii in the distal position, and single transverse palmar creases (Sydney lines). On the feet, they had small distal loops on the hallucal area and distal loops in the 4th interdigital areas. The translocation carriers also had significantly more often than non-carrier relatives symmetrical high terminations of the A line, open fields in the 4th interdigital areas, distal axial triradii, and Sydney lines. On the feet, they had small distal loops on the hallucal areas, distal loops in the 4th interdigital areas, and tibial loops on the proximal hypothenar areas. The data obtained from this study, and especially the values of the Walker and general indices, indicate that some of the dermatoglyphic stigmata of Down's syndrome are directly associated with the 15;21 translocation carrier state and can therefore be used for predicting that state. PMID:6451704

  19. Surface modification of graphene nanopores for protein translocation

    PubMed Central

    Shan, Y. P.; Tiwari, P. B.; Krishnakumar, P.; Vlassiouk, I.; Li, W.Z.; Wang, X.W.; Darici, Y.; Lindsay, S.M.; Wang, H. D.; Smirnov, S.; He, J.

    2014-01-01

    Studies of DNA translocation through graphene nanopores have revealed their potential for DNA sequencing. Here we report a study of protein translocation through chemically modified graphene nanopores. A transmission electron microscope (TEM) was used to cut nanopores with diameters between 5-20 nm in multilayer graphene prepared by chemical vapor deposition (CVD). After oxygen plasma treatment, the dependence of the measured ionic current on salt concentration and pH was consistent with a small surface charge induced by the formation of carboxyl groups. While translocation of gold nanoparticles (10 nm) was readily detected through such treated pores of a larger diameter, translocation of protein ferritin was not observed either for oxygen plasma treated pores, or for pores modified with mercaptohexadecanoic acid. Ferritin translocation events were reliably observed after the pores were modified with the phospholipid-PEG (DPPE-PEG750) amphiphile. The ion current signature of translocation events was complex, suggesting that a series of interactions between the protein and pore occur during the process. PMID:24231385

  20. Atomic structure of anthrax protective antigen pore elucidates toxin translocation.

    PubMed

    Jiang, Jiansen; Pentelute, Bradley L; Collier, R John; Zhou, Z Hong

    2015-05-28

    Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Protective antigen forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes lethal factor and oedema factor into the cytosol of target cells. Protective antigen is not only a vaccine component and therapeutic target for anthrax infections but also an excellent model system for understanding the mechanism of protein translocation. On the basis of biochemical and electrophysiological results, researchers have proposed that a phi (?)-clamp composed of phenylalanine (Phe)427 residues of protective antigen catalyses protein translocation via a charge-state-dependent Brownian ratchet. Although atomic structures of protective antigen prepores are available, how protective antigen senses low pH, converts to active pore, and translocates lethal factor and oedema factor are not well defined without an atomic model of its pore. Here, by cryo-electron microscopy with direct electron counting, we determine the protective antigen pore structure at 2.9-Å resolution. The structure reveals the long-sought-after catalytic ?-clamp and the membrane-spanning translocation channel, and supports the Brownian ratchet model for protein translocation. Comparisons of four structures reveal conformational changes in prepore to pore conversion that support a multi-step mechanism by which low pH is sensed and the membrane-spanning channel is formed. PMID:25778700

  1. Surface modification of graphene nanopores for protein translocation

    NASA Astrophysics Data System (ADS)

    Shan, Y. P.; Tiwari, P. B.; Krishnakumar, P.; Vlassiouk, I.; Li, W. Z.; Wang, X. W.; Darici, Y.; Lindsay, S. M.; Wang, H. D.; Smirnov, S.; He, J.

    2013-12-01

    Studies of DNA translocation through graphene nanopores have revealed their potential for DNA sequencing. Here we report a study of protein translocation through chemically modified graphene nanopores. A transmission electron microscope (TEM) was used to cut nanopores with diameters between 5 and 20 nm in multilayer graphene prepared by chemical vapor deposition (CVD). After oxygen plasma treatment, the dependence of the measured ionic current on salt concentration and pH was consistent with a small surface charge induced by the formation of carboxyl groups. While translocation of gold nanoparticles (10 nm) was readily detected through such treated pores of a larger diameter, translocation of the protein ferritin was not observed either for oxygen plasma treated pores, or for pores modified with mercaptohexadecanoic acid. Ferritin translocation events were reliably observed after the pores were modified with the phospholipid-PEG (DPPE-PEG750) amphiphile. The ion current signature of translocation events was complex, suggesting that a series of interactions between the protein and pores occurs during the process.

  2. Translocation of the Palila, an endangered Hawaiian honeycreeper

    USGS Publications Warehouse

    Fancy, S.G.

    1997-01-01

    The Palila Loxioides bailleui is an endangered Hawaiian honeycreeper that is restricted to high-elevation dry woodlands on Mauna Kea volcano, Hawaii. Palila are absent or occur in small numbers throughout most of their historic range because of habitat loss, predation and avian disease. The Paula's habitat is regenerating as a result of feral ungulate control, but the species is likely to be slow in recolonizing former ranges because of strong site tenacity. In March 1993, we translocated 35 Palila to Kanakaleonui on the eastern slope of Mauna Kea to determine whether we could speed recovery by releasing adult birds in new areas where predators were controlled. At least two pairs of translocated Palila successfully nested at the release site during their first breeding season, and two other pairs constructed nests. The density of Palila at Kanakaleonui in the three years following the translocation was higher than that before translocation. Approximately half of the translocated birds remained at the release site for 2-6 weeks and then homed back to their capture site, >20 km away. Translocations of adult birds and release of captive-reared juvenile Palila, in combination with additional habitat restoration, may be an effective management tool for speeding the recovery of this species.

  3. Prevalence of Emanuel syndrome: theoretical frequency and surveillance result.

    PubMed

    Ohye, Tamae; Inagaki, Hidehito; Kato, Takema; Tsutsumi, Makiko; Kurahashi, Hiroki

    2014-08-01

    Constitutional t(11;22)(q23;q11) is the most frequent recurrent non-Robertsonian translocation in humans. Balanced carriers of t(11;22) usually manifest no clinical symptoms, and are often identified after the birth of offspring with an unbalanced form of this translocation, known as Emanuel syndrome. To determine the prevalence of the disorder, we sent surveillance questionnaires to 735 core hospitals in Japan. The observed number of Emanuel syndrome cases was 36 and that of t(11;22) balanced translocation carriers, 40. On the basis of the de novo t(11;22) translocation frequency in sperm from healthy men, we calculated the frequency of the translocations in the general population. Accordingly, the prevalence of Emanuel syndrome was estimated at 1 in 110,000. Based on this calculation, the estimated number of Emanuel syndrome cases in Japan is 1063 and of t(11;22) balanced translocation carriers, 16,604, which are much higher than the numbers calculated from the questionnaire responses. It is possible that this discordance is partly attributable to a lack of disease identification. Further efforts should be made to increase the awareness of Emanuel syndrome to ensure a better quality of life for affected patients and their families. PMID:24980921

  4. Cytologically integrated physical restriction fragment length polymorphism maps for the barley genome based on translocation breakpoints.

    PubMed Central

    Künzel, G; Korzun, L; Meister, A

    2000-01-01

    We have developed a new technique for the physical mapping of barley chromosomes using microdissected translocation chromosomes for PCR with sequence-tagged site primers derived from >300 genetically mapped RFLP probes. The positions of 240 translocation breakpoints were integrated as physical landmarks into linkage maps of the seven barley chromosomes. This strategy proved to be highly efficient in relating physical to genetic distances. A very heterogeneous distribution of recombination rates was found along individual chromosomes. Recombination is mainly confined to a few relatively small areas spaced by large segments in which recombination is severely suppressed. The regions of highest recombination frequency (frequencies and marker densities are highly conserved between the genomes of barley and wheat. The findings for barley support the conclusions drawn from deletion mapping in wheat that for all plant genomes, notwithstanding their size, the marker-rich regions are all of similar gene density and recombination activity and, therefore, should be equally accessible to map-based cloning. PMID:10628998

  5. Carbon translocation in zooanthaellae-coelenterate symbioses

    SciTech Connect

    Battey, J.F.

    1985-01-01

    When host and algal triglycerides synthesized in the symbiotic sea anemone Condylactis gigantea during light and dark incubations in /sup 14/C-bicarbonate and /sup 14/C-acetate were deacylated, more then 80% of the radioactivity was found in the fatty acid moiety. In contrast, triglycerides isolated from zooxanthellae and host incubated in /sup 14/C-glycerol in the dark were found to have more then 95% of their radioactivity in the glycerol moiety. During /sup 14/C-glycerol incubations in the light, radioactivity in the fatty acid moiety of zooxanthellae triglyceride fatty acid moiety stayed below 5% during /sup 14/C-glycerol incubations in the light. These results show neither the zooxanthellae nor host can rapidly convert glycerol to fatty acid. Radioactivity from /sup 14/C-glycerol that does eventually appear in host lipid may have been respired to /sup 14/CO/sub 2/ then photosynthetically fixed by the zooxanthellae and synthesized into lipid fatty acid. The isolated zooxanthellae of C. gigantea contained 3.62 +/- 0.33 mM glycerol, which was 26x the 0.141 +/- 0.02 mM found in the coelenterate tissue. Aposymbiotic coelenterate tissue contained 0.169 +/- 0.05 mM glycerol. The metabolic inhibitors, sodium cyanide, aminooxyacetic acid and cerulenin were used to try and uncouple the production of glycerol by the zooxanthellae from its utilization by the coelenterate host. 10/sup -5/ M NaCN increased the ratio of cross photosynthesis to respiration in both intact tentacles and isolated zooxanthellae, increased translocation from 17.7 +/- 3.5% of total fixed carbon in controls to 43.5 +/- 5.79%, and doubled the amount of photosynthetically fixed carbon accumulating in the coelenterate host over that in controls.

  6. TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals

    PubMed Central

    Chase, Andrew; Ernst, Thomas; Fiebig, Andreas; Collins, Andrew; Grand, Francis; Erben, Philipp; Reiter, Andreas; Schreiber, Stefan; Cross, Nicholas C.P.

    2010-01-01

    Background The formation of fusion genes plays roles in both oncogenesis and evolution by facilitating the acquisition of novel functions. Here we describe the first example of a human polymorphic in-frame fusion of two unrelated genes associated with a copy number variant. Design and Methods Array comparative genomic hybridization was used to identify cryptic oncogenic fusion genes. Fusion gene structure and origin was examined using molecular biological and computational methods. Phenotype associations were examined using PopGen cohorts. Results Targeted array comparative genomic hybridization to identify cryptic oncogenic fusion genes in patients with atypical myeloproliferative neoplasms identified a 111 kb amplification with breakpoints within the TRK-fused gene (TFG, a target of translocations in lymphoma and thyroid tumors) and G-protein-coupled receptor 128 (GPR128) resulting in an expressed in-frame TFG-GPR128 fusion transcript. The fusion gene was also identified in healthy individuals at a frequency of 0.02 (3/120). Normally both genes are in identical orientations with TFG immediately downstream of GPR128. In individuals with a copy number variant amplification, one or two copies of the TFG-GPR128 fusion are found between the two parental genes. The breakpoints share a region of microhomology, and haplotype and microsatellite analysis indicate a single ancestral origin. Analysis of PopGen cohorts showed no obvious phenotype association. An in silico search of EST databases found no other copy number variant amplification-associated fusion transcripts, suggesting that this is an uncommon event. Conclusions The finding of a polymorphic gene fusion in healthy individuals adds another layer to the complexity of human genome variation and emphasizes the importance of careful discrimination of oncogenic changes found in tumor samples from non-pathogenic normal variation. PMID:19797732

  7. Computer simulation of viral-assembly and translocation

    NASA Astrophysics Data System (ADS)

    Mahalik, Jyoti Prakash

    We investigated four different problems using coarse grained computational models : self-assembly of single stranded (ss) DNA virus, ejection dynamics of double stranded(ds) DNA from phages, translocation of ssDNA through MspA protein pore, and segmental dynamics of a polymer translocating through a synthetic nanopore. In the first part of the project, we investigated the self-assembly of a virus with and without its genome. A coarse-grained model was proposed for the viral subunit proteins and its genome (ssDNA). Langevin dynamics simulation, and replica exchange method were used to determine the kinetics and energetics of the self-assembly process, respectively. The self-assembly follows a nucleation-growth kind of mechanism. The ssDNA plays a crucial role in the self-assembly by acting as a template and enhancing the local concentration of the subunits. The presence of the genome does not changes the mechanism of the self-assembly but it reduces the nucleation time and enhances the growth rate by almost an order of magnitude. The second part of the project involves the investigation of the dynamics of the ejection of dsDNA from phages. A coarse-grained model was used for the phage and dsDNA. Langevin dynamics simulation was used to investigate the kinetics of the ejection. The ejection is a stochastic process and a slow intermediate rate kinetics was observed for most ejection trajectories. We discovered that the jamming of the DNA at the pore mouth at high packing fraction and for a disordered system is the reason for the intermediate slow kinetics. The third part of the project involves translocation of ssDNA through MspA protein pore. MspA protein pore has the potential for genome sequencing because of its ability to clearly distinguish the four different nucleotides based on their blockade current, but it is a challenge to use this pore for any practical application because of the very fast traslocation time. We resolved the state of DNA translocation reported in the recent experimental work . We also investigated two methods for slowing down the translocation process: pore mutation and use of alternating voltage. Langevin dynamics simulation and Poisson Nernst Planck solver were used for the investigation. We demonstrated that mutation of the protein pore or applying alternating voltage is not a perfect solution for increasing translocation time deterministically. Both strategies resulted in enhanced average translocation time as well as the width of the translocation time distribution. The increase in the width of the translocation time distribution is undesired. In the last part of the project, we investigated the applicability of the polyelectrolyte theory in the computer simulation of polyelectrolyte translocation through nanopores. We determined that the Debye Huckel approximation is acceptable for most translocation simulations as long as the coarse grained polymer bead size is comparable or larger than the Debye length. We also determined that the equilibrium translocation theory is applicable to the polyelectrolyte translocation through a nanopore under biasing condition. The unbiased translocation behavior of a polyelectrolyte chain is qualitatively different from the Rouse model predictions, except for the case where the polyelectrolyte is very small compared to the nanopore.

  8. Dialysis dose and frequency

    Microsoft Academic Search

    Francesco Locatelli; Umberto Buoncristiani; Bernard Canaud; Hans Kohler; Thierry Petitclerc; Pietro Zucchelli; Ospedale A. Manzoni; CHU Montpellier; Schwerpunkt Nephrologie

    2004-01-01

    Background. From the beginning of the dialysis era, the issue of optimal dialysis dose and frequency has been a central topic in the delivery of dialysis treatment. Methods. We undertook a discussion to achieve a consensus on key points relating to dialysis dose and frequency, focusing on the relationships with clinical and patient outcomes. Results. Traditionally, dialysis adequacy has been

  9. Strandwise translocation of a DNA glycosylase on undamaged DNA

    PubMed Central

    Qi, Yan; Nam, Kwangho; Spong, Marie C.; Banerjee, Anirban; Sung, Rou-Jia; Zhang, Michael; Karplus, Martin; Verdine, Gregory L.

    2012-01-01

    Base excision repair of genotoxic nucleobase lesions in the genome is critically dependent upon the ability of DNA glycosylases to locate rare sites of damage embedded in a vast excess of undamaged DNA, using only thermal energy to fuel the search process. Considerable interest surrounds the question of how DNA glycosylases translocate efficiently along DNA while maintaining their vigilance for target damaged sites. Here, we report the observation of strandwise translocation of 8-oxoguanine DNA glycosylase, MutM, along undamaged DNA. In these complexes, the protein is observed to translocate by one nucleotide on one strand while remaining untranslocated on the complementary strand. We further report that alterations of single base-pairs or a single amino acid substitution (R112A) can induce strandwise translocation. Molecular dynamics simulations confirm that MutM can translocate along DNA in a strandwise fashion. These observations reveal a previously unobserved mode of movement for a DNA-binding protein along the surface of DNA. PMID:22219368

  10. Twin-Arginine Translocation Pathway in Streptomyces lividans

    PubMed Central

    Schaerlaekens, Kristien; Schierová, Michaela; Lammertyn, Elke; Geukens, Nick; Anné, Jozef; Van Mellaert, Lieve

    2001-01-01

    The recently discovered bacterial twin-arginine translocation (Tat) pathway was investigated in Streptomyces lividans, a gram-positive organism with a high secretion capacity. The presence of one tatC and two hcf106 homologs in the S. lividans genome together with the several precursor proteins with a twin-arginine motif in their signal peptide suggested the presence of the twin-arginine translocation pathway in the S. lividans secretome. To demonstrate its functionality, a tatC deletion mutant was constructed. This mutation impaired the translocation of the Streptomyces antibioticus tyrosinase, a protein that forms a complex with its transactivator protein before export. Also the chimeric construct pre-TorA-23K, known to be exclusively secreted via the Tat pathway in Escherichia coli, could be translocated in wild-type S. lividans but not in the tatC mutant. In contrast, the secretion of the Sec-dependent S. lividans subtilisin inhibitor was not affected. This study therefore demonstrates that also in general in Streptomyces spp. the Tat pathway is functional. Moreover, this Tat pathway can translocate folded proteins, and the E. coli TorA signal peptide can direct Tat-dependent transport in S. lividans. PMID:11698358

  11. No evidence for cerium dioxide nanoparticle translocation in maize plants.

    PubMed

    Birbaum, Karin; Brogioli, Robert; Schellenberg, Maya; Martinoia, Enrico; Stark, Wendelin J; Günther, Detlef; Limbach, Ludwig K

    2010-11-15

    The rapidly increasing production of engineered nanoparticles has raised questions regarding their environmental impact and their mobility to overcome biological important barriers. Nanoparticles were found to cross different mammalian barriers, which is summarized under the term translocation. The present work investigates the uptake and translocation of cerium dioxide nanoparticles into maize plants as one of the major agricultural crops. Nanoparticles were exposed either as aerosol or as suspension. Our study demonstrates that 50 ?g of cerium/g of leaves was either adsorbed or incorporated into maize leaves. This amount could not be removed by a washing step and did not depend on closed or open stomata investigated under dark and light exposure conditions. However, no translocation into newly grown leaves was found when cultivating the maize plants after airborne particle exposure. The use of inductively coupled mass spectrometer allowed detection limits of less than 1 ng of cerium/g of leaf. Exposure of plants to well-characterized nanoparticle suspensions in the irrigation water resulted also in no detectable translocation. These findings may indicate that the biological barriers of plants are more resistant against nanoparticle translocation than mammalian barriers. PMID:20964359

  12. Uptake and translocation of hexachlorobenzene: Oilpumpkin and sunflower

    SciTech Connect

    NONE

    1993-10-01

    The uptake of hexachlorobenzene (HCB) and its translocation to seeds were studied with oil pumpkin and sunflower plants. Open air pot experiments were conducted with soil treated with different amounts of HCB. 14C-labelled HCB was used in solution culture experiments with young plants to investigate the distribution of HCB within the plants. During the experiments the contaminant was taken up by the root system of pumkin plant and translocated intensity to the reproductive organs. Autoradiographic pictures of crossections of stems and young fruits confirm this. Such translocation mechanism was not found in sunflower. Nevertheless it can be assumed that under field conditions the uptake of vaporized HCB from contamination soil by foliage and fruits of oil pumpkin is the main pathway of contamination.

  13. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

    PubMed Central

    Kim, YongTae; Lobatto, Mark E.; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J.; Sanchez-Gaytan, Brenda L.; Fay, Francois; Senders, Max L.; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E.; Stroes, Erik S. G.; Ma, Mingming; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.; Langer, Robert

    2014-01-01

    Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system. PMID:24395808

  14. Combined Effects of Tauroursodeoxycholic Acid and Glutamine on Bacterial Translocation in Obstructive Jaundiced Rats:

    PubMed Central

    Hatipo?lu, Ahmet Rahmi; O?uz, Serhat; Gürcan, ?aban; Yalta, Tülin; Albayrak, Do?an; Ereno?lu, Cengiz; Sa??ro?lu, Tamer; Sezer, Yavuz Atakan

    2013-01-01

    Background: Bacterial Translocation is believed to be an important factor on mortality and morbidity in Obstructive Jaundiced. Aims: We investigated the probable or estimated positive effects of tauroursodeoxycholic acid, which has antibacterial and regulatory effects on intestinal flora, together with glutamine on BT in an experimental obstructive jaundiced rat model. Study Design: Animal experimentation. Methods: Forty adult, male, Sprague Dawley rats were used in this study. Animals were randomised and divided into five groups of eight each: sham (Sh); control (common bile duct ligation, CBDL); and supplementation groups administered tauroursodeoxycholic acid (CBDL+T), glutamine (CBDL+G), or tauroursodeoxycholic acid plus glutamine (CBDL+TG). Blood and liver, spleen, MLN, and ileal samples were taken via laparotomy under sterile conditions for investigation of bacterial translocation and intestinal mucosal integrity and hepatic function tests on the tenth postoperative day. Results: There were statistically significant differences in BT rates in all samples except the spleen of the CBDL+TG group compared with the CBDL group (p=0.041, p=0.026, and p=0.041, respectively). Conclusion: It is essential to protect hepatic functions besides maintaining intestinal mucosal integrity in the active struggle against BT occurring in obstructive jaundice. The positive effect on intestinal mucosal integrity can be increased if glutamine is used with tauroursodeoxycholic acid, which also has hepatoprotective and immunomodulatory features. PMID:25207142

  15. Techniques for analyzing the effects of translocation on fox squirrels (Sciurus niger)

    E-print Network

    Ten Brink, Craig Eric

    1996-01-01

    Translocation, the movement of wild animals from one location to another, is thought to be a humane method of controlling damage caused by fox squirrels (Sciurus niger), yet little is known about the effects of translocation at the population level...

  16. Clustering of Translocation Breakpoints Mark R. Segal and Joseph L. Wiemels

    E-print Network

    Sen, Saunak

    clustering. We apply this battery to TEL-AML1 translocations, the most common translocation in childhood with swapped arms can be viewed on a glass slide preparation of chromosomes, or karyotype, of a patient's cells

  17. Yeast Pol4 Promotes Tel1-Regulated Chromosomal Translocations

    PubMed Central

    Sastre-Moreno, Guillermo; Aguilera, Andrés; Blanco, Luis

    2013-01-01

    DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB ends that cannot be directly ligated due to their particular ability to bind to and insert nucleotides at the imperfect template-primer structures formed during NHEJ. Herein, we have devised genetic assays in yeast to induce simultaneous DSBs in different chromosomes in vivo. The repair of these breaks in trans could result in reciprocal chromosomal translocations that were dependent on classical Ku-dependent NHEJ. End-joining events leading to translocations were mainly based on the formation of short base pairing between 3?-overhanging DNA ends coupled to gap-filling DNA synthesis. A major proportion of these events were specifically dependent on yeast DNA polymerase Pol4 activity. In addition, we have discovered that Pol4-Thr540 amino acid residue can be phosphorylated by Tel1/ATM kinase, which could modulate Pol4 activity during NHEJ. Our data suggest that the role of Tel1 in preventing break-induced chromosomal translocations can, to some extent, be due to its stimulating effect on gap-filling activity of Pol4 to repair DSBs in cis. Overall, this work provides further insight to the molecular mechanisms of DSB repair by NHEJ and presents a new perspective to the understanding of how chromosomal translocations are formed in eukaryotic cells. PMID:23874240

  18. Microbial translocation and cardiometabolic risk factors in HIV infection.

    PubMed

    Trøseid, Marius; Manner, Ingjerd W; Pedersen, Karin K; Haissman, Judith M; Kvale, Dag; Nielsen, Susanne D

    2014-06-01

    The widespread access to antiretroviral treatment during the past decades has transformed HIV infection from a lethal disease to a chronic condition, in which the relative burden of non-AIDS-related chronic disorders such as cardiovascular disease, malignancy, renal, liver, and bone disease has increased. The adjusted relative risk for myocardial infarction is reported to be around 2-fold compared to that of the general population, which over time is likely to translate into increased absolute risk in an aging population. Thus, delineating potentially HIV-specific pathogenetic mechanisms is crucial in order to tailor novel strategies for prophylaxis and treatment. This review will focus on advances in the field that possibly link HIV-induced alterations of the gut mucosa and consequent microbial translocation to cardiometabolic risk factors in HIV infection. Recent work suggests that markers of microbial translocation are closely associated with several cardiovascular risk factors such as dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis. Future studies should investigate whether associations between microbial translocation and cardiovascular risk factors will translate into increased risk of acute events, and whether strategies to target gut microbiota and microbial translocation might reduce such a risk. PMID:24521167

  19. Comparison of Translocations of Ring and Linear Polymers

    NASA Astrophysics Data System (ADS)

    Ouyang, Ning; Muthukumar, Murugappan

    2015-03-01

    We compare the translocation dynamics of ring and linear polymer chains (pertinent to circular and linear DNA) through a nanopore under a driving force, using the Fokker-Planck formalism and scaling arguments. We report qualitatively different dynamics between these topologies arising from the conformational entropy of the polymer and pore-polymer interaction.

  20. Driven DNA translocation through thin and long nanopores

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Aniket; Morrison, William H.

    2006-03-01

    We utilize Brownian dynamics simulation to study polymer translocation through a nanopore driven by an electric field using a coarse-grained bead-spring model for the translocating DNA. We study mean translocation time as a function of the chain length N, the width w of the pore, and external bias F. Unlike many previous studies, we critically examine the scaling of as a function of the ratio N/w and F. For a thin pore, our preliminary results indicate that the mean translocation time ˜N^2?, where ? is the Flory exponent, although the slope shows a weak but non-negligible dependence on the external bias F for the chain lengths considered so far. Our simulation results are consistent with experiments done in solid-state nanopore^*,+.^*Work done in collaboration with Heath Morrison, Prof. Kurt Binder and Prof. Andrey Milchev.^+ A. J. Storm, C. Storm, J. Chen, H. Zandbergen, J-F Joanny, C. Dekker, Nano Letters, 5, 1193 (2005).

  1. ORIGINAL ARTICLE Translocator Protein PET Imaging for Glial Activation

    E-print Network

    Shen, Jun

    ORIGINAL ARTICLE Translocator Protein PET Imaging for Glial Activation in Multiple Sclerosis Unsong) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy

  2. DNA translocation through low-noise glass nanopores.

    PubMed

    Steinbock, Lorenz J; Bulushev, Roman D; Krishnan, Swati; Raillon, Camille; Radenovic, Aleksandra

    2013-12-23

    The effect of electron irradiation-induced shrinking on glass nanocapillaries with diameters ranging from 75 to 14 nm was analyzed by measuring the conductance characteristics with and without DNA translocation. We have investigated nanocapillary shrinking with a scanning electron microscope from several perspectives to understand the geometry of the shrunken nanocapillary. On the basis of this observation, the conductance was modeled with respect to the nanocapillary diameter, which allowed reproducing the experimental results. We then translocated DNA through the shrunken nanocapillaries and measured higher conductance drops for smaller diameters, reaching 1.7 nS for the 14 nm diameter nanocapillary. A model taking into account the conical shape of the shrunken nanocapillaries also supported this dependence. Next, we calculated the noise in the form of the standard deviation of the ionic conductance (between 0.04 and 0.15 nS) to calculate a signal-to-noise ratio (SNR) and compared it with nanopores embedded in 20 nm thick silicon nitride membranes. This shows that although nanocapillaries have smaller signal amplitudes due to their conical shape, they benefit from a lower noise. The glass nanocapillaries have a good SNR of about 25 compared with the SNR of 15 for smaller sized nanopores in silicon nitride membranes. The ability to use a modified model of nanopores to mimic the block conductance by DNA translocation provides a theoretical framework to support experimental results from translocating polymers such as DNA. PMID:24274458

  3. DNA Translocating Through a Carbon Nanotube Can Increase Ionic Current

    PubMed Central

    Park, Jae Hyun; He, Jin; Gyarfas, Brett; Lindsay, Stuart; Krsti?, Predrag S.

    2012-01-01

    DNA translocation through a narrow, single-walled carbon nanotube can be accompanied by large increases of ion current, recently observed in contrast to the ion current blockade. We use molecular dynamics simulations to show large electro-osmotic flow can be turned into a large net current via ion-selective filtering by a DNA molecule inside the carbon nanotube. PMID:23090315

  4. Climate change and trans-local solidarities Paul Routledge

    E-print Network

    Guo, Zaoyang

    Climate change and trans-local solidarities Paul Routledge Paul.Routledge@ges.gla.ac.uk This project will consider local responses and adaptations to climate change across a range of different sites in the Global North and Global South, and consider how effective, carbon-sensitive solidarities around climate

  5. Bacterial Translocation and Prognosis of Criti- cally Ill Patients

    Microsoft Academic Search

    Woon Won Kim; Chun Ki Sung

    Purpose: To identify Bacterial translocation (BT) from the gut to the blood in the critically ill patients by using the polymerase chain reaction (PCR) to confirm the sensitivity of PCR in the detection of intestinal bacterial deoxyribo- nucleic acid (DNA) in human blood. Further, to determine the relationship between the identification of BT and the prognosis of these patients. Methods

  6. Chemistry & Biology pHLIP-Mediated Translocation of Membrane-

    E-print Network

    be exploited for targeting. Rapidly expanding cancer cells have abnormal nutritional requirements and metabolic, 1996). Acidosis results in part from the specially evolved metabolism of cancer cells, of which of lipid vesicles and cancer cells. Our results also indi- cate that the translocation of these cargo

  7. Reciprocal translocation versus centric fusion between two No. 13 chromosomes

    Microsoft Academic Search

    Lillian Y. F. Hsu; Hyon J. Kim; Eva Sujansky; B. Kousseff; K. Hirschhorn

    1973-01-01

    The centric fusion, or Robertsonian, type of translocation has been considered as a fusion of the entire long arms of two acrocentric chromosomes preceded by breakage of the centric heterochromatin. Reunion of the long arms is considered to include the centromeres, only one of which is visible by conventional staining methods. Prior to the development of the current banding techniques

  8. Rearrangements in genomes with centromeres part I: translocations

    E-print Network

    Shamir, Ron

    Rearrangements in genomes with centromeres part I: translocations Michal Ozery-Flato and Ron Shamir,rshamir}@post.tau.ac.il Abstract. A centromere is a special region in the chromosome that plays a vital role during cell division. Every new chromosome created by a genome rearrange- ment event must have a centromere in order

  9. Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

    PubMed Central

    Manner, Ingjerd W.; Pedersen, Karin K.; Haissman, Judith M.; Kvale, Dag; Nielsen, Susanne D.

    2014-01-01

    Abstract The widespread access to antiretroviral treatment during the past decades has transformed HIV infection from a lethal disease to a chronic condition, in which the relative burden of non-AIDS-related chronic disorders such as cardiovascular disease, malignancy, renal, liver, and bone disease has increased. The adjusted relative risk for myocardial infarction is reported to be around 2-fold compared to that of the general population, which over time is likely to translate into increased absolute risk in an aging population. Thus, delineating potentially HIV-specific pathogenetic mechanisms is crucial in order to tailor novel strategies for prophylaxis and treatment. This review will focus on advances in the field that possibly link HIV-induced alterations of the gut mucosa and consequent microbial translocation to cardiometabolic risk factors in HIV infection. Recent work suggests that markers of microbial translocation are closely associated with several cardiovascular risk factors such as dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis. Future studies should investigate whether associations between microbial translocation and cardiovascular risk factors will translate into increased risk of acute events, and whether strategies to target gut microbiota and microbial translocation might reduce such a risk. PMID:24521167

  10. DNA Translocation Governed by Interactions with Solid-State Nanopores

    E-print Network

    Meller, Amit

    DNA Translocation Governed by Interactions with Solid-State Nanopores Meni Wanunu, Jason Sutin, Ben dynamics of individual DNA molecules through solid-state nanopores in the diameter range 2.7­5 nm. Our with DNA length by two power laws: for short DNA molecules, in the range 150­3500 bp, we find an exponent

  11. HSP70 inhibits Bax translocation during Photofrin-PDT apoptosis

    NASA Astrophysics Data System (ADS)

    Zhou, Feifan; Chen, Wei R.; Song, Sheng

    2009-02-01

    Apoptosis is an important cellular event that plays a key role in therapy of many diseases. The mechanisms of the initiation and regulation of photodynamic therapy (PDT) -induced apoptosis is complex. Some PDT-associated apoptosis pathways involved plasma membrane death receptors, mitochondria, lysosomes and endoplasmic reticulum (ER). Our previous study found that Photofrin were localized primarily in mitochondria, the primary targets of Photofrin-PDT. The key role of Bax in the mitochondrion-mediated apoptosis has been demonstrated in many systems. In order to determine the role of Bax in the mitochondrion-mediated apoptosis induced by Photofrin-PDT, we used the CFP/GFP-Bax plasmid to monitor the dynamics of Bax activation and translocation after PDT treatment. With laser scanning confocal microscopy, we found that PDT induced Bax translocation from the cytosol to mitochondria; however, with cells over-expressing YFP-HSP70 plasmids, Bax translocation was not detected. Thus, for Photofrin-PDT, Bax activation and translocation were inhibited by HSP70, not influence the cell death.

  12. Polymer translocation into and out of an ellipsoidal cavity

    E-print Network

    James M. Polson

    2015-02-19

    Monte Carlo simulations are used to study the translocation of a polymer into and out of a ellipsoidal cavity through a narrow pore. We measure the polymer free energy F as a function of a translocation coordinate, s, defined to be the number of bonds that have entered the cavity. To study polymer insertion, we consider the case of a driving force acting on monomers inside the pore, as well as monomer attraction to the cavity wall. We examine the changes to F(s) upon variation in the shape anisometry and volume of the cavity, the polymer length, and the strength of the interactions driving the insertion. For athermal systems, the free energy functions are analyzed using a scaling approach, where we treat the confined portion of the polymer to be in the semi-dilute regime. The free energy functions are used with the Fokker-Planck equation to measure mean translocation times, as well as translocation time distributions. We find that both polymer ejection and insertion is faster for ellipsoidal cavities than for spherical cavities. The results are in qualitative agreement with those of a Langevin dynamics study in the case of ejection but not for insertion. The discrepancy is likely due to out-of-equilibrium conformational behaviour that is not accounted for in the FP approach

  13. A 1/29 chromosome translocation in Southern African Nguni cattle.

    E-print Network

    Paris-Sud XI, Université de

    A 1/29 chromosome translocation in Southern African Nguni cattle. The identification, occurrence/29 chromosome translocation was found in 10.2 p. 100 of a sample of 305 Nguni cattle. Investigations environment. Normal and translocation hetero- and homozygous cattle are being produced in order to investigate

  14. Salt Dependence of Ion Transport and DNA Translocation through Solid-State

    E-print Network

    Dekker, Cees

    Salt Dependence of Ion Transport and DNA Translocation through Solid-State Nanopores Ralph M. M of the salt dependence of ion transport and DNA translocation through solid-state nanopores. The ionic salt concentrations. DNA translocation is shown to result in either a decrease ([KCl] > 0.4 M

  15. A genetic screen to isolate type III effectors translocated into pepper cells during

    E-print Network

    Mudgettt, Mary Beth

    A genetic screen to isolate type III effectors translocated into pepper cells during Xanthomonas these fusions translocated the AvrBs2 reporter in a TTSS-dependent manner into resistant BS2 pepper cells during repeat and is required for full Xcv pathogenicity in pepper and tomato. The translocated effectors

  16. Factors affecting the success of translocations of the black-faced impala in Namibia

    Microsoft Academic Search

    Tammie K. Matson; Anne W. Goldizen; Peter J. Jarman

    2004-01-01

    This study analysed 21 translocations of the vulnerable black-faced impala (Aepyceros melampus petersi) to 20 Namibian game farms that occurred between 1970 and 2001, seeking characteristics of the translocated populations and the release sites that significantly correlated with the success of the translocations. Characteristics considered were: initial population size; presence of cheetah and leopard; area; habitat type; occurrence within the

  17. The prevalence of translocations in parents of children with regular trisomy 21: a possible interchromosomal effect?

    Microsoft Academic Search

    R H Lindenbaum; M Hultén; A McDermott; M Seabright

    1985-01-01

    It has been suggested that translocations, and perhaps other chromosome rearrangements, disturb meiotic disjunction of uninvolved chromosome pairs and predispose to trisomic offspring. If so, then one would expect an excess of translocations not involving chromosome 21 among the parents of regular trisomic Down's syndrome patients. Such translocations have been reported, but mostly as anecdotal single case reports or very

  18. Interchromosome effects on chiasma distribution due to translocations in Locusta migratoria

    Microsoft Academic Search

    M. Diez; M. J. Puertas

    1984-01-01

    Two different strains carrying translocations were obtained by irradiation of Locusta migratoria males. The presence of translocations produced an increase in chiasma number in the chromosomes not involved in the translocation, compared to the same chromosomes in wild-type individuals. This increase was higher in the individuals carrying the octovalent than in those carrying the quadrivalent.

  19. Langevin dynamics simulations of polymer translocation through nanopores

    NASA Astrophysics Data System (ADS)

    Huopaniemi, Ilkka; Luo, Kaifu; Ala-Nissila, Tapio; Ying, See-Chen

    2006-09-01

    We investigate the dynamics of polymer translocation through a nanopore using two-dimensional Langevin dynamics simulations. In the absence of an external driving force, we consider a polymer which is initially placed in the middle of the pore and study the escape time ?e required for the polymer to completely exit the pore on either side. The distribution of the escape times is wide and has a long tail. We find that ?e scales with the chain length N as ?e˜N1+2?, where ? is the Flory exponent. For driven translocation, we concentrate on the influence of the friction coefficient ?, the driving force E, and the length of the chain N on the translocation time ?, which is defined as the time duration between the first monomer entering the pore and the last monomer leaving the pore. For strong driving forces, the distribution of translocation times is symmetric and narrow without a long tail and ? ˜E-1. The influence of ? depends on the ratio between the driving and frictional forces. For intermediate ?, we find a crossover scaling for ? with N from ? ˜N2? for relatively short chains to ? ˜N1+? for longer chains. However, for higher ?, only ? ˜N1+? is observed even for short chains, and there is no crossover behavior. This result can be explained by the fact that increasing ? increases the Rouse relaxation time of the chain, in which case even relatively short chains have no time to relax during translocation. Our results are in good agreement with previous simulations based on the fluctuating bond lattice model of polymers at intermediate friction values, but reveal additional features of dependency on friction.

  20. Cold-inhibited phloem translocation in sugar beet

    SciTech Connect

    Grusak, M.A.

    1985-01-01

    Experimental studies were undertaken on a simplified single source leaf-single sink leaf, or single source leaf-double sink leaf sugar beet system to investigate the responsive nature of the long-distance phloem translocation system to localized cooling perturbations on the source leaf petiole. Experiments were performed by using a steady state (/sup 14/C)-labelling system for the source leaf, and translocation into the sink leaf (leaves) was monitored with a Geiger-Mueller system. A specially designed Peltier apparatus enabled cooling of the source petiole to 1/sup 0/C (or other desired temperatures) at various positions on the petiole, over different lengths, and at different rates of cooling. Initial experiment were designed to test the predictions of a mathematical recovery model of translocation inhibited by cold. The results did not support the mathematical model, but did suggest that vascular anastomoses may be involved in the recovery response. Selective petiolar incision/excision experiments showed that anastomoses were capable of re-establishing translocation following a disruption of flow. Studies with two monitored sink levels suggested that the inhibition to slow-coolings was not due to reduced translocation through the cooled source petiole region, but rather, was due to a repartitioning of flow among the terminal sinks (sink leaves and hypocotyl/crown region above the heat-girdled root). This repartitioning occurred via a redirection of flow through the vascular connections in the crown region of the plant, and appeared to be promoted by rapid, physical signals originating from the cooled region of the petiole.

  1. Thermal inflation and the gravitational wave background

    SciTech Connect

    Easther, Richard; Giblin Jr, John T [Department of Physics, Yale University, New Haven, CT 06520 (United States)] [Department of Physics, Yale University, New Haven, CT 06520 (United States); Lim, Eugene A [ISCAP and Physics Department, Columbia University, NY 10027 (United States)] [ISCAP and Physics Department, Columbia University, NY 10027 (United States); Park, Wan-Il; Stewart, Ewan D, E-mail: richard.easther@yale.edu, E-mail: john.giblin@yale.edu, E-mail: eugene.a.lim@gmail.com, E-mail: wipark@muon.kaist.ac.kr, E-mail: stewart@hep.kaist.ac.kr [Department of Physics, KAIST, Daejeon (Korea, Republic of)

    2008-05-15

    We consider the impact of thermal inflation-a short, secondary period of inflation that can arise in supersymmetric scenarios-on the stochastic gravitational wave background. We show that while the primordial inflationary gravitational wave background is essentially unchanged at cosmic microwave background scales, it is massively diluted at solar system scales and would be unobservable by a Big Bang Observer (BBO) style experiment. Conversely, bubble collisions at the end of thermal inflation can generate a new stochastic background. We calculate the likely properties of the bubbles created during this phase transition, and show that the expected amplitude and frequency of this signal would fall within the BBO range.

  2. Effects of Mitochondrial Translocation of Telomerase on Drug Resistance in Hepatocellular Carcinoma Cells

    PubMed Central

    Yan, Jing; Zhou, Yuan; Chen, DaiXing; Li, LiLi; Yang, Xin; You, Yang; Ling, Xianlong

    2015-01-01

    Hepatocellular carcinoma (HCC) cells exhibit multidrug resistance (MDR), but the underlying mechanisms remain unclear. Cancer cells that overexpress telomerase are resistant to chemotherapeutic drugs. This study aimed to determine the effects of mitochondrial translocation of telomerase on MDR in HCC cells. HepG2 cells were transfected with negative plasmid and PTPN11 (Shp-2) short hairpin RNA (ShRNA) plasmid to establish HepG2-negative (HepG2 transfected with negative plasmid) and HepG2-ShShp-2 (HepG2 transfected with Shp-2 ShRNA plasmid) cells. Sensitivity to chemotherapeutic drugs was assessed by Cell Counting Kit-8 (CCK-8) assays. Distribution of human telomerase reverse transcriptase (hTERT) within mitochondria was detected by western blotting and immunofluorescence combined with laser scanning confocal microscopy. Mitochondrial reactive oxygen species (ROS) generation was demonstrated by flow cytometry with the mitochondrial superoxide (Mito-Sox) indicator. The frequency of damaged mitochondrial DNA (mtDNA) was illustrated by quantitative real-time polymerase chain reaction (Q-PCR). Expression of mitochondrial respiratory chain complex subunits ND1 and COXII were also demonstrated by western blotting. Knockdown of Shp-2 in HepG2 cells resulted in upregulation of mitochondrial TERT expression and increased resistance to cisplatin (CDDP) and 5-fluorouracil (5-FU) (resistance indices, 2.094 and 1.863, respectively). In addition, both the mitochondrial ROS and the frequency of mtDNA damage were decreased, and COXII expression was upregulated. Our results suggest that Mitochondrial translocation of hTERT may lead to chemotherapeutic resistance in HCC cells. Mitochondrial hTERT contributes to the drug resistance of tumor cells by reducing ROS production and mtDNA damage, and exerting a protective effect on the mitochondrial respiratory chain. PMID:25561980

  3. Effects of mitochondrial translocation of telomerase on drug resistance in hepatocellular carcinoma cells.

    PubMed

    Yan, Jing; Zhou, Yuan; Chen, DaiXing; Li, LiLi; Yang, Xin; You, Yang; Ling, Xianlong

    2015-01-01

    Hepatocellular carcinoma (HCC) cells exhibit multidrug resistance (MDR), but the underlying mechanisms remain unclear. Cancer cells that overexpress telomerase are resistant to chemotherapeutic drugs. This study aimed to determine the effects of mitochondrial translocation of telomerase on MDR in HCC cells. HepG2 cells were transfected with negative plasmid and PTPN11 (Shp-2) short hairpin RNA (ShRNA) plasmid to establish HepG2-negative (HepG2 transfected with negative plasmid) and HepG2-ShShp-2 (HepG2 transfected with Shp-2 ShRNA plasmid) cells. Sensitivity to chemotherapeutic drugs was assessed by Cell Counting Kit-8 (CCK-8) assays. Distribution of human telomerase reverse transcriptase (hTERT) within mitochondria was detected by western blotting and immunofluorescence combined with laser scanning confocal microscopy. Mitochondrial reactive oxygen species (ROS) generation was demonstrated by flow cytometry with the mitochondrial superoxide (Mito-Sox) indicator. The frequency of damaged mitochondrial DNA (mtDNA) was illustrated by quantitative real-time polymerase chain reaction (Q-PCR). Expression of mitochondrial respiratory chain complex subunits ND1 and COXII were also demonstrated by western blotting. Knockdown of Shp-2 in HepG2 cells resulted in upregulation of mitochondrial TERT expression and increased resistance to cisplatin (CDDP) and 5-fluorouracil (5-FU) (resistance indices, 2.094 and 1.863, respectively). In addition, both the mitochondrial ROS and the frequency of mtDNA damage were decreased, and COXII expression was upregulated. Our results suggest that Mitochondrial translocation of hTERT may lead to chemotherapeutic resistance in HCC cells. Mitochondrial hTERT contributes to the drug resistance of tumor cells by reducing ROS production and mtDNA damage, and exerting a protective effect on the mitochondrial respiratory chain. PMID:25561980

  4. Cigarette smoking during pregnancy: chromosome translocations and phenotypic susceptibility in mothers and newborns.

    PubMed

    Bennett, L Michelle; Wang, Yun; Ramsey, Marilyn J; Harger, Gail F; Bigbee, William L; Tucker, James D

    2010-02-01

    The effects of maternal cigarette smoking during pregnancy on structural chromosome aberrations were evaluated in peripheral lymphocytes from 239 mothers and their 241 newborns to determine whether smoking during pregnancy, genetic susceptibility, and race are associated with chromosome aberrations including translocations. Demographic information and cigarette smoking data were obtained via questionnaire. There were 119 Caucasian Americans, 118 African Americans, and 2 Asian Americans. The average maternal age was 24.9+/-5.8 (mean+/-S.D.) years. Thirty-nine percent of the Caucasian Americans and 45.4% of the African Americans self-reported that they were active smokers during the index pregnancy. The average number of cigarettes smoked per day was 2.65+/-5.75 and 1.37+/-3.17 for Caucasian and African American mothers, respectively. Peripheral blood lymphocytes from the mother and from the fetal side of the placenta were evaluated for chromosome aberrations by whole chromosome painting. Aliquots from the same blood samples were also used to assess genetic susceptibility with an in vitro bleomycin challenge assay. Spontaneous translocation frequencies in both maternal and newborn lymphocytes were not associated with cigarette smoking, socioeconomic status, or education. The absence of a smoking effect may be attributable to the low level of cigarette usage in these subjects. The average bleomycin-induced damage in the maternal and newborn populations was 0.37+/-0.27 and 0.15+/-0.14 breaks per cell, respectively, a difference that was highly significant (p<0.0001). In newborns there was a positive association between bleomycin sensitivity and the frequencies of aberrations as measured by chromosome painting: ptranslocations. Caucasian American newborns demonstrated a significant association between dicentrics and fragments as measured by painting, and bleomycin sensitivity (p

  5. Noninvolvement of the X chromosome in radiation-induced chromosome translocations in the human lymphoblastoid cell line TK6

    SciTech Connect

    Jordan, R.; Schwartz, J.L. (Argonne National Lab., IL (United States))

    1994-03-01

    Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by [sup 60]Co [gamma] rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab.

  6. Building Background Knowledge

    ERIC Educational Resources Information Center

    Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

    2014-01-01

    This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

  7. Background Subtraction Techniques

    Microsoft Academic Search

    Alan M. McIvor

    Background subtraction is a commonly used class of techniques for segmenting out objects of interest in a scene for applications such as surveillance. This paper surveys a repre- sentative sample of the published techiques for background subtraction, and analyses them with respect to three important attributes: foreground detection; background maintenance; and postprocessing.

  8. Electric field-induced translocation of single-stranded DNA through a polarized carbon nanotube membrane.

    PubMed

    Xie, Yinghong; Kong, Yong; Soh, A K; Gao, Huajian

    2007-12-14

    Molecular dynamics simulations based on a novel polarizable nanotube model were performed to study the dynamics in translocation of a single-stranded deoxyribonucleic acid oligonucleotide through a polarized carbon nanotube membrane by an applied electric field. The study revealed a nonlinear dependence of translocation velocity and an inverse quadratic dependence of translocation time on the electric field strength, as well as a threshold electric field below which the translocation process becomes impossible. The translocation rate was found to be pore-size dependent. The polarizable nanotube model developed for this study provides a useful platform for investigating the dynamics of a range of bionanosystems. PMID:18081421

  9. Retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: long-term results

    Microsoft Academic Search

    Kristel Maaijwee; Heinrich Heimann; Tom Missotten; Paul Mulder; Antonia Joussen; Jan van Meurs

    2007-01-01

    Background  To study the results of the translocation of a free autologous retinal pigment epithelium (RPE)-choroid graft after removal\\u000a of a subfoveal choroidal neovascular membrane in patients with exudative age-related macular degeneration (AMD), and to determine\\u000a whether preoperative variables may predict visual outcome at 1 year after surgery.\\u000a \\u000a \\u000a \\u000a Methods  Prospective interventional case series of 84 eyes of 83 consecutive eligible patients with exudative

  10. Spontaneous recombination between wp+ and the translocation breakpoint in the T:Y(wp+ )30C genetic sexing strain of Ceratitis capitata (Wied.)

    Microsoft Academic Search

    A A Kafu; R J Wood; G S Mani; E Busch-Petersen

    1993-01-01

    The frequency of male recombination (r) between the translocation breakpoint and the wp+ gene, and the selection coefficient (s) against wp\\/wp, in the genetic sexing strain T:Y(wp+)30C of the Mediterranean fruit fly Ceratitis capitata (Wied.) were measured in population experiments over 11 generations. The population was 50 females and 50 males in the first generation, after which 150 pupae were

  11. Translocation of platelets into Disse spaces and their entry into hepatocytes in response to lipopolysaccharides, interleukin-1 and tumour necrosis factor: the role of Kupffer cells

    Microsoft Academic Search

    Masanori Nakamura; Masahiko Shibazaki; Yasutaka Nitta; Yasuo Endo

    1998-01-01

    Background\\/Aims: Injection into mice of a small dose of either a lipopolysaccharide or interleukin-1 induces a slowly developing accumulation of 5-hydroxytryptamine, predominantly in the liver. We have established that this 5-hydroxytryptamine accumulation is the result of the translocation of platelets to hepatic sinusoidal spaces and, further, into Disse spaces, and that the platelets make direct contact with hepatocytes. In the

  12. Adenosine Transporter ENT4 Is a Direct Target of EWS\\/WT1 Translocation Product and Is Highly Expressed in Desmoplastic Small Round Cell Tumor

    Microsoft Academic Search

    Hongjie Li; Gromoslaw A. Smolen; Lisa F. Beers; Li Xia; William Gerald; Joanne Wang; Daniel A. Haber; Sean Bong Lee; Dong-Yan Jin

    2008-01-01

    BackgroundDesmoplastic Small Round Cell Tumor (DSRCT) is a highly aggressive malignancy that affects mainly adolescents and young adults. A defining characteristic of DSRCT is a specific chromosomal translocation, t(11;22)(p13;q12), that fuses EWS with WT1, leading to a production of two isoforms of chimeric transcription factor, EWS\\/WT1(?KTS) and EWS\\/WT1(+KTS). The chimeric proteins are thought to play critical roles in various stages

  13. Frequency Modulation

    Microsoft Academic Search

    B. Van Der Pol

    1930-01-01

    The differential equation of a frequency modulated transmitter is considered and the expression of the current as a function of time is derived. Frequency analysis of this function is made for two specific cases, (A) sinusoidal frequency modulation (telephony) and (B), right-angle frequency modulation (telegraphy with \\

  14. Frequency curves

    USGS Publications Warehouse

    Riggs, H.C.

    1968-01-01

    This manual describes graphical and mathematical procedures for preparing frequency curves from samples of hydrologic data. It also discusses the theory of frequency curves, compares advantages of graphical and mathematical fitting, suggests methods of describing graphically defined frequency curves analytically, and emphasizes the correct interpretations of a frequency curve.

  15. General issues on microbial translocation in HIV-infected patients.

    PubMed

    Novati, S; Sacchi, P; Cima, S; Zuccaro, V; Columpsi, P; Pagani, L; Filice, G; Bruno, R

    2015-01-01

    The lumen of the gastrointestinal tract is home to an enormous quantity of different bacterial species that thrive in an often symbiotic relationship with the host. It is the principal source of microbial products because of its massive bacterial load. Injury to the immune component of the gastrointestinal mucosal surface, along with damage to the intestinal epithelial microenvironment with its antimicrobial functions, may affect systemic immune activation during the chronic phase of HIV infection through the increased translocation of luminal microbial products. Moreover, microbial translocation, which is defined as "the passage of both viable and nonviable microbes and microbial products such as endotoxin across anatomically intact intestinal barrier", may be a fundamental mechanism through which HIV accelerates progression of chronic viral hepatitis. Improvements in the tools available to microbiota research, and especially advancement of our knowledge in this area may help us in controlling the evolution of HIV disease, although population complexity and diversity between individuals make this challenging. PMID:25807441

  16. Mechanism of DNA Translocation in a Replicative Hexameric Helicase

    SciTech Connect

    Enemark,E.; Joshua-Tor, L.

    2006-01-01

    The E1 protein of papillomavirus is a hexameric ring helicase belonging to the AAA + family. The mechanism that couples the ATP cycle to DNA translocation has been unclear. Here we present the crystal structure of the E1 hexamer with single-stranded DNA discretely bound within the hexamer channel and nucleotides at the subunit interfaces. This structure demonstrates that only one strand of DNA passes through the hexamer channel and that the DNA-binding hairpins of each subunit form a spiral 'staircase' that sequentially tracks the oligonucleotide backbone. Consecutively grouped ATP, ADP and apo configurations correlate with the height of the hairpin, suggesting a straightforward DNA translocation mechanism. Each subunit sequentially progresses through ATP, ADP and apo states while the associated DNA-binding hairpin travels from the top staircase position to the bottom, escorting one nucleotide of single-stranded DNA through the channel. These events permute sequentially around the ring from one subunit to the next.

  17. Fast DNA translocation through a solid-state nanopore

    E-print Network

    Storm, Arnold J; Chen, Jianghua; Zandbergen, Henny; Joanny, Jean-Francois; Dekker, Cees

    2015-01-01

    We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the driving. We show that this is the case in our experiments and derive a power-law scaling with an exponent of 1.18, in excellent agreement with our data.

  18. Sorting by reversals, generalized transpositions, and translocations using permutation groups.

    PubMed

    Huang, Yen-Lin; Lu, Chin Lung

    2010-05-01

    In this article, we consider the problem of sorting a linear/circular, multi-chromosomal genome by reversals, block-interchanges (i.e., generalized transpositions), and translocations (including fusions and fissions) where the used operations can be weighted differently, which aims to find a sequence of reversal, block-interchange, and translocation operations such that the sum of these operation weights in the sequence is minimum. It is known that this sorting problem can be solved in polynomial time on the basis of breakpoint graphs, when block-interchanges are weighted 2 (or >or=3) and the others are weighted 1. In this study, we design a novel and easily implemented algorithm for this problem by utilizing the permutation group theory in algebra. PMID:20500022

  19. Anthrax toxin: receptor binding, internalization, pore formation, and translocation.

    PubMed

    Young, John A T; Collier, R John

    2007-01-01

    Anthrax toxin consists of three nontoxic proteins that self-assemble at the surface of receptor-bearing mammalian cells or in solution, yielding a series of toxic complexes. Two of the proteins, called Lethal Factor (LF) and Edema Factor (EF), are enzymes that act on cytosolic substrates. The third, termed Protective Antigen (PA), is a multifunctional protein that binds to receptors, orchestrates the assembly and internalization of the complexes, and delivers them to the endosome. There, the PA moiety forms a pore in the endosomal membrane and promotes translocation of LF and EF to the cytosol. Recent advances in understanding the entry process include insights into how PA recognizes its two known receptors and its ligands, LF and EF; how the PA:receptor interaction influences the pH-dependence of pore formation; and how the pore functions in promoting translocation of LF and EF across the endosomal membrane. PMID:17335404

  20. The Cosmic Background Explorer.

    ERIC Educational Resources Information Center

    Gulkis, Samuel; And Others

    1990-01-01

    Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

  1. Seaside transportation—from structure to function of translocation machines

    PubMed Central

    Lithgow, Trevor; Waksman, Gabriel

    2013-01-01

    The EMBO conference ‘From Structure to Function of Translocation Machines' took place in April 2013 in Dubrovnik, Croatia. The meeting brought together a mix of established and aspiring researchers to discuss a wealth of unpublished data and ideas in a lively scientific programme of talks designed to shatter the established dogma. From new ways to envisage known protein transport pathways to a brand new and totally unconventional protein transport system, surprises were part and parcel of this excellent EMBO conference. PMID:23764920

  2. Reducing atelectasis attenuates bacterial growth and translocation in experimental pneumonia

    Microsoft Academic Search

    Kaam van A. H. L. C; Robert A. Lachmann; Egbert Herting; Anne De Jaegere; F. Iwaarden; L. Arnold Noorduyn; Joke H. Kok; Jack J. Haitsma; Burkhard Lachmann

    2004-01-01

    Abstract Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined,the effect of reducing the degree of atelectasis by natural modified surfactant and\\/or open lung ventilation, on bacterial growth and translocation in a piglet model of group B streptococcal pneumonia. After creating surfactant-deficiency by

  3. Protein translocation: checkpoint role for SRP GTPase activation.

    PubMed

    Bange, Gert; Wild, Klemens; Sinning, Irmgard

    2007-11-20

    Co-translational protein targeting by the signal recognition particle (SRP) relies on a complex series of structural rearrangements in the SRP and its receptor (SR). In order to precisely coordinate the individual steps, the GTPases of the SRP and the SR form a unique complex in which GTP hydrolysis is activated in a composite active site. A recent study provides new insights on the link between the GTPases and protein translocation. PMID:18029258

  4. Child with Sotos phenotype and a 5:15 translocation

    SciTech Connect

    Maround, C.; Schmerler, S.; Hutcheon, R.G. [St. Joseph`s Hospital and Medical Center, Paterson, NJ (United States)

    1994-04-15

    The authors report on a 4-year-old girl with Sotos phenotype and a de novo balanced translocation between the long arms of chromosome 5 and chromosome 15 [46,XX,t(5,15)(q35;q22)]. They suggest a relationship between genetic material at 5q35 or 15q22 and the expression of an autosomal dominant gene. 18 refs., 2 figs.

  5. Translocator Protein PET Imaging for Glial Activation in Multiple Sclerosis

    Microsoft Academic Search

    Unsong Oh; Masahiro Fujita; Vasiliki N. Ikonomidou; Iordanis E. Evangelou; Eiji Matsuura; Erin Harberts; Joan Ohayon; Victor W. Pike; Yi Zhang; Sami S. Zoghbi; Robert B. Innis; Steven Jacobson

    Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology.\\u000a Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity.\\u000a The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission\\u000a tomography (PET).

  6. Translocation of Immunoglobulin VH Genes in Burkitt lymphoma

    Microsoft Academic Search

    Jan Erikson; Janet Finan; Peter C. Nowell; Carlo M. Croce

    1982-01-01

    We have produced cell hybrids between mouse myeloma cells, which do not produce immunoglobulin chains, and Burkitt lymphoma cells (Daudi), which express surface IgM. Daudi cells carry a reciprocal chromosome translocation between chromosomes 8 and 14, described as t(8;14)(q24;q32). The hybrids were studied for the expression of human immunoglobulin chains and human isozyme markers, for the presence of human chromosomes,

  7. Control of insects and spider mites by translocated compounds 

    E-print Network

    Ivy, Edward Everett

    1951-01-01

    * Octamethyl pyrophosphoramide was translocated by cotton plants when applied to soils in which the plants were growing* A single soil application of 4. to 8 pounds per acre of the technical compound caused the plants to remain toxic to cotton aphids, Aphis... grown from seed treated with 1 pound of octamethyl pyrophosphoramide per 100 pounds of seed were toxic to spider mites and aphids for 6 weeks. Higher dosages reduced seed germination* Octamethyl pyrophosphoramide was ineffective against the boll...

  8. Subcellular distribution and translocation of radionuclides in plants

    Microsoft Academic Search

    S. Gouthu; R. Weginwar; Tsutomu Arie; Shizuko Ambe; Takuo Ozaki; Shuichi Enomoto; Fumitoshi Ambe; Isamu Yamaguchi

    1999-01-01

    The subcellular distribution of radionuclides in Glycine max Merr. (soybean) and Cucumis sativus L. (cucumber) and translocation of plant absorbed radionuclides with growth in soybean were studied. More than 60% of cellular incorporated Rb⁻⁸³, Sr⁻⁸⁵, Mn⁻⁵⁴, Nb⁻⁹⁵, and Se⁻⁷⁵ remained in the supernatant fraction; 55% and 20% of Cr⁻⁵¹ was bound to soybean and cucumber cell wall fractions, respectively; 70%

  9. Differential Nuclear Translocation and Transactivation Potential of ?-Catenin and Plakoglobin

    PubMed Central

    Simcha, Inbal; Shtutman, Michael; Salomon, Daniela; Zhurinsky, Jacob; Sadot, Einat; Geiger, Benjamin; Ben-Ze'ev, Avri

    1998-01-01

    ?-Catenin and plakoglobin are homologous proteins that function in cell adhesion by linking cadherins to the cytoskeleton and in signaling by transactivation together with lymphoid-enhancing binding/T cell (LEF/TCF) transcription factors. Here we compared the nuclear translocation and transactivation abilities of ?-catenin and plakoglobin in mammalian cells. Overexpression of each of the two proteins in MDCK cells resulted in nuclear translocation and formation of nuclear aggregates. The ?-catenin-containing nuclear structures also contained LEF-1 and vinculin, while plakoglobin was inefficient in recruiting these molecules, suggesting that its interaction with LEF-1 and vinculin is significantly weaker. Moreover, transfection of LEF-1 translocated endogenous ?-catenin, but not plakoglobin to the nucleus. Chimeras consisting of Gal4 DNA-binding domain and the transactivation domains of either plakoglobin or ?-catenin were equally potent in transactivating a Gal4-responsive reporter, whereas activation of LEF-1– responsive transcription was significantly higher with ?-catenin. Overexpression of wild-type plakoglobin or mutant ?-catenin lacking the transactivation domain induced accumulation of the endogenous ?-catenin in the nucleus and LEF-1–responsive transactivation. It is further shown that the constitutive ?-catenin–dependent transactivation in SW480 colon carcinoma cells and its nuclear localization can be inhibited by overexpressing N-cadherin or ?-catenin. The results indicate that (a) plakoglobin and ?-catenin differ in their nuclear translocation and complexing with LEF-1 and vinculin; (b) LEF-1–dependent transactivation is preferentially driven by ?-catenin; and (c) the cytoplasmic partners of ?-catenin, cadherin and ?-catenin, can sequester it to the cytoplasm and inhibit its transcriptional activity. PMID:9628899

  10. Jumping translocations, a novel finding in chronic lymphocytic leukaemia.

    PubMed

    Miller, Cecelia R; Stephens, Deborah; Ruppert, Amy S; Racke, Frederick; McFaddin, Andrew; Breidenbach, Heather; Lin, Huey-Jen; Waller, Kathy; Bannerman, Tammy; Jones, Jeffrey A; Woyach, Jennifer A; Andritsos, Leslie A; Maddocks, Kami; Zhao, Weiqiang; Lozanski, Gerard; Flynn, Joseph M; Grever, Michael; Byrd, John C; Heerema, Nyla A

    2015-07-01

    A jumping translocation (JT) is a rare cytogenetic aberration that can occur in haematological malignancy. It involves the translocation of the same fragment of donor chromosome onto two or more recipient chromosomes, typically in different cells. In this study, we describe the first series of chronic lymphocytic leukaemia (CLL) patients with JTs reported to date. Following a review of 878 CLL patient karyotypes, we identified 26 patients (3%) with 97 JTs. The most commonly occurring breakpoint in these translocations was 17p11.2. Loss of TP53 was identified prior to or at the same time as JT in 23 of 26 patients (88%). All patients eventually developed a complex karyotype. All but one patient has required treatment for CLL, with estimated median time to treatment of 11·5 months. This study establishes JTs as a recurrent abnormality found in CLL patients with aggressive disease. JTs contribute to complex karyotypes and, in many cases, are involved in chromosomal rearrangements that result in loss of the tumour suppressor gene TP53. PMID:25891862

  11. Twin-arginine-dependent translocation of folded proteins.

    PubMed

    Fröbel, Julia; Rose, Patrick; Müller, Matthias

    2012-04-19

    Twin-arginine translocation (Tat) denotes a protein transport pathway in bacteria, archaea and plant chloroplasts, which is specific for precursor proteins harbouring a characteristic twin-arginine pair in their signal sequences. Many Tat substrates receive cofactors and fold prior to translocation. For a subset of them, proofreading chaperones coordinate maturation and membrane-targeting. Tat translocases comprise two kinds of membrane proteins, a hexahelical TatC-type protein and one or two members of the single-spanning TatA protein family, called TatA and TatB. TatC- and TatA-type proteins form homo- and hetero-oligomeric complexes. The subunits of TatABC translocases are predominantly recovered from two separate complexes, a TatBC complex that might contain some TatA, and a homomeric TatA complex. TatB and TatC coordinately recognize twin-arginine signal peptides and accommodate them in membrane-embedded binding pockets. Advanced binding of the signal sequence to the Tat translocase requires the proton-motive force (PMF) across the membranes and might involve a first recruitment of TatA. When targeted in this manner, folded twin-arginine precursors induce homo-oligomerization of TatB and TatA. Ultimately, this leads to the formation of a transmembrane protein conduit that possibly consists of a pore-like TatA structure. The translocation step again is dependent on the PMF. PMID:22411976

  12. Growth factor deprivation induces cytosolic translocation of SIRT1

    NASA Astrophysics Data System (ADS)

    Meng, Chengbo; Xing, Da; Wu, Shengnan; Huang, Lei

    2010-02-01

    Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter, we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation, because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together, we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible connection between cytoplasm-localized SIRT1 and the aging process.

  13. Controlling polymer translocation and ion transport via charge correlations

    E-print Network

    Sahin Buyukdagli; Tapio Ala-Nissila

    2014-10-10

    We develop a correlation-corrected transport theory in order to predict ionic and polymer transport properties of membrane nanopores in physical conditions where mean-field electrostatics breaks down. The experimentally observed low KCl conductivity of open alpha-Hemolysin pores is quantitatively explained by the presence of surface polarization effects. Upon the penetration of a DNA molecule into the pore, these polarization forces combined with the electroneutrality of DNA sets a lower boundary for the ionic current, explaining the weak salt dependence of blocked pore conductivities at dilute ion concentrations. The addition of multivalent counterions into the solution results in the reversal of the polymer charge and the direction of the electroosmotic flow. With trivalent spermidine or quadrivalent spermine molecules, the charge inversion is strong enough to stop the translocation of the polymer and to reverse its motion. This mechanism can be used efficiently in translocation experiments in order to improve the accuracy of DNA sequencing by minimizing the translocation velocity of the polymer.

  14. Low frequency of PAX8-PPAR? rearrangement in follicular thyroid carcinomas in Japanese patients.

    PubMed

    Mochizuki, Kunio; Kondo, Tetsuo; Oishi, Naoki; Tahara, Ippei; Inoue, Tomohiro; Kasai, Kazunari; Nakazawa, Tadao; Okamoto, Takahiro; Shibata, Noriyuki; Katoh, Ryohei

    2015-05-01

    Paired-box gene 8 (PAX8)-peroxisome proliferator-activated receptor-? (PPAR?) gene fusion has been identified at significant frequency in follicular thyroid carcinomas (FTCs) with cytogenetically detectable translocation t(2;3)(q13;p25). This represents a possible specific molecular marker for follicular carcinoma. In this study, we examined PAX8-PPAR? rearrangement in 24 FTC samples from Japanese patients by reverse transcribed-polymerase chain reaction (RT-PCR) using two upstream PAX8 primers located in exons 7 and 8 and a downstream primer in exon 1 of PPAR?. The fusion gene was detected in only one of 24 FTCs (4%). The FTC with PAX8-PPAR? rearrangement from a 56-year-old man showed a product consistent with fusion between exon 8 of PAX8 and exon 1 of PPAR?. It was confirmed by direct sequencing. This FTC was histologically encapsulated, composed of trabeculae and small follicles and had complete penetration of the capsule by tumor tissues (minimally invasive type). The frequency of the fusion gene in this study was much lower than the 29-63% noted in reports from other countries suggesting that FTCs in Japanese patients may have a special genetic background, and that the high iodine intake from a typical Japanese diet might influence the frequency of the fusion gene in FTCs. PMID:25708358

  15. Gene deregulation and spatial genome reorganization near breakpoints prior to formation of translocations in anaplastic large cell lymphoma

    Microsoft Academic Search

    Stephan Mathas; Stephan Kreher; Karen J. Meaburn; Korinna Jöhrens; Björn Lamprecht; Chalid Assaf; Wolfram Sterry; Marshall E. Kadin; Masanori Daibata; Stefan Joos; Michael Hummel; Harald Stein; Martin Janz; Ioannis Anagnostopoulos; Evelin Schrock; Tom Misteli; Bernd Dörken

    2009-01-01

    Although the identification and characterization of translocations have rapidly increased, little is known about the mechanisms of how translocations occur in vivo. We used anaplastic large cell lymphoma (ALCL) with and without the characteristic t(2;5)(p23;q35) translocation to study the mechanisms of formation of translocations and of ALCL transformation. We report deregulation of several genes located near the ALCL translocation breakpoint,

  16. Regulation of Yersinia Yop-effector delivery by translocated YopE.

    PubMed

    Aili, Margareta; Isaksson, Elin L; Carlsson, Sara E; Wolf-Watz, Hans; Rosqvist, Roland; Francis, Matthew S

    2008-04-01

    The bacterial pathogen Yersinia pseudotuberculosis uses a type III secretion (T3S) system to translocate Yop effectors into eukaryotic cells. Effectors are thought to gain access to the cytosol via pores formed in the host cell plasma membrane. Translocated YopE can modulate this pore formation through its GTPase-activating protein (GAP) activity. In this study, we analysed the role of translocated YopE and all the other known Yop effectors in the regulation of effector translocation. Elevated levels of Yop effector translocation into HeLa cells occurred by YopE-defective strains, but not those defective for other Yop effectors. Only Yersinia devoid of YopK exhibits a similar hyper-translocation phenotype. Since both yopK and yopE mutants also failed to down-regulate Yop synthesis in the presence of eukaryotic cells, these data imply that translocated YopE specifically regulates subsequent effector translocation by Yersinia through at least one mechanism that involves YopK. We suggest that the GAP activity of YopE might be working as an intra-cellular probe measuring the amount of protein translocated by Yersinia during infection. This may be a general feature of T3S-associated GAP proteins, since two homologues from Pseudomonas aeruginosa, exoenzyme S (ExoS) and exoenzyme T (ExoT), can complement the hyper-translocation phenotypes of the yopE GAP mutant. PMID:17597003

  17. The IBEX background monitor

    E-print Network

    Crew, Geoffrey B.

    The IBEX Background Monitor (IBaM) provides a small and lightweight method for independently measuring IBEX’s high-energy proton background by integrating the flux of >~14 keV protons over a ~7° conical FOV. The IBaM is ...

  18. The microwave background radiation

    Microsoft Academic Search

    Juan M. Uson; David T. Wilkinson

    1988-01-01

    Contents: 1. Introduction. 2. The spectrum of the microwave background: Heterodyne radiometer methods (lambda >= 3 mm). Bolometric measurements (lambda <= 3 mm). Measurements using interstellar molecules. Summary and future prospects. 3. Polarization of the microwave background. 4. Anisotropy searches. 5. The Sunyaev-Zel'dovich effect: Concept and cosmological consequences. Measurements. Cosmological applications.

  19. Fitness costs of neighborhood disruption in translocations of a solitary mammal.

    PubMed

    Shier, Debra M; Swaisgood, Ronald R

    2012-02-01

    Translocation is used to reestablish wild populations of animals, but translocation projects often do not meet their objectives because postrelease mortality of animals is high. One reason for translocation failure is that the behavioral or ecological requirements of released animals are unmet. Maintaining founder-group social relationships during release can affect reestablishment of social species. Solitary territorial species with stable neighbors (restricted dispersal and lifetime occupation of a home range) of the same species may also benefit from the maintenance of these social relationships during translocation. We translocated Stephens' kangaroo rats (Dipodomys stephensi), a solitary species listed as endangered under the U.S. Endangered Species Act, with and without neighboring kangaroo rats. We compared the settlement (establishment of a stable home range) decisions and fitness of kangaroo rats between the 2 treatments. Kangaroo rats translocated with neighbors traveled shorter distances before establishing territories, had higher survival rates, and had significantly higher reproductive success than kangaroo rats translocated without neighbors. Number of offspring was 24-fold higher for kangaroo rats translocated with neighbors than those translocated without neighbors. Differences in behavior following release may partially explain differences in survival between the 2 groups. Immediately following release, animals translocated with neighbors fought less and spent significantly more time foraging and digging burrows than animals translocated without neighbors. Our results indicate that even for solitary species, maintaining relationships among members of a translocated group of animals can influence translocation success. This study is the first empirical demonstration of the fitness consequences of disrupting social relationships among territorial neighbors. PMID:21978094

  20. Correlators in nontrivial backgrounds

    SciTech Connect

    Mello Koch, Robert de [National Institute for Theoretical Physics, Department of Physics and Centre for Theoretical Physics, University of the Witwatersrand, Wits, 2050 (South Africa); Stellenbosch Institute for Advanced Studies, Stellenbosch (South Africa); Ives, Norman; Stephanou, Michael [National Institute for Theoretical Physics, Department of Physics and Centre for Theoretical Physics, University of the Witwatersrand, Wits, 2050 (South Africa)

    2009-01-15

    Operators in N=4 super Yang-Mills theory with an R-charge of O(N{sup 2}) are dual to backgrounds which are asymtotically AdS{sub 5}xS{sup 5}. In this article we develop efficient techniques that allow the computation of correlation functions in these backgrounds. We find that (i) contractions between fields in the string words and fields in the operator creating the background are the field theory accounting of the new geometry, (ii) correlation functions of probes in these backgrounds are given by the free field theory contractions but with rescaled propagators and (iii) in these backgrounds there are no open string excitations with their special end point interactions; we have only closed string excitations.

  1. A jumping Robertsonian translocation; a molecular and cytogenetic study

    SciTech Connect

    Park, V.M.; Gross, S.J.; Tharapel, A.T. [Univ. of Tennessee, Memphis, TN (United States)] [and others

    1994-09-01

    Lejeune et al. were the first to use the term {open_quotes}translocation sauteuse{close_quotes} or jumping translocation to describe mosaicism due to the presence of multiple structural rearrangements. In this study, we report the cytogenetic and molecular analyses of a patient with mosaicism for two different Robertsonian translocations, both involving chromosome 21. The proband`s karyotype based on lymphocyte cultures is 45,XX,t(21q22q)/46,XX,-21,+i(21q21q) (98%/2%). Chromosome analysis of skin fibroblasts showed 100% of cells with a 45,XX,t(21q22q) complement. A high level of mosaicism was seen in an ovarian biopsy, where 1/3 of cells exhibited the unbalanced cell line with the 21/21 rearrangement. The proband`s pregnancy history is consistent with the high proportion of the 21/21 rearrangement in her ovary. She has had spontaneous abortions and two livebirths, both of whom are affected with Down syndrome [46,XX,-21,+i(21q21q) and 46,XY,-21,+i(21q21q)]. Analysis of cord blood cultures showed that the second child exhibits low level mosaicism for a normal cell line, which further suggests instability of the 21/21 rearrangement. FISH with alphoid probes showed that the 21/21 and 21/22 rearrangements are dicentric and that each long arm segment retains its appropriate centromere. Segregation studies using microsatellite polymorphisms indicated that the 21/21 rearrangement is an isochromosome. The same technique was used to establish that the proband`s rearrangements formed de novo from her mother`s chromosome 21. An uncommon chromosome 22p polymorphism is maternally derived and is present in the proband`s unbalanced cell line. However, this 22 is absent in the balanced 45,XX,t(21q22q) cell line of the proband because it is involved in the translocation. Therefore, we propose a model in which the i(21q) was the progenitor rearrangement and participated in subsequent nonreciprocal rearrangements characteristic of a jumping translocation.

  2. Voltage-Driven Translocation of DNA through a High Throughput Conical Solid-State Nanopore

    PubMed Central

    Liu, Quanjun; Wu, Hongwen; Wu, Lingzhi; Xie, Xiao; Kong, Jinglin; Ye, Xiaofeng; Liu, Liping

    2012-01-01

    Nanopores have become an important tool for molecule detection at single molecular level. With the development of fabrication technology, synthesized solid-state membranes are promising candidate substrates in respect of their exceptional robustness and controllable size and shape. Here, a 30–60 (tip-base) nm conical nanopore fabricated in 100 nm thick silicon nitride (Si3N4) membrane by focused ion beam (FIB) has been employed for the analysis of ?-DNA translocations at different voltage biases from 200 to 450 mV. The distributions of translocation time and current blockage, as well as the events frequencies as a function of voltage are investigated. Similar to previously published work, the presence and configurations of ?-DNA molecules are characterized, also, we find that greater applied voltages markedly increase the events rate, and stretch the coiled ?-DNA molecules into linear form. However, compared to 6–30 nm ultrathin solid-state nanopores, a threshold voltage of 181 mV is found to be necessary to drive DNA molecules through the nanopore due to conical shape and length of the pore. The speed is slowed down ?5 times, while the capture radius is ?2 fold larger. The results show that the large nanopore in thick membrane with an improved stability and throughput also has the ability to detect the molecules at a single molecular level, as well as slows down the velocity of molecules passing through the pore. This work will provide more motivations for the development of nanopores as a Multi-functional sensor for a wide range of biopolymers and nano materials. PMID:23029365

  3. Aquaporin-1 Translocation and Degradation Mediates the Water Transportation Mechanism of Acetazolamide

    PubMed Central

    Gao, Junwei; Han, Jing; Pan, Xueyang; Pan, Yan; Tie, Lu; Li, Xuejun

    2012-01-01

    Background Diuretic agents are widely used on the treatment of water retention related diseases, among which acetazolamide (AZA) acts originally as a carbonic anhydrase (CA) inhibitor. Aquaporin-1 (AQP1) being located in renal proximal tubules is required for urine concentration. Previously our lab has reported AZA putatively modulated AQP1. Aim of this study is to testify our hypothesis that regulating AQP1 may mediate diuretic effect of AZA. Methodology/Principal Findings For in vivo study, we utilized Sprague Dawley rats, as well as AQP1 knock-out (AQP1?/?) mice to examine urine volume, and human kidney-2 (HK-2) cell line was used for in vitro mechanism study. In our present study we found that AZA decreased CAs activity initially but the activity gradually recovered. Contrarily, diuretic effect was consistently significant. AQP1 protein expression was significantly decreased on day 7 and 14. By utilizing AQP1?/? mice, we found diuretic effect of AZA was cancelled on day 14, while urine volume continuously increased in wild-type mice. Surface plasmon resonance (SPR) results indicated AQP1 was physiologically bound by myosin heavy chain (MHC), immunoprecipitation and immunofluorescence results confirmed this protein interaction. In vitro study results proved AZA facilitated AQP1 translocation onto cell membrane by promoting interaction with MHC, dependent on ERK/ myosin light chain kinase (MLCK) pathway activation. MHC inhibitor BDM and ERK inhibitor U0126 both abolished above effect of AZA. Eventually AZA induced AQP1 ubiquitination, while proteasome inhibitor MG132 reversed AZA's down-regulating effect upon AQP1. Conclusions/Significance Our results identified AZA exerted diuretic effect through an innovative mechanism by regulating AQP1 and verified its inhibitory mechanism was via promoting MHC-dependent translocation onto cell membrane and then ubiquitin mediated degradation, implicating a novel mechanism and target for diuretic agent discovering. PMID:23029347

  4. Translocation of Inhaled Ultrafine Manganese Oxide Particles to the Central Nervous System

    PubMed Central

    Elder, Alison; Gelein, Robert; Silva, Vanessa; Feikert, Tessa; Opanashuk, Lisa; Carter, Janet; Potter, Russell; Maynard, Andrew; Ito, Yasuo; Finkelstein, Jacob; Oberdörster, Günter

    2006-01-01

    Background Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; < 100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. Methods To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; ~ 500 ?g/m3) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. Results After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; there were also increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-? mRNA (~ 8-fold) and protein (~ 30-fold) were found after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFPs was < 1.5% per day. Conclusions We conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans. PMID:16882521

  5. The cosmic neutrino background

    NASA Technical Reports Server (NTRS)

    Dar, Arnon

    1991-01-01

    The cosmic neutrino background is expected to consist of relic neutrinos from the big bang, of neutrinos produced during nuclear burning in stars, of neutrinos released by gravitational stellar collapse, and of neutrinos produced by cosmic ray interactions with matter and radiation in the interstellar and intergalactic medium. Formation of baryonic dark matter in the early universe, matter-antimatter annihilation in a baryonic symmetric universe, and dark matter annihilation could have also contributed significantly to the cosmic neutrino background. The purpose of this paper is to review the properties of these cosmic neutrino backgrounds, the indirect evidence for their existence, and the prospects for their detection.

  6. Genetic profile of T-cell acute lymphoblastic leukemias with MYC translocations.

    PubMed

    La Starza, Roberta; Borga, Chiara; Barba, Gianluca; Pierini, Valentina; Schwab, Claire; Matteucci, Caterina; Lema Fernandez, Anair G; Leszl, Anna; Cazzaniga, Gianni; Chiaretti, Sabina; Basso, Giuseppe; Harrison, Christine J; Te Kronnie, Geertruy; Mecucci, Cristina

    2014-12-01

    MYC translocations represent a genetic subtype of T-lineage acute lymphoblastic leukemia (T-ALL), which occurs at an incidence of ?6%, assessed within a cohort of 196 T-ALL patients (64 adults and 132 children). The translocations were of 2 types; those rearranged with the T-cell receptor loci and those with other partners. MYC translocations were significantly associated with the TAL/LMO subtype of T-ALL (P = .018) and trisomies 6 (P < .001) and 7 (P < .001). Within the TAL/LMO subtype, gene expression profiling identified 148 differentially expressed genes between patients with and without MYC translocations; specifically, 77 were upregulated and 71 downregulated in those with MYC translocations. The poor prognostic marker, CD44, was among the upregulated genes. MYC translocations occurred as secondary abnormalities, present in subclones in one-half of the cases. Longitudinal studies indicated an association with induction failure and relapse. PMID:25270907

  7. Use of chromosome translocations for measuring prior environment exposures in humans

    SciTech Connect

    Tucker, J. D.

    1997-05-01

    Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.

  8. Scaling exponents of Forced Polymer Translocation through a nano-pore

    E-print Network

    Aniket Bhattacharya; William H. Morrison; Kaifu Luo; Tapio Ala-Nissila; See-Chen Ying; Andrey Milchev; Kurt Binder

    2008-11-10

    We investigate several scaling properties of a translocating homopolymer through a thin pore driven by an external field present inside the pore only using Langevin Dynamics (LD) simulation in three dimension (3D). Specifically motivated by several recent theoretical and numerical studies that are apparently at odds with each other, we determine the chain length dependence of the scaling exponents of the average translocation time, the average velocity of the center of mass, $$, the effective radius of gyration during the translocation process, and the scaling exponent of the translocation coordinate ($s$-coordinate) as a function of the translocation time. We further discuss the possibility that in the case of driven translocation the finite pore size and its geometry could be responsible that the veclocity scaling exponent is less than unity and discuss the dependence of the scaling exponents on the pore geometry for the range of $N$ studied here.

  9. Entropic effects in formation of chromosome territories: towards understanding of radiation-induced gene translocation frequency

    NASA Astrophysics Data System (ADS)

    Gudowska-Nowak, Ewa; Ritter, Sylvia; Durante, Marco; Deperas-Standylo, Joanna; Ciesla, Michal

    2012-07-01

    A detailed understanding of structural organization of biological target, such as geometry of an inter-phase chromosome, is an essential prerequisite for gaining deeper insight into relationship between radiation track structure and radiation-induced biological damage [1]. In particular, coupling of biophysical models aimed to describe architecture of chromosomes and their positioning in a cell nucleus [2-4] with models of local distribution of ionizations caused by passing projectiles, are expected to result in more accurate estimates of aberration induction caused by radiation. There is abundant experimental evidence indicating that arrangements of chromosomes in eukaryotic cell nucleus is non-random and has been evolutionary conserved in specific cell types. Moreover, the radial position of a given chromosome territory (CT) within the cell nucleus has been shown to correlate with its size and gene density. Usually it is assumed that chromosomal geometry and positioning result from the action of specific forces acting locally, such as hydrogen bonds, electrostatic, Van der Waals or hydrophobic interactions operating between nucleosomes and within their interiors. However, it is both desirable and instructive to learn to what extend organization of inter-phase chromosomes is affected by nonspecific entropic forces. In this study we report results of a coarse-grained analysis of a chromatin structure modeled by two distinct approaches. In the first method, we adhere to purely statistical analysis of chromatin packing within a chromosome territory. On the basis of the polymer theory, the chromatin fiber of diameter 30nm is approximated by a chain of spheres, each corresponding to about 30 kbp. Random positioning of the center of the domain is repeated for 1000 spherical nuclei. Configuration of the domain is determined by a random packing of a polymer (a string of identical beads) in estimated fraction of space occupied by a chromosome of a given length and mass. The degree of condensation of the chromatin fiber is modeled by changing length of the string: e.g. loosening of the structure is achieved by distributing the chromosome mass into a higher number of smaller beads and tighter configuration corresponds to a lower number of fragments (balls) with a bigger radius. Additionally, for each configuration, a degree of possible overlapping between domains is assumed. This procedure effectively intensifies loosening/tightening of the chromosome structure by changing the radial dimension of the domain while keeping a constant volume of the polymer chain. Such a positioning model is confronted with a minimalistic molecular dynamics model [5] on a similar structure, in which a chain of beads becomes connected by entropic spring energy and subjected to thermal fluctuations. Comparison of both Monte Carlo models allows to discuss variability of possible configurations as observed in static and dynamic models of chromosome territories along with the effect of compaction and relative arrangements of territorial polymer structures. Acknowledgements: Project is operated within the Foundation for Polish Science International Ph.D. Projects Programme co-financed by the European Regional Development Fund covering, under the agreement no. MPD/2009/6, the Jagiellonian University International Ph.D. Studies in Physics of Complex Systems. References: [1] F. Ballarini, M. Biaggi, and A. Ottolenghi, Radiation Protection Dosimetry 99, 175 (2002). [2] M. Nicodemi and A. Prisco, Biophysical Journal 96, 2168 (2009). [3] P. Cook and D. Marenduzzo, Journal of Cell Biology 186, 825 (2009). [4] M. Tark-Dame, R. van Driel, and D. Heermann, Journal of Cell Science 124, 839 (2011). [5] W. Swope, H. Andersen, P. Berens, and K. Wilson, J. Chem. Phys. 76, 637 (1982).

  10. The Cosmic Microwave Background

    Microsoft Academic Search

    Joseph Silk

    2003-01-01

    .  I review the discovery of the temperature fluctuations in the cosmic microwave background radiation. The underlying theory\\u000a and the implications for cosmology are described, and I summarize the prospects for future progress.

  11. Building Background Knowledge

    NSDL National Science Digital Library

    Donna Ross

    2010-01-01

    Too often, students enter our classrooms with insufficient knowledge of physical science. As a result, they have a difficult time understanding content in texts, lectures, and laboratory activities. This lack of background knowledge can have an impact on

  12. Background and Statistics

    MedlinePLUS

    Background & Statistics FAQ About Homeless Veterans Homeless Veterans Facts Demographics of Homeless Veterans Incarcerated Veterans Research Briefs Sources FAQ ... VETERANS In May 2007, the Bureau of Justice Statistics released a special report on incarcerated veterans. The ...

  13. Finding of widespread viral and bacterial revolution dsDNA translocation motors distinct from rotation motors by channel chirality and size

    PubMed Central

    2014-01-01

    Background Double-stranded DNA translocation is ubiquitous in living systems. Cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging and cell entry all involve biomotor-driven dsDNA translocation. Previously, biomotors have been primarily classified into linear and rotational motors. We recently discovered a third class of dsDNA translocation motors in Phi29 utilizing revolution mechanism without rotation. Analogically, the Earth rotates around its own axis every 24 hours, but revolves around the Sun every 365 days. Results Single-channel DNA translocation conductance assay combined with structure inspections of motor channels on bacteriophages P22, SPP1, HK97, T7, T4, Phi29, and other dsDNA translocation motors such as bacterial FtsK and eukaryotic mimiviruses or vaccinia viruses showed that revolution motor is widespread. The force generation mechanism for revolution motors is elucidated. Revolution motors can be differentiated from rotation motors by their channel size and chirality. Crystal structure inspection revealed that revolution motors commonly exhibit channel diameters larger than 3 nm, while rotation motors that rotate around one of the two separated DNA strands feature a diameter smaller than 2 nm. Phi29 revolution motor translocated double- and tetra-stranded DNA that occupied 32% and 64% of the narrowest channel cross-section, respectively, evidencing that revolution motors exhibit channel diameters significantly wider than the dsDNA. Left-handed oriented channels found in revolution motors drive the right-handed dsDNA via anti-chiral interaction, while right-handed channels observed in rotation motors drive the right-handed dsDNA via parallel threads. Tethering both the motor and the dsDNA distal-end of the revolution motor does not block DNA packaging, indicating that no rotation is required for motors of dsDNA phages, while a small-angle left-handed twist of dsDNA that is aligned with the channel could occur due to the conformational change of the phage motor channels from a left-handed configuration for DNA entry to a right-handed configuration for DNA ejection for host cell infection. Conclusions The revolution motor is widespread among biological systems, and can be distinguished from rotation motors by channel size and chirality. The revolution mechanism renders dsDNA void of coiling and torque during translocation of the lengthy helical chromosome, thus resulting in more efficient motor energy conversion. PMID:24940480

  14. Background Studies for EXIST

    NASA Technical Reports Server (NTRS)

    Wilson, Colleen A.; Pendleton, G. N.; Fishman, G. J.

    2004-01-01

    We present results from a study of the trapped proton and electron background for several orbital inclinations and altitudes. This study includes time dependent effects. In addition we describe a 3 component cosmic background model developed at the University of Southampton, UK. The three components are cosmic diffuse gamma rays, atmospheric albedo gamma rays, and cosmic ray protons. We present examples of how this model was applied to BATSE and discuss its application to EXIST.

  15. Kinetics of Cryptdin-4 Translocation Coupled with Peptide-Induced Vesicle Leakage †

    Microsoft Academic Search

    Jason E. Cummings; T. Kyle Vanderlick

    2007-01-01

    The antimicrobial peptide cryptdin-4 (Crp4), a member of the R-defensin family, is shown to translocate cooperatively across phospholipid bilayers. The cooperativity of the process is manifested by translocation kinetics which vary with the peptide to lipid molar ratio. A simple association model suggests dimerization. Black lipid membrane experiments reveal that Crp4 translocation does not create well- defined aqueous pores, as

  16. 8-[14C]Benzylaminopurine Translocation in Phaseolus vulgaris1

    PubMed Central

    Ramina, Angelo; Pimpini, Ferdinando; Boniolo, Antonio; Bergamasco, Ferruccio

    1979-01-01

    [8-14C]Benzylaminopurine (BA) translocation was studied in whole plants of Phaseolus vulgaris L. under three different light regimes (continuous light, 8-hour light + 16-hour dark, dark). Applications were made to the apex, to a cotyledonary leaf, or to the root system. Results showed that no BA basipetal translocation occurred, however BA is easily absorbed by the root system and is translocated acropetally. The amount of BA absorbed and its acropetal translocation rate depend on the light regime. The hypothesis of a passive cytokinin transport through the xylem, regulated by the transpiration stream, is discussed. PMID:16660716

  17. Translocation of a Polymer Chain across a Nanopore: A Brownian Dynamics Simulation Study

    NASA Technical Reports Server (NTRS)

    Tian, Pu; Smith, Grant D.

    2003-01-01

    We carried out Brownian dynamics simulation studies of the translocation of single polymer chains across a nanosized pore under the driving of an applied field (chemical potential gradient). The translocation process can be either dominated by the entropic barrier resulted from restricted motion of flexible polymer chains or by applied forces (or chemical gradient across the wall), we focused on the latter case in our studies. Calculation of radius of gyrations at the two opposite sides of the wall shows that the polymer chains are not in equilibrium during the translocation process. Despite this fact, our results show that the one-dimensional diffusion and the nucleation model provide an excellent description of the dependence of average translocation time on the chemical potential gradients, the polymer chain length and the solvent viscosity. In good agreement with experimental results and theoretical predictions, the translocation time distribution of our simple model shows strong non-Gaussian characteristics. It is observed that even for this simple tubelike pore geometry, more than one peak of translocation time distribution can be generated for proper pore diameter and applied field strengths. Both repulsive Weeks-Chandler-Anderson and attractive Lennard-Jones polymer-nanopore interaction were studied, attraction facilitates the translocation process by shortening the total translocation time and dramatically improve the capturing of polymer chain. The width of the translocation time distribution was found to decrease with increasing temperature, increasing field strength, and decreasing pore diameter.

  18. Mitochondrial Function in Antarctic Nototheniids with ND6 Translocation

    PubMed Central

    Mark, Felix C.; Lucassen, Magnus; Strobel, Anneli; Barrera-Oro, Esteban; Koschnick, Nils; Zane, Lorenzo; Patarnello, Tomaso; Pörtner, Hans O.; Papetti, Chiara

    2012-01-01

    Fish of the suborder Notothenioidei have successfully radiated into the Southern Ocean and today comprise the dominant fish sub-order in Antarctic waters in terms of biomass and species abundance. During evolution in the cold and stable Antarctic climate, the Antarctic lineage of notothenioids developed several unique physiological adaptations, which make them extremely vulnerable to the rapid warming of Antarctic waters currently observed. Only recently, a further phenomenon exclusive to notothenioid fish was reported: the translocation of the mitochondrial gene encoding the NADH Dehydrogenase subunit 6 (ND6), an indispensable part of complex I in the mitochondrial electron transport system. This study investigated the potential physiological consequences of ND6 translocation for the function and thermal sensitivity of the electron transport system in isolated liver mitochondria of the two nototheniid species Notothenia coriiceps and Notothenia rossii, with special attention to the contributions of complex I (NADH DH) and complex II (Succinate DH) to oxidative phosphorylation. Furthermore, enzymatic activities of NADH?Cytochrome c Oxidoreductase and Cytochrome C Oxidase were measured in membrane-enriched tissue extracts. During acute thermal challenge (0–15°C), capacities of mitochondrial respiration and enzymatic function in the liver could only be increased until 9°C. Mitochondrial complex I (NADH Dehydrogenase) was fully functional but displayed a higher thermal sensitivity than the other complexes of the electron transport system, which may specifically result from its unique amino acid composition, revealing a lower degree of stability in notothenioids in general. We interpret the translocation of ND6 as functionally neutral but the change in amino acid sequence as adaptive and supportive of cold stenothermy in Antarctic nototheniids. From these findings, an enhanced sensitivity to ocean warming can be deduced for Antarctic notothenioid fish. PMID:22363756

  19. Biopersistence and Brain Translocation of Aluminum Adjuvants of Vaccines

    PubMed Central

    Gherardi, Romain Kroum; Eidi, Housam; Crépeaux, Guillemette; Authier, François Jerome; Cadusseau, Josette

    2015-01-01

    Aluminum oxyhydroxide (alum) is a crystalline compound widely used as an immunological adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF) lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytosed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy) until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV), that obeys to CCL2, signaling the major inflammatory monocyte chemoattractant. PMID:25699008

  20. Frequency-Shift Hearing Aid

    NASA Technical Reports Server (NTRS)

    Weinstein, Leonard M.

    1994-01-01

    Proposed hearing aid maps spectrum of speech into band of lower frequencies at which ear remains sensitive. By redirecting normal speech frequencies into frequency band from 100 to 1,500 Hz, hearing aid allows people to understand normal conversation, including telephone calls. Principle operation of hearing aid adapted to other uses such as, clearing up noisy telephone or radio communication. In addition, loud-speakers more easily understood in presence of high background noise.

  1. The presequence of a chimeric construct dictates which of two mechanisms are utilized for translocation across the thylakoid membrane: evidence for the existence of two distinct translocation systems.

    PubMed Central

    Robinson, C; Cai, D; Hulford, A; Brock, I W; Michl, D; Hazell, L; Schmidt, I; Herrmann, R G; Klösgen, R B

    1994-01-01

    The translocation of plastocyanin across the thylakoid membrane in Pisum sativum has been studied in reconstitution assays and using chimeric constructs. The reconstitution assays demonstrate that plastocyanin translocation is absolutely dependent on the presence of a stromal factor(s) and nucleotide triphosphates (NTPs), whereas neither element is required for the translocation of the 23 or 16 kDa proteins of the oxygen-evolving complex. Previous studies had revealed that the transthylakoidal delta pH is essential for translocation of the 23 and 16 kDa proteins but unnecessary for plastocyanin translocation. The basis for these mechanistic differences has been tested by analysing the translocation of a chimeric construct consisting of the presequence of the 23 kDa protein linked to the mature plastocyanin sequence. This construct is efficiently imported into thylakoids in the absence of stromal extracts or NTPs and translocation across the thylakoid membrane within intact chloroplasts is totally inhibited by the uncoupler nigericin: the translocation requirements are thus identical to those of the pre-23 kDa protein and diametrically opposite to those of pre-plastocyanin. Transport across the thylakoid membrane of a second fusion protein, consisting of the presequence of the 16 kDa protein linked to mature plastocyanin, is also dependent on a delta pH. The data suggest that two distinct systems are involved in the translocation of proteins across the thylakoid membrane, with each system recognizing specific signals within the presequences of a subset of lumenal protein precursors. Images PMID:8313873

  2. Langevin Dynamics Simulations of Polymer Translocation through Nanopores

    E-print Network

    Ilkka Huopaniemi; Kaifu Luo; Tapio Ala-Nissila; See-Chen Ying

    2006-08-23

    We investigate the dynamics of polymer translocation through a nanopore using two-dimensional Langevin dynamics simulations. In the absence of external driving force, we consider a polymer which is initially placed in the middle of the pore and study the escape time $\\tau_e$ required for the polymer to completely exit the pore on either side. The distribution of the escape times is wide and has a long tail. We find that $\\tau_e$ scales with the chain length $N$ as $\\tau_e \\sim N^{1+2\

  3. The twin-arginine translocation (Tat) protein export pathway.

    PubMed

    Palmer, Tracy; Berks, Ben C

    2012-07-01

    The twin-arginine translocation (Tat) protein export system is present in the cytoplasmic membranes of most bacteria and archaea and has the highly unusual property of transporting fully folded proteins. The system must therefore provide a transmembrane pathway that is large enough to allow the passage of structured macromolecular substrates of different sizes but that maintains the impermeability of the membrane to ions. In the Gram-negative bacterium Escherichia coli, this complex task can be achieved by using only three small membrane proteins: TatA, TatB and TatC. In this Review, we summarize recent advances in our understanding of how this remarkable machine operates. PMID:22683878

  4. Rotational Streaming in Fiber Cells and Its Role in Translocation

    PubMed Central

    Worley, J. F.

    1968-01-01

    All visible protoplasmic streaming in sections of various plant stems was reversibly stopped by 2,4-dinitrophenol (DNP). Sections contained epidermal, cortical, and fiber cell types. Cells treated with DNP retained their semipermeability as evidenced by their plasmolysis in sucrose solutions. Washing out the DNP resulted in the rapid resumption of protoplasmic streaming in all 3 cell types. Both the rate of movement of sodium fluorescein and the shape of the advancing dye front were greatly altered by DNP treatment. Dye transport was decreased in the fibers and little affected in cortical cells. The results suggest that rotational streaming accelerates the translocation of soluble substances in fiber cells. Images PMID:16656950

  5. Discovery of the Microwave Background Cosmic microwave background radiation

    E-print Network

    Barnes, Joshua Edward

    Discovery of the Microwave Background Cosmic microwave background radiation Signals from the early universe, or pigeon droppings? #12;Microwave Background Radiation The spectrum is a near- perfect match background. Fluctuations in the Cosmic Microwave Background MWMW 370 km/s #12;Microwave Background Features

  6. Refinement of background environmental monitoring measurements using meteorological frequency distribution

    SciTech Connect

    Schwartz, P.E. (GPU Nuclear Corp., Forked River, NJ (United States))

    1991-01-01

    Since the Radiological Environmental Monitoring Program's inception in 1969, the direct radiation monitoring network around the Oyster Creek nuclear generating station has incorporated both monthly and quarterly thermoluminescent dosimetry (TLD). In 1988, the environmental controls department of GPU Nuclear decided to eliminate the monthly TLD network for scientific and economic reasons. The most obvious scientific basis on which to designate TLD stations is by meteorology. It would be the plume path that dictates off-site direct radiation contribution from the plant and not simply distance from the site. Through meteorological and statistical analysis of existing TLD results, the appropriate basis for designating TLD stations has been accomplished that will provide the most accurate and comprehensive data on environmental measurement of releases from Oyster Creek.

  7. Tactual Frequency and Amplitude Discrimination with Fixed and Roving Background

    E-print Network

    Tan, Hong Z.

    are discussed in terms of their implications for tactual displays of speech in communication aids for the deaf-amplitude space for transmitting broad- band modified speech signals through such a device. Although previous

  8. Refinement of background environmental monitoring measurements using meteorological frequency distribution

    Microsoft Academic Search

    1991-01-01

    Since the Radiological Environmental Monitoring Program's inception in 1969, the direct radiation monitoring network around the Oyster Creek nuclear generating station has incorporated both monthly and quarterly thermoluminescent dosimetry (TLD). In 1988, the environmental controls department of GPU Nuclear decided to eliminate the monthly TLD network for scientific and economic reasons. The most obvious scientific basis on which to designate

  9. The Cosmic Background Explorer

    NASA Technical Reports Server (NTRS)

    Gulkis, Samuel; Lubin, Philip M.; Meyer, Stephan S.; Silverberg, Robert F.

    1990-01-01

    The Cosmic Background Explorer (CBE), NASA's cosmological satellite which will observe a radiative relic of the big bang, is discussed. The major questions connected to the big bang theory which may be clarified using the CBE are reviewed. The satellite instruments and experiments are described, including the Differential Microwave Radiometer, which measures the difference between microwave radiation emitted from two points on the sky, the Far-Infrared Absolute Spectrophotometer, which compares the spectrum of radiation from the sky at wavelengths from 100 microns to one cm with that from an internal blackbody, and the Diffuse Infrared Background Experiment, which searches for the radiation from the earliest generation of stars.

  10. Cosmic Microwave Background

    NSDL National Science Digital Library

    2012-08-03

    In this lesson, students explore the cosmic microwave background to understand why it permeates the universe and why it peaks as microwave radiation. Students should be able to explain that the origin of the background radiation is the uniform thermal radiation of the big bang and that the radiation produced was evenly distributed around the small early universe, causing it to permeate today's universe. This activity is part of the Cosmic Times teachers guide and is intended to be used in conjunction with the 1965 Cosmic Times Poster.

  11. Matching Background Color

    NSDL National Science Digital Library

    David Ipsen

    2008-04-01

    This chapter introduces an especially important subject in the concealment of animals--countershading. One observes many animals with colors that match the general color of their usual backgrounds. Many leaf-eating insects appear green, for example, making them relatively inconspicuous against their normal background of leaves. The manner of coloration that will provide such a color match is not as obvious as one might imagine. It depends significantly on the nature of the lighting. The inquiry-based activities included in this section effectively illustrate this concept.

  12. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1991-01-01

    Recent limits on spectral distortions and angular anisotropies in the cosmic microwave background are reviewed. The various backgrounds are described, and the theoretical implications are assessed. Constraints on inflationary cosmology dominated by cold dark matter (CDM) and on open cosmological models dominated by baryonic dark matter (BDM), with, respectively, primordial random phase scale-invariant curvature fluctuations or non-gaussian isocurvature fluctuations are described. More exotic theories are addressed, and I conclude with the 'bottom line': what theorists expect experimentalists to be measuring within the next two to three years without having to abandon their most cherished theories.

  13. Out of Equilibrium Characteristics of a Forced Translocating Chain through a Nanopore

    E-print Network

    Aniket Bhattacharya; Kurt Binder

    2010-02-24

    Polymer translocation through a nano-pore in a thin membrane is studied using a coarse-grained bead-spring model and Langevin dynamics simulation with a particular emphasis to explore out of equilibrium characteristics of the translocating chain. We analyze the out of equilibrium chain conformations both at the $cis$ and the $trans$ side separately either as a function of the time during the translocation process or as as function of the monomer index $m$ inside the pore. A detailed picture of translocation emerges by monitoring the center of mass of the translocating chain, longitudinal and transverse components of the gyration radii and the end to end vector. We observe that polymer configurations at the $cis$ side are distinctly different from those at the $trans$ side. During the translocation, and immediately afterwards, the chain is clearly out of equilibrium, as different parts of the chain are characterized by a series of effective Flory exponents. We further notice that immediately after the translocation the last set of beads that have just translocated take a relatively compact structure compared to the first set of beads that translocated earlier, and the chain immediately after translocation is described by an effective Flory exponent $0.45 \\pm 0.01$. The analysis of these results is further strengthened by looking at the conformations of chain segments of equal length as they cross from the $cis$ to the $trans$ side, We discuss implications of these results to the theoretical estimates and numerical simulation studies of the translocation exponent reported by various groups.

  14. Mitochondrial translocation of APE1 relies on the MIA pathway

    PubMed Central

    Barchiesi, Arianna; Wasilewski, Michal; Chacinska, Agnieszka; Tell, Gianluca; Vascotto, Carlo

    2015-01-01

    APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria. The MIA pathway is an import machinery that uses a redox system for cysteine enriched proteins to drive them in this compartment. It is composed by two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's mitochondrial translocation and, consequently, play a role in the maintenance of mitochondrial DNA integrity. In summary, our data strongly support the hypothesis of a redox-assisted mechanism, dependent on Mia40, in controlling APE1 translocation into the mitochondrial inner membrane space and thus highlight the role of this protein transport pathway in the maintenance of mitochondrial DNA stability and cell survival. PMID:25956655

  15. Exertional myopathy in translocated river otters from New York.

    PubMed

    Hartup, B K; Kollias, G V; Jacobsen, M C; Valentine, B A; Kimber, K R

    1999-07-01

    Lesions consistent with exertional myopathy (EM) were documented postmortem in four North American river otters (Lutra canadensis) during translocation for a population restoration project. Clinical signs in these otters included depression, anorexia and shock. Gross lesions in one otter included locally extensive linear, pale areas within the subscapularis, rectus abdominis, quadriceps, and dorsal laryngeal muscles. Microscopic lesions were characterized by acute to subacute myofiber necrosis of varying severity, and occurred in a variety of skeletal muscles as well as cardiac muscle in one otter. Based on these observations, we conducted a retrospective review of records of otters which experienced similar capture, transfer, and holding protocols between 1995 and 1997, but with a successful outcome (n = 69). Significant elevations in serum aspartate aminotransferase (AST) and creatine kinase (CK) were observed in 19 (28%) of the otters, but may have been higher due to delayed sample collection from some otters. However, none of the otters with elevated enzymes exhibited clinical signs suggestive of EM. These findings indicate that river otters may develop EM when translocated, but many cases may be mild or clinically inapparent. PMID:10479089

  16. Translocator protein PET imaging for glial activation in multiple sclerosis.

    PubMed

    Oh, Unsong; Fujita, Masahiro; Ikonomidou, Vasiliki N; Evangelou, Iordanis E; Matsuura, Eiji; Harberts, Erin; Fujimura, Yota; Richert, Nancy D; Ohayon, Joan; Pike, Victor W; Zhang, Yi; Zoghbi, Sami S; Innis, Robert B; Jacobson, Steven

    2011-09-01

    Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [(11)C]PBR28, a newly developed translocator protein-specific radioligand. The [(11)C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p?=?0.019). Focal increases in [(11)C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p?=?0.0039). Furthermore, increase in [(11)C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [(11)C]PBR28 binding showed correlation with disease duration (p?=?0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS. PMID:20872081

  17. Programmed -1 frameshifting by kinetic partitioning during impeded translocation.

    PubMed

    Caliskan, Neva; Katunin, Vladimir I; Belardinelli, Riccardo; Peske, Frank; Rodnina, Marina V

    2014-06-19

    Programmed -1 ribosomal frameshifting (-1PRF) is an mRNA recoding event utilized by cells to enhance the information content of the genome and to regulate gene expression. The mechanism of -1PRF and its timing during translation elongation are unclear. Here, we identified the steps that govern -1PRF by following the stepwise movement of the ribosome through the frameshifting site of a model mRNA derived from the IBV 1a/1b gene in a reconstituted in vitro translation system from Escherichia coli. Frameshifting occurs at a late stage of translocation when the two tRNAs are bound to adjacent slippery sequence codons of the mRNA. The downstream pseudoknot in the mRNA impairs the closing movement of the 30S subunit head, the dissociation of EF-G, and the release of tRNA from the ribosome. The slippage of the ribosome into the -1 frame accelerates the completion of translocation, thereby further favoring translation in the new reading frame. PMID:24949973

  18. The specificity of proton-translocating transhydrogenase for nicotinamide nucleotides.

    PubMed

    Huxley, Lucinda; Quirk, Philip G; Cotton, Nick P J; White, Scott A; Jackson, J Baz

    2011-01-01

    In its forward direction, transhydrogenase couples the reduction of NADP(+) by NADH to the outward translocation of protons across the membrane of bacteria and animal mitochondria. The enzyme has three components: dI and dIII protrude from the membrane and dII spans the membrane. Hydride transfer takes place between nucleotides bound to dI and dIII. Studies on the kinetics of a lag phase at the onset of a "cyclic reaction" catalysed by complexes of the dI and dIII components of transhydrogenase from Rhodospirillum rubrum, and on the kinetics of fluorescence changes associated with nucleotide binding, reveal two features. Firstly, the binding of NADP(+) and NADPH to dIII is extremely slow, and is probably limited by the conversion of the occluded to the open state of the complex. Secondly, dIII can also bind NAD(+) and NADH. Extrapolating to the intact enzyme this binding to the "wrong" site could lead to slip: proton translocation without change in the nucleotide redox state, which would have important consequences for bacterial and mitochondrial metabolism. PMID:20732298

  19. Electronic transduction of proton translocations in nanoassembled lamellae of bacteriorhodopsin.

    PubMed

    Palazzo, Gerardo; Magliulo, Maria; Mallardi, Antonia; Angione, Maria Daniela; Gobeljic, Danka; Scamarcio, Gaetano; Fratini, Emiliano; Ridi, Francesca; Torsi, Luisa

    2014-08-26

    An organic field-effect transistor (OFET) integrating bacteriorhodopsin (bR) nanoassembled lamellae is proposed for an in-depth study of the proton translocation processes occurring as the bioelectronic device is exposed either to light or to low concentrations of general anesthetic vapors. The study involves the morphological, structural, electrical, and spectroscopic characterizations necessary to assess the functional properties of the device as well as the bR biological activity once integrated into the functional biointerlayer (FBI)-OFET structure. The electronic transduction of the protons phototranslocation is shown as a current increase in the p-type channel only when the device is irradiated with photons known to trigger the bR photocycle, while Raman spectroscopy reveals an associated C?C isomer switch. Notably, higher energy photons bring the cis isomer back to its trans form, switching the proton pumping process off. The investigation is extended also to the study of a PM FBI-OFET exposed to volatile general anesthetics such as halothane. In this case an electronic current increase is seen upon exposure to low, clinically relevant, concentrations of anesthetics, while no evidence of isomer-switching is observed. The study of the direct electronic detection of the two different externally triggered proton translocation effects allows gathering insights into the underpinning of different bR molecular switching processes. PMID:25077939

  20. Mitochondrial translocation of APE1 relies on the MIA pathway.

    PubMed

    Barchiesi, Arianna; Wasilewski, Michal; Chacinska, Agnieszka; Tell, Gianluca; Vascotto, Carlo

    2015-06-23

    APE1 is a multifunctional protein with a fundamental role in repairing nuclear and mitochondrial DNA lesions caused by oxidative and alkylating agents. Unfortunately, comprehensions of the mechanisms regulating APE1 intracellular trafficking are still fragmentary and contrasting. Recent data demonstrate that APE1 interacts with the mitochondrial import and assembly protein Mia40 suggesting the involvement of a redox-assisted mechanism, dependent on the disulfide transfer system, to be responsible of APE1 trafficking into the mitochondria. The MIA pathway is an import machinery that uses a redox system for cysteine enriched proteins to drive them in this compartment. It is composed by two main proteins: Mia40 is the oxidoreductase that catalyzes the formation of the disulfide bonds in the substrate, while ALR reoxidizes Mia40 after the import. In this study, we demonstrated that: (i) APE1 and Mia40 interact through disulfide bond formation; and (ii) Mia40 expression levels directly affect APE1's mitochondrial translocation and, consequently, play a role in the maintenance of mitochondrial DNA integrity. In summary, our data strongly support the hypothesis of a redox-assisted mechanism, dependent on Mia40, in controlling APE1 translocation into the mitochondrial inner membrane space and thus highlight the role of this protein transport pathway in the maintenance of mitochondrial DNA stability and cell survival. PMID:25956655

  1. Molecular determinants of nucleolar translocation of RNA helicase A

    SciTech Connect

    Liu Zhe; Kenworthy, Rachael; Green, Christopher [Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370 (United States); Tang, Hengli [Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370 (United States)], E-mail: tang@bio.fsu.edu

    2007-10-15

    RNA helicase A (RHA) is a member of the DEAH-box family of DNA/RNA helicases involved in multiple cellular processes and the life cycles of many viruses. The subcellular localization of RHA is dynamic despite its steady-state concentration in the nucleoplasm. We have previously shown that it shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus. Here, we investigate the molecular determinants for its translocation within the nucleus and, more specifically, its redistribution from the nucleoplasm to nucleolus or the perinucleolar region. We found that low temperature treatment, transcription inhibition or replication of hepatitis C virus caused the intranuclear redistribution of the protein, suggesting that RHA shuttles between the nucleolus and nucleoplasm and becomes trapped in the nucleolus or the perinucleolar region upon blockade of transport to the nucleoplasm. Both the NTD and ATPase activity were essential for RHA's transport to the nucleolus or perinucleolar region. One of the double-stranded RNA binding domains (dsRBD II) was also required for this nucleolar translocation (NoT) phenotype. RNA interference studies revealed that RHA is essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role.

  2. David Smith Academic background

    E-print Network

    David Smith Academic background Ph.D. in Mathematics (Algebra), Université de Sherbrooke, Canada project program (I. Assem, F. Bergeron, C. Reutenauer, D. Smith) $132,000 ($44,000 per year for 3 years. Schiffler and D. Smith, Friezes, strings and cluster variables, to appear in Glasgow Mathematcal Journal. 2

  3. PANDEMIC INFLUENZA background briefing

    E-print Network

    Rambaut, Andrew

    PANDEMIC INFLUENZA background briefing Biomedicine Forum 5 November 2008 compiled by David Evans, Dave Carr, David Lynn and Phil Green Transmission electron micrograph of Influenza A virus (Wellcome influenza!' Page 2 #12;Consequences of an influenza pandemic THE PANDEMIC THREAT DEATH If the next pandemic

  4. Country background Forest history

    E-print Network

    Paris-Sud XI, Université de

    season prone to forest fires. Atlantic climate is wet with temperatures moderated by the ocean33 Country background Forest history During the Gallo-Roman period (1st­4th century AD), forests this proportion decreased dramatically to only 15­17 % of the land area. This residual forest was then severely

  5. Shark Species Profiles Background

    E-print Network

    Watson, Craig A.

    skeletons that are made of bone. Although all sharks have some similarities such as having gills and fins there are small spots long the sides of the shark and a black blotch near the pectoral fin Diet: Marine mammalsShark Species Profiles Background: Sharks have existed for about 400 million years, before

  6. Disulfide bridge formation between SecY and a translocating polypeptide localizes the translocation pore to the center of SecY

    PubMed Central

    Cannon, Kurt S.; Or, Eran; Clemons, William M.; Shibata, Yoko; Rapoport, Tom A.

    2005-01-01

    During their biosynthesis, many proteins pass through the membrane via a hydrophilic channel formed by the heterotrimeric Sec61/SecY complex. Whether this channel forms at the interface of multiple copies of Sec61/SecY or is intrinsic to a monomeric complex, as suggested by the recently solved X-ray structure of the Methanococcus jannaschii SecY complex, is a matter of contention. By introducing a single cysteine at various positions in Escherichia coli SecY and testing its ability to form a disulfide bond with a single cysteine in a translocating chain, we provide evidence that translocating polypeptides pass through the center of the SecY complex. The strongest cross-links were observed with residues that would form a constriction in an hourglass-shaped pore. This suggests that the channel makes only limited contact with a translocating polypeptide, thus minimizing the energy required for translocation. PMID:15851514

  7. Assessment of published literature pertaining to the uptake/accumulation, translocation, adhesion and biotransformation of organic chemicals by vascular plants

    SciTech Connect

    Nellessen, J.E.; Fletcher, J.S. (Univ., of Oklahoma, Norman, OK (United States). Dept. of Botany and Microbiology)

    1993-11-01

    Information in the UTAB data base was used to determine the general makeup of published data pertaining to how vascular plants influence organic chemicals in the environment. UTAB contains information on the uptake-accumulation, translocation, adhesion, and biotransformation of xenobiotic organic chemicals by vascular plants. The percentage distribution of data in UTAB among four important fate processes was 58, 16, 7, and 19 for uptake/accumulation, translocation, adhesion, and biotransformation, respectively. The tabulated data show the 30 most frequently reported chemicals, the 30 plants most often studied, and the frequency of examining plants maintained under different experimental conditions (contaminated site, controlled environments, etc.). Sixty-five percent of the 1,047 chemicals in the data base are pesticides, and data pertaining to these compounds account for 90% of the information in the data base. Crop species account for 33% of the plants and 77% of the data in UTAB. These summary values illustrate the imbalance of attention given to agrichemicals vs. industrial and municipal waste compounds, and emphasize the need for additional research addressing influence of plants on environmental pollutants with special attention given to industrial pollutants and native plants.

  8. HELMINTH PARASITES OF TRANSLOCATED RACCOONS (Procyon lotor) IN THE SOUTHEASTERN UNITED STATES n

    Microsoft Academic Search

    GARY D. SCHAFFER; WILLIAM R DAVIDSON; VICTOR F. NETTLES; A. ROLLOR

    Raccoons (Pnocyon lotor) typical of animals released by private hunting clubs in the Appalachian Mountains were examined for helminth parasites to evaluate the influence raccoon translocation might have on parasitic diseases. Results were compared with data from resident raccoons from characteristic release areas. Translocated raccoons harbored 19 helminth species that were exotic to resident animals. Most of these exotic parasites

  9. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia

    Microsoft Academic Search

    Scott A. Armstrong; Jane E. Staunton; Lewis B. Silverman; Rob Pieters; Monique L. den Boer; Mark D. Minden; Stephen E. Sallan; Eric S. Lander; Todd R. Golub; Stanley J. Korsmeyer

    2001-01-01

    Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly

  10. Effect of phenological development on radiophosphorus translocation from leaves in crested wheatgrass

    Microsoft Academic Search

    Ronald E. Sosebee; Herman H. Wiebe

    1973-01-01

    The effect of phenological development on the pattern of photosynthate translocation was studied in crested wheatgrass [Agropyron cristatum (L.) Gaertn.] plants grown in a nursery under semi-natural environmental conditions at Logan, Utah. Radiophosphorus was used to trace the photosynthate translocation from April 13, 1968, through December 2, 1968.

  11. Dynamics of initiation, termination and reinitiation of DNA translocation by the motor protein

    E-print Network

    Dekker, Nynke

    by amino-acid motifs typical for superfamily 2 helicases, although DNA unwinding is not observed. Using translocation. Termination of translocation occurs owing to dissociation of the motors from the core unit to deduce a complete kinetic reinitiation scheme. The dissociation/reassociation of mo- tors during

  12. Equine half sibs with an unbalanced X;15 translocation or trisomy 28

    Microsoft Academic Search

    M. M. Power

    1987-01-01

    Two unrelated chromosome abnormalities were found in equine half sibs. The proposita, Case 1, which was short in stature and infertile, had a de novo unbalanced X;15 translocation involving loss of Xp. Replication studies indicated that the translocated X was preferentially late replicating and that this late replication spread variably into the autosomal segment. Case 2, a half brother of

  13. Oxidative Bax dimerization promotes its translocation to mitochondria independently of apoptosis

    Microsoft Academic Search

    M. D'Alessio; M. De Nicola; S. Coppola; G. Gualandi; L. Pugliese; C. Cerella; S. Cristofanon; P. Civitareale; M. R. Ciriolo; A. Bergamaschi; A. Magrini; L. Ghibelli; Tor Vergata

    2005-01-01

    Bax is a cytosolic protein, which in response to stressing apoptotic stimuli, is activated and translocates to mitochondria, thus initiating the intrinsic apoptotic pathway. In spite of many studies and the importance of the issue, the molecular mechanisms that trigger Bax translocation are still obscure. We show by computer simulation that the two cysteine residues of Bax may form disulfide

  14. Translocation of the Eastern Bristlebird and factors associated with a successful program

    Microsoft Academic Search

    David Bain

    2006-01-01

    In the ongoing concern for the conservation of biodiversity around the globe, intensive, hands-on management of threatened species is becoming commonplace. The translocation of organisms to establish, re-establish or augment populations is one of the intensive strategies being used. This thesis explores the contemporary use of translocation in conservation, with a focus on the reintroduction of the Eastern Bristlebird (Dasyornis

  15. Fall fertilization enhanced nitrogen storage and translocation in Larix olgensis seedlings

    E-print Network

    loading of deciduous forest nursery seedlings is of special interest because of foliage abscission use efficiency Á Deciduous forest seedling Á Nitrogen storage Á Nutrient translocation Introduction and varied translocation patterns. For non-deciduous seed- lings in the nursery, fall fertilization typically

  16. Identification of reciprocal translocations observed in several Melilotus species (subgenus Eumelilotus) by interspecific triple crossings

    Microsoft Academic Search

    Masahiko Maekawa; Hasen; Fumiji Kita

    1991-01-01

    Melilotus alba differs by a reciprocal translocation from 7 other species which are categorized into M. officinalis and M. dentata groups. The two species groups, however, remained to be studied in relation to their cytological relations because of early degeneration of hybrid embryo. Interspecific triple crosses were successfully made in order to examine whether or not the reciprocal translocations observed

  17. Absence probable de la translocation robertsonienne 1/29 en race bovine

    E-print Network

    Paris-Sud XI, Université de

    Note Absence probable de la translocation robertsonienne 1/29 en race bovine Blanc Bleu Belge N voulu connaître sa fréquence en race bovine Blanc Bleu Belge, jusqu'alors non étudiée pour ce facteur. Au sein d'un échantillon de 138 taureaux de race Blanc Bleu Belge, la translocation 1/29 n'a pas pu

  18. A rupture detection algorithm for the DNA translocation detection though biological nanopore

    E-print Network

    Boyer, Edmond

    on a microfluidic 96 wells microarray. The signal treatment algorithm is capable to detect translocation events. Introduction In view of the DNA sequencing, we fabricated a biochip dedicated to the DNA translocation through proteins which can be used once assembled as natural nanopore. The bilayer is facing microfluidic channel

  19. Antigenicity of Fusion Proteins from Sarcoma-associated Chromosomal Translocations1

    Microsoft Academic Search

    B. Scott Worley; Leon T. van den Broeke; Theresa J. Goletz; C. David Pendleton; Emily M. Daschbach; Elaine K. Thomas; Francesco M. Marincola; Lee J. Helman; Jay A. Berzofsky

    2001-01-01

    Synovial sarcoma (SS), clear cell sarcoma (CCS), and desmoplastic small round cell tumor (DSRCT) are soft-tissue malignancies occurring primarily in adolescents and young adults. These tumors contain specific chromosomal translocations that fuse the 5 region of one gene with the 3 region of another, resulting in the formation of characteristic fusion proteins. These translocations are unique to tumor cells and

  20. Translocation as a tool for conservation of the Hawaiian monk seal

    Microsoft Academic Search

    J. D. Baker; B. L. Becker; T. A. Wurth; T. C. Johanos; C. L. Littnan; J. R. Henderson

    2011-01-01

    The deteriorating demographic status of the endangered Hawaiian monk seal has motivated renewed and expanded proposals for conservation action, including translocation of seals to improve survival. Over the past three decades, numerous monk seal translocations have been conducted with a variety of objectives, including mitigating shark predation and conspecific male aggression, reducing human–seal interactions, and taking advantage of favorable foraging

  1. Carboxybiotin Translocation Mechanisms Suggested by Diffraction Studies of Biotin and Its Vitamers

    Microsoft Academic Search

    George T. Detitta; R. Parthasarathy; Robert H. Blessing; William Stallings

    1980-01-01

    Biotin is a coenzyme that fixes CO2 for transfer in a family of carboxylase, decarboxylase, and transcarboxylase enzymes. Their enzyme reactions involve two basic steps during which a carboxybiotinyl intermediate forms at one site and translocates to a second (distinct) site for CO2 transfer. Our diffraction studies of biotin and its vitamers suggest that translocation involves rotation about one, or

  2. Analysis of X-ray-induced chromosomal translocations in human and marmoset spermatogonial stem cells

    Microsoft Academic Search

    J. Grant Brewen; R. Julian Preston

    1975-01-01

    ONE of the major classes of genetic damage produced by ionising radiations is heritable reciprocal translocation. In a series of earlier publications, Brewen and Preston1-3 demonstrated that each of several mammalian species had its own unique sensitivity to translocation induction in peripheral leukocytes and that human and marmoset leukocytes, although approximately equal in sensitivity, were twice as sensitive as mouse

  3. Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family

    PubMed Central

    Hasanzadeh-NazarAbadi, Mohammad; Baghbani, Fatemeh; Namazi, Iman; Mirzaee, Salmeh

    2014-01-01

    Background: Approximately 205 million pregnancies occur each year in the worldwide. On the other hand, Spontaneous abortion has been reported in 15-20% of all diagnosed pregnancies. The most common cause of spontaneous abortion is chromosomal abnormalities of the embryo. Robertsonian translocation carriers specially 21-14 are the most common balanced rearrangement among the carrier couples with the history of spontaneous abortion. In order to search for balanced chromosomal rearrangement and cytogenetic disorders, 10 members of related family with consanguinity marriage with the history of recurrent miscarriage were assessed. Case: Cytogenetic evaluation on the basis G-banding technique at high resolution was performed in 3 couples and their related family with the history of idiopathic RSA in order to postulate any balanced chromosomal rearrangement. Conclusion: six members of them appeared with robertsonian balanced translocation between chromosome No.21 to No. 14 with the karyotype of 45, XX, t (14, 21) and 45, XY, t (14, 21), which this results are in agreement with several similar works which claimed that the risk of spontaneous abortion in couples with balanced chromosomal rearrangements is higher compared with general population. Considering to results of present study, it seems as if the cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer wills valuable information for genetic consulting. PMID:25408709

  4. Stochastic gravitational wave background from exoplanets

    NASA Astrophysics Data System (ADS)

    Ain, Anirban; Kastha, Shilpa; Mitra, Sanjit

    2015-06-01

    Recent exoplanet surveys have predicted a very large population of planetary systems in our galaxy, more than one planet per star on the average, perhaps totaling about two hundred billion. These surveys, based on electromagnetic observations, are limited to a very small neighborhood of the solar system and the estimations rely on the observations of only a few thousand planets. On the other hand, orbital motions of planets around stars are expected to emit gravitational waves (GW), which could provide information about the planets not accessible to electromagnetic astronomy. The cumulative effect of the planets, with periods ranging from a few hours to several years, is expected to create a stochastic GW background (SGWB). We compute the characteristic GW strain of this background based on the observed distribution of planet parameters. We also show that the integrated extragalactic background is comparable to or less than the galactic background at different frequencies. Our estimate shows that the net background is significantly below the sensitivities of the proposed GW experiments in different frequency bands. However, we notice that the peak of the spectrum, at around 10-5 Hz , is not too far below the proposed space-based GW missions. A future space-based mission may be able to observe or tightly constrain this signal, which will possibly be the only way to probe the galactic population of exoplanets as a whole.

  5. Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy.

    PubMed

    Tian, Weili; Li, Wen; Chen, Yinqin; Yan, Zeming; Huang, Xia; Zhuang, Haixia; Zhong, Wangtao; Chen, Yusen; Wu, Wenxian; Lin, Chunxia; Chen, Hao; Hou, Xiaoyan; Zhang, Liangqing; Sui, Senfang; Zhao, Bin; Hu, Zhe; Li, Longxuan; Feng, Du

    2015-07-01

    UNC-51 like kinase (ULK1) translocates to dysfunctional mitochondria and is involved in mitophagy, but the mechanisms responsible for ULK1 activation and translocation remain unclear. Here, we found that hypoxia induces phosphorylation of ULK1 at Serine-555 by Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK). Unlike wild-type ULK1, an ULK1 (S555A) mutant cannot translocate to mitochondria in response to hypoxia. Inhibition or knockdown of AMPK prevents ULK1 translocation and inhibits mitophagy. Finally, the phospho-mimic ULK1 (S555D) mutant, but not ULK1 (S555A), rescues mitophagy in AMPK-knockdown cells. Thus, we conclude that AMPK-dependent phosphorylation of ULK1 is critical for translocation of ULK1 to mitochondria and for mitophagy in response to hypoxic stress. PMID:25980607

  6. Controlling the translocation of proteins through nanopores with bioinspired fluid walls

    PubMed Central

    Yusko, Erik C.; Johnson, Jay M.; Majd, Sheereen; Prangkio, Panchika; Rollings, Ryan C.; Li, Jiali; Yang, Jerry; Mayer, Michael

    2011-01-01

    Synthetic nanopores have been used to study individual biomolecules in high thoroughput but their performance as sensors does not match biological ion channels. Controlling the translocation times of single-molecule analytes and their non-specific interaction with pore walls remain a challenge. Inspired by the olfactory sensilla of the insect antenna, here we show that coating nanopores with fluid bilayer lipids allows the pore diameters to be fine-tuned in sub-nanometre increments. Incorporation of mobile ligands in the lipid conferred specificity and slowed down the translocation of targeted proteins sufficiently to time-resolve translocation events of individual proteins. The lipid coatings also prevented pores from clogging, eliminated non-specific binding and enabled the translocation of amyloid-beta (A?) oligomers and fibrils. Through combined analysis of translocation time, volume, charge, shape and ligand affinity, different proteins were identified. PMID:21336266

  7. Rotation of the head of the 30S ribosomal subunit during mRNA translocation.

    PubMed

    Guo, Zhuojun; Noller, Harry F

    2012-12-11

    Elongation factor-G-catalyzed translocation of mRNA and tRNAs during protein synthesis involves large-scale conformational changes in the ribosome. Formation of hybrid-state intermediates is coupled to counterclockwise (forward) rotation of the body of the 30S subunit. Recent structural studies implicate intrasubunit rotation of the 30S head in translocation. Here, we observe rotation of the head during translocation in real time using ensemble stopped-flow FRET with ribosomes containing fluorescent probes attached to specific positions in the head and body of the 30S subunit. Our results allow ordering of the rates of movement of the 30S subunit body and head during translocation: body forward > head forward > head reverse ? body reverse. The rate of quenching of pyrene-labeled mRNA is consistent with coupling of mRNA translocation to head rotation. PMID:23188795

  8. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection.

    PubMed

    Shan, Liang; Siliciano, Robert F

    2014-06-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  9. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

    PubMed Central

    Shan, Liang; Siliciano, Robert F.

    2014-01-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  10. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1989-01-01

    Recent observational and theoretical investigations of the cosmic microwave background radiation (CMBR) are reviewed. Particular attention is given to spectral distortions and CMBR temperature anisotropies at large, intermediate, and small angular scales. The implications of the observations for inflationary cosmological models with curvature fluctuation are explored, and it is shown that the limits determined for intermediate-scale CMBR anisotropy almost rule out a baryon-dominated cosmology.

  11. Quantum backgrounds and QFT

    E-print Network

    Jae-Suk Park; John Terilla; Thomas Tradler

    2009-09-21

    We introduce the concept of a quantum background and a functor QFT. In the case that the QFT moduli space is smooth formal, we construct a flat quantum superconnection on a bundle over QFT which defines algebraic structures relevant to correlation functions in quantum field theory. We go further and identify chain level generalizations of correlation functions which should be present in all quantum field theories.

  12. A Detailed Clinicopathologic Study of ALK-translocated Papillary Thyroid Carcinoma

    PubMed Central

    Chou, Angela; Fraser, Sheila; Toon, Christopher W.; Clarkson, Adele; Sioson, Loretta; Farzin, Mahtab; Cussigh, Carmen; Aniss, Ahmad; O’Neill, Christine; Watson, Nicole; Clifton-Bligh, Roderick J.; Learoyd, Diana L.; Robinson, Bruce G.; Selinger, Christina I.; Delbridge, Leigh W.; Sidhu, Stanley B.; O’Toole, Sandra A.; Sywak, Mark

    2015-01-01

    Pathogenic ALK translocations have been reported in papillary thyroid carcinoma (PTC). We developed and validated a screening algorithm based on immunohistochemistry (IHC), followed by fluorescence in situ hybridization (FISH) in IHC-positive cases to identify ALK-rearranged PTC. IHC and FISH were performed in a cohort of 259 thyroid carcinomas enriched for aggressive variants. IHC was positive in 8 cases, 6 confirmed translocated by FISH (specificity 75%). All 251 IHC-negative cases were FISH negative (sensitivity 100%). Having validated this approach, we performed screening IHC, followed by FISH in IHC-positive cases in an expanded cohort. ALK translocations were identified in 11 of 498 (2.2%) of all consecutive unselected PTCs and 3 of 23 (13%) patients with diffuse sclerosing variant PTCs. No ALK translocations were identified in 36 PTCs with distant metastases, 28 poorly differentiated (insular) carcinomas, and 20 anaplastic carcinomas. All 14 patients with ALK translocations were female (P=0.0425), and translocations occurred at a younger age (mean 38 vs. 48 y, P=0.0289 in unselected patients). ALK translocation was an early clonal event present in all neoplastic cells and mutually exclusive with BRAFV600E mutation. ALK translocation was not associated with aggressive clinicopathologic features (size, stage, metastasis, vascular invasion, extrathyroidal extension, multifocality, risk for recurrence, radioiodine resistance). We conclude that 2.2% of PTCs are ALK-translocated and can be identified by screening IHC followed by FISH. ALK translocations may be more common in young females and diffuse sclerosing variant PTC but do not connote more aggressive disease. PMID:25501013

  13. Studies of dicentric Robertsonian translocations provide evidence for a funcitonal centromeric hierarchy and structural heterogeneity

    SciTech Connect

    Sullivan, B.A. [Case Western Reserve Univ., Cleveland, OH (United States)]|[Univ. of Maryland, Baltimore, MD (United States); Schwartz, S. [Case Western Reserve Univ., Cleveland, OH (United States)

    1994-09-01

    To characterize the pericentromeric structure of Robertsonian translocations, we used dual color fluorescence in situ hybridization (FISH) to analyze centromeric activity and delineate breakpoints in 39 dicentric translocations. In the majority of translocations (36/39), one fluorescent {alpha}-satellite signal consistently lacked typical centromeric constriction. In the Robertsonian translocations involving chromosome 14, its centromere was almost always active (24/31); in contrast, the chromosome 15 centromere was rarely the active centromere (1/12). These data strongly support a hierarchy of centromeric activity in Robertsonian translocations. Furthermore, the preferential activity of a particular centromere is both meiotically stable and consistent within multiple tissues. Breakpoints in 22 dicentric translocations were localized using probes to two satellite III DNA subfamilies, chromosome 15-specific classical satellite, and {beta}-satellite DNA. The breaks in translocations involving chromosome 14 occurred within the more distal satellite III DNA array (6/10), while three of the four remaining chromosome 14 translocations demonstrated breakpoints in proximal satellite III DNA. Most chromosome 15 breakpoints occurred in classical satellite (satellite III) DNA. These results indicate that the structure of Robertsonian translocations is heterogeneous within repetitive DNA subfamilies, although satellite III DNA is the general site of chromosomal breakage and exchange. Immunofluorescence using CREST antibodies to CENPs A, B, and C has confirmed the FISH assignments of active centromeres in four translocations studied thus far. While {alpha}-satellite DNA has been implicated as a major component of functional centromeres, our data suggest that the selection of active and inactive centromeres of dicentric chromosomes may require additional centromeric elements or specific (i.e. breakpoint-dependent) structural chromosomal features.

  14. Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes

    PubMed Central

    Ou, Zhishuo; Stankiewicz, Pawe?; Xia, Zhilian; Breman, Amy M.; Dawson, Brian; Wiszniewska, Joanna; Szafranski, Przemyslaw; Cooper, M. Lance; Rao, Mitchell; Shao, Lina; South, Sarah T.; Coleman, Karlene; Fernhoff, Paul M.; Deray, Marcel J.; Rosengren, Sally; Roeder, Elizabeth R.; Enciso, Victoria B.; Chinault, A. Craig; Patel, Ankita; Kang, Sung-Hae L.; Shaw, Chad A.; Lupski, James R.; Cheung, Sau W.

    2011-01-01

    Four unrelated families with the same unbalanced translocation der(4)t(4;11)(p16.2;p15.4) were analyzed. Both of the breakpoint regions in 4p16.2 and 11p15.4 were narrowed to large ?359-kb and ?215-kb low-copy repeat (LCR) clusters, respectively, by aCGH and SNP array analyses. DNA sequencing enabled mapping the breakpoints of one translocation to 24 bp within interchromosomal paralogous LCRs of ?130 kb in length and 94.7% DNA sequence identity located in olfactory receptor gene clusters, indicating nonallelic homologous recombination (NAHR) as the mechanism for translocation formation. To investigate the potential involvement of interchromosomal LCRs in recurrent chromosomal translocation formation, we performed computational genome-wide analyses and identified 1143 interchromosomal LCR substrate pairs, >5 kb in size and sharing >94% sequence identity that can potentially mediate chromosomal translocations. Additional evidence for interchromosomal NAHR mediated translocation formation was provided by sequencing the breakpoints of another recurrent translocation, der(8)t(8;12)(p23.1;p13.31). The NAHR sites were mapped within 55 bp in ?7.8-kb paralogous subunits of 95.3% sequence identity located in the ?579-kb (chr 8) and ?287-kb (chr 12) LCR clusters. We demonstrate that NAHR mediates recurrent constitutional translocations t(4;11) and t(8;12) and potentially many other interchromosomal translocations throughout the human genome. Furthermore, we provide a computationally determined genome-wide “recurrent translocation map.” PMID:21205869

  15. Visual signal detection in structured backgrounds. II. Effects of contrast gain control, background variations, and white noise

    NASA Technical Reports Server (NTRS)

    Eckstein, M. P.; Ahumada, A. J. Jr; Watson, A. B.

    1997-01-01

    Studies of visual detection of a signal superimposed on one of two identical backgrounds show performance degradation when the background has high contrast and is similar in spatial frequency and/or orientation to the signal. To account for this finding, models include a contrast gain control mechanism that pools activity across spatial frequency, orientation and space to inhibit (divisively) the response of the receptor sensitive to the signal. In tasks in which the observer has to detect a known signal added to one of M different backgrounds grounds due to added visual noise, the main sources of degradation are the stochastic noise in the image and the suboptimal visual processing. We investigate how these two sources of degradation (contrast gain control and variations in the background) interact in a task in which the signal is embedded in one of M locations in a complex spatially varying background (structured background). We use backgrounds extracted from patient digital medical images. To isolate effects of the fixed deterministic background (the contrast gain control) from the effects of the background variations, we conduct detection experiments with three different background conditions: (1) uniform background, (2) a repeated sample of structured background, and (3) different samples of structured background. Results show that human visual detection degrades from the uniform background condition to the repeated background condition and degrades even further in the different backgrounds condition. These results suggest that both the contrast gain control mechanism and the background random variations degrade human performance in detection of a signal in a complex, spatially varying background. A filter model and added white noise are used to generate estimates of sampling efficiencies, an equivalent internal noise, an equivalent contrast-gain-control-induced noise, and an equivalent noise due to the variations in the structured background.

  16. In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia

    E-print Network

    California at Berkeley, University of

    NEOPLASIA In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia Greaves Recent reports have established the prena- tal origin of leukemia translocations and resultant leukemia (AML). The t(8;21) AML1- ETO translocations were sequenced at the genomic level in 10 diagnostic

  17. Autoradiographic studies on an X-autosomal translocation in man: 45, X,15–, tan(15qXq+)+

    Microsoft Academic Search

    W. Engel; W. Vogel; H. Reinwein

    1971-01-01

    In a female infant exhibiting cleft palate, hydrocephalus communicans, vitium cordis congenitum, and other anomalies, chromosome analysis revealed a C\\/D translocation. According to its replication pattern, the translocation chromosome comprised almost a whole X and the long arm of a chromosome 15. In accordance with the Lyon-hypothesis, in a number of the cells the translocated X, Xt, or the normal

  18. Retro-translocation of mitochondrial intermembrane space proteins

    PubMed Central

    Bragoszewski, Piotr; Wasilewski, Michal; Sakowska, Paulina; Gornicka, Agnieszka; Böttinger, Lena; Qiu, Jian; Wiedemann, Nils; Chacinska, Agnieszka

    2015-01-01

    The content of mitochondrial proteome is maintained through two highly dynamic processes, the influx of newly synthesized proteins from the cytosol and the protein degradation. Mitochondrial proteins are targeted to the intermembrane space by the mitochondrial intermembrane space assembly pathway that couples their import and oxidative folding. The folding trap was proposed to be a driving mechanism for the mitochondrial accumulation of these proteins. Whether the reverse movement of unfolded proteins to the cytosol occurs across the intact outer membrane is unknown. We found that reduced, conformationally destabilized proteins are released from mitochondria in a size-limited manner. We identified the general import pore protein Tom40 as an escape gate. We propose that the mitochondrial proteome is not only regulated by the import and degradation of proteins but also by their retro-translocation to the external cytosolic location. Thus, protein release is a mechanism that contributes to the mitochondrial proteome surveillance. PMID:26056291

  19. The changing landscape in translocator protein (TSPO) function.

    PubMed

    Selvaraj, Vimal; Stocco, Douglas M

    2015-07-01

    Translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is an outer mitochondrial membrane protein. TSPO has been shown to cooperate with steroidogenic acute regulatory protein (StAR) and function in the transport of cholesterol into mitochondria. TSPO has also been considered as a structural component of the mitochondrial permeability transition pore (MPTP). However, recent advances have changed these views of TSPO's functions and have prompted a re-evaluation of established concepts. This review summarizes the history of TSPO, key elements of the debate, and functional experiments that have changed our understanding. Moving forward, we examine how this fundamental change impacts our understanding of TSPO and affects the future of TSPO as a therapeutic and diagnostic target. PMID:25801473

  20. Mechanism of long-range proton translocation along biological membranes.

    PubMed

    Medvedev, Emile S; Stuchebrukhov, Alexei A

    2013-02-14

    Recent experiments suggest that protons can travel along biological membranes up to tens of micrometers, but the mechanism of transport is unknown. To explain such a long-range proton translocation we describe a model that takes into account the coupled bulk diffusion that accompanies the migration of protons on the surface. We show that protons diffusing at or near the surface before equilibrating with the bulk desorb and re-adsorb at the surface thousands of times, giving rise to a power-law desorption kinetics. As a result, the decay of the surface protons occurs very slowly, allowing for establishing local gradient and local exchange, as was envisioned in the early local models of biological energy transduction. PMID:23268201

  1. Structure and Activity of Tryptophan-rich TSPO Translocator Proteins

    PubMed Central

    Guo, Youzhong; Kalathur, Ravi C.; Liu, Qun; Kloss, Brian; Bruni, Renato; Ginter, Christopher; Kloppmann, Edda; Rost, Burkhard; Hendrickson, Wayne A.

    2015-01-01

    TSPO translocator proteins bind steroids and porphyrins, and they are implicated in many human diseases, for which they serve as biomarkers and therapeutic targets. TSPOs have tryptophan-rich sequences that are fhighly conserved from bacteria to mammals. We report crystal structures for Bacillus cereus TSPO (BcTSPO) down to 1.7Å resolution, including a complex with the benzodiazepine-like inhibitor PK11195. We also describe BcTSPO-mediated protoporphyrin IX (PpIX) reactions, including catalytic degradation to a previously undescribed heme derivative. We used structure-inspired mutations to investigate reaction mechanisms, and we showed that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress. PMID:25635100

  2. Nanoparticle translocation through a lipid bilayer tuned by surface chemistry.

    PubMed

    da Rocha, Edroaldo Lummertz; Caramori, Giovanni Finoto; Rambo, Carlos Renato

    2013-02-21

    An enhanced understanding about the interactions between nanomaterials and cell membranes may have important implications for biomedical applications. In this work, coarse-grained molecular dynamics simulations of gold nanoparticles interacting with lipid bilayers were performed to evaluate the effect of hydrophobicity, charge density and ligand length on lipid bilayers. The simulations accomplished indicate that hydrophobic and anionic nanoparticles do not exhibit significant interactions and different charge densities may induce pore formation or nanoparticle wrapping, resembling first stages of endocytosis. The suggested interplay between charge density and ligand length has important implications when designing nanoparticles for drug and gene delivery applications. Moreover, control of charge densities may induce internalization of nanoparticles into cells through different mechanisms such as passive translocation, for nanoparticles with low charge density, or endocytosis for higher charge densities, highlighting the role of surface chemistry in nanoparticle-cell interactions. PMID:23223270

  3. Complex Karyotype with Novel Translocation in Pure Erythroid Leukemia Patient

    PubMed Central

    Aljabry, Mansour

    2015-01-01

    Pure erythroid leukemia (PEL) is rare hematopoietic neoplasm characterized by uncontrolled proliferation of immature erythroid precursors – mainly abnormal proery-throblasts – comprising at least 80% of bone marrow cells. In this paper, I present a case of 48 years old patient, who presented with pancytopenia and circulating erythroblast in peripheral blood after long history of alcohol abuse. Bone marrow examination revealed hypercellular marrow which is markedly infiltrated with immature erythroid precursors. An expanded panel of immunophenotyping markers has confirmed the diagnosis of PEL. Cytogenetics analysis detected a complex karyotype with multiple chromosomal abnormalities and a novel translocation, t(8;9) (p11.2;q12), which has not been reported in acute myeloid leukemia (AML) in the past. The patient was treated with standard AML chemotherapy but he did not show an optimal response and passed away. An updated and short review about various aspects of PEL has been made with special focus on immunophenotyping and genetic studies. PMID:25852849

  4. Retro-translocation of mitochondrial intermembrane space proteins.

    PubMed

    Bragoszewski, Piotr; Wasilewski, Michal; Sakowska, Paulina; Gornicka, Agnieszka; Böttinger, Lena; Qiu, Jian; Wiedemann, Nils; Chacinska, Agnieszka

    2015-06-23

    The content of mitochondrial proteome is maintained through two highly dynamic processes, the influx of newly synthesized proteins from the cytosol and the protein degradation. Mitochondrial proteins are targeted to the intermembrane space by the mitochondrial intermembrane space assembly pathway that couples their import and oxidative folding. The folding trap was proposed to be a driving mechanism for the mitochondrial accumulation of these proteins. Whether the reverse movement of unfolded proteins to the cytosol occurs across the intact outer membrane is unknown. We found that reduced, conformationally destabilized proteins are released from mitochondria in a size-limited manner. We identified the general import pore protein Tom40 as an escape gate. We propose that the mitochondrial proteome is not only regulated by the import and degradation of proteins but also by their retro-translocation to the external cytosolic location. Thus, protein release is a mechanism that contributes to the mitochondrial proteome surveillance. PMID:26056291

  5. Heterologous protein production using the twin arginine translocation pathway

    DOEpatents

    Pohlschroder, Mechtild (Philadelphia, PA); Kissinger, Jessica C (Athens, GA); Rose, R. Wesley (Glenside, PA); Brueser, Thomas (Halle, DE); Dilks, Kieran (Collingswood, NJ)

    2008-11-04

    Provided are means for evaluating and identifying putative substrates of the twin arginine translocation (Tat) secretory pathway in Streptomyces and other bacterial species. Also provided, therefore, are simple ways to express, secrete and purify correctly folded heterologous proteins on a large scale using host microorganisms, such as, Streptomyces and the Tat pathway therein. Many of the thus-produced proteins are of significant therapeutic value in the pharmaceutical and biochemical industries, particularly when they can be secreted from the host in fully-folded active form. Accordingly, there are further provided the heterologous proteins produced by the Tat secretion pathway using the foregoing methods, and the computer algorithm used to identify the Tat signal sequence and putative substrates.

  6. Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis.

    PubMed

    Papadopoulos, Vassilios; Aghazadeh, Yasaman; Fan, Jinjiang; Campioli, Enrico; Zirkin, Barry; Midzak, Andrew

    2015-06-15

    Steroidogenesis begins with cholesterol transfer into mitochondria through the transduceosome, a complex composed of cytosolic proteins that include steroidogenesis acute regulatory protein (STAR), 14-3-3 adaptor proteins, and the outer mitochondrial membrane proteins Translocator Protein (TSPO) and Voltage-Dependent Anion Channel (VDAC). TSPO is a drug- and cholesterol-binding protein found at particularly high levels in steroid synthesizing cells. Its aberrant expression has been linked to cancer, neurodegeneration, neuropsychiatric disorders and primary hypogonadism. Brain steroids serve as local regulators of neural development and excitability. Reduced levels of these steroids have been linked to depression, anxiety and neurodegeneration. Reduced serum testosterone is common among subfertile young men and aging men, and is associated with depression, metabolic syndrome and reduced sexual function. Although testosterone-replacement therapy is available, there are undesired side-effects. TSPO drug ligands have been proposed as therapeutic agents to regulate steroid levels in the brain and testis. PMID:25818881

  7. DNA translocation through an array of kinked nanopores.

    PubMed

    Chen, Zhu; Jiang, Yingbing; Dunphy, Darren R; Adams, David P; Hodges, Carter; Liu, Nanguo; Zhang, Nan; Xomeritakis, George; Jin, Xiaozhong; Aluru, N R; Gaik, Steven J; Hillhouse, Hugh W; Brinker, C Jeffrey

    2010-08-01

    Synthetic solid-state nanopores are being intensively investigated as single-molecule sensors for detection and characterization of DNA, RNA and proteins. This field has been inspired by the exquisite selectivity and flux demonstrated by natural biological channels and the dream of emulating these behaviours in more robust synthetic materials that are more readily integrated into practical devices. So far, the guided etching of polymer films, focused ion-beam sculpting, and electron-beam lithography and tuning of silicon nitride membranes have emerged as three promising approaches to define synthetic solid-state pores with sub-nanometre resolution. These procedures have in common the formation of nominally cylindrical or conical pores aligned normal to the membrane surface. Here we report the formation of 'kinked' silica nanopores, using evaporation-induced self-assembly, and their further tuning and chemical derivatization using atomic-layer deposition. Compared with 'straight through' proteinaceous nanopores of comparable dimensions, kinked nanopores exhibit up to fivefold reduction in translocation velocity, which has been identified as one of the critical issues in DNA sequencing. Additionally, we demonstrate an efficient two-step approach to create a nanopore array exhibiting nearly perfect selectivity for ssDNA over dsDNA. We show that a coarse-grained drift-diffusion theory with a sawtooth-like potential can reasonably describe the velocity and translocation time of DNA through the pore. By control of pore size, length and shape, we capture the main functional behaviours of protein pores in our solid-state nanopore system. PMID:20651807

  8. Translocation of cell penetrating peptide engrafted nanoparticles across skin layers.

    PubMed

    Patlolla, Ram R; Desai, Pinaki R; Belay, Kalayu; Singh, Mandip S

    2010-07-01

    The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24h, fluorescence was observed upto a depth of 120 microm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 microm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers. PMID:20413152

  9. Bound cardiolipin is essential for cytochrome c oxidase proton translocation.

    PubMed

    Musatov, Andrej; Robinson, Neal C

    2014-10-01

    The proton pumping activity of bovine heart cytochrome c oxidase (CcO) is completely inhibited when all of the cardiolipin (CL) is removed from the enzyme to produce monomeric CcO containing only 11 subunits. Only dimeric enzyme containing all 13 subunits and 2-4 cardiolipin per CcO monomer exhibits a "normal" proton translocating stoichiometry of ?1.0 H(+) per/e(-) when reconstituted into phospholipid vesicles. These fully active proteoliposomes have high respiratory control ratios (RCR = 7-15) with 75-85% of the CcO oriented with the cytochrome c binding sites exposed to the external medium. In contrast, reconstitution of CL-free CcO results in low respiratory control ratios (RCR < 5) with the enzyme randomly oriented in the vesicles, i.e., ?50 percent oriented with the cytochrome c binding site exposed on the outside of the vesicle. Addition of exogenous CL to the CL-free enzyme completely restores electron transport activity, but restoration of proton pumping activity does not occur. This is true whether CL is added to CL-free CcO prior to reconstitution into phospholipid vesicles, or whether CL is included in the phospholipid mixture that is used to form the vesicles. Another consequence of CL removal is the inability of the 11-subunit, CL-free enzyme to dimerize upon exposure to either cholate or the cholate/PC/PE/CL mixture used during proteoliposome formation (monomeric, 13-subunit, CL-containing CcO completely dimerizes under these conditions). Therefore, a major difference between reconstitution of CL-free and CL-containing CcO is the incorporation of monomeric, rather than dimeric CcO into the vesicles. We conclude that bound CL is necessary for proper insertion of CcO into phospholipid vesicles and normal proton translocation. PMID:25038566

  10. Markers of immunity and bacterial translocation in cirrhosis.

    PubMed

    Mortensen, Christian

    2015-07-01

    Bacterial translocation (BT), the migration of enteric bacteria to extraintestinal sites, is related to immune stimulation and haemodynamic changes in experimental cirrhosis. These changes may be highly relevant to patients with cirrhosis, where changes in the circulation cause serious complications. The optimal surrogate marker of BT in patients with cirrhosis, however, is a matter of controversy. In the first study, we investigated the relationship between markers of inflammation, haemodynamics and prognosis in 45 patients and 12 controls. We found high-sensitive C-reactive protein to be correlated to portal hypertension, a clinically relevant haemodynamic alteration, and appeared to be associated with increased mortality. To assess the consequences of BT on immunity, we developed an assay for the detection of bacterial DNA (bDNA), a novel marker of BT. Using the assay in the second study, in 38 patients with ascites, we found no association between bDNA and immunity, in contrast to some previous findings. In the final paper, exploring one possible translocation route, we hypothesized a difference in bDNA levels between the blood from the veins draining the gut on one hand and the liver on the other. Collecting samples during the insertion of a shunt between the two vessels in 28 patients, our finding did not suggest marked differences in bDNA, but conversely to expectations, suggested marked hepatic production of two markers of inflammation. The main results of the present thesis support some concepts of current thinking on cirrhosis pathophysiology, including the relationship of markers of inflammation to  haemodynamics, disease stage and prognosis. Our results also add to a growing body of evidence suggesting that bDNA is not a clinically relevant marker of BT. PMID:26183053

  11. Biosynthesis and Translocation of Unsulfated Acyltrehaloses in Mycobacterium tuberculosis*

    PubMed Central

    Belardinelli, Juan Manuel; Larrouy-Maumus, Gérald; Jones, Victoria; Sorio de Carvalho, Luiz Pedro; McNeil, Michael R.; Jackson, Mary

    2014-01-01

    A number of species-specific polymethyl-branched fatty acid-containing trehalose esters populate the outer membrane of Mycobacterium tuberculosis. Among them, 2,3-diacyltrehaloses (DAT) and penta-acyltrehaloses (PAT) not only play a structural role in the cell envelope but also contribute to the ability of M. tuberculosis to multiply and persist in the infected host, promoting the intracellular survival of the bacterium and modulating host immune responses. The nature of the machinery, topology, and sequential order of the reactions leading to the biosynthesis, assembly, and export of these complex glycolipids to the cell surface are the object of the present study. Our genetic and biochemical evidence corroborates a model wherein the biosynthesis and translocation of DAT and PAT to the periplasmic space are coupled and topologically split across the plasma membrane. The formation of DAT occurs on the cytosolic face of the plasma membrane through the action of PapA3, FadD21, and Pks3/4; that of PAT occurs on the periplasmic face via transesterification reactions between DAT substrates catalyzed by the acyltransferase Chp2 (Rv1184c). The integral membrane transporter MmpL10 is essential for DAT to reach the cell surface, and its presence in the membrane is required for Chp2 to be active. Disruption of mmpL10 or chp2 leads to an important build-up of DAT inside the cells and to the formation of a novel form of unsulfated acyltrehalose esterified with polymethyl-branched fatty acids normally found in sulfolipids that is translocated to the cell surface. PMID:25124040

  12. Biosynthesis and translocation of unsulfated acyltrehaloses in Mycobacterium tuberculosis.

    PubMed

    Belardinelli, Juan Manuel; Larrouy-Maumus, Gérald; Jones, Victoria; Sorio de Carvalho, Luiz Pedro; McNeil, Michael R; Jackson, Mary

    2014-10-01

    A number of species-specific polymethyl-branched fatty acid-containing trehalose esters populate the outer membrane of Mycobacterium tuberculosis. Among them, 2,3-diacyltrehaloses (DAT) and penta-acyltrehaloses (PAT) not only play a structural role in the cell envelope but also contribute to the ability of M. tuberculosis to multiply and persist in the infected host, promoting the intracellular survival of the bacterium and modulating host immune responses. The nature of the machinery, topology, and sequential order of the reactions leading to the biosynthesis, assembly, and export of these complex glycolipids to the cell surface are the object of the present study. Our genetic and biochemical evidence corroborates a model wherein the biosynthesis and translocation of DAT and PAT to the periplasmic space are coupled and topologically split across the plasma membrane. The formation of DAT occurs on the cytosolic face of the plasma membrane through the action of PapA3, FadD21, and Pks3/4; that of PAT occurs on the periplasmic face via transesterification reactions between DAT substrates catalyzed by the acyltransferase Chp2 (Rv1184c). The integral membrane transporter MmpL10 is essential for DAT to reach the cell surface, and its presence in the membrane is required for Chp2 to be active. Disruption of mmpL10 or chp2 leads to an important build-up of DAT inside the cells and to the formation of a novel form of unsulfated acyltrehalose esterified with polymethyl-branched fatty acids normally found in sulfolipids that is translocated to the cell surface. PMID:25124040

  13. Stochastic background from inspiralling double neutron stars

    E-print Network

    Tania Regimbau

    2006-12-30

    We review the contribution of extra galactic inspiralling double neutron stars, to the LISA astrophysical gravitational wave foreground. Using recent fits of the star formation rate, we show that sources beyond $z_*=0.005$ contribute to a truly continuous background, which may dominate the LISA instrumental noise in the range $3 \\simeq 10^{-4}$ - $1 \\times 10^{-2}$ Hz and overwhelm the galactic WD-WD confusion noise at frequencies larger than $\

  14. Recombination suppression in the vicinity of the breakpoints of a balanced 1:11 autosomal translocation associated with schizophrenia and other forms of major mental illness

    SciTech Connect

    He, L.; Blackwood, D.H.R.; Maclean, A.W. [MRC Human Genetics Unit, Edinburgh (United Kingdom)] [and others

    1994-09-01

    The frequency and extent of pairing failure around human translocations is unknown. We have examined the pattern of recombination around the breakpoints of a balanced autosomal translocation t(1:11)(q43:q21) associated with major mental illness. We have postulated that the association with mental illness in the family has not arisen by chance, but rather that functional disruption of a gene at or near a breakpoint site is responsible. Efforts to isolate the breakpoints for molecular analysis of the region are now at an advanced stage. On the other hand if pairing failure is occurring in the family in the region of the breakpoints, a susceptibility allele for mental illness, acting independently of the translocation, may be located some distance away. DNA was available from seventeen carriers and ten non-translocation carriers, giving a total of thirty-one informative meioses spanning 4 generations. The derivative one and eleven chromosomes were also isolated in somatic cell hybrids and were used to confirm allele phase. We genotyped the pedigree members using nine markers covering 30 cMs on either side of both the chromosome one and eleven breakpoints. No recombinants were found with markers within 3 cMs of either breakpoint. Four markers at an average of 7 cMs respectively on either side of the two breakpoints gave a total of three crossovers from thirty-one meioses versus an expected 9, demonstrating (p<0.05) significant recombination suppression. By contrast, examination of chromosome regions at greater distances from the breakpoints showed recombination rates similar to those expected from CEPH data with no evidence of suppression. We conclude that crossover suppression occurs in this family but is restricted to a region within 7 cMs of the breakpoints.

  15. Cosmic microwave?background?theory

    PubMed Central

    Bond, J. Richard

    1998-01-01

    A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in ?-space are consistent with a ?T flat in frequency and broadly follow inflation-based expectations. That the levels are ?(10?5)2 provides strong support for the gravitational instability theory, while the Far Infrared Absolute Spectrophotometer (FIRAS) constraints on energy injection rule out cosmic explosions as a dominant source of LSS. Band-powers at ? ? 100 suggest that the universe could not have re-ionized too early. To get the LSS of Cosmic Background Explorer (COBE)-normalized fluctuations right provides encouraging support that the initial fluctuation spectrum was not far off the scale invariant form that inflation models prefer: e.g., for tilted ? cold dark matter sequences of fixed 13-Gyr age (with the Hubble constant H0 marginalized), ns = 1.17 ± 0.3 for Differential Microwave Radiometer (DMR) only; 1.15 ± 0.08 for DMR plus the SK95 experiment; 1.00 ± 0.04 for DMR plus all smaller angle experiments; 1.00 ± 0.05 when LSS constraints are included as well. The CMB alone currently gives weak constraints on ? and moderate constraints on ?tot, but theoretical forecasts of future long duration balloon and satellite experiments are shown which predict percent-level accuracy among a large fraction of the 10+ parameters characterizing the cosmic structure formation theory, at least if it is an inflation variant. PMID:9419321

  16. Gravitational Wave Background from Population III Stars

    E-print Network

    Yudai Suwa; Tomoya Takiwaki; Kei Kotake; Katsuhiko Sato

    2007-06-24

    We estimate the gravitational wave (GW) background from Population III (Pop III) stars using the results from our hydrodynamic simulations (Suwa et al. 2007). We calculate gravitational waveforms from matter motions and anisotropic neutrino emissions for single Pop III stars. We find that the GW amplitudes from matter motions are dominant until just after bounce, but those from neutrinos dominate later on at frequencies below $\\sim 10$ Hz in the GW spectrum. Computing the overall signal produced by the ensemble of such Pop III stars, we find that the resultant density parameter of the GW background peaks at the amplitude of $\\Omega_\\mathrm{GW}\\sim 10^{-10}$ in the frequency interval $\\sim 1-10$ Hz. We show that such signals, depending on the formation rate of Pop III stars, can be within the detection limits of future planned interferometers such as DECIGO and BBO in the frequency interval of $\\sim 0.1-1$ Hz. Our results suggest that the detection of the GW background from Pop III stars can be an important tool to supply the information about the star formation history in the early universe.

  17. The Backgrounds Data Center

    NASA Technical Reports Server (NTRS)

    Snyder, W. A.; Gursky, H.; Heckathorn, H. M.; Lucke, R. L.; Berg, S. L.; Dombrowski, E. G.; Kessel, R. A.

    1993-01-01

    The Strategic Defense Initiative Organization has created data centers for midcourse, plumes, and backgrounds phenomenologies. The Backgrounds Data Center (BDC) has been designated as the prime archive for data collected by SDIO programs. The BDC maintains a Summary Catalog that contains 'metadata,' that is, information about data, such as when the data were obtained, what the spectral range of the data is, and what region of the Earth or sky was observed. Queries to this catalog result in a listing of all data sets (from all experiments in the Summary Catalog) that satisfy the specified criteria. Thus, the user can identify different experiments that made similar observations and order them from the BDC for analysis. On-site users can use the Science Analysis Facility (SAFE for this purpose. For some programs, the BDC maintains a Program Catalog, which can classify data in as many ways as desired (rather than just by position, time, and spectral range as in the Summary Catalog). For example, data sets could be tagged with such diverse parameters as solar illumination angle, signal level, or the value of a particular spectral ratio, as long as these quantities can be read from the digital record or calculated from it by the ingest program. All unclassified catalogs and unclassified data will be remotely accessible.

  18. Effects of nanoparticle charge and shape anisotropy on translocation through cell membranes.

    PubMed

    Nangia, Shikha; Sureshkumar, Radhakrishna

    2012-12-21

    Nanotoxicity is becoming a major concern as the use of nanoparticles in imaging, therapeutics, diagnostics, catalysis, sensing, and energy harvesting continues to grow dramatically. The tunable functionalities of the nanoparticles offer unique chemical interactions in the translocation process through cell membranes. The overall translocation rate of the nanoparticle can vary immensely on the basis of the charge of the surface functionalization along with shape and size. Using advanced molecular dynamics simulation techniques, we compute translocation rate constants of functionalized cone-, cube-, rod-, rice-, pyramid-, and sphere-shaped nanoparticles through lipid membranes. The computed results indicate that depending on the nanoparticle shape and surface functionalization charge, the translocation rates can span 60 orders of magnitude. Unlike isotropic nanoparticles, positively charged, faceted, rice-shaped nanoparticles undergo electrostatics-driven reorientation in the vicinity of the membrane to maximize their contact area and translocate instantaneously, disrupting lipid self-assembly and thereby causing significant membrane damage. In contrast, negatively charged nanoparticles are electrostatically repelled from the cell membrane and are less likely to translocate. Differences in translocation rates among various shapes may have implications on the structural evolution of pathogens from spherical to rodlike morphologies for enhanced efficacy. PMID:23088323

  19. Detergent disruption of bacterial inner membranes and recovery of protein translocation activity

    SciTech Connect

    Cunningham, K.; Wickner, W.T. (Univ. of California, Los Angeles (USA))

    1989-11-01

    Isolation of the integral membrane components of protein translocation requires methods for fractionation and functional reconstitution. The authors treated inner-membrane vesicles of Escherichia coli with mixtures of octyl {beta}-D-glucoside, phospholipids, and an integral membrane carrier protein under conditions that extract most of the membrane proteins into micellar solution. Upon dialysis, proteoliposomes were reconstituted that supported translocation of radiochemically pure ({sup 35}S)pro-OmpA (the precursor of outer membrane protein A). Translocation into these proteoliposomes required ATP hydrolysis and membrane proteins, indicating that the reaction is that of the inner membrane. The suspension of membranes in detergent was separated into supernatant and pellet fractions by ultracentrifugation. After reconstitution, translocation activity was observed in both fractions, but processing by leader peptidase of translocated pro-OmpA to OmpA was not detectable in the reconstituted pellet fraction. Processing activity was restored by addition of pure leader peptidase as long as this enzyme was added before detergent removal, indicating that the translocation activity is not associated with detergent-resistant membrane vesicles. These results show that protein translocation activity can be recovered from detergent-disrupted membrane vesicles, providing a first step towards the goal of isolating the solubilized components.

  20. Mechanism of Cationic Nanoparticles and Cell-Penetrating Peptides Direct Translocate Across Cell Membranes

    NASA Astrophysics Data System (ADS)

    Lin, Jiaqi; Alexander-Katz, Alfredo

    2014-03-01

    Cationic Nanoparticles (NPs) and cell-penetrating peptides (CPPs) are known effective intracellular delivery agents. These positively charged particles can bypass traditional endocytosis route to enter the cytosol, which is known as direct translocation. However, mechanism of direct translocation of both NPs and CPPs is not well understood. Using Coarse-grained (CG) molecular dynamics simulation, we found that gold nanoparticles (AuNPs) as well as HIV-1 Tat peptides can translocate across model biological membranes through nanoscale holes under a transmembrane (TM) potential. After the translocation, the TM is strongly weakened and the holes gradually reseal themselves, while the NPs/CPPs roam freely in the ``intracellular region.'' Both size and shape of the NPs/ CPPs are found to be a determine factor of their translocation behaviour, and the relationship between direct translocation and endocytosis is also discussed. The results provided here establish fundamental rules of direct translocation entry of NPs/CPPs, which may guide the rational design of cationic intracellular nanocarriers.

  1. The E Block motif is associated with Legionella pneumophila translocated substrates

    PubMed Central

    Huang, Li; Boyd, Dana; Amyot, Whitney M; Hempstead, Andrew D; Luo, Zhao-Qing; O'Connor, Tamara J; Chen, Cui; Machner, Matthias; Montminy, Timothy; Isberg, Ralph R

    2011-01-01

    Summary Legionella pneumophila promotes intracellular growth by moving bacterial proteins across membranes via the Icm/Dot system. A strategy was devised to identify large numbers of Icm/Dot translocated proteins, and the resulting pool was used to identify common motifs that operate as recognition signals. The 3? end of the sidC gene, which encodes a known translocated substrate, was replaced with DNA encoding 200 codons from the 3? end of 442 potential substrate-encoding genes. The resulting hybrid proteins were then tested in a high throughput assay, in which translocated SidC antigen was detected by indirect immunofluorescence. Among translocated substrates, regions of 6–8 residues called E Blocks were identified that were rich in glutamates. Analysis of SidM/DrrA revealed that loss of three Glu residues, arrayed in a triangle on an ?-helical surface, totally eliminated translocation of a reporter protein. Based on this result, a second strategy was employed to identify Icm/Dot substrates having carboxyl terminal glutamates. From the fusion assay and the bioinformatic queries, carboxyl terminal sequences from 49 previously unidentified proteins were shown to promote translocation into target cells. These studies indicate that by analysing subsets of translocated substrates, patterns can be found that allow predictions of important motifs recognized by Icm/Dot. PMID:20880356

  2. Translocation to a fragmented landscape: survival, movement, and site fidelity of Northern Bobwhites.

    PubMed

    Terhune, Theron M; Sisson, D Clay; Palmer, William E; Faircloth, Brant C; Stribling, H Lee; Carroll, John P

    2010-06-01

    Habitat fragmentation, degradation, and loss have taxed early-successional species including the Northern Bobwhite (Colinus virginianus) and numerous grassland obligate birds. Translocation is often applied to counteract the consequences of habitat fragmentation through the creation, reestablishment, or augmentation of wild populations for the purposes of conservation, biodiversity maintenance. However, the implementation of these techniques is often conducted without valid experimental designs and therefore lacks robust, empirical data needed to evaluate and advance the knowledge and application of translocation. Despite the increasing amount of habitat management applied to patches among fragmented landscapes, a paucity of source populations often limits natural (re)colonization. As such, translocation may serve as a surrogate to natural dispersal, but its efficacy among fragmented landscapes is uncertain. Few studies exist that have assessed site fidelity, movement, and survival of individuals following translocation among fragmented landscapes. Thus, we experimentally evaluated the efficacy of translocation using known-fate and multi-strata models to evaluate hypotheses of temporal, biological, and group effects on survival and movement of translocated and resident bobwhites. We did not detect differences in survival or movement between translocated and resident bobwhites, suggesting that movement of individuals to a fragmented habitat does not negatively influence these demographic attributes. Based on these data, we suggest that two site-specific criteria should be met prior to instituting translocation: habitat management should be conducted to ensure that quality habitat exists and the patch size should be a minimum of 600 ha of quality habitat (poorer sites may warrant even larger patches). Translocation is a viable conservation method for increasing abundance in patches when habitat quality is high but source populations are limited. PMID:20597288

  3. Differential Control of Presynaptic CamKII Activation and Translocation to Active Zones

    PubMed Central

    Shakiryanova, Dinara; Morimoto, Takako; Zhou, Chaoming; Chouhan, Amit K.; Sigrist, Stephan J.; Nose, Akinao; Macleod, Gregory T.; Deitcher, David L.; Levitan, Edwin S.

    2011-01-01

    The release of neurotransmitters, neurotrophins and neuropeptides is modulated by Ca2+ mobilization from the endoplasmic reticulum (ER) and activation of Ca2+/calmodulin-dependent protein kinase II (CamKII). Furthermore, when neuronal cultures are subjected to prolonged depolarization, presynaptic CamKII redistributes from the cytoplasm to accumulate near active zones (AZs), a process that is reminiscent of CamKII translocation to the postsynaptic side of the synapse. However, it is not known how presynaptic CamKII activation and translocation depend on neuronal activity and ER Ca2+ release. Here these issues are addressed in Drosophila motoneuron terminals by imaging a fluorescent reporter of CamKII activity and subcellular distribution. We report that neuronal excitation acts with ER Ca2+ stores to induce CamKII activation and translocation to a subset of AZs. Surprisingly, activation is slow reflecting T286 autophosphorylation and the function of presynaptic ER ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs). Furthermore, translocation is not simply proportional to CamKII activity, as T286 autophosphorylation promotes activation, but does not affect translocation. In contrast, RNAi-induced knockdown of the AZ scaffold protein Bruchpilot (BRP) disrupts CamKII translocation without affecting activation. Finally, RyRs comparably stimulate both activation and translocation, but IP3Rs preferentially promote translocation. Thus, Ca2+ provided by different presynaptic ER Ca2+ release channels is not equivalent. These results suggest that presynaptic CaMKII activation depends on autophosphorylation and global Ca2+ in the terminal, while translocation to AZs requires Ca2+ microdomains generated by IP3Rs. PMID:21697360

  4. TMED6-COG8 is a novel molecular marker of TFE3 translocation renal cell carcinoma

    PubMed Central

    Xu, Yongcan; Rao, Qiu; Xia, Qiuyuan; Shi, Shanshan; Shi, Qunli; Ma, Henghui; Lu, Zhenfeng; Chen, Hui; Zhou, Xiaojun

    2015-01-01

    TFE3 translocation renal cell carcinoma is a highly aggressive malignancy which often occurs primarily in children and young adults. The pathognomonic molecular lesion in this subtype is a translocation event involving the TFE3 transcription factor at chromosome Xp11.2. Hence, the pathological diagnosis of an Xp11.2 translocation RCC is based upon morphology, TFE3 immunohistochemistry, or genetic analyses. However, due to the false-positive immunoreactivity for TFE3 IHC and expensive for TFE3 break-apart FISH assay, additional molecular markers are necessary to help provide early diagnose and individualization treatment. Owing to recent advances in microarray and RNA-Seq, Pflueger et al. have discovered that TMED6-COG8 is dramatically increased in TFE3 translocation RCCs, compared with clear cell RCCs and papillary RCCs, implying that TMED6-COG8 might be a new molecular tumor marker of TFE3 translocation RCCs. To extend this observation, we firstly validated the TMED6-COG8 expression level by qRT-PCR in RCCs including Xp11.2 translocation RCCs (n = 5), clear cell RCCs (n = 7) and papillary RCCs (n = 5). Then, we also examined the expression level of TMED6-COG8 chimera in Xp11.2 translocation alveolar soft part sarcoma. We found that TMED6-COG8 chimera expression level was higher in Xp11.2 translocation RCCs than in ASPS (P < 0.05). What’s more, the expression levels of TMED6-COG8 chimera in esophagus cancers (n = 32), gastric cancers (n = 11), colorectal cancers (n = 12), hepatocellular carcinomas (n = 10) and non-small-cell lung cancers (n = 12) were assessed. Unexpectedly, TMED6-COG8 chimera was decreased in these five human types. Therefore, our observations from this study indicated that TMED6-COG8 chimera might act as a novel diagnostic marker in Xp11.2 translocation RCCs. PMID:26045774

  5. A voltage-gated pore for translocation of tRNA

    SciTech Connect

    Koley, Sandip; Adhya, Samit, E-mail: nilugrandson@gmail.com

    2013-09-13

    Highlights: •A tRNA translocating complex was assembled from purified proteins. •The complex translocates tRNA at a membrane potential of ?60 mV. •Translocation requires Cys and His residues in the Fe–S center of RIC6 subunit. -- Abstract: Very little is known about how nucleic acids are translocated across membranes. The multi-subunit RNA Import Complex (RIC) from mitochondria of the kinetoplastid protozoon Leishmania tropica induces translocation of tRNAs across artificial or natural membranes, but the nature of the translocation pore remains unknown. We show that subunits RIC6 and RIC9 assemble on the membrane in presence of subunit RIC4A to form complex R3. Atomic Force Microscopy of R3 revealed particles with an asymmetric surface groove of ?20 nm rim diameter and ?1 nm depth. R3 induced translocation of tRNA into liposomes when the pH of the medium was lowered to ?6 in the absence of ATP. R3-mediated tRNA translocation could also be induced at neutral pH by a K{sup +} diffusion potential with an optimum of 60–70 mV. Point mutations in the Cys{sub 2}–His{sub 2} Fe-binding motif of RIC6, which is homologous to the respiratory Complex III Fe–S protein, abrogated import induced by low pH but not by K{sup +} diffusion potential. These results indicate that the R3 complex forms a pore that is gated by a proton-generated membrane potential and that the Fe–S binding region of RIC6 has a role in proton translocation. The tRNA import complex of L. tropica thus contains a novel macromolecular channel distinct from the mitochondrial protein import pore that is apparently involved in tRNA import in some species.

  6. Secretory protein translocation in a yeast cell-free system can occur posttranslationally and requires ATP hydrolysis

    PubMed Central

    1986-01-01

    We describe an in vitro system with all components derived from the yeast Saccharomyces cerevisiae that can translocate a yeast secretory protein across microsomal membranes. In vitro transcribed prepro-alpha- factor mRNA served to program a membrane-depleted yeast translation system. Translocation and core glycosylation of prepro-alpha-factor were observed when yeast microsomal membranes were added during or after translation. A membrane potential is not required for translocation. However, ATP is required for translocation and nonhydrolyzable analogues of ATP cannot serve as a substitute. These findings suggest that ATP hydrolysis may supply the energy required for translocation of proteins across the endoplasmic reticulum. PMID:3517001

  7. Amiloride inhibition of the proton-translocating NADH-quinone oxidoreductase of mammals and bacteria.

    PubMed

    Nakamaru-Ogiso, Eiko; Seo, Byoung Boo; Yagi, Takao; Matsuno-Yagi, Akemi

    2003-08-14

    The proton-translocating NADH-quinone oxidoreductase in mitochondria (complex I) and bacteria (NDH-1) was shown to be inhibited by amiloride derivatives that are known as specific inhibitors for Na(+)/H(+) exchangers. In bovine submitochondrial particles, the effective concentrations were about the same as those for the Na(+)/H(+) exchangers, whereas in bacterial membranes the inhibitory potencies were lower. These results together with our earlier observation that the amiloride analogues prevent labeling of the ND5 subunit of complex I with a fenpyroximate analogue suggest the involvement of ND5 in H(+) (Na(+)) translocation and no direct involvement of electron carriers in H(+) (Na(+)) translocation. PMID:12914922

  8. Light-Dependent Translocation of Arrestin in Rod Photoreceptors is Signaled Through a Phospholipase C Cascade and Requires ATP

    PubMed Central

    Orisme, Wilda; Li, Jian; Goldmann, Tobias; Bolch, Susan; Wolfrum, Uwe; Smith, W. Clay

    2009-01-01

    Partitioning of cellular components is a critical mechanism by which cells can regulate their activity. In rod photoreceptors, light induces a large-scale translocation of arrestin from the inner segments to the outer segments. The purpose of this project is to elucidate the signaling pathway necessary to initiate arrestin translocation to the outer segments and the mechanism for arrestin translocation. Mouse retinal organotypic cultures and eyes from transgenic Xenopus tadpoles expressing a fusion of GFP and rod arrestin were treated with both activators and inhibitors of proteins in the phosphoinositide pathway. Confocal microscopy was used to image the effects of the pharmacological agents on arrestin translocation in rod photoreceptors. Retinas were also depleted of ATP using potassium cyanide to assess the requirement for ATP in arrestin translocation. In this study, we demonstrate that components of the G-protein-linked phospholipase C (PLC) pathway play a role in initiating arrestin translocation. Our results show that arrestin translocation can be stimulated by activators of PLC and protein kinase C (PKC), and by cholera toxin in the absence of light. Arrestin translocation to the outer segments is significantly reduced by inhibitors of PLC and PKC. Importantly, we find that treatment with potassium cyanide inhibits arrestin translocation in response to light. Collectively, our results suggest that arrestin translocation is initiated by a G-protein-coupled cascade through PLC and PKC signaling. Furthermore, our results demonstrate that at least the initiation of arrestin translocation requires energy input. PMID:19887106

  9. SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

    SciTech Connect

    Joo, Hyun-Yoo [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of) [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Woo, Seon Rang; Shen, Yan-Nan; Yun, Mi Yong; Shin, Hyun-Jin; Park, Eun-Ran; Kim, Su-Hyeon; Park, Jeong-Eun; Ju, Yeun-Jin; Hong, Sung Hee; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)] [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of)] [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Joon, E-mail: joonkim@korea.ac.kr [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)] [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)] [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer SIRT1 serves to retain GAPDH in the cytosol, preventing GAPDH nuclear translocation. Black-Right-Pointing-Pointer When SIRT1 is depleted, GAPDH translocation occurs even in the absence of stress. Black-Right-Pointing-Pointer Upon irradiation, SIRT1 interacts with GAPDH. Black-Right-Pointing-Pointer SIRT1 prevents irradiation-induced nuclear translocation of GAPDH. Black-Right-Pointing-Pointer SIRT1 presence rather than activity is essential for inhibiting GAPDH translocation. -- Abstract: Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggered nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation.

  10. Background sources in optical communications

    NASA Technical Reports Server (NTRS)

    Vilnrotter, V. A.

    1983-01-01

    The characterization and measurement of background radiation relevant to optical communications system performance is addressed. The necessary optical receiver parameters are described, and radiometric concepts required for the calculation of collected background power are developed. The most important components of optical background power are discussed, and their contribution to the total collected background power in various communications scenarios is examined.

  11. The Planck Low Frequency Instrument

    E-print Network

    N. Mandolesi; M. Bersanelli; C. Burigana; F. Villa; on behalf of LFI Consortium

    1999-04-12

    The Low Frequency Instrument (LFI) of the "Planck Surveyor" ESA mission will perform high-resolution imaging of the Cosmic Microwave Background anisotropies at four frequencies in the 30-100 GHz range. We review the LFI main scientific objectives, the current status of the instrument design and the on-going effort to develop software simulations of the LFI observations. In particular we discuss the design status of the PLANCK telescope, which is critical for reaching adequate effective angular resolution.

  12. Discriminability measures for predicting readability of text on textured backgrounds

    NASA Technical Reports Server (NTRS)

    Scharff, L. F.; Hill, A. L.; Ahumada, A. J. Jr; Watson, A. B. (Principal Investigator)

    2000-01-01

    Several discriminability measures were examined for their ability to predict reading search times for three levels of text contrast and a range of backgrounds (plain, a periodic texture, and four spatial-frequency-filtered textures created from the periodic texture). Search times indicate that these background variations only affect readability when the text contrast is low, and that spatial frequency content of the background affects readability. These results were not well predicted by the single variables of text contrast (Spearman rank correlation = -0.64) and background RMS contrast (0.08), but a global masking index and a spatial-frequency-selective masking index led to better predictions (-0.84 and -0.81, respectively). c2000 Optical Society of America.

  13. Muscle contraction increases carnitine uptake via translocation of OCTN2

    SciTech Connect

    Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan)] [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan)] [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)] [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan)] [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan)] [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)] [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  14. Translocation of Small Interfering RNA and Cholesterol Molecules in Biomembranes

    NASA Astrophysics Data System (ADS)

    Kalia, Rajiv

    2013-03-01

    This presentation will focus on all-atom molecular dynamics (MD) simulation studies of (1) structural and mechanical barriers to translocation of small interfering RNA (siRNA) across a phospholipid bilayer, and (2) flip-flop dynamics of cholesterol (CHOL) molecules across a phospholipid bilayer. In the first case, we find that the siRNA induces a liquid-to-gel phase transformation. In the gel phase we find large compressive lateral stresses in the hydrocarbon chains of lipid molecules, which present a considerable barrier to siRNA passage across the bilayer. In the second case, we study spontaneous CHOL inter-leaflet transport (flip-flop), the effect of this process on mechanical stresses across the bilayer, and the role of CHOL in inducing molecular order in bilayer leaflets. The simulation was run for 15 microseconds and we found 24 CHOL flip-flop events over that duration. On average, a CHOL molecule migrates across the lipid bilayer in about 73 ns after a flip-flop event is triggered. We have calculated diffusion maps and determined free energy surfaces and flip-flop mechanisms for CHOL molecules. This presentation will focus on all-atom molecular dynamics (MD) simulation studies of (1) structural and mechanical barriers to translocation of small interfering RNA (siRNA) across a phospholipid bilayer, and (2) flip-flop dynamics of cholesterol (CHOL) molecules across a phospholipid bilayer. In the first case, we find that the siRNA induces a liquid-to-gel phase transformation. In the gel phase we find large compressive lateral stresses in the hydrocarbon chains of lipid molecules, which present a considerable barrier to siRNA passage across the bilayer. In the second case, we study spontaneous CHOL inter-leaflet transport (flip-flop), the effect of this process on mechanical stresses across the bilayer, and the role of CHOL in inducing molecular order in bilayer leaflets. The simulation was run for 15 microseconds and we found 24 CHOL flip-flop events over that duration. On average, a CHOL molecule migrates across the lipid bilayer in about 73 ns after a flip-flop event is triggered. We have calculated diffusion maps and determined free energy surfaces and flip-flop mechanisms for CHOL molecules. Work supported by NSF-OCI-0749360 and NSF-IOS-125317.

  15. Uptake, translocation, and toxicity of gold nanorods in maize

    NASA Astrophysics Data System (ADS)

    Moradi Shahmansouri, Nastaran

    Nanomaterials are widely used in many different products, such as electronics, cosmetics, industrial goods, biomedical uses, and other material applications. The heavy emission of nanomaterials into the environment has motived increasing concern regarding the effects on ecosystems, food chains, and, human health. Plants can tolerate a certain amount of natural nanomaterials, but large amounts of ENMs released from a variety of industries could be toxic to plants and possibly threaten the ecosystem. Employing phytoremediation as a contamination treatment method may show promise. However a pre-requisite to successful treatment is a better understanding of the behavior and effects of nanomaterials within plant systems. This study is designed to investigate the uptake, translocation, bioavailability, and toxicity of gold nanorods in maize plants. Maize is an important food and feed crop that can be used to understand the potential hazardous effects of nanoparticle uptake and distribution in the food chain. The findings could be an important contribution to the fields of phytoremediation, agri-nanotechnology, and nanoparticle toxicity on plants. In the first experiment, hydroponically grown maize seedlings were exposed to similar doses of commercial non-coated gold nanorods in three sizes, 10x34 nm, 20x75 nm, and 40x96 nm. The three nanorod species were suspended in solutions at concentrations of 350 mg/l, 5.8 mg/l, and 14 mg/l, respectively. Maize plants were exposed to all three solutions resulting in considerably lower transpiration and wet biomass than control plants. Likewise, dry biomass was reduced, but the effect is less pronounced than that of transpiration and wet biomass. The reduced transpiration and water content, which eventually proved fatal to exposed plants, were most likely a result of toxic effect of gold nanorod, which appeared to physically hinder the root system. TEM images proved that maize plants can uptake gold particles and accumulate them in root and leaf cells. However, the translocation factor of gold nanorods from root to leaf was very low in this experiment. In the second experiment, maize seedlings were exposed to different (lower) concentrations of gold nanorods measured at 4.5x10-3 mg/l, 0.45 mg/l, and 2.25 mg/l for 10 days. Transpiration and biomass measurements demonstrated that the higher concentration of gold nanorods caused lower water uptake and growth, but lower concentrations did not show a significant toxic effect. According to ICP-MS results, root systems of the exposed plants were surrounded by high concentrations of sorbed nanorods, which physically interfered with uptake pathways and, thus, inhibited plant growth and nutritional uptake.

  16. Cosmic Microwave Background

    NASA Astrophysics Data System (ADS)

    Mather, John; Hinshaw, Gary; Page, Lyman

    The cosmic microwave background (CMB) radiation, the relic of the early phases of the expanding universe, is bright, full of information, and difficult to measure. Along with the recession of galaxies and the primordial nucleosynthesis, it is one of the strongest signs that the Hot Big Bang Model of the universe is correct. It is brightest around 2 mm wavelength, has a temperature of T_{cmb} = 2.72548 ± 0.00057 K, and has a blackbody spectrum within 50 parts per million. Its spatial fluctuations (around 0.01% on 1{}^{circ } scales) are possibly the relics of quantum mechanical processes in the early universe, modified by processes up to the decoupling at a redshift of about 1,000 (when the primordial plasma became mostly transparent). In the cold dark matter (DM) model with cosmic acceleration (? CDM), the fluctuation statistics are consistent with the model of inflation and can be used to determine other parameters within a few percent, including the Hubble constant, the ? constant, the densities of baryonic and dark matter, and the primordial fluctuation amplitude and power spectrum slope. In addition, the polarization of the fluctuations reveals the epoch of reionization at a redshift approximately twice that determined from the Gunn-Peterson trough due to optically thick Lyman ? absorption in QSO spectra. It is of historic importance, and a testament to the unity of theory and experiment, that we now have a standard model of cosmology that is consistent with all of the observations.Current observational challenges include (1) improvement of the spectrum distortion measurements, especially at long wavelengths, where the measured background is unexpectedly bright; (2) the search for the B-mode polarization (the divergence-free part of the polarization map), arising from propagating gravitational waves; and (3) the extension of fluctuation measurements to smaller angular scales. Much more precise spectrum observations near 2 mm are likely and would test some very interesting theories. Current theoretical challenges include explanation of the dark matter and dark energy; understanding, estimating, and removing the interference of foreground sources that limit the measurements of the CMB; detailed understanding of the influence of nonequilibrium processes on the decoupling and reionization phases; and searches for signs of the second order or exotic processes (e.g., isocurvature fluctuations, cosmic strings, non-Gaussian fluctuations). At this writing, we await the cosmological results of the Planck mission.

  17. Cosmic Microwave Background Data Analysis

    NASA Astrophysics Data System (ADS)

    Paykari, Paniez; Starck, Jean-Luc Starck

    2012-03-01

    About 400,000 years after the Big Bang the temperature of the Universe fell to about a few thousand degrees. As a result, the previously free electrons and protons combined and the Universe became neutral. This released a radiation which we now observe as the cosmic microwave background (CMB). The tiny fluctuations* in the temperature and polarization of the CMB carry a wealth of cosmological information. These so-called temperature anisotropies were predicted as the imprints of the initial density perturbations which gave rise to the present large-scale structures such as galaxies and clusters of galaxies. This relation between the present-day Universe and its initial conditions has made the CMB radiation one of the most preferred tools to understand the history of the Universe. The CMB radiation was discovered by radio astronomers Arno Penzias and Robert Wilson in 1965 [72] and earned them the 1978 Nobel Prize. This discovery was in support of the Big Bang theory and ruled out the only other available theory at that time - the steady-state theory. The crucial observations of the CMB radiation were made by the Far-Infrared Absolute Spectrophotometer (FIRAS) instrument on the Cosmic Background Explorer (COBE) satellite [86]- orbited in 1989-1996. COBE made the most accurate measurements of the CMB frequency spectrum and confirmed it as being a black-body to within experimental limits. This made the CMB spectrum the most precisely measured black-body spectrum in nature. The CMB has a thermal black-body spectrum at a temperature of 2.725 K: the spectrum peaks in the microwave range frequency of 160.2 GHz, corresponding to a 1.9mmwavelength. The results of COBE inspired a series of ground- and balloon-based experiments, which measured CMB anisotropies on smaller scales over the next decade. During the 1990s, the first acoustic peak of the CMB power spectrum (see Figure 5.1) was measured with increasing sensitivity and by 2000 the BOOMERanG experiment [26] reported that the highest power fluctuations occur at scales of about one degree. A number of ground-based interferometers provided measurements of the fluctuations with higher accuracy over the next three years, including the Very Small Array [16], Degree Angular Scale Interferometer (DASI) [61], and the Cosmic Background Imager (CBI) [78]. DASI was the first to detect the polarization of the CMB and the CBI provided the first E-mode polarization spectrum with compelling evidence that it is out of phase with the T-mode spectrum. In June 2001, NASA launched its second CMB mission (after COBE), Wilkinson Microwave Anisotropy Explorer (WMAP) [44], to make much more precise measurements of the CMB sky. WMAP measured the differences in the CMB temperature across the sky creating a full-sky map of the CMB in five different frequency bands. The mission also measured the CMB's E-mode and the foreground polarization. As of October 2010, the WMAP spacecraft has ended its mission after nine years of operation. Although WMAP provided very accurate measurements of the large angular-scale fluctuations in the CMB, it did not have the angular resolution to cover the smaller-scale fluctuations that had been observed by previous ground-based interferometers. A third space mission, the Planck Surveyor [1], was launched by ESA* in May 2009 to measure the CMB on smaller scales than WMAP, as well as making precise measurements of the polarization of CMB. Planck represents an advance over WMAP in several respects: it observes in higher resolution, hence allowing one to probe the CMB power spectrum to smaller scales; it has a higher sensitivity and observes in nine frequency bands rather than five, hence improving the astrophysical foreground models. The mission has a wide variety of scientific aims, including: (1) detecting the total intensity/polarization of the primordial CMB anisotropies; (2) creating a galaxy-cluster catalogue through the Sunyaev-Zel'dovich (SZ) effect [93]; (3) observing the gravitational lensing of the CMB and the integrated Sachs Wolfe (ISW) effect [82]; (4) observing br

  18. Translocation of 239Pu in mice following inhalation of sized 239PuO2.

    PubMed

    Morgan, A; Black, A; Moores, S R; Lambert, B E

    1986-04-01

    This study showed that when SAS/4 mice were exposed to sized 239PuO2 only about 0.5% of the 239Pu was translocated from lung to other organs. The fraction of 239Pu translocated appeared to be independent of the particle size of the administered 239PuO2 within the range of AMADs investigated (0.8-2.2 microns). The distribution of translocated 239Pu was similar to that observed with other species in that most of the activity was associated with the lung-associated lymph nodes followed by bone and liver. The fraction of 239Pu translocated was comparable to that found in studies with rats (ICRP72) but less than that found in more extended studies with beagle dogs. PMID:3957675

  19. Translocation of cave fish (Poecilia mexicana) within and between natural habitats along a

    E-print Network

    Schlupp, Ingo

    Translocation of cave fish (Poecilia mexicana) within and between natural habitats along a toxicity. In a system where incipient speciation of populations of the Atlantic molly (Poecilia mexicana) appears (Poecilia mexicana) from Ta

  20. [A case of IUD translocation to the peritoneal cavity--diagnostic procedures and treatment].

    PubMed

    Nowakowski, B; Paczkowska, A; Friebe, Z; Pawlaczyk, M; Grys, E

    1997-08-01

    The case of Cooper-T IUD translocation to peritoneal cavity diagnosed 5 years after its insertion is presented. Authors show diagnostic problems resulting from non typical complaints and incomplete documentation. PMID:9499016

  1. Crystal structures of EF-G-ribosome complexes trapped in intermediate states of translocation.

    PubMed

    Zhou, Jie; Lancaster, Laura; Donohue, John Paul; Noller, Harry F

    2013-06-28

    Translocation of messenger and transfer RNA (mRNA and tRNA) through the ribosome is a crucial step in protein synthesis, whose mechanism is not yet understood. The crystal structures of three Thermus ribosome-tRNA-mRNA-EF-G complexes trapped with ?,?-imidoguanosine 5'-triphosphate (GDPNP) or fusidic acid reveal conformational changes occurring during intermediate states of translocation, including large-scale rotation of the 30S subunit head and body. In all complexes, the tRNA acceptor ends occupy the 50S subunit E site, while their anticodon stem loops move with the head of the 30S subunit to positions between the P and E sites, forming chimeric intermediate states. Two universally conserved bases of 16S ribosomal RNA that intercalate between bases of the mRNA may act as "pawls" of a translocational ratchet. These findings provide new insights into the molecular mechanism of ribosomal translocation. PMID:23812722

  2. Germline translocations in mice: unique tools for analyzing gene function and long-distance regulatory mechanisms.

    PubMed

    Elso, Colleen; Lu, Xiaochen; Morrison, Stephanie; Tarver, Angela; Thompson, Heather; Thurkow, Hillary; Yamada, N Alice; Stubbs, Lisa

    2008-01-01

    Translocations have provided invaluable tools for identifying both cancer-linked genes and loci associated with heritable human diseases, but heritable human translocations are rare and few mouse models exist. Here we report progress on analysis of a collection of heritable translocations generated by treatment of mice with specific chemicals or radiation during late spermatogenic stages. The translocation mutants exhibit a range of visible phenotypes reflecting the disruption of coding sequences or the separation of genes from essential regulatory elements. The breakpoints of both radiation-induced and chemically induced mutations in these mice are remarkably clean, with very short deletions, duplications, or inversions in some cases, and ligation mediated by microhomology, suggesting nonhomologous end joining as the major path of repair. These mutations provide new tools for the discovery of novel genes and regulatory elements linked to human developmental disorders and new clues to the molecular basis of human genetic disease. PMID:18648012

  3. Investigating the translocation of lambda-DNA molecules through PDMS nanopores

    E-print Network

    Karnik, Rohit N.

    We investigate the translocation of ?-DNA molecules through resistive-pulse polydimethylsiloxane (PDMS) nanopore sensors. Single molecules of ?-DNA were detected as a transient current increase due to the effect of DNA ...

  4. Sequence dependence of the binding energy in chaperone-driven polymer translocation through a nanopore

    NASA Astrophysics Data System (ADS)

    Abdolvahab, Rouhollah Haji; Ejtehadi, Mohammad Reza; Metzler, Ralf

    2011-01-01

    We study the translocation of stiff polymers through a nanopore, driven by the chemical-potential gradient exerted by binding proteins (chaperones) on the trans side of the pore. Bound chaperones prevent backsliding through the pore and, therefore, partially rectify the polymer passage. We show that the sequence of chain monomers with different binding affinity for the chaperones significantly affects the translocation dynamics. In particular, we investigate the effect of the nearest-neighbor adjacency probability of the two monomer types. Depending on the magnitude of the involved binding energies, the translocation speed may either increase or decrease with the adjacency probability. We determine the mean first passage time and show that, by tuning the effective binding energy, the motion changes continuously from purely diffusive to ballistic translocation.

  5. Patient selection for macular translocation surgery using the scanning laser ophthalmoscope

    Microsoft Academic Search

    Gildo Y Fujii; Eugene de Juan; Janet Sunness; Mark S Humayun; Dante J Pieramici; Tom S Chang

    2002-01-01

    ObjectivesTo evaluate the use of the scanning laser ophthalmoscope (SLO) as a predictor for potential visual improvement in eyes with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) undergoing limited macular translocation.

  6. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication

    PubMed Central

    Kristoff, Jan; Haret-Richter, George; Ma, Dongzhu; Ribeiro, Ruy M.; Xu, Cuiling; Cornell, Elaine; Stock, Jennifer L.; He, Tianyu; Mobley, Adam D.; Ross, Samantha; Trichel, Anita; Wilson, Cara; Tracy, Russell; Landay, Alan; Apetrei, Cristian; Pandrea, Ivona

    2014-01-01

    Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS. PMID:24837437

  7. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication.

    PubMed

    Kristoff, Jan; Haret-Richter, George; Ma, Dongzhu; Ribeiro, Ruy M; Xu, Cuiling; Cornell, Elaine; Stock, Jennifer L; He, Tianyu; Mobley, Adam D; Ross, Samantha; Trichel, Anita; Wilson, Cara; Tracy, Russell; Landay, Alan; Apetrei, Cristian; Pandrea, Ivona

    2014-06-01

    Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS. PMID:24837437

  8. Techniques for analyzing the effects of translocation on fox squirrels (Sciurus niger) 

    E-print Network

    Ten Brink, Craig Eric

    1996-01-01

    virginianus) was an acceptable alternative for a sensitive public. However, O'Bryan and McCullough (1985) found it difficult to justify translocation of Columbian black-tailed deer (Odocoileus hemionus columbiantrs) in California, because only 15/s...

  9. Absorption and translocation of zinc in pecan trees [Carya illinoensis (Wang.) K. Koch] 

    E-print Network

    Wadsworth, Grady Lynn

    1970-01-01

    ABSORPTION AND TRANSLOCATION OF ZINC IN PECAN TREES CARYA ILLINOENSIS (WANG. ) K. KOCH A Thesis by GRADY LYNN WADSWORTH Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree... of MASTER OF SCIENCE May 1970 Major Subject: Horticulture ABSORPTION AND TRANSLOCATION OF ZINC IN PECAN TREES CARYA ILLINOENSIS (WANG. ) K. KOCH A Thesis by GRADY LYNN WADSWORTH Approved as to style and content by; arrman o ommrttee ea o epartment...

  10. Lattice-Boltzmann Simulations of Ionic Current Modulation by DNA Translocation

    Microsoft Academic Search

    Sylvain Reboux; Fabrizio Capuani; Nelido Gonzalez-Segredo; D. Frenkel

    2006-01-01

    We present a numerical study of the effect of DNA translocation on the ionic current through a nanopore. We use a coarse-grained model to solve the electrokinetic equations at the Poisson-Boltzmann level for the microions, coupled to a lattice-Boltzmann equation for the solvent hydrodynamics. In most cases, translocation leads to a reduction in the ionic current. However, at low salt

  11. Ligand-Independent GLUT4 Translocation Induced by Guanosine 5'-O-(3-Thiotriphosphate) Involves Tyrosine Phosphorylation

    Microsoft Academic Search

    TETSURO HARUTA; AARON J. MORRIS; PETER VOLLENWEIDER; JAMES G. NELSON; DAVID W. ROSE; MICHAEL MUECKLER; JERROLD M. OLEFSKY

    1998-01-01

    To delineate the signaling pathway leading to glucose transport protein (GLUT4) translocation, we examined the effect of microin- jection of the nonhydrolyzable GTP analog, guanosine 59-O-(3-thio- triphosphate) (GTPgS), into 3T3-L1 adipocytes. Thirty minutes after the injection of 5 mM GTPgS, 40% of injected cells displayed surface GLUT4 staining indicative of GLUT4 translocation compared with 55% for insulin-treated cells and 10%

  12. Protein Translocation in Photoreceptor Light Adaptation: A Common Theme in Vertebrate and Invertebrate Vision

    NSDL National Science Digital Library

    Vadim Y. Arshavsky (Harvard Medical School and the Massachusetts Eye and Ear Infirmary; REV)

    2003-10-14

    How do our eyes adjust to daily light levels that vary by almost 11 orders of magnitude? Research shows that, in both vertebrates and invertebrates, signaling proteins are translocated in a light-dependent manner between the photoreceptor cellular compartments where visual transduction takes place, and the rest of the photoreceptor cell. Protein translocation is likely to contribute to photoreceptor light adaptation by adjusting the sensitivity and speed of photoresponse to ever-changing conditions of ambient illumination.

  13. In vivo Dissection of the Tat Translocation Pathway in Escherichia coli

    E-print Network

    Palmer, Tracy

    . The translocation of the RR-GFP fusion required TatA, TatB and TatC proteins. By exploiting the periplasmic and this strain exhibited a normal growth phenotype. Interestingly, the growth of ÁtatA and tatB mutantsA or TatB was suf®cient for the translocation of RR-ColV or KR-ColV. In contrast, TatA plus the conserved N

  14. Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development

    Microsoft Academic Search

    Elizabeth J Bhoj; Purita Ramos; Linda A Baker; Agneta Nordenskjöld; Frederick F Elder; Steven B Bleyl; Neil E Bowles; Cammon B Arrington; Brigitte Delhomme; Amandine Vanhoutteghem; Philippe Djian; Andrew R Zinn

    2011-01-01

    We studied a man with distal hypospadias, partial anomalous pulmonary venous return, mild limb-length inequality and a balanced translocation involving chromosomes 9 and 13. To gain insight into the etiology of his birth defects, we mapped the translocation breakpoints by high-resolution comparative genomic hybridization (CGH), using chromosome 9- and 13-specific tiling arrays to analyze genetic material from a spontaneously aborted

  15. Disruption of two novel genes by a translocation co-segregating with schizophrenia

    Microsoft Academic Search

    J. Kirsty Millar; Julie C. Wilson-Annan; Susan Anderson; Sheila Christie; M artin S. Taylor; Colin A. M. Semple; Rebecca S. Devon; D avid M. St Clair; W alter J. Muir; Douglas H. R. Blackwood; David J. Porteous

    2000-01-01

    A balanced (1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related psychiatric disorders in a large Scottish family (maximum LOD = 6.0). We hypoth- esize that the translocation is the causative event and that it directly disrupts gene function. We previously reported a dearth of genes in the breakpoint region of chromosome 11 and it is therefore unlikely that the expression of

  16. Absorption, translocation, and metabolism of propoxycarbazone-sodium in ALS-inhibitor resistant Bromus tectorum biotypes

    Microsoft Academic Search

    Kee Woong Park; Lynn Fandrich; Carol A. Mallory-Smith

    2004-01-01

    Experiments were conducted to investigate the absorption, translocation, and metabolism of propoxycarbazone-sodium in acetolactate synthase-inhibitor resistant (AR and MR) and susceptible (AS and MS) Bromus tectorum biotypes. Absorption and translocation of l4C-propoxycarbazone-sodium were similar in all biotypes. One major and three minor metabolites were identified using reverse-phase high performance liquid chromatography. In all biotypes, 80% of the propoxycarbazone-sodium was metabolized

  17. Presentation and Treatment of Subfertile Men with Balanced Translocations: The Cleveland Clinic Experience

    Microsoft Academic Search

    Christina B. Ching; Edmund Ko; Bryan Hecht; Marissa Smith; Edmund Sabanegh

    2012-01-01

    Introduction: Balanced chromosomal translocations are a relatively common (2–7%) finding among infertile couples. We report clinical features of males with translocations at our institution. Materials and Methods: Data was collected on men presenting for infertility evaluation between July 2006 March 2010, including presentation, medical history, and infertility treatments. Criteria for genetic evaluation, consisting of karyotype and Y-linked microdeletion assay, included

  18. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia

    Microsoft Academic Search

    Annelies De Klein; Ad Geurts Van Kessel; Gerard Grosveld; Claus R. Bartram; Anne Hagemeijer; Dirk Bootsma; Nigel K. Spurr; Nora Heisterkamp; John Groffen; John R. Stephenson

    1982-01-01

    The transforming genes of oncogenic retroviruses are homologous to a group of evolutionary conserved cellular onc genes1. The human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuLV) was recently shown2 to be located on chromosome 9. The long arm of this chromosome is involved in a specific translocation with chromosome 22, the Philadelphia translocation (Ph1),

  19. Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections

    PubMed Central

    Estes, Jacob D.; Harris, Levelle D.; Klatt, Nichole R.; Tabb, Brian; Pittaluga, Stefania; Paiardini, Mirko; Barclay, G. Robin; Smedley, Jeremy; Pung, Rhonda; Oliveira, Kenneth M.; Hirsch, Vanessa M.; Silvestri, Guido; Douek, Daniel C.; Miller, Christopher J.; Haase, Ashley T.; Lifson, Jeffrey; Brenchley, Jason M.

    2010-01-01

    The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication. PMID:20808901

  20. Slowing down DNA translocation through solid-state nanopores by pressure.

    PubMed

    Zhang, Hengbin; Zhao, Qing; Tang, Zhipeng; Liu, Song; Li, Qingtao; Fan, Zhongchao; Yang, Fuhua; You, Liping; Li, Xuemei; Zhang, Jingmin; Yu, Dapeng

    2013-12-20

    The effect of applied pressure on event duration distributions in 3 kb dsDNA translocation is systematically investigated. The effects of pressure magnitude and nanopore size on the length discrimination between 615 bp and 1.14 kbp dsDNA is studied. The pressure-controlled DNA translocation in solid-state nanopores makes a significant contribution to improve the temporal resolution in DNA single-molecule detection. PMID:23828716

  1. Statistical Inference of DNA Translocation using Parallel Expectation Maximization

    NASA Astrophysics Data System (ADS)

    Emmett, Kevin; Rosenstein, Jacob; Pfau, David; Bamberger, Akiva; Shepard, Ken; Wiggins, Chris

    2013-03-01

    DNA translocation through a nanopore is an attractive candidate for a next-generation DNA sequencing platform, however the stochastic motion of the molecules within the pore, allowing both forward and backward movement, prevents easy inference of the true sequence from observed data. We model diffusion of an input DNA sequence through a nanopore as a biased random walk with noise, and describe an algorithm for efficient statistical reconstruction of the input sequence, given data consisting of a set of time series traces. The data is modeled as a Hidden Markov Model, and parallel expectation maximization is used to learn the most probable input sequence generating the observed traces. Bounds on inference accuracy are analyzed as a function of model parameters, including forward bias, error rate, and the number of traces. The number of traces is shown to have the strongest influence on algorithm performance, allowing for high inference accuracy even in extremely noisy environments. Incorrectly identified state transitions account for the majority of inference errors, and we introduce entropy-based metaheuristics for identifying and eliminating these errors. Inference is robust, fast, and scales to input sequences on the order of several kilobases.

  2. Absence of plant uptake and translocation of polybrominated biphenyls (PBBs).

    PubMed

    Chou, S F; Jacobs, L W; Penner, D; Tiedje, J M

    1978-04-01

    Studies of polybrominated biphenyl (PBB) uptake by plants have been conducted in hydroponic solutions and in greenhouse experiments with soil. Autoradiograms of corn and soybean seedlings grown in hydroponic solutions showed no translocation of 14C-PBB from 14C-PBB-treated solutions to plant tops or within the leaf from 14C-PBB-treated spots on the upper leaf surface. A significant portion of the 14C-PBB associated with the roots was removed when the roots were dipped in acetone. Three root crops (radishes, carrots, and onions) were grown in two soils, each treated with a mixture of FireMaster BP-6 (PBB) and 14C-PBB to achieve final concentrations of 100 ppm and 100 ppb. All roots showed more PBB when grown in the soil with the lower clay and organic matter content than they did when grown in the soil with more clay and organic matter. In the latter soil (clay loam) no PBB was detected in any roots from the 100 ppb treatment. More PBB was associated with roots of carrot than of radish or onion. Corn leaf whorls containing dust from a PBB contamination soil and washed radishes from a heavily contaminated garden showed no PBB. PMID:210006

  3. Role of Numb expression and nuclear translocation in endometrial cancer

    PubMed Central

    WANG, CHAO; CUI, TAO; FENG, WEIWEI; LI, HUASHUN; HU, LINA

    2015-01-01

    The cell fate determinant Numb orchestrates numerous cell physiological and pathological processes and previous evidence has indicated that Numb expression is associated with tumorigenesis. The present study investigated the potential role of Numb in endometrial cancer (EC). Numb expression was compared between the normal endometrium and EC tissue by immunohistochemistry, and the protein levels were assessed by western blotting and confocal microscopy in the human endometrial HEC-1B cancer cell line and normal epithelial cells. The intracellular localization of Numb in HEC-1B cells was examined by immunofluorescence. Numb was found to be expressed at higher levels in endometrial cancer compared with the normal endometrium. Although Numb localizes to the cytoplasm and plasma membrane in the normal epithelium, the present study found that Numb accumulated in the nucleus of HEC-1B cells. The present data reveals the upregulation of Numb expression in EC tissues and indicates that Numb plays a role in the occurrence of EC, which may be mediated by its translocation into the nucleus. The role of Numb in cancer development requires additional investigation. PMID:25788995

  4. LPS induces translocation of TLR4 in amniotic epithelium.

    PubMed

    Adams, K M; Lucas, J; Kapur, R P; Stevens, A M

    2007-01-01

    Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) induced immune responses, which may contribute to preterm labor associated with intraamniotic gram-negative bacterial infections. The study objective was to investigate gestational age and LPS-induced changes in TLR4 subcellular localization within amniotic epithelium, the first line of host defense against intraamniotic bacteria. TLR4 localization in amniotic epithelium was assessed using immunohistochemistry on 24 placentas of different gestational ages: first trimester (n=6), second trimester (n=6), and third trimester (n=12). Immunofluorescence was used to determine TLR4 localization following ex vivo LPS stimulation of amnion from women undergoing cesarean section without labor at term. TLR4 was expressed in the cytoplasm of amniotic epithelium starting at 9weeks with apical polarization by 25weeks gestation. TLR4 localization to the basal membrane was significantly associated with chorioamnionitis (p=0.01). After LPS stimulation, TLR4 was expressed sequentially within the apical membrane, cytoplasm, and finally in the basal cellular compartment. This suggests that TLR4 expression in amniotic epithelium is poised to monitor amniotic fluid for pathogens. TLR4 translocation to the basal membrane may decrease LPS signaling early in an infection, but allow the amniotic epithelium to remain competent to invasive or intracellular bacteria. PMID:17055575

  5. Translocation of Nickel in Xylem Exudate of Plants

    PubMed Central

    Tiffin, Lee O.

    1971-01-01

    Topped plants of tomato (Lycopersicon esculentum), cucumber (Cucumis sativus), corn (Zea mays), carrot (Daucus carota), and peanut (Arachis hypogaea) were treated with 0.5 to 50 micromolar Ni (containing 63Ni) in nutrient solutions. Xylem exudate was collected for 10 hours or, in the case of corn, for 20 hours at 5-hour intervals. Electrophoresis of nutrient solution distributed all Ni cathodically as inorganic Ni2+. Low concentrations of Ni in tomato exudate migrated anodically, presumably bound to organic anion (carrier). However, this carrier became saturated at about 2 micromolar Ni in exudate, and excess Ni ran cathodically. Most of the Ni in cucumber, corn, carrot, and peanut exudate ran anodically, and its migration rate was identical for all exudates. Peanut root sap contained 14 to 735 micromolar Ni. The anodic Ni carriers in root sap and exudate appear identical. The carrier in root sap became saturated near 100 micromolar Ni, as shown by cathodic streaking of Ni exceeding that concentration. It appears that all five species translocate low concentrations of Ni in the same anionic form. Images PMID:16657780

  6. Does the intestinal bifidobacterial colonisation affect bacterial translocation?

    PubMed

    Romond, Marie-Bénédicte; Colavizza, Michel; Mullié, Catherine; Kalach, Nicolas; Kremp, Odile; Mielcarek, Christine; Izard, Daniel

    2008-02-01

    The aim of this work was to investigate the possible role of the intestinal anaerobic flora (especially bifidobacteria) in regulating bacterial translocation (BT) which can be defined as the passage of intestinal microbes through the mucosa to internal organs. Default in BT regulation concurs with pathogenesis of sepsis in various human conditions, such as acute pancreatitis, cirrhosis, necrotising enterocolitis or multiple organ failure. The intestinal flora was studied in human flora associated mice (HF mice) and BT was quantified in Peyer's patches (PP), blood, spleen, liver and lungs. HF mice displayed a heterogenic intestinal colonisation with bifidobacteria. High colonisation of both caecum and colon by bifidobacteria led to a poorer bacterial contamination of blood, liver and lungs. Moreover, ileal, caecal and colonic bifidobacterial counts negatively correlated with the bacterial dissemination (number of contaminated organs per mouse). In contrast, Bacteroides fragilis group counts positively correlated with bacteraemia, lungs contamination or bacterial dissemination. Additionally, clostridia localised in the colon affected bacterial uptake by PP and lungs contamination as indicated by positive correlations between bacterial populations in these respective locations. These results indicate that bifidobacteria, when established in high counts, reduced BT to liver, blood and lungs, whereas B. fragilis group favoured the bacterial passage. Clostridia established in the distal ileum also seemed to favour BT to lungs. The manipulation of the bacterial flora to optimise the regulatory effect on BT should therefore focus on the selective promotion of bifidobacteria and avoid an increase in potentially detrimental populations such as B. fragilis group and clostridia. PMID:17988900

  7. Evolution of the Translocation and Assembly Module (TAM)

    PubMed Central

    Heinz, Eva; Selkrig, Joel; Belousoff, Matthew J.; Lithgow, Trevor

    2015-01-01

    Bacterial outer membrane proteins require the beta-barrel assembly machinery (BAM) for their correct folding and function. The central component of this machinery is BamA, an Omp85 protein that is essential and found in all Gram-negative bacteria. An additional feature of the BAM is the translocation and assembly module (TAM), comprised TamA (an Omp85 family protein) and TamB. We report that TamA and a closely related protein TamL are confined almost exclusively to Proteobacteria and Bacteroidetes/Chlorobi respectively, whereas TamB is widely distributed across the majority of Gram-negative bacterial lineages. A comprehensive phylogenetic and secondary structure analysis of the TamB protein family revealed that TamB was present very early in the evolution of bacteria. Several sequence characteristics were discovered to define the TamB protein family: A signal-anchor linkage to the inner membrane, beta-helical structure, conserved domain architecture and a C-terminal region that mimics outer membrane protein beta-strands. Taken together, the structural and phylogenetic analyses suggest that the TAM likely evolved from an original combination of BamA and TamB, with a later gene duplication event of BamA, giving rise to an additional Omp85 sequence that evolved to be TamA in Proteobacteria and TamL in Bacteroidetes/Chlorobi. PMID:25994932

  8. A Critical Reassessment of Penetratin Translocation Across Lipid Membranes

    PubMed Central

    Bárány-Wallje, Elsa; Keller, Sandro; Serowy, Steffen; Geibel, Sebastian; Pohl, Peter; Bienert, Michael; Dathe, Margitta

    2005-01-01

    Penetratin is a short, basic cell-penetrating peptide able to induce cellular uptake of a vast variety of large, hydrophilic cargos. We have reassessed the highly controversial issue of direct permeation of the strongly cationic peptide across negatively charged lipid membranes. Confocal laser scanning microscopy on rhodamine-labeled giant vesicles incubated with carboxyfluorescein-labeled penetratin yielded no evidence of transbilayer movement, in contradiction to previously reported results. Confocal fluorescence spectroscopy on black lipid membranes confirmed this finding, which was also not affected by application of a transmembrane electric potential difference. A novel dialysis assay based on tryptophan absorbance and fluorescence spectroscopy demonstrated that the permeability of small and large unilamellar vesicles to penetratin is <10?13 m/s. Taken together, the results show that penetratin is not capable of overcoming model membrane systems irrespective of the bilayer curvature or the presence of a transmembrane voltage. Thus, direct translocation across the hydrophobic core of the plasma membrane cannot account for the efficient uptake of penetratin into live cells, which is in accord with recent in vitro studies underlining the importance of endocytosis in the internalization process of cationic cell-penetrating peptides. PMID:16040762

  9. Characterization of nuclear ferritin and mechanism of translocation

    PubMed Central

    2005-01-01

    Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in cell nuclei. It is an established fact that H-ferritin is the major form of nuclear ferritin, but little is known about the roles of ferritin in nuclei or about the mechanisms that control its appearance within the nuclear volume. In the present study, we show that, for human SW1088 astrocytoma cells, the nuclear and cytoplasmic forms of H-ferritin are products of the same mRNA. Histochemical and biochemical evidence is presented showing that ferritin is distributed non-randomly within the nuclear volume and that it preferentially associates with heterochromatin. Both cytoplasmic and nuclear populations of H-ferritin contain mixtures of non- and O-glycosylated forms, but the nuclear population is enriched in O-glycosylated forms. Cells treated with alloxan, a potent inhibitor of O-glycosylation, contained significantly less nuclear ferritin compared with cells grown in control media. Alloxan inhibited the reappearance of H-ferritin in nuclei of cells released from conditions of iron depletion, but did not prevent its disappearance from nuclei of cells undergoing iron depletion. These results suggest that O-glycosylation accompanies the transfer of ferritin from the cytoplasm to the nucleus, but does not influence the reverse process. The picture that emerges is one in which ferritin translocation between the cytoplasm and the nucleus is post-translationally regulated and responds to environmental and nutritional cues. PMID:15675895

  10. Algorithms for Bayesian background-subtracted Fourier darkfield imaging.

    PubMed

    Fraundorf, P; Pollack, K

    1991-08-01

    Formal consideration of prior information on the Fourier amplitude of background contrast in an image, using the same Bayesian principles of statistical inference which underlie thermodynamics, allows one to subtract background without favoring only selected parts of frequency space. Without the bias in frequency space which causes periodicity bleeding and mars literal interpretation of Fourier-filtered images, the shape transform of aperiodic objects can be left intact. Algorithms for Bayesian background subtraction from one- and two-dimensional images are presented which further consider, in ad hoc fashion, one's uncertainty about background amplitude. The results help explain the reported success of Fourier truncation, and indicate that Bayesian background-subtracted images can minimize root-mean-square image error, as well as periodicity bleeding, in comparison to Fourier-filtered and Fourier-truncated alternatives. PMID:1750150

  11. Does your gene need a background check? How genetic background

    E-print Network

    Dworkin, Ian

    best to exploit genetic background effects to broaden genetic research programs. What are geneticDoes your gene need a background check? How genetic background impacts the analysis of mutations, USA 2 Department of Biological Sciences, SUNY Oswego, Oswego, NY, USA The premise of genetic analysis

  12. Bacterial protein translocation requires only one copy of the SecY complex in vivo

    PubMed Central

    Park, Eunyong

    2012-01-01

    The transport of proteins across the plasma membrane in bacteria requires a channel formed from the SecY complex, which cooperates with either a translating ribosome in cotranslational translocation or the SecA ATPase in post-translational translocation. Whether translocation requires oligomers of the SecY complex is an important but controversial issue: it determines channel size, how the permeation of small molecules is prevented, and how the channel interacts with the ribosome and SecA. Here, we probe in vivo the oligomeric state of SecY by cross-linking, using defined co- and post-translational translocation intermediates in intact Escherichia coli cells. We show that nontranslocating SecY associated transiently through different interaction surfaces with other SecY molecules inside the membrane. These interactions were significantly reduced when a translocating polypeptide inserted into the SecY channel co- or post-translationally. Mutations that abolish the interaction between SecY molecules still supported viability of E. coli. These results show that a single SecY molecule is sufficient for protein translocation. PMID:22927464

  13. Translocation of Non-Canonical Polypeptides into Cells Using Protective Antigen

    PubMed Central

    Rabideau, Amy E.; Liao, Xiaoli; Akçay, Gizem; Pentelute, Bradley L.

    2015-01-01

    A variety of pathogenic bacteria infect host eukaryotic cells using protein toxins, which enter the cytosol and exert their cytotoxic effects. Anthrax lethal toxin, for example, utilizes the membrane-spanning translocase, protective antigen (PA) pore, to deliver the protein toxin lethal factor (LF) from the endosome into the cytosol of cells. Previous work has investigated the delivery of natural peptides and enzymatic domains appended to the C-terminus of the PA-binding domain of lethal factor (LFN) into the cytosol via PA pore. Here, we move beyond natural amino acids and systematically investigate the translocation of polypeptide cargo containing non-canonical amino acids and functionalities through PA pore. Our results indicate translocation is not perturbed with alterations to the peptide backbone or side-chain. Moreover, despite their structural complexity, we found that the small molecule drugs, doxorubicin and monomethyl auristatin F (MMAF) translocated efficiently through PA pore. However, we found cyclic peptides and the small molecule drug docetaxel abrogated translocation due to their large size and structural rigidity. For cargos that reached the cytosol, we demonstrated that each remained intact after translocation. These studies show PA is capable of translocating non-canonical cargo provided it is in a conformational state conducive for passage through the narrow pore. PMID:26178180

  14. Mapping polypeptide interactions of the SecA ATPase during translocation

    PubMed Central

    Bauer, Benedikt W.; Rapoport, Tom A.

    2009-01-01

    Many bacterial proteins, including most secretory proteins, are translocated across the plasma membrane by the interplay of the cytoplasmic SecA ATPase and a protein-conducting channel formed by the SecY complex. SecA catalyzes the sequential movement of polypeptide segments through the SecY channel. How SecA interacts with a broad range of polypeptide segments is unclear, but structural data raise the possibility that translocation substrates bind into a “clamp” of SecA. Here, we have used disulfide bridge cross-linking to test this hypothesis. To analyze polypeptide interactions of SecA during translocation, two cysteines were introduced into a translocation intermediate: one that cross-links to the SecY channel and the other one for cross-linking to a cysteine placed at various positions in SecA. Our results show that a translocating polypeptide is indeed captured inside SecA's clamp and moves in an extended conformation through the clamp into the SecY channel. These results define the polypeptide path during SecA-mediated protein translocation and suggest a mechanism by which ATP hydrolysis by SecA is used to move a polypeptide chain through the SecY channel. PMID:19933328

  15. Movements and survival of black-footed ferrets associated with an experimental translocation in South Dakota

    USGS Publications Warehouse

    Biggins, D.E.; Godbey, J.L.; Horton, B.M.; Livieri, T.M.

    2011-01-01

    Black-footed ferrets (Mustela nigripes) apparently were extirpated from all native habitats by 1987, and their repatriation requires a combination of captive breeding, reintroductions, and translocations among sites. Improvements in survival rates of released ferrets have resulted from experience in quasi-natural environments during their rearing. Reestablishment of a self-sustaining wild population by 1999 provided the 1st opportunity to initiate new populations by translocating wild-born individuals. Using radiotelemetry, we compared behaviors and survival of 18 translocated wild-born ferrets and 18 pen-experienced captive-born ferrets after their release into a prairie dog colony not occupied previously by ferrets. Translocated wild-born ferrets moved significantly less and had significantly higher short-term survival rates than their captive-born counterparts. Using markrecapture methods, we also assessed potential impacts to the established donor population of removing 37% of its estimated annual production of kits. Annual survival rates for 30 ferret kits remaining at the donor subcomplex were higher than rates for 54 ferret kits at the control subcomplex (unmanipulated) for males (+82%) and females (+32%). Minimum survival of translocated kits did not differ significantly from survival of those at the control subcomplex. Direct translocation of young, wild-born ferrets from site to site appears to be an efficient method to establish new populations. ?? 2011 American Society of Mammalogists.

  16. Twin-arginine translocation-arresting protein regions contact TatA and TatB.

    PubMed

    Taubert, Johannes; Brüser, Thomas

    2014-07-01

    Tat systems translocate folded proteins across biological membranes of prokaryotes and plant plastids. TatBC complexes recognize N-terminal Tat signal peptides that contain a sequence motif with two conserved arginines (RR-motif), and transport takes place after a recruitment of TatA. Unfolded Tat substrate domains lower translocation efficiency and too long linkers lead to translocation arrest. To identify the components that interact with transported proteins during their passage through the translocon, we used a Tat substrate that arrests translocation at a long unfolded linker region, and we chose in vivo site-directed photo cross-linking to specifically detect the interactions of this linker region. For comparison, we included the interactions of the signal peptide and of the folded domain at the C-terminus of this construct. The data show that the linker contacts only two, structurally similar Tat components, namely TatA and TatB. These contacts depend on the recognition of the Tat-specific signal peptide. Only when membrane translocation of the globular domain was allowed--i.e., in the absence of the linker--we observed the same TatAB-contacts also to the globular domain. The data thus suggest that mature protein domains are translocated through a TatAB environment. PMID:25003386

  17. A kinetic Monte Carlo approach to investigate antibiotic translocation through bacterial porins.

    PubMed

    Ceccarelli, Matteo; Vargiu, Attilio V; Ruggerone, Paolo

    2012-03-14

    Many relevant biological processes take place on time scales not reachable by standard all-atom computer simulations. The translocation of antibiotics through non-specific bacterial porins is an example. Microscopic effects compete to determine penetration routes and, consequently, free energy barriers to be overcome. Since bacteria can develop resistance to treatment also by reducing their antibiotic permeability, to understand the microscopic aspects of antibiotic translocation is an important step to rationalize drug design. Here, to investigate the translocation we propose a complete numerical model that combines the diffusion-controlled rate theory and a kinetic Monte Carlo scheme based on both experimental data and microscopically well-founded all-atom simulations. Within our model, an antibiotic translocating through an hour-glass-shaped channel can be described as a molecule moving on a potential of mean force featuring several affinity sites and a high central barrier. The implications of our results for the characterization of antibiotic translocation at in vivo concentrations are discussed. The presence of an affinity site close to the mouth of the channel seems to favor the translocation of antibiotics, the affinity site acting as a particle reservoir. Possible connections between results and the appearance of mutations in clinical strains are also outlined. PMID:22353387

  18. 180-kD ribosome receptor is essential for both ribosome binding and protein translocation

    PubMed Central

    1993-01-01

    We have previously isolated a 180-kD ribosome receptor (p180) from mammalian rough ER that, when incorporated into liposomes, bound ribosomes with an affinity similar to intact membranes. To directly assess the contribution of p180 to ribosome binding as well as protein translocation, monoclonal antibodies were used to selectively deplete p180 from the detergent extracts of rough ER membranes used in the preparation of translocation-competent proteoliposomes. Proteoliposomes prepared from p180-depleted extracts showed a reduction in ribosome binding to the level of trypsin-inactivated controls as well as a loss in their ability to cotranslationally translocate two different secretory protein precursors. When purified p180 was added back to depleted extracts before proteoliposome formation, both ribosome binding and translocation activity were restored. In addition, the monoclonal antibodies, as well as their Fab' fragments, were able to inhibit ribosome binding and protein translocation when bound to intact rough microsomes. These data provide direct evidence that the 180-kD ribosome receptor is essential for ribosome binding and for the translocation of nascent proteins across the membrane of the rough ER. PMID:8381785

  19. Flow-induced translocation of polymers through a fluidic channel: a dissipative particle dynamics simulation study.

    PubMed

    Guo, Jiayi; Li, Xuejin; Liu, Yuan; Liang, Haojun

    2011-04-01

    The dynamics of flow-induced translocation of polymers through a fluidic channel has been studied by dissipative particle dynamics (DPD) approach. Unlike implicit solvent models, the many-body energetic and hydrodynamic interactions are preserved naturally by incorporating explicit solvent particles in this approach. The no-slip wall boundary and the adaptive boundary conditions have been implemented in the modified DPD approach to model the hydrodynamic flow within a specific wall structure of fluidic channel and control the particles' density fluctuations. The results show that the average translocation time versus polymer chain length satisfies a power-law scaling of ? ?N(1.152). The conformational changes and translocation dynamics of polymers through the fluidic channel have also been investigated in our simulations, and two different translocation processes, i.e., the single-file and double-folded translocation events, have been observed in detail. These findings may be helpful in understanding the conformational and dynamic behaviors of such polymer and/or DNA molecules during the translocation processes. PMID:21476773

  20. Flow-induced translocation of polymers through a fluidic channel: A dissipative particle dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Guo, Jiayi; Li, Xuejin; Liu, Yuan; Liang, Haojun

    2011-04-01

    The dynamics of flow-induced translocation of polymers through a fluidic channel has been studied by dissipative particle dynamics (DPD) approach. Unlike implicit solvent models, the many-body energetic and hydrodynamic interactions are preserved naturally by incorporating explicit solvent particles in this approach. The no-slip wall boundary and the adaptive boundary conditions have been implemented in the modified DPD approach to model the hydrodynamic flow within a specific wall structure of fluidic channel and control the particles' density fluctuations. The results show that the average translocation time versus polymer chain length satisfies a power-law scaling of ? ˜N1.152. The conformational changes and translocation dynamics of polymers through the fluidic channel have also been investigated in our simulations, and two different translocation processes, i.e., the single-file and double-folded translocation events, have been observed in detail. These findings may be helpful in understanding the conformational and dynamic behaviors of such polymer and/or DNA molecules during the translocation processes.

  1. JEM-X background models

    E-print Network

    J. Huovelin; S. Maisala; J. Schultz; N. J. Westergaard; C. A. Oxborrow; P. Kretschmar; N. Lund

    2003-09-10

    Background and determination of its components for the JEM-X X-ray telescope on INTEGRAL are discussed. A part of the first background observations by JEM-X are analysed and results are compared to predictions. The observations are based on extensive imaging of background near the Crab Nebula on revolution 41 of INTEGRAL. Total observing time used for the analysis was 216502 s, with the average of 25 cps of background for each of the two JEM-X telescopes. JEM-X1 showed slightly higher average background intensity than JEM-X2. The detectors were stable during the long exposures, and weak orbital phase dependence in the background outside radiation belts was observed. The analysis yielded an average of 5 cps for the diffuse background, and 20 cps for the instrument background. The instrument background was found highly dependent on position, both for spectral shape and intensity. Diffuse background was enhanced in the central area of a detector, and it decreased radially towards the edge, with a clear vignetting effect for both JEM-X units. The instrument background was weakest in the central area of a detector and showed a steep increase at the very edges of both JEM-X detectors, with significant difference in spatial signatures between JEM-X units. According to our modelling, instrument background dominates over diffuse background in all positions and for all energies of JEM-X.

  2. Microwave Frequency Polarizers

    NASA Technical Reports Server (NTRS)

    Ha, Vien The; Mirel, Paul; Kogut, Alan J.

    2013-01-01

    This article describes the fabrication and analysis of microwave frequency polarizing grids. The grids are designed to measure polarization from the cosmic microwave background. It is effective in the range of 500 to 1500 micron wavelength. It is cryogenic compatible and highly robust to high load impacts. Each grid is fabricated using an array of different assembly processes which vary in the types of tension mechanisms to the shape and size of the grids. We provide a comprehensive study on the analysis of the grids' wire heights, diameters, and spacing.

  3. Heteroplasmy and Ancient Translocation of Mitochondrial DNA to the Nucleus in the Chinese Horseshoe Bat (Rhinolophus sinicus) Complex

    PubMed Central

    Hua, Panyu; He, Guimei; Zhang, Shuyi; Rossiter, Stephen J.

    2014-01-01

    The utility and reliability of mitochondrial DNA sequences in phylogenetic and phylogeographic studies may be compromised by widespread and undetected nuclear mitochondrial copies (numts) as well as heteroplasmy within individuals. Both numts and heteroplasmy are likely to be common across diverse taxa yet few studies have characterised their frequencies and variation at the intra-specific level. Here we report the presence of both numts and heteroplasmy in the mitochondrial control region of the Chinese horseshoe bat Rhinolophus sinicus. In total we generated 123 sequences from 18 bats, which contained two different numt clades (i.e. Numt-1 and Numt-2) and one mtDNA clade. The sequence divergence between Numt-1 and Numt-2 was 16.8% and each numt type was found in all four R. sinicus taxa, suggesting either two ancient translocations of mitochondrial DNA into the nucleus from the same source taxon, or a single translocation from different source taxa that occurred before the split of R. sinicus into different lineages. Within the mtDNA clade, phylogenetic relationships among the four taxa of R. sinicus were similar to those seen in previous results. Based on PCR comparisons, heteroplasmy was inferred between almost all individuals of R. sinicus with respect to sequence variation. Consistent with introgression of mtDNA between Central sinicus and septentrionalis, individuals from these two taxa exhibited similar signatures of repeated sequences in the control region. Our study highlights the importance of testing for the presence of numts and heteroplasmy when applying mtDNA markers to phylogenetic studies. PMID:24842827

  4. Moraxella catarrhalis uses a twin-arginine translocation system to secrete the ?-lactamase BRO-2

    PubMed Central

    2013-01-01

    Background Moraxella catarrhalis is a human-specific gram-negative bacterium readily isolated from the respiratory tract of healthy individuals. The organism also causes significant health problems, including 15-20% of otitis media cases in children and ~10% of respiratory infections in adults with chronic obstructive pulmonary disease. The lack of an efficacious vaccine, the rapid emergence of antibiotic resistance in clinical isolates, and high carriage rates reported in children are cause for concern. Virtually all Moraxella catarrhalis isolates are resistant to ?-lactam antibiotics, which are generally the first antibiotics prescribed to treat otitis media in children. The enzymes responsible for this resistance, BRO-1 and BRO-2, are lipoproteins and the mechanism by which they are secreted to the periplasm of M. catarrhalis cells has not been described. Results Comparative genomic analyses identified M. catarrhalis gene products resembling the TatA, TatB, and TatC proteins of the well-characterized Twin Arginine Translocation (TAT) secretory apparatus. Mutations in the M. catarrhalis tatA, tatB and tatC genes revealed that the proteins are necessary for optimal growth and resistance to ?-lactams. Site-directed mutagenesis was used to replace highly-conserved twin arginine residues in the predicted signal sequence of M. catarrhalis strain O35E BRO-2, which abolished resistance to the ?-lactam antibiotic carbanecillin. Conclusions Moraxella catarrhalis possesses a TAT secretory apparatus, which plays a key role in growth of the organism and is necessary for secretion of BRO-2 into the periplasm where the enzyme can protect the peptidoglycan cell wall from the antimicrobial activity of ?-lactam antibiotics. PMID:23782650

  5. Oleanolic acid attenuates renal fibrosis in mice with unilateral ureteral obstruction via facilitating nuclear translocation of Nrf2

    PubMed Central

    2014-01-01

    Background Renal interstitial fibrosis is a common final pathological process in the progression of kidney disease. This is primarily due to oxidative stress, which contributes to renal inflammation and fibrosis. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is known to coordinate induction of genes that encode antioxidant enzymes. We investigated the effects of oleanolic acid, a known Nrf2 activator, on oxidative stress-induced renal inflammation and fibrosis. Methods One day before unilateral ureteral obstruction (UUO) performed in C57BL/6 mice, oleanolic acid treatment was initiated and was continued until 3 and 7 days after UUO. Renal inflammation and fibrosis, markers of oxidative stress, and changes in Nrf2 expression were subsequently evaluated. Results In the obstructed kidneys of UUO mice, oleanolic acid significantly attenuated UUO-induced collagen deposition and fibrosis on day 7. Additionally, significantly less inflammatory cell infiltration, a lower ratio of Bax to Bcl-2 expression, and fewer apoptotic cells on TUNEL staining were observed in the obstructed kidneys of oleanolic acid-treated mice. Oleanolic acid increased the expression of nuclear Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and heat shock protein 70, and decreased lipid peroxidation in the obstructed kidney of UUO mice. There were no changes in the expression of total Nrf2 and Kelch-like ECH-associated protein 1, indicating that oleanolic acid enhanced nuclear translocation of Nrf2. Conclusions These results suggest that oleanolic acid may exert beneficial effects on renal fibrosis by increasing nuclear translocation of Nrf2 and subsequently reducing renal oxidative stress. PMID:24393202

  6. Cosmic Microwave Background Polarization and Inflation

    NASA Technical Reports Server (NTRS)

    Chuss, David T.

    2011-01-01

    Measurements of the cosmic microwave background (CMB) offer a means to explore the universe at a very early epoch. Specifically, if the universe went through a brief period of exponential expansion called inflation as current data suggest, gravitational waves from this period would polarize the CMB in a specific pattern. At GSFC, we are currently working towards two experiments that work in concert to measure this polarization pattern in search of evidence for inflation. The Cosmology Large Angular Scale Surveyor (CLASS) will measure the polarization at frequencies between 40 and 150 GHz from the Atacama Desert in Chile. The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne experiment that will make similar measurements at frequencies between 200 and 600 GHz.

  7. Targeting Na(+) /K(+) -translocating adenosine triphosphatase in cancer treatment.

    PubMed

    Durlacher, Cameron T; Chow, Kevin; Chen, Xiao-Wu; He, Zhi-Xu; Zhang, Xueji; Yang, Tianxin; Zhou, Shu-Feng

    2015-05-01

    The Na(+) /K(+) -translocating adenosine triphosphatase (ATPase) transports sodium and potassium across the plasma membrane and represents a potential target in cancer chemotherapy. Na(+) /K(+) -ATPase belongs to the P-type ATPase family (also known as E1-E2 ATPase), which is involved in transporting certain ions, metals, and lipids across the plasma membrane of mammalian cells. In humans, the Na(+) /K(+) -ATPase is a binary complex of an ?-subunit that has four isoforms (?1 -?4 ) and a ?-subunit that has three isoforms (?1 -?3 ). This review aims to update our knowledge on the role of Na(+) /K(+) -ATPase in cancer development and metastasis, as well as on how Na(+) /K(+) -ATPase inhibitors kill tumour cells. The Na(+) /K(+) -ATPase has been found to be associated with cancer initiation, growth, development, and metastasis. Cardiac glycosides have exhibited anticancer effects in cell-based and mouse studies via inhibition of the Na(+) /K(+) -ATPase and other mechanisms. Na(+) /K(+) -ATPase inhibitors may kill cancer cells via induction of apoptosis and autophagy, radical oxygen species production, and cell cycle arrest. They also modulate multiple signalling pathways that regulate cancer cell survival and death, which contributes to their antiproliferative activities in cancer cells. The clinical evidence supporting the use of Na(+) /K(+) -ATPase inhibitors as anticancer drugs is weak. Several phase I and phase II clinical trials with digoxin, Anvirzel, and huachansu (an intravenous formulated extract of the venom of the wild toad), either alone or more often in combination with other anticancer agents, have shown acceptable safety profiles but limited efficacy in cancer patients. Well-designed randomized clinical trials with reasonable sample sizes are certainly warranted to confirm the efficacy and safety of cardiac glycosides for the treatment of cancer. PMID:25739707

  8. Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity.

    PubMed

    Boydstun, I; Najjar, S; Kashgarian, M; Carpenter, T; Siegel, N

    1995-04-01

    Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates recovery of renal function. This effect is not related to global improvement in cell integrity. To determine the mechanism by which recovery of cellular ATP is enhanced, the effect of T4 on mitochondrial ATP production was evaluated using specific inhibitor stop assays for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T4 (20 micrograms/kg) during the reflow period. By 30-min reflow; the values for apparent endpoint of phosphate transport (PiTm, nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic animals (10.3 +/- 0.9) and remained stable at 120 min. T4 treatment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 +/- 0.5) and 120-min (13.7 +/- 1.0) reflow compared with nonischemic control rats (24.7 +/- 2.4). T4 significantly improved ADPTm by 30 min (10.1 +/- 0.6, P < 0.05). By 120 min T4 stimulated ADPTm (37.7 +/- 5.2, P < 0.05) to exceed nonischemic control values. These data suggest the following: 1) postischemic mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which exceeds control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7733309

  9. [Molecular model of anthrax toxin translocation into target-cells].

    PubMed

    Noskov, A N

    2014-01-01

    Anthrax toxin is formed from three components: protective antigen (PA), lethal (LF) and edema (EF) factors. PA83 is cleaved by cell surface protease furin to produce a 63-kDa fragment (PA63). PA63 and LF/EF molecules are assembled to anthrax toxin complexes: oligomer PA63 x 7 + LF/EF x 3. Assembly is occurred during of binding with cellular receptor or near surface of target-cell. This toxin complex forms pore and induces receptor-mediated endocytosis. Formed endosome consists extracellular liquid with LF/EF and membrane-associated ferments (H+ and K+/Na+-ATPases) and proteins (receptors and others). H+ concentration is increased into endosome as result of K/Na-ATPase-dependent- activity of H+-ATPase. Difference of potentials (between endosome and intracellular liquid) is increased and LF/EF molecules are moved to pore and bound with PA63-oligomer to PA63 x 7 + LF/EF x 7 and full block pore (ion-selective channel). Endosome is increased in volume and induces increasing of PA63-oligomer pore to.size of effector complex: LF/EF x 7 + PAl7 x 7 = 750 kDa. Effector complex is translocated from endosome to cytosol by means high difference of potentials (H+) and dissociates from PA47 x 7 complex after cleavage of FFD315-sait by intracellular chymotrypsin-like proteases in all 7 molecules PA63. PA47 x 7 complex (strongly fixed in membrane with debris of hydrophobic loops) return into endosome and pore is destroyed. Endosome pH is decreased rapidly and PA47 x 7 complex is destroyed by endosomal/lysosomal proteases. Receptor-mediated endocytosis is ended by endosome recycling in cell-membrane. PMID:25898749

  10. Hepatitis B Virus Translocates across a Trophoblastic Barrier?

    PubMed Central

    Bhat, Purnima; Anderson, David A.

    2007-01-01

    Mother-infant transmission of hepatitis B virus (HBV) accounts for up to 30% of worldwide chronic infections. The mechanism and high-risk period of HBV transmission from mother to infant are unknown. Although largely prevented by neonatal vaccination, significant transmission continues to occur in high-risk populations. It is unclear whether HBV can traverse an intact epithelial barrier to infect a new host. Transplacental transmission of a number of viruses relies on transcytotic pathways across placental cells. We wished to determine whether infectious HBV can traverse a polarized trophoblast monolayer. We used a human placenta-derived cell line, BeWo, cultured on membranes as polarized monolayers, to model the maternal-fetal barrier. We assessed the effects of placental maturity and maternal immunoglobulin on viral transport. Intracellular viral trafficking pathways were investigated by confocal microscopy. Free HBV (and infectious duck hepatitis B virus) transcytosed across trophoblastic cells at a rate of 5% in 30 min. Viral transport occurred in microtubule-dependent endosomal vesicles. Additionally, confocal microscopy showed that the internalized virus traverses a monensin-sensitive endosomal compartment. Differentiation of the cytotrophoblasts to syncytiotrophoblasts resulted in a 25% reduction in viral transcytosis, suggesting that placental maturity may protect the fetus. Virus translocation was also reduced in the presence of HBV immunoglobulin. We show for the first time that transcytosis of infectious hepadnavirus can occur across a trophoblastic barrier early in gestation, with the risk of transmission being reduced by placental maturity and specific maternal antibody. This study suggests a mechanism by which mother-infant transmission may occur. PMID:17442714

  11. Nonparametric Inference for the Cosmic Microwave Background

    E-print Network

    Genovese, C R; Nichol, R C; Arjunwadkar, M; Wasserman, L; Genovese, Christopher R.; Miller, Christopher J.; Nichol, Robert C.; Arjunwadkar, Mihir; Wasserman, Larry

    2004-01-01

    The Cosmic Microwave Background (CMB), which permeates the entire Universe, is the radiation left over from just 380,000 years after the Big Bang. On very large scales, the CMB radiation field is smooth and isotropic, but the existence of structure in the Universe - stars, galaxies, clusters of galaxies - suggests that the field should fluctuate on smaller scales. Recent observations, from the Cosmic Microwave Background Explorer to the Wilkinson Microwave Anisotropy Project, have strikingly confirmed this prediction. CMB fluctuations provide clues to the Universe's structure and composition shortly after the Big Bang that are critical for testing cosmological models. For example, CMB data can be used to determine what portion of the Universe is composed of ordinary matter versus the mysterious dark matter and dark energy. To this end, cosmologists usually summarize the fluctuations by the power spectrum, which gives the variance as a function of angular frequency. The spectrum's shape, and in particular the ...

  12. Stochastic background of gravitational waves from fermions

    NASA Astrophysics Data System (ADS)

    Enqvist, Kari; Figueroa, Daniel G.; Meriniemi, Tuukka

    2012-09-01

    Preheating and other particle production phenomena in the early Universe can give rise to high-energy out-of-equilibrium fermions with an anisotropic stress. We develop a formalism to calculate the spectrum of gravitational waves due to fermions, and apply it to a variety of scenarios after inflation. We pay particular attention to regularization issues. We show that fermion production sources a stochastic background of gravitational waves with a significant amplitude, but we find that typical frequencies oef this new background are not within the presently accessible direct detection range. However, small-coupling scenarios might still produce a signal observable by planned detectors, and thus open a new window into the physics of the very early Universe.

  13. Bordetella pertussis adenylate cyclase toxin translocation across a tethered lipid bilayer

    PubMed Central

    Veneziano, Rémi; Rossi, Claire; Chenal, Alexandre; Devoisselle, Jean-Marie; Ladant, Daniel; Chopineau, Joel

    2013-01-01

    Numerous bacterial toxins can cross biological membranes to reach the cytosol of mammalian cells, where they exert their cytotoxic effects. Our model toxin, the adenylate cyclase (CyaA) from Bordetella pertussis, is able to invade eukaryotic cells by translocating its catalytic domain directly across the plasma membrane of target cells. To characterize its original translocation process, we designed an in vitro assay based on a biomimetic membrane model in which a tethered lipid bilayer (tBLM) is assembled on an amine-gold surface derivatized with calmodulin (CaM). The assembled bilayer forms a continuous and protein-impermeable boundary completely separating the underlying calmodulin (trans side) from the medium above (cis side). The binding of CyaA to the tBLM is monitored by surface plasmon resonance (SPR) spectroscopy. CyaA binding to the immobilized CaM, revealed by enzymatic activity, serves as a highly sensitive reporter of toxin translocation across the bilayer. Translocation of the CyaA catalytic domain was found to be strictly dependent on the presence of calcium and also on the application of a negative potential, as shown earlier in eukaryotic cells. Thus, CyaA is able to deliver its catalytic domain across a biological membrane without the need for any eukaryotic components besides CaM. This suggests that the calcium-dependent CyaA translocation may be driven in part by the electrical field across the membrane. This study’s in vitro demonstration of toxin translocation across a tBLM provides an opportunity to explore the molecular mechanisms of protein translocation across biological membranes in precisely defined experimental conditions. PMID:24297899

  14. Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation.

    PubMed

    Ventura, Mireia; Mateo, Francesca; Serratosa, Joan; Salaet, Ignasi; Carujo, Sonia; Bachs, Oriol; Pujol, María Jesús

    2010-10-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is considered a housekeeping glycolitic enzyme that recently has been implicated in cell signaling. Under apoptotic stresses, cells activate nitric oxide formation leading to S-nitrosylation of GAPDH that binds to Siah and translocates to the nucleus. The GAPDH-Siah interaction depends on the integrity of lysine 227 in human GAPDH, being the mutant K227A unable to associate with Siah. As lysine residues are susceptible to be modified by acetylation, we aimed to analyze whether acetylation could mediate transport of GAPDH from cytoplasm to the nucleus. We observed that the acetyltransferase P300/CBP-associated factor (PCAF) interacts with and acetylates GAPDH. We also found that over-expression of PCAF induces the nuclear translocation of GAPDH and that for this translocation its intact acetylase activity is needed. Finally, the knocking down of PCAF reduces nuclear translocation of GAPDH induced by apoptotic stimuli. By spot mapping analysis we first identified Lys 117 and 251 as the putative GAPDH residues that could be acetylated by PCAF. We further demonstrated that both Lys were necessary but not sufficient for nuclear translocation of GAPDH after apoptotic stimulation. Finally, we identified Lys 227 as a third GAPDH residue whose acetylation is needed for its transport from cytoplasm to the nucleus. Thus, results reported here indicate that nuclear translocation of GAPDH is mediated by acetylation of three specific Lys residues (117, 227 and 251 in human cells). Our results also revealed that PCAF participates in the GAPDH acetylation that leads to its translocation to the nucleus. PMID:20601085

  15. Tracking translocation of industrially relevant engineered nanomaterials (ENMs) across alveolar epithelial monolayers in vitro.

    PubMed

    Cohen, Joel M; Derk, Raymond; Wang, Liying; Godleski, John; Kobzik, Lester; Brain, Joseph; Demokritou, Philip

    2014-08-01

    Abstract Relatively little is known about the fate of industrially relevant engineered nanomaterials (ENMs) in the lungs that can be used to convert administered doses to delivered doses. Inhalation exposure and subsequent translocation of ENMs across the epithelial lining layer of the lung might contribute to clearance, toxic effects or both. To allow precise quantitation of translocation across lung epithelial cells, we developed a method for tracking industrially relevant metal oxide ENMs in vitro using neutron activation. The versatility and sensitivity of the proposed in vitro epithelial translocation (INVET) system was demonstrated using a variety of industry relevant ENMs including CeO2 of various primary particle diameter, ZnO, and SiO2-coated CeO2 and ZnO particles. ENMs were neutron activated, forming gamma emitting isotopes (141)Ce and (65)Zn, respectively. Calu-3 lung epithelial cells cultured to confluency on transwell inserts were exposed to neutron-activated ENM dispersions at sub-lethal doses to investigate the link between ENM properties and translocation potential. The effects of ENM exposure on monolayer integrity was monitored by various methods. ENM translocation across the cellular monolayer was assessed by gamma spectrometry following 2, 4 and 24?h of exposure. Our results demonstrate that ENMs translocated in small amounts (e.g. <0.01% of the delivered dose at 24?h), predominantly via transcellular pathways without compromising monolayer integrity or disrupting tight junctions. It was also demonstrated that the delivery of particles in suspension to cells in culture is proportional to translocation, emphasizing the importance of accurate dosimetry when comparing ENM-cellular interactions for large panels of materials. The reported INVET system for tracking industrially relevant ENMs while accounting for dosimetry can be a valuable tool for investigating nano-bio interactions in the future. PMID:24479615

  16. Tracking translocation of industrially relevant engineered nanomaterials (ENMs) across alveolar epithelial monolayers in vitro

    PubMed Central

    Cohen, Joel M.; Derk, Raymond; Wang, Liying; Godleski, John; Kobzik, Lester; Brain, Joseph; Demokritou, Philip

    2015-01-01

    Relatively little is known about the fate of industrially relevant engineered nanomaterials (ENMs) in the lungs. Inhalation exposure and subsequent translocation of ENMs across the epithelial lining layer of the lung might contribute to clearance, toxic effects or both. To allow precise quantitation of translocation across lung epithelial cells, we developed a method for tracking industrially-relevant metal oxide ENMs in vitro using neutron activation. The versatility and sensitivity of the proposed In Vitro Epithelial Translocation (INVET) system was demonstrated using a variety of industry relevant ENMs including CeO2 of various primary particle diameter, ZnO, and SiO2-coated-CeO2 and ZnO particles. ENMs were neutron activated, forming gamma emitting isotopes 141Ce and 65Zn respectively. Calu-3 lung epithelial cells cultured to confluency on transwell inserts were exposed to neutron-activated ENM dispersions at sub-lethal doses to investigate the link between ENM properties and translocation potential. The effects of ENM exposure on monolayer integrity was monitored by various methods. ENM translocation across the cellular monolayer was assessed by gamma spectrometry following 2, 4 and 24 hours of exposure. Our results demonstrate that ENMs translocated in small amounts (e.g. <0.01% of the delivered dose at 24 h), predominantly via transcellular pathways without compromising monolayer integrity or disrupting tight junctions. It was also demonstrated that the delivery of particles in suspension to cells in culture is proportional to translocation, emphasizing the importance of accurate dosimetry when comparing ENM-cellular interactions for large panels of materials. The reported INVET system for tracking industrially relevant ENMs while accounting for dosimetry can be a valuable tool for investigating nano-bio interactions in the future. PMID:24479615

  17. Ranging behavior of translocated and established groups of black howler monkeys Alouatta pigra in Belize, Central America

    Microsoft Academic Search

    Linde E. T. Ostro; Scott C. Silver; Fred W. Koontz; Truman P. Young; Robert H. Horwich

    1999-01-01

    We studied the ranging behavior of translocated and non-translocated groups of Alouatta pigra in Belize, Central America from March 1994 to May 1995. Home range size, day-range length and monthly range size were determined for all groups. In high density populations, home range size and day-range length increased with group size. Home range size increased with translocation to a low

  18. Viability of X-autosome translocations in mammals: an epigenomic hypothesis from a rodent case-study

    Microsoft Academic Search

    G. Dobigny; C. Ozouf-Costaz; C. Bonillo; V. Volobouev

    2004-01-01

    X-autosome translocations are highly deleterious chromosomal rearrangements due to meiotic disruption, the effects of X-inactivation on the autosome, and the necessity of maintaining different replication timing patterns between the two segments. In spite of this, X-autosome translocations are not uncommon. We here focus on the genus Taterillus (Rodentia, Gerbillinae) which provides two sister lineages differing by two autosome–gonosome translocations. Despite

  19. Sec-dependent membrane protein biogenesis: SecYEG, preprotein hydrophobicity and translocation kinetics control the stop-transfer function.

    PubMed Central

    Duong, F; Wickner, W

    1998-01-01

    Preprotein translocase catalyzes membrane protein integration as well as complete translocation. Membrane proteins must interrupt their translocation and be laterally released from the translocase into the lipid bilayer. We have analyzed the translocation arrest and lateral release activities of Escherichia coli preprotein translocase with an in vitro reaction and the preprotein proOmpA carrying a synthetic stop-transfer sequence. Membrane protein integration is catalytic, occurs with kinetics similar to those of proOmpA itself and only requires the functions of SecYEG and SecA. Though a strongly hydrophobic segment will direct the protein to leave the translocase and enter the lipid bilayer, a protein with a segment of intermediate hydrophobicity partitions equally between the translocated and membrane-integrated states. Analysis of the effects of PMF, varied ATP concentrations or synthetic translocation arrest show that the stop-translocation efficiency of a mildly hydrophobic segment depends on the translocation kinetics. In contrast, the lateral partitioning from translocase to lipids depends solely on temperature and does not require SecA ATP hydrolysis or SecA membrane cycling. Thus translocation arrest is controlled by the SecYEG translocase activity while lateral release and membrane integration are directed by the hydrophobicity of the segment itself. Our results suggest that a greater hydrophobicity is required for efficient translocation arrest than for lateral release into the membrane. PMID:9450995

  20. Interactions of histatin 5 and histatin 5-derived peptides with liposome membranes: surface effects, translocation and permeabilization.

    PubMed Central

    Den Hertog, Alice L; Wong Fong Sang, Harro W; Kraayenhof, Ruud; Bolscher, Jan G M; Van't Hof, Wim; Veerman, Enno C I; Nieuw Amerongen, Arie V

    2004-01-01

    A number of cationic antimicrobial peptides, among which are histatin 5 and the derived peptides dhvar4 and dhvar5, enter their target cells and interact with internal organelles. There still are questions about the mechanisms by which antimicrobial peptides translocate across the membrane. We used a liposome model to study membrane binding, translocation and membrane-perturbing capacities of histatin 5, dhvar4 and dhvar5. Despite the differences in amphipathic characters of these peptides, they bound equally well to liposomes, whereas their membrane activities differed remarkably: dhvar4 translocated at the fastest rate, followed by dhvar5, whereas the histatin 5 translocation rate was much lower. The same pattern was seen for the extent of calcein release: highest with dhvar4, less with dhvar5 and almost none with histatin 5. The translocation and disruptive actions of dhvar5 did not seem to be coupled, because translocation occurred on a much longer timescale than calcein release, which ended within a few minutes. We conclude that peptide translocation can occur through peptide-phospholipid interactions, and that this is a possible mechanism by which antimicrobial peptides enter cells. However, the translocation rate was much lower in this model membrane system than that seen in yeast cells. Thus it is likely that, at least for some peptides, additional features promoting the translocation across biological membranes are involved as well. PMID:14733612

  1. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    PubMed Central

    Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

    2012-01-01

    Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

  2. Regulation of translocated c-myc genes transfected into plasmacytoma cells

    SciTech Connect

    Feo, S.; Harvey, R.; Showe, L.; Croce, C.M.

    1986-02-01

    The authors have transfected two translocated c-myc oncogene clones, derived from two human lymphomas carrying the t(8;14) chromosome translocation, into mouse plasmacytoma cells to study the regulation of their expression. In one case, the transfected clone contained the two coding exons of the c-myc oncogene translocated to an immunoglobulin heavy-chain switch region; in the other case, the two coding exons were translocated 5' of the enhancer element located between the heavy-chain joining region (J/sub H/) and the switch region S/sub ..mu../. Nuclease S1 protection experiments indicate that only the c-myc translocated 5' of the enhancer element is transcribed in the plasmacytoma cells. Thus, 5'-truncation of the c-myc gene per se does not lead to c-myc deregulation. Further, since the level of c-myc transcripts in the parental human lymphoma cells was 3- to 4-fold higher than in the transfectants, it seems likely that additional elements within the heavy-chain locus may play a role in the enhancement of c-myc gene transcription in lymphoma cells.

  3. Preserving the membrane barrier for small molecules during bacterial protein translocation

    PubMed Central

    Park, Eunyong; Rapoport, Tom A.

    2011-01-01

    Many proteins are translocated through the SecY channel in bacteria and archaea, and the related Sec61 channel in eukaryotes1. The channel has an hourglass shape with a narrow constriction approximately halfway across the membrane, formed by a pore ring of amino acids2. While the cytoplasmic cavity of the channel is empty, the extra-cellular cavity is filled with a short helix, the plug2, which moves out of the way during protein translocation3,4. The mechanism by which the channel transports large polypeptides and yet prevents the passage of small molecules, such as ions or metabolites, has been controversial2,5–8. Here, we have addressed this issuein intact E. coli cells by testing the permeation of small molecules through wild-type and mutant SecY channels, which are either in the resting state or contain a defined translocating polypeptide chain. In the resting state, the channel is sealed by both the pore ring and the plug domain. During translocation the pore ring forms a gasket-like seal around the polypeptide chain, preventing the permeation of small molecules. The structural conservation of the channel in all organisms suggests a universal mechanism by which the membrane barrier is maintained during protein translocation. PMID:21562565

  4. A comparative study on the uptake and translocation of organochlorines by Phragmites australis.

    PubMed

    San Miguel, Angélique; Ravanel, Patrick; Raveton, Muriel

    2013-01-15

    Organochlorines (OCs) are persistent chemicals found in various environmental compartments. The differences in the uptake of (14)C-labeled 1,4-dichlorobenzene (DCB), 1,2,4-trichlorobenzene (TCB) and ?-hexachlorocyclohexane (?HCH) by Phragmites australis were investigated under hydroponic conditions. The first step in sorption appears to be correlated with the hydrophobic nature of the compounds, since log-linear correlations were obtained between root concentration factor and partition coefficient (LogK(ow)). After 7 days of exposure, plant uptake of DCB, TCB, ?HCH was significant with bioconcentration factors reaching 14, 19 and 15, respectively. Afterwards, uptake and translocation were seen to be more complex, with a loss of the simple relationship between uptake and LogK(ow). Linear correlations between the bioconcentration/translocation factors and the physico-chemical properties of OCs were shown, demonstrating that translocation from roots to shoots increases with solubility and volatility of the OCs. This suggests that OC-translocation inside plants might result from the combination of two processes, xylem sap flow and vapor fluxes. (14)C-phytovolatilization was measured and was correlated with the volatility of the compounds; the more volatile OCs being most the likely to be phytovolatilized from foliar surfaces (p=0.0008). Thus, OC-uptake/translocation appears to proceed at a rate that depends mostly on the OCs hydrophobicity, solubility and volatility. PMID:23246941

  5. Detection of a complex translocation using fluorescent in situ hybridization (FISH)

    SciTech Connect

    Rosen, B.A. [Brandeis Univ., Waltham, MA (United States); Abuelo, D.N. [Rhode Island Hospital, Providence, RI (United States); Mark, H.F. [Brown Univ. School of Medicine, Providence, RI (United States)

    1994-09-01

    The use of fluorescent in situ hybridization (FISH) allowed the detection of a complex 3-way translocation in a patient with multiple congenital malformations and mental retardation. The patient was a 10-year-old girl with mental retardation, seizures, repaired cleft palate, esotropia, epicanthal folds, broad nasal bridge, upward slanting palpebral fissures, single transverse palmar crease, brachydactyly, hypoplastic nails, ectrodactyly between the third and fourth right toes, and hypoplasia of the left third toe. Chromosome analysis performed at birth was reported as normal. We performed high resolution banding analysis which revealed an apparently balanced translocation between chromosomes 2 and 9. However, because of her multiple abnormalities, further studies were ordered. Fluorescent in situ hybridization (FISH) using chromosome painting probes revealed a karyotype of 46,XX,t(2;8;9) (2pter{yields}q31::8q21.2{yields}8qter; 8pter{yields}q21.2::2q31{yields}q34::9q34{yields}qter; 9pter{yields}q34::2q34{yields}qter). The 3-way translocation appears to be de novo, as neither parent is a translocation carrier. This case illustrates the importance of using FISH to further investigate cases of apparently balanced translocations in the presence of phenotypic abnormalities and/or mental retardation.

  6. Identification and characterization of small-molecule inhibitors of Yop translocation in Yersinia pseudotuberculosis.

    PubMed

    Harmon, Dana E; Davis, Alison J; Castillo, Cynthia; Mecsas, Joan

    2010-08-01

    Type three secretion systems (TTSSs) are virulence factors found in many pathogenic Gram-negative species, including the family of pathogenic Yersinia spp. Yersinia pseudotuberculosis requires the translocation of a group of effector molecules, called Yops, to subvert the innate immune response and establish infection. Polarized transfer of Yops from bacteria to immune cells depends on several factors, including the presence of a functional TTSS, the successful attachment of Yersinia to the target cell, and translocon insertion into the target cell membrane. Here we employed a high-throughput screen to identify small molecules that block translocation of Yops into mammalian cells. We identified 6 compounds that inhibited translocation of effectors without affecting synthesis of TTSS components and secreted effectors, assembly of the TTSS, or secretion of effectors. One compound, C20, reduced adherence of Y. pseudotuberculosis to target cells. Additionally, the compounds caused leakage of Yops into the supernatant during infection and thus reduced polarized translocation. Furthermore, several molecules, namely, C20, C22, C24, C34, and C38, also inhibited ExoS-mediated cell rounding, suggesting that the compounds target factors that are conserved between Pseudomonas aeruginosa and Y. pseudotuberculosis. In summary, we have identified 6 compounds that specifically inhibit translocation of Yops into mammalian cells but not Yop synthesis or secretion. PMID:20498321

  7. Folding of Active ?-Lactamase in the Yeast Cytoplasm before Translocation into the Endoplasmic Reticulum

    PubMed Central

    Paunola, Eija; Suntio, Taina; Jämsä, Eija; Makarow, Marja

    1998-01-01

    Polypeptides targeted to the yeast endoplasmic reticulum (ER) posttranslationally are thought to be kept in the cytoplasm in an unfolded state by Hsp70 chaperones before translocation. We show here that Escherichia coli ?-lactamase associated with Hsp70, but adopted a native-like conformation before translocation in living Saccharomyces cerevisiae cells. ?-Lactamase is a globular trypsin-resistant molecule in authentic form. For these studies, it was linked to the C terminus of a yeast polypeptide Hsp150?, which conferred posttranslational translocation and provided sites for O-glycosylation. We devised conditions to retard translocation of Hsp150?-?-lactamase. This enabled us to show by protease protection assays that an unglycosylated precursor was associated with the cytoplasmic surface of isolated microsomes, whereas a glycosylated form resided inside the vesicles. Both proteins were trypsin resistant and had similar ?-lactamase activity and Km values for nitrocefin. The enzymatically active cytoplasmic intermediate could be chased into the ER, followed by secretion of the activity to the medium. Productive folding in the cytoplasm occurred in the absence of disulfide formation, whereas in the ER lumen, proper folding required oxidation of the sulfhydryls. This suggests that the polypeptide was refolded in the ER and consequently, at least partially unfolded for translocation. PMID:9529380

  8. Numerical and theoretical study on the mechanism of biopolymer translocation process through a nano-pore

    NASA Astrophysics Data System (ADS)

    Alapati, Suresh; Fernandes, Dolfred Vijay; Suh, Yong Kweon

    2011-08-01

    We conducted a numerical study on the translocation of a biopolymer from the cis side to the trans side of a membrane through a synthetic nano-pore driven by an external electric field in the presence of hydrodynamic interactions (HIs). The motion of the polymer is simulated by 3D Langevin dynamics technique using a worm-like chain model of N identical beads, while HI between the polymer and fluid are incorporated by the lattice Boltzmann equation. The translocation process is induced by electrophoretic force, which sequentially straightens out the folds of the initial random configuration of the polymer chain on the cis side. Our simulation results on translocation time and velocity are in good quantitative agreement with the corresponding experimental ones when the surface charge on the nano-pore and the HI effect are considered explicitly. We found that the translocation velocity of each bead inside the nano-pore mainly depends upon the length of the straightened portion of the polymer in forced motion near the pore. We confirmed this by a theoretical formula. After performing simulations with different pore lengths, we observed that translocation velocity mainly depends upon the applied potential difference rather than upon the electric field inside the nano-pore.

  9. Hydrodynamics of diamond-shaped gradient nanopillar arrays for effective DNA translocation into nanochannels.

    PubMed

    Wang, Chao; Bruce, Robert L; Duch, Elizabeth A; Patel, Jyotica V; Smith, Joshua T; Astier, Yann; Wunsch, Benjamin H; Meshram, Siddharth; Galan, Armand; Scerbo, Chris; Pereira, Michael A; Wang, Deqiang; Colgan, Evan G; Lin, Qinghuang; Stolovitzky, Gustavo

    2015-02-24

    Effective DNA translocation into nanochannels is critical for advancing genome mapping and future single-molecule DNA sequencing technologies. We present the design and hydrodynamic study of a diamond-shaped gradient pillar array connected to nanochannels for enhancing the success of DNA translocation events. Single-molecule fluorescence imaging is utilized to interrogate the hydrodynamic interactions of the DNA with this unique structure, evaluate key DNA translocation parameters, including speed, extension, and translocation time, and provide a detailed mapping of the translocation events in nanopillar arrays coupled with 10 and 50 ?m long channels. Our analysis reveals the important roles of diamond-shaped nanopillars in guiding DNA into as small as 30 nm channels with minimized clogging, stretching DNA to nearly 100% of their dyed contour length, inducing location-specific straddling of DNA at nanopillar interfaces, and modulating DNA speeds by pillar geometries. Importantly, all critical features down to 30 nm wide nanochannels are defined using standard photolithography and fabrication processes, a feat aligned with the requirement of high-volume, low-cost production. PMID:25626162

  10. Optoelectronic control of surface charge and translocation dynamics in solid-state nanopores

    PubMed Central

    Di Fiori, Nicolas; Squires, Allison; Bar, Daniel; Gilboa, Tal; Moustakas, Theodore D.; Meller, Amit

    2013-01-01

    Nanopores can be used to detect and analyse biomolecules. However, controlling and tuning the translocation speed of molecules through a pore is difficult, limiting the wider application of these sensors. Here we show that low-power visible light can be used to control surface charge in solid-state nanopores and can influence the translocation dynamics of DNA and proteins. We find that laser light precisely focused at a nanopore can induce reversible negative surface charge densities as high as 1 C/m2, and that the effect is tuneable on sub-millisecond timescales by adjusting the photon density. By modulating surface charge, we can control the amount of electro-osmotic flow through the nanopore, which affects the speed of translocating biomolecules. In particular, a few mW of green light can reduce the translocation speed of double-stranded DNA by more than an order of magnitude and the translocation speed of small globular proteins such as ubiquitin by more than two orders of magnitude. The laser light can also be used to unclog blocked pores. Finally, we discuss a mechanism to account for the observed optoelectronic phenomenon. PMID:24185943

  11. Dendritic translocation establishes the winner in cerebellar climbing fiber synapse elimination

    PubMed Central

    Carrillo, Jennifer; Nishiyama, Naoko; Nishiyama, Hiroshi

    2013-01-01

    In many regions of the developing mammalian nervous system, functional synaptic circuitry is formed by competitive elimination of early-formed redundant synapses. However, how winning synapses emerge through competition remains unclear in the brain owing largely to the technical difficulty of directly observing this dynamic cellular process in vivo. Here, we developed a method of two-photon multi-color vital imaging to observe competitive elimination of supernumerary climbing fibers (CFs) in the cerebellum of live mouse pups. At birth, each Purkinje cell (PC) in the cerebellar cortex is innervated by multiple CFs; an activity-dependent regression of supernumerary CFs ultimately yields a single innervation for most PCs by postnatal day (P) 21. As supernumerary CFs are pruned, the terminal field of CFs translocates from the soma to the dendrites of PCs. In vivo time-lapse imaging of CF elimination revealed that: 1) CF terminals were highly motile on the soma, but their motility was significantly reduced on dendrites, 2) only one CF could translocate to the dendrites whereas their competitors were restricted to perisomatic regions, and 3) the CF that began dendritic translocation became the winner. Moreover, selective photo-ablation of the winning CF (that undergoes dendritic translocation) reversed the fate of its losing competitor. These results indicate that dendritic translocation is a key cellular event that determines the winner during CF elimination. We propose that CF terminals are selectively stabilized on dendrites, providing irreversible competitive vigor to the first CF to form dendritic synapses. PMID:23637158

  12. Nutrient translocation in the outer canopy and understory of an eastern deciduous forest

    SciTech Connect

    Luxmoore, R.J.; Grizzard, T.; Strand, R.H.

    1981-09-01

    The translocation of nutrients into and out of outer canopy leaves of ten eastern deciduous forest species was calculated from the temporal patterns of foliar nutrient pools sampled through a growing season. The calculations accounted for average chemical leaching effects due to rainfall. There were no significant differences in translocation rate between species within the evergreen, understory, or overstory-deciduous tree groups. Evergreen species had lower translocation rates than deciduous trees. Translocation rates into leaves of deciduous species showed a very rapid increase during spring; however, by late May, foliar phosphorus was being translocated at a slow rate back to stems. A similar trend was established for nitrogen by mid-June. An internal storage pool is suggested as the major source of foliar nitrogen during the spring flush since a simulation of nitrogen uptake from soil could only account for one-fourth of the quantity of nitrogen transported to leaves by the end of May. Simulation further showed that trace levels of soluble nitrogen (0.01 ppm) in soil were sufficient to supply a deciduous forest with an estimated nitrogen uptake of 100 kg N ha/sup -1/ year/sup -1/.

  13. Evidence that small proteins translocate through silicon nitride pores in a folded conformation

    NASA Astrophysics Data System (ADS)

    Stefureac, Radu I.; Trivedi, Dhruti; Marziali, Andre; Lee, Jeremy S.

    2010-11-01

    The interaction of three proteins (histidine-containing phosphocarrier protein, HPr, calmodulin, CaM, and maltose binding protein, MBP) with synthetic silicon nitride (SiNx) membranes has been studied. The proteins which have a net negative charge were electrophoretically driven into pores of 7 and 5 nm diameter with a nominal length of 15 nm. The % blockade current and event duration were measured at three different voltages. For a translocation event it was expected that the % block would be constant with voltage whilst the event duration would decrease with increasing voltage. On the basis of these criteria, we deduce that MBP whose largest dimension is 6.5 nm does not translocate whereas up to 40% of CaM molecules can translocate the 7 nm pore as can a majority of HPr molecules, with some translocations being observed for the 5 nm pore. For translocation events the magnitude of the % blockade current is consistent with a folded conformation of the proteins surrounded by a hydration shell of 0.5-1.0 nm.

  14. Tau proteins harboring neurodegeneration-linked mutations impair kinesin translocation in vitro.

    PubMed

    Yu, Dezhi; LaPointe, Nichole E; Guzman, Elmer; Pessino, Veronica; Wilson, Leslie; Feinstein, Stuart C; Valentine, Megan T

    2014-01-01

    We tested the hypothesis that mutant tau proteins that cause neurodegeneration and dementia differentially alter kinesin translocation along microtubules (MTs) relative to normal tau in vitro. We employed complementary in vitro motility assays using purified recombinant kinesin, purified recombinant tau, and purified bovine brain ?:? tubulin to isolate interactions among these components without any contribution by cellular regulatory mechanisms. We found that kinesin translocates slower along MTs assembled by any of three independent tau mutants (4-repeat P301L tau, 4-repeat ?N296 tau, and 4-repeat R406W tau) relative to its translocation rate along MTs assembled by normal, 4-repeat wild type (WT) tau. Moreover, the R406W mutation exhibited isoform specific effects; while kinesin translocation along 4-repeat R406W tau assembled MTs is slower than along MTs assembled by 4-repeat WT tau, the R406W mutation had no effect in the 3-repeat tau context. These data provide strong support for the notion that aberrant modulation of kinesin translocation is a component of tau-mediated neuronal cell death and dementia. Finally, we showed that assembling MTs with taxol before coating them with mutant tau obscured effects of the mutant tau that were readily apparent using more physiologically relevant MTs assembled with tau alone, raising important issues regarding the use of taxol as an experimental reagent and novel insights into therapeutic mechanisms of taxol action. PMID:24150109

  15. Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity.

    PubMed Central

    Moroianu, J; Riordan, J F

    1994-01-01

    The intracellular pathway of human angiogenin in calf pulmonary artery endothelial (CPAE) cells has been studied by immunofluorescence microscopy. Proliferating CPAE cells specifically endocytose native angiogenin and translocate it to the nucleus, where it accumulates in the nucleoli. Nuclear translocation of angiogenin does not occur in nonproliferative, confluent CPAE cells. These cells were previously found to express an angiogenin-binding protein (AngBP) that was identified as smooth muscle alpha-actin. Exogenous actin, an anti-actin antibody, heparin, and heparinase treatment all inhibit the internalization of angiogenin, suggesting the involvement of cell surface AngBP/actin and heparan sulfate proteoglycans in this process. It has been established that two regions of angiogenin are essential for its angiogenic activity, one is its endothelial cell binding site and the other its catalytic site capable of cleaving RNA. CPAE cells do not internalize four enzymatically active angiogenin derivatives whose cell binding site is modified, but they do internalize two enzymatically inactive mutants whose cell binding site is intact. Thus, the putative cell binding site of angiogenin is necessary for both endocytosis and nuclear translocation, but the catalytic site is not. Three other angiogenic molecules are also translocated to the nucleus of growing CPAE cells. Overall, the results suggest that nuclear translocation of angiogenin and other angiogenic molecules is a critical step in the process of angiogenesis. Images PMID:8127865

  16. Human lymphoid translocation fragile zones are hypomethylated and have accessible chromatin.

    PubMed

    Lu, Zhengfei; Lieber, Michael R; Tsai, Albert G; Pardo, Carolina E; Müschen, Markus; Kladde, Michael P; Hsieh, Chih-Lin

    2015-04-01

    Chromosomal translocations are a hallmark of hematopoietic malignancies. CG motifs within translocation fragile zones (typically 20 to 600 bp in size) are prone to chromosomal translocation in lymphomas. Here we demonstrate that the CG motifs in human translocation fragile zones are hypomethylated relative to the adjacent DNA. Using a methyltransferase footprinting assay on isolated nuclei (in vitro), we find that the chromatin at these fragile zones is accessible. We also examined in vivo accessibility using cellular expression of a prokaryotic methylase. Based on this assay, which measures accessibility over a much longer time interval than is possible with in vitro methods, these fragile zones were found to be more accessible than the adjacent DNA. Because DNA within the fragile zones can be methylated by both cellular and exogenous methyltransferases, the fragile zones are predominantly in a duplex DNA conformation. These observations permit more-refined models for why these zones are 100- to 1,000-fold more prone to undergo chromosomal translocation than the adjacent regions. PMID:25624348

  17. Optoelectronic control of surface charge and translocation dynamics in solid-state nanopores

    NASA Astrophysics Data System (ADS)

    di Fiori, Nicolas; Squires, Allison; Bar, Daniel; Gilboa, Tal; Moustakas, Theodore D.; Meller, Amit

    2013-12-01

    Nanopores can be used to detect and analyse biomolecules. However, controlling the translocation speed of molecules through a pore is difficult, which limits the wider application of these sensors. Here, we show that low-power visible light can be used to control surface charge in solid-state nanopores and can influence the translocation dynamics of DNA and proteins. We find that laser light precisely focused at a nanopore can induce reversible negative surface charge densities as high as 1 C m-2, and that the effect is tunable on submillisecond timescales by adjusting the photon density. By modulating the surface charge, we can control the amount of electroosmotic flow through the nanopore, which affects the speed of translocating biomolecules. In particular, a few milliwatts of green light can reduce the translocation speed of double-stranded DNA by more than an order of magnitude and the translocation speed of small globular proteins such as ubiquitin by more than two orders of magnitude. The laser light can also be used to unclog blocked pores. Finally, we discuss a mechanism to account for the observed optoelectronic phenomenon.

  18. BECN1 is involved in the initiation of mitophagy: it facilitates PARK2 translocation to mitochondria.

    PubMed

    Choubey, Vinay; Cagalinec, Michal; Liiv, Joanna; Safiulina, Dzhamilja; Hickey, Miriam A; Kuum, Malle; Liiv, Mailis; Anwar, Tahira; Eskelinen, Eeva-Liisa; Kaasik, Allen

    2014-06-01

    The autophagy protein BECN1/Beclin 1 is known to play a central role in autophagosome formation and maturation. The results presented here demonstrate that BECN1 interacts with the Parkinson disease-related protein PARK2. This interaction does not require PARK2 translocation to mitochondria and occurs mostly in cytosol. However, our results suggest that BECN1 is involved in PARK2 translocation to mitochondria because loss of BECN1 inhibits CCCP- or PINK1 overexpression-induced PARK2 translocation. Our results also demonstrate that the observed PARK2-BECN1 interaction is functionally important. Measurements of the level of MFN2 (mitofusin 2), a PARK2 substrate, demonstrate that depletion of BECN1 prevents PARK2 translocation-induced MFN2 ubiquitination and loss. BECN1 depletion also rescues the MFN2 loss-induced suppression of mitochondrial fusion. In sum, our results demonstrate that BECN1 interacts with PARK2 and regulates PARK2 translocation to mitochondria as well as PARK2-induced mitophagy prior to autophagosome formation. PMID:24879156

  19. Translocation domain mutations affecting cellular toxicity identify the Clostridium difficile toxin B pore

    PubMed Central

    Zhang, Zhifen; Park, Minyoung; Tam, John; Auger, Anick; Beilhartz, Greg L.; Lacy, D. Borden; Melnyk, Roman A.

    2014-01-01

    Disease associated with Clostridium difficile infection is caused by the actions of the homologous toxins TcdA and TcdB on colonic epithelial cells. Binding to target cells triggers toxin internalization into acidified vesicles, whereupon cryptic segments from within the 1,050-aa translocation domain unfurl and insert into the bounding membrane, creating a transmembrane passageway to the cytosol. Our current understanding of the mechanisms underlying pore formation and the subsequent translocation of the upstream cytotoxic domain to the cytosol is limited by the lack of information available regarding the identity and architecture of the transmembrane pore. Here, through systematic perturbation of conserved sites within predicted membrane-insertion elements of the translocation domain, we uncovered highly sensitive residues—clustered between amino acids 1,035 and 1,107—that when individually mutated, reduced cellular toxicity by as much as >1,000-fold. We demonstrate that defective variants are defined by impaired pore formation in planar lipid bilayers and biological membranes, resulting in an inability to intoxicate cells through either apoptotic or necrotic pathways. These findings along with the unexpected similarities uncovered between the pore-forming “hotspots” of TcdB and the well-characterized ?-helical diphtheria toxin translocation domain provide insights into the structure and mechanism of formation of the translocation pore for this important class of pathogenic toxins. PMID:24567384

  20. Predisposition for breast cancer in carriers of constitutional translocation 11q; 22q

    SciTech Connect

    Lindblom, A.; Dumanski, J.; White, I.; Nordenskjoeld, M.; Larsson, C.; Sandelin, K.; Iselius, L. (Karolinska Hospital, Stockholm (Sweden))

    1994-05-01

    A translocation between the long arms of chromosomes 11 and 22, t(11;22)(q23;q11), is the most frequent constitutional reciprocal translocation in man. This chromosome abnormality has not previously been reported to be associated with an increased risk for neoplasia. The observation of one patient with a constitutional translocation t(11q;22q) and breast cancer prompted study of the relationship between these two conditions. The incidence of breast cancer was determined in carriers of t(11q;22q). The karyotypes were determined by QFQ-banding, and the breakpoints were then further characterized by fluorescent in situ hybridization. Eight families with a total of 22 balanced carriers were found. In five of these families there was one case of breast cancer each. In another family a case of an unknown malignancy was reported in one member. No other malignancies were found among these patients. The number of breast cancer cases were significantly higher than expected among the translocation carriers (P<.0001). The chromosomal breakpoints showed the same localization with the markers used, in the seven families studied. The association of constitutional translocation t(11q;22q) and breast cancer identifies a subset of patients with a highly increased risk for breast cancer who would benefit from counseling and screening. It also suggests the involvement of genes on 11q and/or 22q, in the tumorigenesis of breast cancer. 36 refs., 2 figs.

  1. Direct observation of the translocation mechanism of transcription termination factor Rho

    PubMed Central

    Gocheva, Veronika; Le Gall, Antoine; Boudvillain, Marc; Margeat, Emmanuel; Nollmann, Marcelo

    2015-01-01

    Rho is a ring-shaped, ATP-fueled motor essential for remodeling transcriptional complexes and R-loops in bacteria. Despite years of research on this fundamental model helicase, key aspects of its mechanism of translocation remain largely unknown. Here, we used single-molecule manipulation and fluorescence methods to directly monitor the dynamics of RNA translocation by Rho. We show that the efficiency of Rho activation is strongly dependent on the force applied on the RNA but that, once active, Rho is able to translocate against a large opposing force (at least 7 pN) by a mechanism involving ‘tethered tracking’. Importantly, the ability to directly measure dynamics at the single-molecule level allowed us to determine essential motor properties of Rho. Hence, Rho translocates at a rate of ?56 nt per second under our experimental conditions, which is 2–5 times faster than velocities measured for RNA polymerase under similar conditions. Moreover, the processivity of Rho (?62 nt at a 7 pN opposing force) is large enough for Rho to reach termination sites without dissociating from its RNA loading site, potentially increasing the efficiency of transcription termination. Our findings unambiguously establish ‘tethered tracking’ as the main pathway for Rho translocation, support ‘kinetic coupling’ between Rho and RNA polymerase during Rho-dependent termination, and suggest that forces applied on the nascent RNA transcript by cellular substructures could have important implications for the regulation of transcription and its coupling to translation in vivo. PMID:25662222

  2. Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations.

    PubMed

    Inagaki, Hidehito; Ohye, Tamae; Kogo, Hiroshi; Tsutsumi, Makiko; Kato, Takema; Tong, Maoqing; Emanuel, Beverly S; Kurahashi, Hiroki

    2013-01-01

    Gross chromosomal rearrangements (GCRs), such as translocations, deletions or inversions, are often generated by illegitimate repair between two DNA breakages at regions with nucleotide sequences that might potentially adopt a non-B DNA conformation. We previously established a plasmid-based model system that recapitulates palindrome-mediated recurrent chromosomal translocations in humans, and demonstrated that cruciform DNA conformation is required for the translocation-like rearrangements. Here we show that two sequential reactions that cleave the cruciform structures give rise to the translocation: GEN1-mediated resolution that cleaves diagonally at the four-way junction of the cruciform and Artemis-mediated opening of the subsequently formed hairpin ends. Indeed, translocation products in human sperm reveal the remnants of this two-step mechanism. These two intrinsic pathways that normally fulfil vital functions independently, Holliday-junction resolution in homologous recombination and coding joint formation in rearrangement of antigen-receptor genes, act upon the unusual DNA conformation in concert and lead to a subset of recurrent GCRs in humans. PMID:23481400

  3. Campylobacter jejuni Translocation across Intestinal Epithelial Cells Is Facilitated by Ganglioside-Like Lipooligosaccharide Structures

    PubMed Central

    Nieuwenhuis, Edward E. S.; van Marrewijk, Leonie; Horst-Kreft, Deborah; de Ruiter, Lilian; Heikema, Astrid P.; van Wamel, Willem J. B.; Wagenaar, Jaap A.; Endtz, Hubert P.; Samsom, Janneke; van Baarlen, Peter; Akhmanova, Anna; van Belkum, Alex

    2012-01-01

    Translocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial species Campylobacter jejuni. The number of C. jejuni virulence factors known to be involved in translocation is limited. In the present study, we investigated whether sialylation of C. jejuni lipooligosaccharide (LOS) structures, generating human nerve ganglioside mimics, is important for intestinal epithelial translocation. We here show that C. jejuni isolates expressing ganglioside-like LOS bound in larger numbers to the Caco-2 intestinal epithelial cells than C. jejuni isolates lacking such structures. Next, we found that ganglioside-like LOS facilitated endocytosis of bacteria into Caco-2 cells, as visualized by quantitative microscopy using the early and late endosomal markers early endosome-associated protein 1 (EEA1), Rab5, and lysosome-associated membrane protein 1 (LAMP-1). This increased endocytosis was associated with larger numbers of surviving and translocating bacteria. Next, we found that two different intestinal epithelial cell lines (Caco-2 and T84) responded with an elevated secretion of the T-cell attractant CXCL10 to infection by ganglioside-like LOS-expressing C. jejuni isolates. We conclude that C. jejuni translocation across Caco-2 cells is facilitated by ganglioside-like LOS, which is of clinical relevance since C. jejuni ganglioside-like LOS-expressing isolates are linked with severe gastroenteritis and bloody stools in C. jejuni-infected patients. PMID:22778098

  4. Campylobacter jejuni translocation across intestinal epithelial cells is facilitated by ganglioside-like lipooligosaccharide structures.

    PubMed

    Louwen, Rogier; Nieuwenhuis, Edward E S; van Marrewijk, Leonie; Horst-Kreft, Deborah; de Ruiter, Lilian; Heikema, Astrid P; van Wamel, Willem J B; Wagenaar, Jaap A; Endtz, Hubert P; Samsom, Janneke; van Baarlen, Peter; Akhmanova, Anna; van Belkum, Alex

    2012-09-01

    Translocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial species Campylobacter jejuni. The number of C. jejuni virulence factors known to be involved in translocation is limited. In the present study, we investigated whether sialylation of C. jejuni lipooligosaccharide (LOS) structures, generating human nerve ganglioside mimics, is important for intestinal epithelial translocation. We here show that C. jejuni isolates expressing ganglioside-like LOS bound in larger numbers to the Caco-2 intestinal epithelial cells than C. jejuni isolates lacking such structures. Next, we found that ganglioside-like LOS facilitated endocytosis of bacteria into Caco-2 cells, as visualized by quantitative microscopy using the early and late endosomal markers early endosome-associated protein 1 (EEA1), Rab5, and lysosome-associated membrane protein 1 (LAMP-1). This increased endocytosis was associated with larger numbers of surviving and translocating bacteria. Next, we found that two different intestinal epithelial cell lines (Caco-2 and T84) responded with an elevated secretion of the T-cell attractant CXCL10 to infection by ganglioside-like LOS-expressing C. jejuni isolates. We conclude that C. jejuni translocation across Caco-2 cells is facilitated by ganglioside-like LOS, which is of clinical relevance since C. jejuni ganglioside-like LOS-expressing isolates are linked with severe gastroenteritis and bloody stools in C. jejuni-infected patients. PMID:22778098

  5. Diffuse Cosmic Infrared Background Radiation

    NASA Technical Reports Server (NTRS)

    Dwek, Eli

    2002-01-01

    The diffuse cosmic infrared background (CIB) consists of the cumulative radiant energy released in the processes of structure formation that have occurred since the decoupling of matter and radiation following the Big Bang. In this lecture I will review the observational data that provided the first detections and limits on the CIB, and the theoretical studies explaining the origin of this background. Finally, I will also discuss the relevance of this background to the universe as seen in high energy gamma-rays.

  6. Stochastic background from extra-galactic double neutron stars

    E-print Network

    T. Regimbau; B. Chauvineau

    2007-07-30

    We present Monte Carlo simulations of the extra galactic population of inspiralling double neutron stars, and estimate its contribution to the astrophysical gravitational wave background, in the frequency range of ground based interferometers, corresponding to the last thousand seconds before the last stable orbit when more than 96 percent of the signal is released. We show that sources at redshift z>0.5 contribute to a truly continuous background which may be detected by correlating third generation interferometers.

  7. Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors

    PubMed Central

    2013-01-01

    Background Metabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined. Methods Untargeted metabolomic profiling of plasma was performed for 32 HIV patients with low nadir CD4 counts (<300 cells/ul) on protease inhibitor (PI)-based ART and 20 healthy controls using liquid or gas chromatography and mass spectrometry. Effects of Hepatitis C (HCV) co-infection and relationships between altered lipid metabolites and markers of inflammation, microbial translocation, and hepatic function were examined. Unsupervised hierarchical clustering, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), Random forest, pathway mapping, and metabolite set enrichment analysis (MSEA) were performed using dChip, Metaboanalyst, and MSEA software. Results A 35-metabolite signature mapping to lipid, amino acid, and nucleotide metabolism distinguished HIV patients with advanced disease on PI-based ART from controls regardless of HCV serostatus (p<0.05, false discovery rate (FDR)<0.1). Many altered lipids, including bile acids, sulfated steroids, polyunsaturated fatty acids, and eicosanoids, were ligands of nuclear receptors that regulate metabolism and inflammation. Distinct clusters of altered lipids correlated with markers of inflammation (interferon-? and interleukin-6), microbial translocation (lipopolysaccharide (LPS) and LPS-binding protein), and hepatic function (bilirubin) (p<0.05). Lipid alterations showed substantial overlap with those reported in non-alcoholic fatty liver disease (NALFD). Increased bile acids were associated with noninvasive markers of hepatic fibrosis (FIB-4, APRI, and YKL-40) and correlated with acylcarnitines, a marker of mitochondrial dysfunction. Conclusions Lipid alterations in HIV patients receiving PI-based ART are linked to markers of inflammation, microbial translocation, and hepatic function, suggesting that therapeutic strategies attenuating dysregulated innate immune activation and hepatic dysfunction may be beneficial for prevention and treatment of metabolic disorders in HIV patients. PMID:23641933

  8. Translocation of a Bak C-Terminus Mutant from Cytosol to Mitochondria to Mediate Cytochrome c Release: Implications for Bak and Bax Apoptotic Function

    PubMed Central

    Ferrer, Pedro Eitz; Frederick, Paul; Gulbis, Jacqueline M.

    2012-01-01

    Background One of two proapoptotic Bcl-2 proteins, Bak or Bax, is required to permeabilize the mitochondrial outer membrane during apoptosis. While Bax is mostly cytosolic and translocates to mitochondria following an apoptotic stimulus, Bak is constitutively integrated within the outer membrane. Membrane anchorage occurs via a C-terminal transmembrane domain that has been studied in Bax but not in Bak, therefore what governs their distinct subcellular distribution is uncertain. In addition, whether the distinct subcellular distributions of Bak and Bax contributes to their differential regulation during apoptosis remains unclear. Methodology/Principal Findings To gain insight into Bak and Bax targeting to mitochondria, elements of the Bak C-terminus were mutated, or swapped with those of Bax. Truncation of the C-terminal six residues (C-segment) or substitution of three basic residues within the C-segment destabilized Bak. Replacing the Bak C-segment with that from Bax rescued stability and function, but unexpectedly resulted in a semi-cytosolic protein, termed Bak/BaxCS. When in the cytosol, both Bax and Bak/BaxCS sequestered their hydrophobic transmembrane domains in their hydrophobic surface groove. Upon apoptotic signalling, Bak/BaxCS translocated to the mitochondrial outer membrane, inserted its transmembrane domain, oligomerized, and released cytochrome c. Despite this Bax-like subcellular distribution, Bak/BaxCS retained Bak-like regulation following targeting of Mcl-1. Conclusions/Significance Residues in the C-segment of Bak and of Bax contribute to their distinct subcellular localizations. That a semi-cytosolic form of Bak, Bak/BaxCS, could translocate to mitochondria and release cytochrome c indicates that Bak and Bax share a conserved mode of activation. In addition, the differential regulation of Bak and Bax by Mcl-1 is predominantly independent of the initial subcellular localizations of Bak and Bax. PMID:22442658

  9. Cytogenetic and molecular analyses of de novo translocation dic(9;13)(p11.2;p12) in an infertile male

    PubMed Central

    2014-01-01

    Background Whole arm t(9;13)(p11;p12) translocations are rare and have been described only a few times; all of the previously reported cases were familial. Results We present here an infertile male carrier with a whole-arm reciprocal translocation dic(9;13)(p11.2;p12) revealed by GTG-, C-, and NOR-banding karyotypes with no mature sperm cells in his ejaculate. FISH and genome-wide 400 K CGH microarray (Agilent) analyses demonstrated a balanced chromosome complement and further characterised the abnormality as a dicentric chromosome (9;13): dic(9;13)(pter?p11.2::p12?qter),neo(9)(pter?p12?neo?p11.2). An analysis of the patient’s ejaculated cells identified immature germ cells at different phases of spermatogenesis but no mature spermatozoa. Most (82.5%) of the germ cells were recognised as spermatocytes at stage I, and the cell nuclei were most frequently found in pachytene I (41.8%). We have also undertaken FISH analysis and documented an increased rate of aneuploidy of chromosomes 15, 18, X and Y in the peripheral blood leukocytes of our patient. To study the aneuploidy risk in leukocytes, we have additionally included 9 patients with non-obstructive azoospermia with normal karyotypes. Conclusions We propose that the azoospermia observed in the patient with the dic(9;13)(p11.2;p12) translocation was most likely a consequence of a very high proportion (90%) of association between XY bivalents and quadrivalent formations in prophase I. PMID:24559467

  10. Hepatitis C Virus Nonstructural Protein 5A Inhibits MG132-Induced Apoptosis of Hepatocytes in Line with NF-?B-Nuclear Translocation

    PubMed Central

    Wu, Shuang; Nakamoto, Shingo; Nakamura, Masato; Sasaki, Reina; Haga, Yuki; Wakita, Takaji; Shirasawa, Hiroshi; Yokosuka, Osamu

    2015-01-01

    Background Hepatitis C virus (HCV) infection is one of the major causes of cirrhosis and hepatocellular carcinoma. HCV nonstructural protein 5A (NS5A) is an attractive antiviral target and plays an important role in HCV replication as well as hepatocarcinogenesis. The aim of this study was to assess the effect of HCV NS5A protein in the abrogation of apoptotic cell death induced by the proteasome inhibitor MG132. Methods Apoptotic responses to MG132 and the expression of molecules involved in NF-?B signaling pathways in human hepatocytes were investigated with or without the expression of HCV NS5A. Results HCV NS5A protected HepG2 cells against MG132-induced apoptosis, in line with NF-?B-nuclear translocation. A similar NF-?B-nuclear translocation was observed in Huh7 cells infected with HCV JFH1. In agreement with this, after treatment with MG132, HCV NS5A could elevate the transcription of several NF-?B target genes such as BCL2 and BCLXL to inhibit MG132-induced apoptosis in hepatocytes. HCV HCV NS5A also enhanced phosphorylation of I?B?. Consistent with a conferred prosurvival advantage, HCV NS5A reduced MG132-induced poly(adenosine diphosphate-ribose) polymerase cleavage. Conclusions HCV NS5A expression enhances phosphorylation of I?B?, liberates NF-?B for nuclear translocation and downregulates MG132-induced apoptotic pathways in human hepatocytes. It is possible that the disruption of proteasome-associated apoptosis plays a role in the pathogenesis of HCV infection. PMID:26133378

  11. DNA translocation through short nanofluidic channels under asymmetric pulsed electric field

    PubMed Central

    Gupta, C.; Liao, W.-C.; Gallego-Perez, D.; Castro, C. E.; Lee, L. J.

    2014-01-01

    Investigation of single molecule DNA dynamics in confined environments has led to important applications in DNA analysis, separation, and sequencing. Here, we studied the electrophoretic transport of DNA molecules through nanochannels shorter than the DNA contour length and calculated the associated translocation time curves. We found that the longer T4 DNA molecules required a longer time to traverse a fixed length nanochannel than shorter ? DNA molecules and that the translocation time decreased with increasing electric field which agreed with theoretical predictions. We applied this knowledge to design an asymmetric electric pulse and demonstrate the different responses of ? and T4 DNA to the pulses. We used Brownian dynamics simulations to corroborate our experimental results on DNA translocation behaviour. This work contributes to the fundamental understanding of polymer transport through nanochannels and may help in designing better separation techniques in the future. PMID:24803963

  12. Effect of solvent viscosity on driven translocation of a semi-flexible polymer through a nanopore

    NASA Astrophysics Data System (ADS)

    Adhikari, Ramesh; Bhattacharya, Aniket

    2015-03-01

    We study the effect of solvent viscosity and pore diameter on the driven translocation of a semi-flexible chain using Langevin dynamics simulation. We observe that for a given chain stiffness the mean first passage time (MFPT) has a nonmonotonic dependence on the solvent viscosity. For moderate external biases, the MFPT decreases at very low solvent viscosity exhibiting a minimum before it increases linearly as a function of high solvent viscosity. We demonstrate a stiffer chain translocates faster than a flexible chain of same length at the low viscosity regime while the opposite is true at high viscosity regime. The effect of pore size on the translocation dynamics is more acute at low solvent viscosity (pore friction dominating regime), but has almost negligible effect at the high viscosity regime for the parameters used in our studies. Partially supported by UCF Office of Research and Commercialization & College of Science SEED grant.

  13. Up and down events in nanoparticle translocation through solid-state nanopores

    NASA Astrophysics Data System (ADS)

    Zanjani, Mehdi; Engelke, Rebecca; Lukes, Jennifer; Drndic, Marija

    2015-03-01

    We study translocation of nanoparticles through solid-state nanopores. Normally, nanoparticle passage is expected to decrease ion current inside the nanopores, as in the case of typical Coulter counters. However, recent experiments have reported translocation events that show an increase in the ion current. We refer to such decrease and increase in ion current as down events and up events respectively. We use theoretical methods to study such events and to determine the conditions under which they happen. A transition nanopore diameter, dt, is calculated from the theoretical model; up events are observed for nanopore diameters smaller than dt, while for nanopore diameters larger than dt down events will occur. We also discuss how a simple mechanism can be implemented to distinguish nanoparticles of different shapes and sizes based on such up and down translocation events. This work was supported by the NSF MRSEC Grant DMR-1120901.

  14. Protein co-translocational unfolding depends on the direction of pulling

    NASA Astrophysics Data System (ADS)

    Rodriguez-Larrea, David; Bayley, Hagan

    2014-09-01

    Protein unfolding and translocation through pores occurs during trafficking between organelles, protein degradation and bacterial toxin delivery. In vivo, co-translocational unfolding can be affected by the end of the polypeptide that is threaded into the pore first. Recently, we have shown that co-translocational unfolding can be followed in a model system at the single-molecule level, thereby unravelling molecular steps and their kinetics. Here, we show that the unfolding kinetics of the model substrate thioredoxin, when pulled through an ?-haemolysin pore, differ markedly depending on whether the process is initiated from the C terminus or the N terminus. Further, when thioredoxin is pulled from the N terminus, the unfolding pathway bifurcates: some molecules finish unfolding quickly, while others finish ~100 times slower. Our findings have important implications for the understanding of biological unfolding mechanisms and in the application of nanopore technology for the detection of proteins and their modifications.

  15. Glyceraldehyde-3-phosphate dehydrogenase: Nuclear translocation participates in neuronal and nonneuronal cell?death

    PubMed Central

    Sawa, Akira; Khan, Adil A.; Hester, Lynda D.; Snyder, Solomon H.

    1997-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein levels increase in particulate fractions in association with cell death in HEK293 cells, S49 cells, primary thymocytes, PC12 cells, and primary cerebral cortical neuronal cultures. Subcellular fractionation and immunocytochemistry reveal that this increase primarily reflects nuclear translocation. Nuclear GAPDH is tightly bound, resisting extraction by DNase or salt treatment. Treating primary thymocytes, PC12 cells, and primary cortical neurons with antisense but not sense oligonucleotides to GAPDH prevents cell death. Because cell-death-associated nuclear translocation of GAPDH and antisense protection occur in multiple neuronal and nonneuronal systems, we propose that GAPDH is a general mediator of cell death and uses nuclear translocation as a signaling mechanism. PMID:9326668

  16. Entropic pulling: how Hsp70 chaperones translocate proteins through membrane pores

    NASA Astrophysics Data System (ADS)

    de Los Rios, Paolo; Ben-Zvi, Anat; Slutsky, Olga; Azem, Abdussalam; Goloubinoff, Pierre

    2006-03-01

    Hsp70s are highly conserved ATPase molecular chaperones mediating the translocation of proteins across membranes and the active unfolding and disassembly of stress-induced protein aggregates. Here, we introduce a mechanism named entropic pulling, based on entropy loss due to excluded volume effects, by which Hsp70 molecules can convert the energy of ATP hydrolysis into a force capable to drive the translocation of polypeptides into mitochondria. Entropic pulling represents a possible solution to the long-standing debate between the power-stroke and the Brownian ratchet models for Hsp70-mediated protein translocation across membranes. Moreover, in a very different context devoid of membrane and components of the import pore, the same physical principles apply to the forceful unfolding, solubilization and assisted native refolding of stable protein aggregates by individual Hsp70 molecules, thus providing a unifying mechanism for the different Hsp70 functions.

  17. The effect of using a "soft" release on translocation success of red-cockaded woodpeckers.

    SciTech Connect

    Franzreb, Kathleen, E.

    2004-12-31

    Franzreb, Kathleen, E. 2004 The effect of using a "soft" release on translocation success of red-cockaded woodpeckers. In: Red-cockaded woodpecker; Road to Recovery. Proceedings of the 4th Red-cockaded woodpecker Symposium. Ralph Costa and Susan J. Daniels, eds. Savannah, Georgia. January, 2003. Chapter 6. Translocation. Pp 301-306. Abstract: Translocations of the endangered red-cockaded woodpecker have been conducted since 1986 to enhance critically small subpopulations, to minimize the likelihood of local extirpations, and to reduce the adverse effects of fragmentation and isolation among existing populations. Such attempts have had mixed success. This article compares "hard" releases with a "soft" release technique where the birds are temporarily interned in a large aviary at the release point for a period of 9 to 14 days.

  18. Molecular signals regulating translocation and toxicity of graphene oxide in the nematode Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Wu, Qiuli; Zhao, Yunli; Li, Yiping; Wang, Dayong

    2014-09-01

    Both in vitro and in vivo studies have demonstrated the toxic effects of graphene oxide (GO). However, the molecular basis for the translocation and toxicity of GO is still largely unclear. In the present study, we employed an in vivo Caenorhabditis elegans assay system to identify molecular signals involved in the control of the translocation and toxicity of GO. We identified 7 genes whose mutations altered both the translocation and toxicity of GO. Mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused greater GO translocation into the body and toxic effects on both primary and secondary targeted organs compared with wild type; however, mutations of the isp-1 and clk-1 genes resulted in significantly decreased GO translocation into the body and toxicity on both primary and secondary targeted organs compared with wild-type. Moreover, mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused increased intestinal permeability and prolonged mean defecation cycle length in GO-exposed nematodes, whereas mutations of the isp-1 and clk-1 genes resulted in decreased intestinal permeability in GO-exposed nematodes. Therefore, for the underlying mechanism, we hypothesize that both intestinal permeability and defecation behavior may have crucial roles in controlling the functions of the identified molecular signals. The molecular signals may further contribute to the control of transgenerational toxic effects of GO. Our results provide an important insight into understanding the molecular basis for the in vivo translocation and toxicity of GO.Both in vitro and in vivo studies have demonstrated the toxic effects of graphene oxide (GO). However, the molecular basis for the translocation and toxicity of GO is still largely unclear. In the present study, we employed an in vivo Caenorhabditis elegans assay system to identify molecular signals involved in the control of the translocation and toxicity of GO. We identified 7 genes whose mutations altered both the translocation and toxicity of GO. Mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused greater GO translocation into the body and toxic effects on both primary and secondary targeted organs compared with wild type; however, mutations of the isp-1 and clk-1 genes resulted in significantly decreased GO translocation into the body and toxicity on both primary and secondary targeted organs compared with wild-type. Moreover, mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused increased intestinal permeability and prolonged mean defecation cycle length in GO-exposed nematodes, whereas mutations of the isp-1 and clk-1 genes resulted in decreased intestinal permeability in GO-exposed nematodes. Therefore, for the underlying mechanism, we hypothesize that both intestinal permeability and defecation behavior may have crucial roles in controlling the functions of the identified molecular signals. The molecular signals may further contribute to the control of transgenerational toxic effects of GO. Our results provide an important insight into understanding the molecular basis for the in vivo translocation and toxicity of GO. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02688h

  19. Bax translocation into mitochondria during dihydroartemisinin(DHA)-induced apoptosis in human lung adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Lu, Ying-ying; Chen, Tong-sheng; Qu, Jun-Le

    2009-02-01

    Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. This study was investigated in human lung adenocarconoma ASTC-a-1 cell line and aimed to determine whether the apoptotic process was mediated by Bax activation and translocation during DHA-induced apoptosis. In this study, DHA induced a time-dependent apoptotic cell death, which was assayed by Cell Counting Kit (CCK-8) and Hoechst 33258 staining. Detection of Bax aggregation and translocation to mitochondria was observed in living cells which were co-transfected with GFP-Bax and Dsred-mito plasmid using confocal fluorescence microscope technique. Overall, these results demonstrated that Bax activation and translocation to mitochondria occurred during DHA-induced apoptosis.

  20. A computational approach to the relationship between radiation induced double strand breaks and translocations

    NASA Technical Reports Server (NTRS)

    Holley, W. R.; Chatterjee, A.

    1994-01-01

    A theoretical framework is presented which provides a quantitative analysis of radiation induced translocations between the ab1 oncogene on CH9q34 and a breakpoint cluster region, bcr, on CH 22q11. Such translocations are associated frequently with chronic myelogenous leukemia. The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon, and the 16.5 kbp region between bcr exon 2 and exon 6 interact with each other, resulting in a fusion gene. for an x-ray dose of 100 Gy, there is good agreement between the theoretical estimate and the one available experimental result. The theory has been extended to provide dose response curves for these types of translocations. These curves are quadratic at low doses and become linear at high doses.

  1. Nanopore DNA translocation studies of tri-oligomer DNA with two hybridization segments

    NASA Astrophysics Data System (ADS)

    Balagurusamy, Venkat; Weinger, Paul; Ling, Xinsheng

    2011-03-01

    We have earlier detected 12-base hybridizations in trimer DNA complexes formed by three single-stranded DNA oligomers hybridized at their ends sequentially, using nanopores of ~ 10 nm diameter. These complexes are connected to a polystyrene bead at one end to slow down their translocation. Here, we report translocation experiments at different voltages with nanopores ~ 5 nm diameter. The measured time lapses between the passage of consecutive double-strand DNA segments in a trimer complex allow us to study the translocation dynamics. The measured mean-first-passage time between two consecutive hybridization segments is found to be consistent with theoretical estimates based on the Fokker-Planck equation. This work was supported by a R21 grant from the NIH-NHGRI.

  2. Carboxybiotin translocation mechanisms suggested by diffraction studies of biotin and its vitamers.

    PubMed

    DeTitta, G T; Parthasarathy, R; Blessing, R H; Stallings, W

    1980-01-01

    Biotin is a coenzyme that fixes CO2 for transfer in a family of carboxylase, decarboxylase, and transcarboxylase enzymes. Their enzyme reactions involve two basic steps during which a carboxybiotinyl intermediate forms at one site and translocates to a second (distinct) site for CO2 transfer. Our diffraction studies of biotin and its vitamers suggest that translocation involves rotation about one, or at most two, bonds in biotin's valeryl chain. The rotations are energetically economical gauche in equilibrium trans rotations about the two valeryl bonds nearest the biotin bicyclic ring. They move a carbon atom of a CO2 moiety bound at N-1' approximately 7 A, a distance in accord with spectroscopic measurements of one of the biotin enzymes. From our studies we infer that sulfur in biotin imparts to the valeryl chain a conformational variability necessary for bond rotation and, hence, translocation between catalytic sites. PMID:6928626

  3. Effect of nanopore diameter on translocation speed of single-stranded DNA

    NASA Astrophysics Data System (ADS)

    Akahori, Rena; Haga, Takahobu; Hatano, Toshiyuki; Yanagi, Itaru; Ohura, Takeshi; Hamamura, Hirotaka; Iwasaki, Tomio; Yokoi, Takahide; Anazawa, Takashi

    2014-03-01

    The effect of reducing a nanopore's diameter on the translocation speed of single-stranded DNA (ssDNA) was investigated. Various-sized nanopores (minimum 2.3 nm) were fabricated using transmission electron microscopy and atomic-layer deposition. Reducing the diameter was found to increase the drag force generated from the DNA-nanopore interaction and from viscous drag, thereby slowing down the translocation speed. The drag force of ssDNA was weaker than that of double-stranded DNA (dsDNA). These findings were supported by a molecular dynamics (MD) simulation which predicted that reducing nanopore diameter to almost the same as that of ssDNA (i.e., 1.4 nm) would decrease DNA translocation speed (to 1.4 ?s/base) and decrease its variation. Reducing the nanopore diameter is thus a highly effective means of sequencing nanopore DNA.

  4. Breaking the bacterial protein targeting and translocation model: oral organisms as a case in point

    PubMed Central

    Lewis, N.E.; Brady, L.J.

    2015-01-01

    SUMMARY Insights into the membrane biogenesis of oral and throat bacteria have highlighted key differences in protein localization by the general secretion pathway compared with the well-studied Escherichia coli model system. These intriguing novelties have advanced our understanding of both how these microorganisms have adapted to survive and cause disease in the oral cavity, and the field of protein translocation as a whole. This review focuses on findings that highlight where oral bacteria differ from the E. coli paradigm, why these differences are biologically important, and what questions remain about the differences in pathway function. The majority of insight into protein translocation in microbes of the oral cavity has come from streptococcal species, which will be the main topic of this review. However, other bacteria will be discussed when relevant. An overview of the E. coli model of protein targeting and translocation is provided for comparison. PMID:25400073

  5. Background reduction in cryogenic detectors

    SciTech Connect

    Bauer, Daniel A.; /Fermilab

    2005-04-01

    This paper discusses the background reduction and rejection strategy of the Cryogenic Dark Matter Search (CDMS) experiment. Recent measurements of background levels from CDMS II at Soudan are presented, along with estimates for future improvements in sensitivity expected for a proposed SuperCDMS experiment at SNOLAB.

  6. The cosmic microwave background radiation

    Microsoft Academic Search

    R. W. Wilson

    1979-01-01

    The discovery of the cosmic microwave background radiation is discussed beginning with radio astronomical measuring techniques, followed by the history of the detection of background radiation, and a summary of some of its properties. Attention is given to the design and operation of a radiotelescope, its antenna and radiometer, exhibiting its advantages, including the ability to measure a collecting area

  7. The cosmic microwave background radiation

    Microsoft Academic Search

    Eric Gawiser; Joseph Silk

    2000-01-01

    We summarize the theoretical and observational status of the study of the Cosmic Microwave Background radiation. Its thermodynamic spectrum is a robust prediction of the Hot Big Bang cosmology and has been confirmed observationally. There are now 75 observations of Cosmic Microwave Background anisotropy, which we present in a table with references. We discuss the theoretical origins of these anisotropies

  8. Radar background signal reduction study

    Microsoft Academic Search

    E. F. Knott; C. J. Ray; M. S. West; R. J. Wohlers

    1980-01-01

    This report summarizes a study whose objective was to identify materials and\\/or techniques to reduce radar background signals for ground plane radar cross section (RCS) ranges. Background signal reduction is essential for improving the accuracy of RCS measurements and the primary application is for operations at the RATSCAT range on the White Sands Missile Range in New Mexico. A survey

  9. The Na+-Translocating NADH:quinone Oxidoreductase (NDH I) from Klebsiella pneumoniae and Escherichia coli: Implications for the Mechanism of Redox-Driven Cation Translocation by Complex I

    Microsoft Academic Search

    Julia Steuber

    2001-01-01

    Eukaryotic complex I integrated into the respiratory chain transports at least 4 H+ per NADH oxidized. Recent results indicate that the cation selectivity is altered to Na+ in complex I (NDH I) isolated from the enterobacteria Escherichia coli and Klebsiella pneumoniae. A sequence analysis illustrates the characteristic differences of the enterobacterial, Na+-translocating NDH I compared to the H+-translocating complex I

  10. Background

    Cancer.gov

    The discovery that proteins and peptides are "leaked" by tumors into clinically accessible bodily fluids such as blood has led to the possibility of diagnosing cancer at an early stage or monitoring response to treatment by collecting these fluids and testing for the presence of cancer-related biomarkers. Prostate-specific antigen (PSA) and cancer antigen 125 (CA-125) are examples of blood-borne cancer protein biomarkers that are currently being used in the clinic.

  11. Background events in microchannel plates

    NASA Technical Reports Server (NTRS)

    Siegmund, O. H. W.; Vallerga, J.; Wargelin, B.

    1988-01-01

    Measurements have been made to assess the characteristics and origins of background events in microchannel plates (MCPs). An overall background rate of about 0.4 events/sq cm persec has been achieved consistently for MCPs that have been baked and scrubbed. The temperature and gain of the MCPs are found to have no significant effect on the background rate. Detection of 1.46-MeV gamma rays from the MCP glass confirms the presence of K-40, with a concentration of 0.0007 percent, in MCP glass. It is shown that beta decay from K-40 is sufficient to cause the background rate and spectrum observed. Anticoincidence measurements indicate the the background rate caused by cosmic ray interactions is small (less than 0.016 events/sq cm per sec).

  12. Rewilding the tropics, and other conservation translocations strategies in the tropical Asia-Pacific region.

    PubMed

    Louys, Julien; Corlett, Richard T; Price, Gilbert J; Hawkins, Stuart; Piper, Philip J

    2014-11-01

    Alarm over the prospects for survival of species in a rapidly changing world has encouraged discussion of translocation conservation strategies that move beyond the focus of 'at-risk' species. These approaches consider larger spatial and temporal scales than customary, with the aim of recreating functioning ecosystems through a combination of large-scale ecological restoration and species introductions. The term 'rewilding' has come to apply to this large-scale ecosystem restoration program. While reintroductions of species within their historical ranges have become standard conservation tools, introductions within known paleontological ranges-but outside historical ranges-are more controversial, as is the use of taxon substitutions for extinct species. Here, we consider possible conservation translocations for nine large-bodied taxa in tropical Asia-Pacific. We consider the entire spectrum of conservation translocation strategies as defined by the IUCN in addition to rewilding. The taxa considered are spread across diverse taxonomic and ecological spectra and all are listed as 'endangered' or 'critically endangered' by the IUCN in our region of study. They all have a written and fossil record that is sufficient to assess past changes in range, as well as ecological and environmental preferences, and the reasons for their decline, and they have all suffered massive range restrictions since the late Pleistocene. General principles, problems, and benefits of translocation strategies are reviewed as case studies. These allowed us to develop a conservation translocation matrix, with taxa scored for risk, benefit, and feasibility. Comparisons between taxa across this matrix indicated that orangutans, tapirs, Tasmanian devils, and perhaps tortoises are the most viable taxa for translocations. However, overall the case studies revealed a need for more data and research for all taxa, and their ecological and environmental needs. Rewilding the Asian-Pacific tropics remains a controversial conservation strategy, and would be difficult in what is largely a highly fragmented area geographically. PMID:25540698

  13. Soluble plantain fibre blocks adhesion and M-cell translocation of intestinal pathogens?

    PubMed Central

    Roberts, Carol L.; Keita, Åsa V.; Parsons, Bryony N.; Prorok-Hamon, Maelle; Knight, Paul; Winstanley, Craig; O?Kennedy, Niamh; Söderholm, Johan D.; Rhodes, Jonathan M.; Campbell, Barry J.

    2013-01-01

    Dietary fibres may have prebiotic effects mediated by promotion of beneficial bacteria. This study explores the possibility that soluble plant fibre may also improve health by inhibiting epithelial adhesion and translocation by pathogenic bacteria. We have focussed on soluble non-starch polysaccharide (NSP) from plantain bananas (Musa spp.) which previous studies showed to be particularly effective at blocking Escherichia coli epithelial adherence. In vitro and ex vivo studies assessed the ability of plantain NSP to inhibit epithelial cell adhesion and invasion of various bacterial pathogens, and to inhibit their translocation through microfold (M)-cells and human Peyer?s patches mounted in Ussing chambers. Plantain NSP showed dose-related inhibition of epithelial adhesion and M-cell translocation by a range of pathogens. At 5 mg/ml, a concentration readily achievable in the gut lumen, plantain NSP inhibited adhesion to Caco2 cells by Salmonella Typhimurium (85.0±8.2%, P<.01), Shigella sonnei (46.6±29.3%, P<.01), enterotoxigenic E.coli (56.1±23.7%, P<.05) and Clostridium difficile (67.6±12.3%, P<.001), but did not inhibit adhesion by enteropathogenic E.coli. Plantain NSP also inhibited invasion of Caco2 cells by S. Typhimurium (80.2 ± 9.7%) and Sh. sonnei (46.7±13.4%); P<.01. Plantain NSP, 5 mg/ml, also inhibited translocation of S. Typhimurium and Sh. sonnei across M-cells by 73.3±5.2% and 46.4±7.7% respectively (P<.05). Similarly, S. Typhimurium translocation across Peyer?s patches was reduced 65.9±8.1% by plantain NSP (P<.01). Soluble plantain fibre can block epithelial adhesion and M-cell translocation of intestinal pathogens. This represents an important novel mechanism by which soluble dietary fibres can promote intestinal health and prevent infective diarrhoea. PMID:22818716

  14. Soluble plantain fibre blocks adhesion and M-cell translocation of intestinal pathogens.

    PubMed

    Roberts, Carol L; Keita, Asa V; Parsons, Bryony N; Prorok-Hamon, Maelle; Knight, Paul; Winstanley, Craig; O' Kennedy, Niamh; Söderholm, Johan D; Rhodes, Jonathan M; Campbell, Barry J

    2013-01-01

    Dietary fibres may have prebiotic effects mediated by promotion of beneficial bacteria. This study explores the possibility that soluble plant fibre may also improve health by inhibiting epithelial adhesion and translocation by pathogenic bacteria. We have focussed on soluble non-starch polysaccharide (NSP) from plantain bananas (Musa spp.) which previous studies showed to be particularly effective at blocking Escherichia coli epithelial adherence. In vitro and ex vivo studies assessed the ability of plantain NSP to inhibit epithelial cell adhesion and invasion of various bacterial pathogens, and to inhibit their translocation through microfold (M)-cells and human Peyer's patches mounted in Ussing chambers. Plantain NSP showed dose-related inhibition of epithelial adhesion and M-cell translocation by a range of pathogens. At 5mg/ml, a concentration readily achievable in the gut lumen, plantain NSP inhibited adhesion to Caco2 cells by Salmonella Typhimurium (85.0 ± 8.2%, P<.01), Shigella sonnei (46.6 ± 29.3%, P<.01), enterotoxigenic E.coli (56.1 ± 23.7%, P<.05) and Clostridium difficile (67.6 ± 12.3%, P<.001), but did not inhibit adhesion by enteropathogenic E.coli. Plantain NSP also inhibited invasion of Caco2 cells by S. Typhimurium (80.2 ± 9.7%) and Sh. sonnei (46.7 ± 13.4%); P<.01. Plantain NSP, 5mg/ml, also inhibited translocation of S. Typhimurium and Sh. sonnei across M-cells by 73.3 ± 5.2% and 46.4 ± 7.7% respectively (P<.05). Similarly, S. Typhimurium translocation across Peyer's patches was reduced 65.9 ± 8.1% by plantain NSP (P<.01). Soluble plantain fibre can block epithelial adhesion and M-cell translocation of intestinal pathogens. This represents an important novel mechanism by which soluble dietary fibres can promote intestinal health and prevent infective diarrhoea. PMID:22818716

  15. Heavy smokers have higher bcl-2 mutation frequency and risk for lymphoma than non-smokers

    SciTech Connect

    Liu, Y.; Cortopassi, G.A. [Univ. of Southern California, Los Angeles, CA (United States); Bell, D.A.

    1994-09-01

    Early detection of cells carrying somatic mutations at oncogenic loci could prove useful for identifying individuals at high risk for cancer and permit intervention prior to the onset of clinically recognizable disease. We have determined the frequency of rare t(14;18)(q32;q21) translocations at the bcl-2 proto-oncogene locus in the peripheral blood of 85 smokers and 35 nonsmokers using a sensitive nested PCR assay. The identical translocation occurs in 85% of follicular lymphoma tumors, and about 50% of all non-Hodgkin`s Lymphoma. Smokers with the highest exposure had a 3.6-fold higher mutation frequency relative to the nonsmokers. Logistic regression analysis showed that of the variables tested (age, race, sex, current smoking, years of smoking, and pack-years), the cumulative smoking measure (pack-years) was the best predictor of t(14;18) frequency (p=0.004). These observations are consistent with two recent epidemiological studies showing 2.3-fold and 3.8-fold increased risk for Non-Hodgkins lymphoma among heavy smokers. The results support the hypothesis that smokers have an increased burden of lymphocytes bearing bcl-2 mutations which raises their individual risk for future lymphoid tumors. We speculate that the increased frequency of oncogenic translocations in smokers may result either from the mutagenic or antigenic activity of cigarette smoke.

  16. Cosmic backgrounds of relic gravitons and their absolute normalization

    E-print Network

    Massimo Giovannini

    2014-09-01

    Provided the consistency relations are not violated, the recent Bicep2 observations pin down the absolute normalization, the spectral slope and the maximal frequency of the cosmic graviton background produced during inflation. The properly normalized spectra are hereby computed from the lowest frequencies (of the order of the present Hubble rate) up to the highest frequency range in the GHz region. Deviations from the conventional paradigm cannot be excluded and are examined by allowing for different physical possibilities including, in particular, a running of the tensor spectral index, an explicit breaking of the consistency relations and a spike in the high-frequency tail of the spectrum coming either from a post-inflationary phase dominated by a stiff fluid of from the contribution of waterfall fields in a hybrid inflationary context. The direct determinations of the tensor to scalar ratio at low frequencies, if confirmed by the forthcoming observations, will also affect and constrain the high-frequencies uncertainties. The limits on the cosmic graviton backgrounds coming from wide-band interferometers (such as Ligo/Virgo, Lisa and Bbo/Decigo) together with a more accurate scrutiny of the tensor B mode polarization at low frequencies will set direct bounds on the post-inflationary evolution and on other unconventional completions of the standard lore.

  17. DNA translocation measurements through low-capacitance solid-state nanopore chips at high bandwidths

    NASA Astrophysics Data System (ADS)

    Chien, Chen-Chi; Niedzwiecki, David; Machielse, Bartholomeus; Balan, Adrian; Lin, Jianxun; Ong, Peijie; Shepard, Kenneth; Drndic, Marija

    2015-03-01

    We perform DNA translocation measurements with low-noise solid state nanopore chips. We obtain higher ion current signal-to-noise ratio and better resolution in ion current signals than previously reported in solid state nanopores at high bandwidths with chip capacitance lowering techniques of applying extra insulation on the chip surface. We show measurements of ion current during translocation of DNA molecules through thin silicon nitride (SiN) nanopores of small diameters at megahertz bandwidths with enhanced ionic signal-to-noise ratios. We further discuss how these results possibly pave the way towards identifying intramolecular DNA sequences with solid-state nanopores.

  18. Continuous fluorescence-based measurement of redox-driven sodium ion translocation.

    PubMed

    Muras, Valentin; Claussen, Björn; Karuppasamy, Manikandan; Schaffitzel, Christiane; Steuber, Julia

    2014-08-15

    Investigation of the mechanism of sodium ion pumping enzymes requires methods to follow the translocation of sodium ions by the purified and reconstituted proteins in vitro. Here, we describe a protocol that allows following the accumulation of Na(+) in proteoliposomes by the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) from Vibrio cholerae using the sodium-sensitive fluorophor sodium green. In the presence of a regenerative system for its substrate NADH, the Na(+)-NQR accumulates Na(+) in the proteoliposomes which is visible as a change in fluorescence. PMID:24862438

  19. Hexahydro-1,3,5-trinitro-1,3,5-triazine translocation in poplar trees

    SciTech Connect

    Thompson, P.L. [Seattle Univ., WA (United States). Dept. of Civil and Environmental Engineering; Ramer, L.A.; Schnoor, J.L. [Univ. of Iowa, Iowa City, IA (United States). Dept. of Civil and Environmental Engineering

    1999-02-01

    This article evaluates the translocation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in hybrid poplar trees (Populus deltoides x nigra, DN34) grown in hydroponic solutions. Mass balances with [U-{sup 14}C]RDX were used to assess RDX translocation. Up to 60% of the RDX uptaken by the tree accumulated in leaf tissues. Analysis of plant extracts by high-performance liquid chromatography equipped with radiochemical detection indicated that RDX was not significantly transformed during exposure periods of up to 7 d. The bioaccumulation of RDX may be an important concern for phytoremediation efforts.

  20. Translocation 1; 7 in hematologic disorders: a brief review of 22 cases

    SciTech Connect

    Scheres, J.M.; Hustinx, T.W.; Geraedts, J.P.; Leeksma, C.H.; Meltzer, P.S.

    1985-11-01

    A translocation t(1;7)(p11;p11), previously reported in patients with myelodysplasia or leukemia has been found in seven new cases. The present report briefly reviews the cytogenetic and clinical features of 22 patients with this translocation. The majority of these patients had a history of occupational or therapeutic exposure to toxic substances or radiation. Trisomy 8 or 21 were the most common additional abnormalities, especially in leukemic patients. The t(1;7) should be added to the group of specific cytogenetic abnormalities observed frequently in secondary myelodysplasia and leukemia.