Science.gov

Sample records for background translocation frequencies

  1. Measurement of background translocation frequencies in individuals with clones

    SciTech Connect

    Wade, M.J.

    1996-08-01

    In the leukemia case the unseparated B and T lymphocytes had a high translocation frequency even after 0.0014, respectively. After purging all clones from the data, the translocation frequencies for Bio 8 and Bio 23 were 0.00750.0014 and 0.0073 metaphases were scored for chromosomal aberrations,, specifically reciprocal translocations, using fluorescence in situ hybridization (FISH). Metaphase spreads were used from two healthy, unexposed individuals (not exposed to radiation, chemotherapy or radiotherapy) and one early B- precursor acute lymphocytic leukemia (ALL) patient (metaphase spreads from both separated T lymphocytes and unseparated B and T lymphocytes were scored). All three individuals had an abnormally high translocation frequency. The high translocation frequencies resulted from clonal expansion of specific translocated chromosomes. I show in this thesis that by purging (discounting or removing) clones from the data of unexposed individuals, one can obtain true background translocation frequencies. In two cases, Bio 8 and Bio 23, the measured translocation frequency for chromosomes 1, 2 and 4 was 0.0124 purging all of the clones from the data. This high translocation frequency may be due to a low frequency of some clones and may not be recognized. The separated T lymphocytes had a higher translocation frequency than expected.

  2. Translocation frequency of double-stranded DNA through a solid-state nanopore

    E-print Network

    Nicholas A. W. Bell; Murugappan Muthukumar; Ulrich F. Keyser

    2015-08-18

    Solid-state nanopores are single molecule sensors that measure changes in ionic current as charged polymers such as DNA pass through. Here, we present comprehensive experiments on the length, voltage and salt dependence of the frequency of double-stranded DNA translocations through conical quartz nanopores with mean opening diameter 15 nm. We observe an entropic barrier limited, length dependent translocation frequency at 4M LiCl salt concentration and a drift-dominated, length independent translocation frequency at 1M KCl salt concentration. These observations are described by a unifying convection-diffusion equation which includes the contribution of an entropic barrier for polymer entry.

  3. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

    1996-01-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

  4. Novel effects of chain flexibility, external force, and background stochasticity on polymer translocation

    NASA Astrophysics Data System (ADS)

    Sung, Wokyung

    2011-03-01

    The polymer translocation through membranes and the polymer crossing over activation barriers in general, are ubiquitous in cell biology and biotechnological applications. Because they are interconnected flexible systems, polymers in translocation incur entropic barriers but can thermally surmount them with unusual sensitivity to background biases. In the presence of non-equilibrium noises characteristic of living environments, the translocation can speed up much when resonant activation occurs. As a related issue, I will also discuss the problem of polymer surmounting a potential barrier, where the chain flexibility enhances the crossing. Furthermore, when the chain flexibility leads to conformational changes, the crossing rate can be even more dramatically increased. This conformational flexibility and variability enhance the stochastic resonance, where the chain crossing dynamics at an optimal temperature and chain length is maximally coherent and resonant to a minute periodic force. Utilizing the self-organizing behaviors mentioned above, we may learn about bio-molecular machinery of living as well as clever means of manipulating it. Korea Research Foundation.

  5. 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

  6. A biophysical model for estimating the frequency of radiation-induced mutations resulting from chromosomal translocations

    NASA Astrophysics Data System (ADS)

    Wu, Honglu; Durante, Marco

    Gene mutations can be induced by radiation as a result of chromosomal translocations. A biophysical model is developed to estimate the frequency of this type of mutation induced by low-LET radiation. Mutations resulting from translocations are assumed to be formed by misrejoining of two DNA double strand breaks (DSB), one within the gene and one on a different chromosome. The chromosome containing the gene is assumed to occupy a spherical territory and does not overlap spatially with other chromosomes. Misrejoining between two DSB can occur only if the two DSB are closer than an interaction distance at the time of their induction. Applying the model to mutations of the hprt gene induced in G0 human lymphocyte cells by low-LET radiation, it is calculated that mutations resulting from translocations account for about 14% of the total mutations. The value of the interaction distance is determined to be 0.6 ?m by comparing with the observed frequency of translocations in the X-chromosome.

  7. Frequency Modulated Translocational Oscillations of Nrf2 Mediate the Antioxidant Response Element Cytoprotective Transcriptional Response

    PubMed Central

    Xue, Mingzhan; Momiji, Hiroshi; Rabbani, Naila; Barker, Guy; Bretschneider, Till; Shmygol, Anatoly; Rand, David A.

    2015-01-01

    Abstract Aims: Stress responsive signaling coordinated by nuclear factor erythroid 2-related factor 2 (Nrf2) provides an adaptive response for protection of cells against toxic insults, oxidative stress and metabolic dysfunction. Nrf2 regulates a battery of protective genes by binding to regulatory antioxidant response elements (AREs). The aim of this study was to examine how Nrf2 signals cell stress status and regulates transcription to maintain homeostasis. Results: In live cell microscopy we observed that Nrf2 undergoes autonomous translocational frequency-modulated oscillations between cytoplasm and nucleus. Oscillations occurred in quiescence and when cells were stimulated at physiological levels of activators, they decrease in period and amplitude and then evoke a cytoprotective transcriptional response. We propose a mechanism whereby oscillations are produced by negative feedback involving successive de-phosphorylation and phosphorylation steps. Nrf2 was inactivated in the nucleus and reactivated on return to the cytoplasm. Increased frequency of Nrf2 on return to the cytoplasm with increased reactivation or refresh-rate under stress conditions activated the transcriptional response mediating cytoprotective effects. The serine/threonine-protein phosphatase PGAM5, member of the Nrf2 interactome, was a key regulatory component. Innovation: We found that Nrf2 is activated in cells without change in total cellular Nrf2 protein concentration. Regulation of ARE-linked protective gene transcription occurs rather through translocational oscillations of Nrf2. We discovered cytoplasmic refresh rate of Nrf2 is important in maintaining and regulating the transcriptional response and links stress challenge to increased cytoplasmic surveillance. We found silencing and inhibition of PGAM5 provides potent activation of Nrf2. Conclusion: Frequency modulated translocational oscillations of Nrf2 mediate the ARE-linked cytoprotective transcriptional response. Antioxid. Redox Signal. 23, 613–629. PMID:25178584

  8. Reciprocal translocations

    SciTech Connect

    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.

  9. Comparative evaluation of background micronucleus frequencies in domestic mammals.

    PubMed

    Cristaldi, Mauro; Anna Ieradi, Luisa; Udroiu, Ion; Zilli, Romano

    2004-04-11

    Exposure of human alimentation-destined animals to toxic substances can be an important risk factor for human health. Mutagenicity tests represent a good method for genotoxic effect evaluation of environmental pollutants. The micronucleus frequency in peripheral blood and bone marrow erythrocytes has been evaluated in four domestic Ungulate species (ox, sheep, swine and horse). For each species two or three groups of animals coming from Italy and other European countries were analysed and the results indicate a relatively low mean frequency of micronucleated erythrocytes (ME), both in peripheral blood and bone marrow. The comparison between these two frequencies in the four species studied shows that the ME frequency in sheep and horse is significantly higher in peripheral blood than in bone marrow, whereas in bovines it is higher in the bone marrow, and in swine the difference is not significant. These results could indicate that in ox and swine the spleen is involved in ME removal from the peripheral circulation, as is known for other species including man. Nevertheless, it cannot be excluded that the same occurs in the other two species, since they exhibit a relatively low peripheral blood ME frequency as well. Further studies on domestic mammals are needed to clarify the spleen function and verify the use of the peripheral blood micronucleus test for genotoxic biomonitoring. At present, the application of the micronucleus test to the bone marrow seems a more suitable method, but, being invasive, it can be used only as a control system of animal hygiene and health, in addition to the routine tests, rather than for biomonitoring. PMID:15066568

  10. Cosmic Background dipole measurements with Planck-High Frequency Instrument

    E-print Network

    M. Piat; G. Lagache; J. P. Bernard; M. Giard; J. L. Puget

    2001-10-30

    This paper discusses the Cosmic Background (CB) dipoles observations in the framework of the Planck mission. Dipoles observations can be used in three ways: (i) It gives a measurement of the peculiar velocity of our Galaxy which is an important observation in large scale structures formation model. (ii) Measuring the dipole can give unprecedent information on the monopole (that can be in some cases hard to obtain due to large foreground contaminations). (iii) The dipole can be an ideal absolute calibrator, easily detectable in cosmological experiments. Following the last two objectives, the main goal of the work presented here is twofold. First, we study the accuracy of the Planck-HFI calibration using the Cosmic Microwave Background (CMB) dipole measured by COBE as well as the Earth orbital motion dipole. We show that we can reach for HFI, a relative calibration between rings of about 1% and an absolute calibration better than 0.4% for the CMB channels (in the end, the absolute calibration will be limited by the uncertainties on the CMB temperature). We also show that Planck will be able to measure the CMB dipole direction at better than 1.7 arcmin and improve on the amplitude. Second, we investigate the detection of the Cosmic Far-Infrared Background (FIRB) dipole. Measuring this dipole could give a new and independent determination of the FIRB for which a direct determination is quite difficult due to Galactic dust emission contamination. We show that such a detection would require a Galactic dust emission removal at better than 1%, which will be very hard to achieve.

  11. TALEN-Induced Translocations in Human Cells.

    PubMed

    Piganeau, Marion; Renouf, Benjamin; Ghezraoui, Hind; Brunet, Erika

    2016-01-01

    Induction of chromosomal translocations in human cells is of a great interest to study tumorigenesis and genome instability. Here, we explain in detail a method to induce translocations using the transcription activator-like effector nucleases (TALENs). We describe how to detect translocation formation by PCR, calculate translocation frequency by 96-well PCR screen, and analyze breakpoint junctions. When inducing cancer translocations, it is also possible to detect the fusion gene by FISH analysis or western blot. PMID:26443217

  12. 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

  13. Effects of image background on spatial-frequency thresholds for face recognition.

    PubMed

    Collin, Charles A; Wang, Luisa; O'Byrne, Byron

    2006-01-01

    A great deal of work has been devoted to the question of which spatial frequencies, if any, are optimal for various visual tasks, such as face and object recognition. However, to date these studies have all been carried out with stimuli set against a uniform background. It is possible that this type of stimulus does not produce ecologically valid results. The natural world in which visual tasks normally take place involves a great deal of luminance variation and distracting visual structure, which may alter the spatial frequencies necessary for a task. We conducted two experiments that examined the effects of image background on the spatial-frequency thresholds (50% maximum of a low-pass or high-pass Butterworth filter) for face recognition by the psychophysical methods of adjustment and constant stimuli. In both experiments we found no significant difference in spatial-frequency thresholds between uniform-grey backgrounds and natural-scene backgrounds, and only minor differences between uniform-grey backgrounds and fractal noise backgrounds. This suggests that results obtained with uniform backgrounds are ecologically valid and that background effects, if they exist, are small. PMID:17286117

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

    SciTech Connect

    Bellucci, Stefano; Capozziello, Salvatore; De Laurentis, Mariafelicia; Faraoni, Valerio

    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.

  15. Dolphins Adjust Species-Specific Frequency Parameters to Compensate for Increasing Background Noise

    PubMed Central

    Papale, Elena; Gamba, Marco; Perez-Gil, Monica; Martin, Vidal Martel; Giacoma, Cristina

    2015-01-01

    An increase in ocean noise levels could interfere with acoustic communication of marine mammals. In this study we explored the effects of anthropogenic and natural noise on the acoustic properties of a dolphin communication signal, the whistle. A towed array with four elements was used to record environmental background noise and whistles of short-beaked common-, Atlantic spotted- and striped-dolphins in the Canaries archipelago. Four frequency parameters were measured from each whistle, while Sound Pressure Levels (SPL) of the background noise were measured at the central frequencies of seven one-third octave bands, from 5 to 20 kHz. Results show that dolphins increase the whistles’ frequency parameters with lower variability in the presence of anthropogenic noise, and increase the end frequency of their whistles when confronted with increasing natural noise. This study provides the first evidence that the synergy among SPLs has a role in shaping the whistles' structure of these three species, with respect to both natural and anthropogenic noise. PMID:25853825

  16. Dolphins adjust species-specific frequency parameters to compensate for increasing background noise.

    PubMed

    Papale, Elena; Gamba, Marco; Perez-Gil, Monica; Martin, Vidal Martel; Giacoma, Cristina

    2015-01-01

    An increase in ocean noise levels could interfere with acoustic communication of marine mammals. In this study we explored the effects of anthropogenic and natural noise on the acoustic properties of a dolphin communication signal, the whistle. A towed array with four elements was used to record environmental background noise and whistles of short-beaked common-, Atlantic spotted- and striped-dolphins in the Canaries archipelago. Four frequency parameters were measured from each whistle, while Sound Pressure Levels (SPL) of the background noise were measured at the central frequencies of seven one-third octave bands, from 5 to 20 kHz. Results show that dolphins increase the whistles' frequency parameters with lower variability in the presence of anthropogenic noise, and increase the end frequency of their whistles when confronted with increasing natural noise. This study provides the first evidence that the synergy among SPLs has a role in shaping the whistles' structure of these three species, with respect to both natural and anthropogenic noise. PMID:25853825

  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. Translocation time of periodically forced polymer chains

    E-print Network

    Alessandro Fiasconaro; Juan José Mazo; Fernando Falo

    2010-09-09

    We show the presence of both a minimum and clear oscillations in the frequency dependence of the translocation time of a polymer described as a unidimensional Rouse chain driven by a spatially localized oscillating linear potential. The observed oscillations of the mean translocation time arise from the synchronization between the very mean translocation time and the period of the external force. We have checked the robustness of the frequency value for the minimum translocation time by changing the damping parameter, finding a very simple relationship between this frequency and the correspondent translocation time. The translocation time as a function of the polymer length has been also evaluated, finding a precise $L^2$ scaling. Furthermore, the role played by the thermal fluctuations described as a Gaussian uncorrelated noise has been also investigated, and the analogies with the resonant activation phenomenon are commented.

  19. Background frequency of Bacillus species at the Canberra Airport: A 12 month study.

    PubMed

    Gahan, Michelle E; Thomas, Rory; Rossi, Rebecca; Nelson, Michelle; Roffey, Paul; Richardson, Michelle M; McNevin, Dennis

    2015-12-01

    Anthrax, caused by Bacillus anthracis, is a naturally occurring disease in Australia. Whilst mainly limited to livestock in grazing regions of Victoria and New South Wales, movement of people, stock and vehicles means B. anthracis could be present outside this region. Of particular interest is the "background" prevalence of B. anthracis at transport hubs including airports. The aim of this study was to determine the background frequency of B. anthracis and the commonly used hoax agent Bacillus thuringiensis at the Canberra Airport over a 12 month period. Samples were collected daily for seven days each month from August 2011-July 2012 and analyzed using species specific real-time polymerase chain reaction. Fourteen samples (of a total of 575) were positive for the B. anthracis PL3 genomic marker, 24 for the cya (pXO1) plasmid marker and five for the capB (pXO2) plasmid marker. Whilst five samples were positive for both PL3 and cya, no samples were positive for all three markers hence there is no evidence to suggest the presence of pathogenic B. anthracis strains. B. anthracis targets were detected primarily in February 2012 and B. thuringiensis peaked in October and November 2011 and again in April and May 2012. This study provides a rapid method to screen for, and differentiate, Bacillus species. Armed with this information investigators will be able to discriminate a "threat" from "background" frequencies should the need arise. PMID:26298416

  20. Multi-frequency survey of background radiations of the Universe. The "Cosmological Gene" project. First results

    NASA Astrophysics Data System (ADS)

    Parijskij, Yu. N.; Mingaliev, M. G.; Nizhel'Skii, N. A.; Bursov, N. N.; Berlin, A. B.; Grechkin, A. A.; Zharov, V. I.; Zhekanis, G. V.; Majorova, E. K.; Semenova, T. A.; Stolyarov, V. A.; Tsybulev, P. G.; Kratov, D. V.; Udovitskii, R. Yu.; Khaikin, V. B.

    2011-10-01

    The results of the first stage of the "Cosmological Gene" project of the Russian Academy of Sciences are reported. These results consist in the accumulation of multi-frequency data in 31 frequency channels in the wavelength interval 1-55 cm with maximum achievable statistical sensitivity limited by the noise of background radio sources at all wavelengths exceeding 1.38 cm. The survey region is determined by constraints 00 h < RA < 24 h and 40°30' < DEC < 42°30'. The scientific goals of the project are refined in view of recent proposals to use cosmological background radiation data for the development of a unified physical theory. Experimental data obtained with the RATAN-600 radio telescope are used to refine the contribution of the main "screens" located between the observer and the formation epoch of cosmic background radiation ( z = 1100). Experimental data for synchrotron radiation and free-free noise on scales that are of interest for the anisotropy of cosmic microwave background are reported as well as the contribution of these noise components in millimeter-wave experiments to be performed in the nearest years. The role of dipole radio emission of fullerene-type dust nanostructures is shown to be small. The most precise estimates of the role of background radio sources with inverted spectra are given and these sources are shown to create no serious interference in experiments. The average spectral indices of the weakest sources of the NVSS and FIRST catalogs are estimated. The "saturation" data for all wavelengths allowed a constraint to be imposed on the Sunyaev-Zeldovich noise (the SZ noise) at all wavelengths, and made it possible to obtain independent estimates of the average sky temperature from sources, substantially weaker than those listed in the NVSS catalog. These estimates are inconsistent with the existence of powerful extragalactic synchrotron background associated with radio sources. Appreciable "quadrupole" anisotropy in is detected in the distribution of the spectral index of the synchrotron radiation of the Galaxy, and this anisotropy should be taken into account when estimating the polarization of the cosmic microwave background on small l. All the results are compared to the results obtained by foreign researchers in recent years.

  1. Robertsonian translocations

    SciTech Connect

    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.

  2. 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. .

  3. A measurement of the low frequency spectrum of the cosmic microwave background radiation

    SciTech Connect

    Levin, S.M.

    1987-04-01

    As part of a larger effort to measure the spectrum of the Cosmic Background Radiation (CBR) at low frequencies, the intensity of the CBR has been measured at a frequency of 1.410 GHz. The measurement was made by comparing the power received from the sky with the power received from a specially designed cooled calibration target with known properties. Sources of radiation other than the CBR were then identified and subtracted to calculate the antenna temperature of the CBR at 1.410 GHz. The instrument used to measure the CBR was a total-power microwave radiometer with a 25 MHz bandwidth centered at 1.410 GHz. The radiometer had a noise temperature of 80 K, and sufficient data were taken that radiometer noise did not contribute significantly to the total measurement error. The sources of error were predominantly systematic in nature, and the largest error was due to uncertainty in the reflection characteristics of the cold-load calibrator. Identification and subtraction of signals from the Galaxy (0.7 K) and the Earth's atmosphere (0.8 K) were also significant parts of the data reduction and error analysis. The brightness temperature of the Cosmic Background Radiation at 1.410 GHz is 222. +- 0.55 Kelvin. The spectrum of the CBR, as determined by this measurement and other published results, is consistent with a blackbody spectrum of temperature 2.741 +- 0.016. Constraints on the amount by which the CBR spectrum deviates from Planck spectrum are used to place limits on energy releases early in the history of the universe. 55 refs., 25 figs., 8 tabs.

  4. The Pontin series of recombinant alien translocations in bread wheat: single translocations integrating combinations of Bdv2, Lr19 and Sr25 disease-resistance genes from Thinopyrum intermedium and Th. ponticum.

    PubMed

    Ayala-Navarrete, L I; Mechanicos, A A; Gibson, J M; Singh, D; Bariana, H S; Fletcher, J; Shorter, S; Larkin, Philip J

    2013-10-01

    Two bread wheat lines each with a translocation on chromosome 7DL from either Thinopyrum intermedium (TC5 and TC14) or Thinopyrum ponticum (T4m), were hybridized in a ph1b mutant background to enhance recombination between the two translocated chromosomal segments. The frequency of recombinants was high in lines derived from the larger and similar-sized translocations (TC5/T4m), but much lower when derived from different-sized translocations (TC14/T4m). Recombinant translocations contained combinations of resistance genes Bdv2, Lr19 and Sr25 conferring resistance to Barley yellow dwarf virus (BYDV), leaf rust and stem rust, respectively. Their genetic composition was identified using bioassays and molecular markers specific for the two progenitor Thinopyrum species. This set of 7DL Th. ponticum/intermedium recombinant translocations was termed the Pontin series. In addition to Thinopyrum markers, the size of the translocation was estimated with the aid of wheat markers mapped on each of the 7DL deletion bins. Bioassays for BYDV, leaf rust and stem rust were performed under greenhouse and field conditions. Once separated from ph1b background, the Pontin recombinant translocations were stable and showed normal inheritance in successive backcrosses. The reported Pontin translocations integrate important resistance genes in a single linkage block which will allow simultaneous selection of disease resistance. Combinations of Bdv2 + Lr19 or Lr19 + Sr25 in both long and short translocations, are available to date. The smaller Pontins, comprising only 20 % of the distal portion of 7DL, will be most attractive to breeders. PMID:23807636

  5. Cryocooled terahertz photoconductive detector system with background-limited performance in 1.5-4 THz frequency range.

    PubMed

    Aoki, Makoto; Hiromoto, Norihisa

    2015-10-01

    We describe a 4-K-cryocooled dual-band terahertz (THz) photoconductive detector system with background-limited performance. The detector system comprises two THz photoconductive detectors covering a response in a wide frequency range from 1.5 to 4 THz, low noise amplifiers, optical low-pass filters to eliminate input radiation of higher frequencies, and a mechanical 4 K Gifford-McMahon refrigerator that provides practical and convenient operation without a liquid He container. The electrical and optical performances of the THz detector system were evaluated at a detector temperature of 4 K under 300 K background radiation. We proved that the detector system can achieve background-limited noise-equivalent-power on the order of 10(-14) W/Hz(1/2) in the frequency range from 1.5 to 4 THz even if the vibration noise of the mechanical refrigerator is present. PMID:26520978

  6. Cryocooled terahertz photoconductive detector system with background-limited performance in 1.5-4 THz frequency range

    NASA Astrophysics Data System (ADS)

    Aoki, Makoto; Hiromoto, Norihisa

    2015-10-01

    We describe a 4-K-cryocooled dual-band terahertz (THz) photoconductive detector system with background-limited performance. The detector system comprises two THz photoconductive detectors covering a response in a wide frequency range from 1.5 to 4 THz, low noise amplifiers, optical low-pass filters to eliminate input radiation of higher frequencies, and a mechanical 4 K Gifford-McMahon refrigerator that provides practical and convenient operation without a liquid He container. The electrical and optical performances of the THz detector system were evaluated at a detector temperature of 4 K under 300 K background radiation. We proved that the detector system can achieve background-limited noise-equivalent-power on the order of 10-14 W/Hz1/2 in the frequency range from 1.5 to 4 THz even if the vibration noise of the mechanical refrigerator is present.

  7. Mode of ATM-dependent suppression of chromosome translocation

    SciTech Connect

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

    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.

  8. Spectroscopic measurement of high-frequency electric fields in the interaction of explosive debris plasma with magnetized background plasma

    SciTech Connect

    Bondarenko, A. S. Schaeffer, D. B.; Everson, E. T.; Clark, S. E.; Constantin, C. G.; Niemann, C.

    2014-12-15

    The collision-less transfer of momentum and energy from explosive debris plasma to magnetized background plasma is a salient feature of various astrophysical and space environments. While much theoretical and computational work has investigated collision-less coupling mechanisms and relevant parameters, an experimental validation of the results demands the measurement of the complex, collective electric fields associated with debris-background plasma interaction. Emission spectroscopy offers a non-interfering diagnostic of electric fields via the Stark effect. A unique experiment at the University of California, Los Angeles, that combines the Large Plasma Device (LAPD) and the Phoenix laser facility has investigated the marginally super-Alfvénic, quasi-perpendicular expansion of a laser-produced carbon (C) debris plasma through a preformed, magnetized helium (He) background plasma via emission spectroscopy. Spectral profiles of the He II 468.6?nm line measured at the maximum extent of the diamagnetic cavity are observed to intensify, broaden, and develop equally spaced modulations in response to the explosive C debris, indicative of an energetic electron population and strong oscillatory electric fields. The profiles are analyzed via time-dependent Stark effect models corresponding to single-mode and multi-mode monochromatic (single frequency) electric fields, yielding temporally resolved magnitudes and frequencies. The proximity of the measured frequencies to the expected electron plasma frequency suggests the development of the electron beam-plasma instability, and a simple saturation model demonstrates that the measured magnitudes are feasible provided that a sufficiently fast electron population is generated during C debris–He background interaction. Potential sources of the fast electrons, which likely correspond to collision-less coupling mechanisms, are briefly considered.

  9. Major Existence of Very Low Frequency Earthquakes in Background Seismicity Along Subduction Zone of South-western Japan

    NASA Astrophysics Data System (ADS)

    Ishihara, Y.

    2003-12-01

    The condense, high quality and equalized broadband seismic network provided us to recognize the variety of seismic sources. The active volcanoes excite seismic waves with various frequency characteristics. Some cases show the long period seismic waves greater than 10 sec associates with volcanic activities. The tectonic seismic events originated at the close to trench zone are frequently lack of high frequency, greater than 1 Hz, seismic wave component. Meanwhile, the many low frequency earthquakes and tremors whose sources are not explicated are occurred in lower crust and subcrustal region. The subduction zone of Philippine Sea plate in south-western Japan is actively genetic area of low frequency earthquake group. The broadband seismic array of Japan region observed unknown long period ground motions. The seismograms are higher amplitude between 10 and 30 sec period than ground noise level. The earthquake JMA and USGS catalogues don_ft list about these long period seismograms. The arrival order of wave packet means that these events locate subduction zone around Japan. The hypocenters of unknown events are estimated by arrival times of vertical peak amplitude using the assumption that the ground motion dominates Rayleigh wave. The more detailed determination of major events is performed by combined technique for moment tensor inversion and grid search. The moment magnitude of uncatalogued event is greater than 3.5 because of the detection limitation. The largest event is distributed to about 4.5 Mw level and special event is greater than 5.0. The frequency characteristics show that source time is 7 to 20 sec by comparison with synthetic seismograms. We call these uncatalogued events _gvery low frequency earthquake_h. The hypocenters are located to two kinds of zones along the Philippine Sea subducting plate in south-western Japan. The one zone is very close to the trough. The seismicity listed by earthquake catalogues is low level in the zone and hypocenters are distributed in island arc side. The very low frequency earthquakes occur in outer area of seismic generation zone. The other zone is coincided with extended zone generating low frequency seismic events. Very low frequency earthquake occurs intermittently in limited area. Frequently, activity increases for some days and swarm type activity generates occasionally. To evaluate integrated seismicity for anomalous events, same class magnitude, greater than 3.0, events occurred in same and surrounding area are picked up from JMA earthquake catalogue. The analysis shows that seismicity of very low frequency earthquakes is comparative with one of normal earthquakes in background activity. We concluded that very low frequency earthquake is one of factors playing seismically important role.

  10. Frequency and genetic background of the position 122 (Val----Ile) variant transthyretin gene in the black population.

    PubMed Central

    Jacobson, D R; Reveille, J D; Buxbaum, J N

    1991-01-01

    Transthyretin (TTR) (122 Val----Ile), caused by a point mutation which destroys a MaeIII restriction site, is associated with cardiac amyloidosis in black individuals. To estimate the frequency of the MaeIII(-) gene in the black population without overt cardiac disease, DNA from 177 black individuals without amyloidosis was amplified by the PCR around TTR codon 122 and was digested with MaeIII. The MaeIII(-) gene frequency was 4/354 (1.1%; 95% confidence interval 0.32%2.7%), suggesting that the variant is relatively common in blacks. HLA genotype testing did not suggest that the TTR (122 Val----Ile) heterozygotes were of a closely related genetic background. Images Figure 2 PMID:2063870

  11. Spatial frequency characteristics at image decision-point locations for observers with different radiological backgrounds in lung nodule detection

    NASA Astrophysics Data System (ADS)

    Pietrzyk, Mariusz W.; Manning, David J.; Dix, Alan; Donovan, Tim

    2009-02-01

    Aim: The goal of the study is to determine the spatial frequency characteristics at locations in the image of overt and covert observers' decisions and find out if there are any similarities in different observers' groups: the same radiological experience group or the same accuracy scored level. Background: The radiological task is described as a visual searching decision making procedure involving visual perception and cognitive processing. Humans perceive the world through a number of spatial frequency channels, each sensitive to visual information carried by different spatial frequency ranges and orientations. Recent studies have shown that particular physical properties of local and global image-based elements are correlated with the performance and the level of experience of human observers in breast cancer and lung nodule detections. Neurological findings in visual perception were an inspiration for wavelet applications in vision research because the methodology tries to mimic the brain processing algorithms. Methods: The wavelet approach to the set of postero-anterior chest radiographs analysis has been used to characterize perceptual preferences observers with different levels of experience in the radiological task. Psychophysical methodology has been applied to track eye movements over the image, where particular ROIs related to the observers' fixation clusters has been analysed in the spaces frame by Daubechies functions. Results: Significance differences have been found between the spatial frequency characteristics at the location of different decisions.

  12. Frequency filtering to suppress background noise in fingerprint evidence: quantifying the fidelity of digitally enhanced fingerprint images.

    PubMed

    Speir, Jacqueline A; Hietpas, Jack

    2014-09-01

    Fingerprint evidence can benefit in image quality if transformed using digital image processing techniques. This is especially true when considering prints that cannot be easily lifted (such as those deposited on porous paper substrates), or when the mechanism of lifting does not effectively reduce background interferences. In these instances, frequency filtering is one type of mathematical transformation that can serve to increase image clarity and the ability to extract minutiae relevant to pairwise comparisons. To quantify the impact of frequency filtering on image quality, high quality and low quality (noisy) prints were collected. The high quality prints served as exemplars that were compared to the low quality prints both pre- and post-filtering. The resulting pairwise match scores indicate that: (1) frequency filtering has a low probability of creating false positive associations, (2) 90% of the post-filtered images result in a normalized gain in match score, (3) frequency filtering doubled the probability of obtaining match scores greater than 30% (for the automated algorithm employed in this study), and (4) filtering can double the probability of obtaining 10 or more matching minutiae when comparing same source prints. Overall, the research indicates a reasonable and quantifiable payoff in increased clarity, matching minutiae and pairwise similarity for post-filtered images when compared to known-match exemplars. PMID:25047216

  13. 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. ...

  14. Molecular analysis of nondisjunction in mice heterozygous for a Robertsonian translocation.

    PubMed Central

    Underkoffler, Lara A; Mitchell, Laura E; Localio, A Russell; Marchegiani, Shannon M; Morabito, Justin; Collins, Joelle N; Oakey, Rebecca J

    2002-01-01

    A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: 1. The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%. 2. Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters. 3. There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction. 4. Strain background did not play an appreciable role in nondisjunction frequency. 5. The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males. 6. The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males. These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals. PMID:12136024

  15. 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).

  16. Problem-Elephant Translocation: Translocating the Problem and the Elephant?

    PubMed Central

    Fernando, Prithiviraj; Leimgruber, Peter; Prasad, Tharaka; Pastorini, Jennifer

    2012-01-01

    Human-elephant conflict (HEC) threatens the survival of endangered Asian elephants (Elephas maximus). Translocating “problem-elephants” is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: “homers” returned to the capture site, “wanderers” ranged widely, and “settlers” established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals. PMID:23236404

  17. Translocation-related sarcomas.

    PubMed

    Mertens, Fredrik; Antonescu, Cristina R; Hohenberger, Peter; Ladanyi, Marc; Modena, Piergiorgio; D'Incalci, Maurizio; Casali, Paolo G; Aglietta, Massimo; Alvegård, Thor

    2009-08-01

    Sarcomas with chromosomal translocations represent only about one fourth of sarcoma diagnoses. However, like gastrointestinal stromal tumor (GIST), with its characteristic KIT or PDGFRA mutations, they are particularly interesting since they provide specific biological insights and mechanisms of action that may have an impact upon prognosis or therapy. These are mechanisms we are just beginning to exploit. In this section we will review the biology and clinical impact of translocation-associated sarcomas and review the clinical findings that have made a recent impact upon patients with these diverse diagnoses. PMID:19664492

  18. Oncogene Translocations and NHL

    Cancer.gov

    A colloboration with several large population-based cohorts to determine whether the prevalence or level of t14;18 is associated with risk of NHL and to investigate the clonal relationship between translocation-bearing cells and subsequent tumors

  19. DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

    PubMed Central

    Hakim, Ofir; Resch, Wolfgang; Yamane, Arito; Klein, Isaac; Kieffer-Kwon, Kyong-Rim; Jankovic, Mila; Oliveira, Thiago; Bothmer, Anne; Voss, Ty C.; Ansarah-Sobrinho, Camilo; Mathe, Ewy; Liang, Genqing; Cobell, Jesse; Nakahashi, Hirotaka; Robbiani, Davide F.; Nussenzweig, Andre; Hager, Gordon L.; Nussenzweig, Michel C.; Casellas, Rafael

    2012-01-01

    Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies. PMID:22314321

  20. 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.

    of the radio-frequency background levels as they use the most sensitive radio-wave receivers in the world to study the sky at radio wavelengths. Radio waves can give us information about astronomical phenomena astronomy telescopes are the most sensitive radio-wave receivers in the world. For example, a mobile phone

  1. 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

  2. The adult polyglucosan body disease mutation GBE1 c.1076A>C occurs at high frequency in persons of Ashkenazi Jewish background.

    PubMed

    Hussain, Abrar; Armistead, Joy; Gushulak, Lara; Kruck, Christa; Pind, Steven; Triggs-Raine, Barbara; Natowicz, Marvin R

    2012-09-21

    Mutations of the glycogen branching enzyme gene, GBE1, result in glycogen storage disease (GSD) type IV, an autosomal recessive disorder having multiple clinical forms. One mutant allele of this gene, GBE1 c.1076A>C, has been reported in Ashkenazi Jewish cases of an adult-onset form of GSD type IV, adult polyglucosan body disease (APBD), but no epidemiological analyses of this mutation have been performed. We report here the first epidemiological study of this mutation in persons of Ashkenazi Jewish background and find that this mutation has a gene frequency of 1 in 34.5 (95% CI: 0.0145-0.0512), similar to the frequency of the common mutation causing Tay-Sachs disease among Ashkenazi Jews. This finding reveals APBD to be another monogenic disorder that occurs with increased frequency in persons of Ashkenazi Jewish ancestry. PMID:22943850

  3. Theory of capture rate in polymer translocation.

    PubMed

    Muthukumar, M

    2010-05-21

    The translocation of macromolecules through a nanopore requires the impingement of the molecules at the pore followed by threading through the pore. While most of the discussion on the translocation phenomenon focused so far on the threading process, the phenomenology on the frequency of encounters between the polymer and the pore exhibits diverse features in terms of polymer length, solution conditions, driving force, and pore geometry. We derive a general theory for the capture rate of polyelectrolyte molecules and the probability of successful translocation through a nanopore, under an externally imposed electric field. By considering the roles of entropic barrier at the pore entrance and drift of the polyelectrolyte under the electric field, we delineate two regimes: (a) entropic barrier regime and (b) drift regime. In the first regime dominated by the entropic barrier for the polyelectrolyte, the capture rate is an increasing nonlinear function in the electric field and chain length. In the drift regime, where the electric field dwarfs the role of entropic barriers, the capture rate is independent of chain length and linear in electric field. An analytical formula is derived for the crossover behavior between these regimes, and the general results are consistent with various experimentally observed trends. PMID:20499989

  4. Partial Nephrectomy for the Treatment of Translocation Renal Cell Carcinoma

    PubMed Central

    Gorin, Michael A.; Ball, Mark W.; Pierorazio, Phillip M.; Argani, Pedram; Allaf, Mohamad E.

    2015-01-01

    We describe our experience with partial nephrectomy for the treatment of translocation renal cell carcinoma (RCC). During a 10-year period, 4 patients (0.02% of total RCC cases and 40% of translocation tumors) presented with an incidentally detected translocation RCC and were treated with partial nephrectomy. During a mean follow-up of 37 months, all patients were alive without evidence of disease. These data suggest that partial nephrectomy is a safe treatment option for select cases of translocation RCC. Background The aim of this study was to evaluate the outcome of patients with translocation renal cell carcinoma (RCC) treated with partial nephrectomy. Patients and Methods Our institutional review board-approved renal mass registry was queried for patients who underwent partial nephrectomy for a pathologically confirmed translocation RCC. We describe the demographic, clinical, pathological, and follow-up data for this series of patients. Results Between 2003 and 2013, 1897 patients with RCC were treated at our institution with a radical or partial nephrectomy. In total, 10 (0.5%) patients were diagnosed with a translocation RCC. Of these patients, 4 (40%) underwent treatment with partial nephrectomy for an incidentally detected small renal mass (mean imaging diameter, 2.6 cm [range, 1.0–4.2 cm]). During a mean follow-up of 37 months (range, 8–81 months), all patients were alive without evidence of disease. Conclusion At short-term follow-up, partial nephrectomy appears to be an effective treatment option for patients with small translocation RCCs. Larger studies are required to more extensively investigate the optimal treatment of these potentially aggressive tumors. PMID:25592300

  5. Genomic Comparison of Translocating and Non-Translocating Escherichia coli

    PubMed Central

    Bachmann, Nathan L.; Katouli, Mohammad; Polkinghorne, Adam

    2015-01-01

    Translocation of E. coli across the gut epithelium can result in fatal sepsis in post-surgical patients. In vitro and in vivo experiments have identified the existence of a novel pathotype of translocating E. coli (TEC) that employs an unknown mechanism for translocating across epithelial cells to the mesenteric lymph nodes and the blood stream in both humans and animal models. In this study the genomes of four TEC strains isolated from the mesenteric lymph nodes of a fatal case of hospitalised patient (HMLN-1), blood of pigs after experimental shock (PC-1) and after non-lethal haemorrhage in rats (KIC-1 and KIC-2) were sequenced in order to identify the genes associated with their adhesion and/or translocation. To facilitate the comparison, the genomes of a non-adhering, non-translocating E. coli (46–4) and adhering but non-translocating E. coli (73–89) were also sequenced and compared. Whole genome comparison revealed that three (HMLN-1, PC-1 and KIC-2) of the four TEC strains carried a genomic island that encodes a Type 6 Secretion System that may contribute to adhesion of the bacteria to gut epithelial cells. The human TEC strain HMLN-1 also carried the invasion ibeA gene, which was absent in the animal TEC strains and is likely to be associated with host-specific translocation. Phylogenetic analysis revealed that the four TEC strains were distributed amongst three distinct E. coli phylogroups, which was supported by the presence of phylogroup specific fimbriae gene clusters. The genomic comparison has identified potential genes that can be targeted with knock-out experiments to further characterise the mechanisms of E. coli translocation. PMID:26317913

  6. 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

  7. Abdominal radiation causes bacterial translocation

    SciTech Connect

    Guzman-Stein, G.; Bonsack, M.; Liberty, J.; Delaney, J.P.

    1989-02-01

    The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa.

  8. 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. ...

  9. The mechanics of ribosomal translocation.

    PubMed

    Achenbach, John; Nierhaus, Knud H

    2015-07-01

    The ribosome translates the sequence of codons of an mRNA into the corresponding sequence of amino acids as it moves along the mRNA with a codon-step width of about 10 Å. The movement of the million-dalton complex ribosome is triggered by the universal elongation factor G (EF2 in archaea and eukaryotes) and is termed translocation. Unraveling the molecular details of translocation is one of the most challenging tasks of current ribosome research. In the last two years, enormous progress has been obtained by highly-resolved X-ray and cryo-electron microscopic structures as well as by sophisticated biochemical approaches concerning the trigger and control of the movement of the tRNA2·mRNA complex inside the ribosome during translocation. This review inspects and surveys these achievements. PMID:25514765

  10. Translocation. Incidental phenomenon or true pathology?

    PubMed Central

    Munster, A M; Smith-Meek, M; Dickerson, C; Winchurch, R A

    1993-01-01

    OBJECTIVE: This study was conducted to determine if reduction of early postburn endotoxemia influences the cytokine cascade, clinical manifestations of sepsis, and mortality rate. SUMMARY BACKGROUND DATA: Translocational endotoxemia has been demonstrated postburn in animals and humans. Endotoxin is known to induce the cytokine cascade, which leads to the clinical manifestations of sepsis. Whether reduction of postburn endotoxemia could influence the induction of cytokines has not been demonstrated. METHODS: In a prospective, randomized study, 76 burn patients were given polymyxin intravenously or served as control subjects. Polymyxin B was given intravenously for 1 week postburn in doses designed to neutralize circulating endotoxemia. RESULTS: In the polymyxin group, there was a statistically significant reduction in the plasma endotoxin concentration. There was, however, no reduction in the sepsis score or the interleukin-6 levels, and no differences in mortality rates were seen between the two groups. CONCLUSIONS: Early postburn translocational endotoxemia can be treated with anti-endotoxin agents such as polymyxin B. This, however, does not influence the cytokine cascade or the mortality rate. The systemic inflammatory response syndrome is caused by cytokine induction from the injury and is unaffected by a reduction in the plasma endotoxin concentration. PMID:8373274

  11. Meiotic segregation and interchromosomal effect in the sperm of a double translocation carrier: a case report

    PubMed Central

    2009-01-01

    Background Infertility is a natural mechanism of selection intended to prevent the delivery of a child with malformations or mental retardation. Male infertility is closely related to chromosomal abnormalities. This study was focused on the analysis of meiotic segregation involving a Robertsonian translocation, 45,XY,der(13;13) [56]/45,XY,der(13;14) [44] and the evaluation of possible interchromosomal effects. Results Hybridisation with LSI 13q14 and subtelomere 14q probes and WCP13 SpectrumGreen and WCP14 SpectrumOrange probes showed a high proportion of unbalanced gametes, corresponding to 71.2% of the spermatozoa. The disomic frequencies of the sexual chromosomes and chromosome 18 of the patient were higher (5.28% and 2.55%, respectively) than those of the control (0.6% and 0.59%, respectively). Conclusion Meiotic segregation studies in sperm are an important tool for genetic counselling of chromosomal aberrations, allowing for a prediction of the risks and consequent implications for the reproductive life. The patient with this rare translocation exhibited meiotic segregation fidelity, and a high rate of unbalanced gametes with disomic spermatozoa. PMID:19951420

  12. 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.

  13. [Chromosome translocations and Epstein-Barr virus in Burkitt's lymphoma].

    PubMed

    Bornkamm, G W; Polack, A; Eick, D; Berger, R; Lenoir, G M

    1987-08-01

    Burkitt's lymphoma is characterized by particular epidemiological features. It is a frequent childhood tumor in children in tropical Africa and occurs at a much lesser frequency all over the world. Chromosomal translocation affecting the long arm of chromosome 8 (band 8q24) and one of the chromosomes carrying the immunoglobulin loci (chromosomes 2, 14 or 22) are regularly observed in Burkitt's lymphoma, regardless of whether the tumor occurred in high or low incidence areas. The prevalence of Burkitt's lymphoma in Africa appears to be related to two factors: holo- or hyperendemic malaria and presence of Epstein-Barr virus genomes in the tumor cells. We present a model of pathogenesis, in which stimulation of B cells by malaria is the primary event in the development of the disease. The risk of the chromosomal translocation should be increased by increasing the number of new B cells generated per time. According to our model, the translocation leads to constitutive c-myc activation and makes the cells responsive to growth factors without inducing proliferation on its own. Infection of a translocation-carrying cell with EBV may provide an additional growth advantage and drive the cell further towards a fully malignant state. PMID:2823199

  14. Multiscale control of summertime persistent heavy precipitation events over South China in association with synoptic, intraseasonal, and low-frequency background

    NASA Astrophysics Data System (ADS)

    Li, Richard C. Y.; Zhou, Wen

    2015-08-01

    This study examines persistent and short-lived heavy precipitation events (PHPEs and SHPEs, respectively) in South China during summer (July-September) 1975-2009 in association with large-scale circulation and moisture processes at different timescales. Compared to SHPEs, PHPEs are characterized by long-lasting enhanced convection and cyclonic moisture circulation as well as strengthened moisture convergence over South China. Examination of environmental variables at different timescales suggests that intraseasonal and synoptic components play a deterministic role in regulating the overall changes in convection and moisture convergence, while the low-frequency background state plays only a marginal role. Further analysis of the moisture divergence terms also reveals that the overall changes in moisture divergence during PHPEs and SHPEs stem primarily from variations in the intraseasonal and synoptic wind fields rather than in the humidity fields. Overall, it is found that the location and strength of the intraseasonal oscillation (ISO) and the synoptic disturbances play a decisive role in controlling the severity and duration of rainfall events over South China. The synchronization and persistence of the enhanced convection and moisture circulation of the ISO and synoptic disturbances jointly contribute to prolonged heavy precipitation over South China, while the weakening and asynchrony of the associated convection and moisture circulation at different timescales result in rainfall events of weaker intensity and shorter duration.

  15. 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

  16. Population demographics and genetic diversity in remnant and translocated populations of sea otters

    USGS Publications Warehouse

    Bodkin, J.L.; Ballachey, B.E.; Cronin, M.A.; Scribner, K.T.

    1999-01-01

    The effects of small population size on genetic diversity and subsequent population recovery are theoretically predicted, but few empirical data are available to describe those relations. We use data from four remnant and three translocated sea otter (Enhydra lutris) populations to examine relations among magnitude and duration of minimum population size, population growth rates, and genetic variation. Metochondrial (mt)DNA haplotype diversity was correlated with the number of years at minimum population size (r = -0.741, p = 0.038) and minimum population size (r = 0.709, p = 0.054). We found no relation between population growth and haplotype diversity, altough growth was significantly greater in translocated than in remnant populations. Haplotype diversity in populations established from two sources was higher than in a population established from a single source and was higher than in the respective source populations. Haplotype frequencies in translocated populations of founding sizes of 4 and 28 differed from expected, indicating genetic drift and differential reproduction between source populations, whereas haplotype frequencies in a translocated population with a founding size of 150 did not. Relations between population demographics and genetic characteristics suggest that genetic sampling of source and translocated populations can provide valuable inferences about translocations.

  17. Signal-dependent dynamics of transcription factor translocation controls gene expression.

    PubMed

    Hao, Nan; O'Shea, Erin K

    2012-01-01

    Information about environmental stimuli is often transmitted using common signaling molecules, but the mechanisms that ensure signaling specificity are not entirely known. Here we show that the identities and intensities of different stresses are transmitted by modulation of the amplitude, duration or frequency of nuclear translocation of the Saccharomyces cerevisiae general stress response transcription factor Msn2. Through artificial control of the dynamics of Msn2 translocation, we reveal how distinct dynamical schemes differentially affect reporter gene expression. Using a simple model, we predict stress-induced reporter gene expression from single-cell translocation dynamics. We then demonstrate that the response of natural target genes to dynamical modulation of Msn2 translocation is influenced by differences in the kinetics of promoter transitions and transcription factor binding properties. Thus, multiple environmental signals can trigger qualitatively different dynamics of a single transcription factor and influence gene expression patterns. PMID:22179789

  18. Translocation (Y;12) in lipoma.

    PubMed

    Liang, Cher-Wei; Mariño-Enríquez, Adrian; Johannessen, Catherine; Hornick, Jason L; Dal Cin, Paola

    2011-01-01

    Lipomas are the most common benign mesenchymal neoplasm in adults, and have been extensively characterized at the cytogenetic level. Chromosomal aberrations have been observed in the majority of lipomas, two-thirds of which involve chromosomal region 12q14.3. To date, structural rearrangements have been reported affecting every chromosome except chromosome Y. Here we report a case of a lipoma that shows a novel apparently balanced translocation involving chromosomes Y and 12. Fluorescence in situ hybridization using a break-apart HMGA2 in-house probe set detected a single signal on the normal chromosome 12 but not on either the derivative chromosome Y or 12, indicating a cryptic loss of 12q14.3, where HMGA2 is mapped. Immunohistochemical studies, however, revealed overexpression of HMGA2 with nuclear expression in the majority of tumor cells, whereas MDM2 and CDK4 were negative. The overexpression of HMGA2 may be caused by a cryptic chromosomal aberration affecting either the cytogenetically unaltered HMGA2 allele or HMGA2 regulators elsewhere. The current case broadens our knowledge about the translocation partners of HMGA2 in lipomas and highlights the biological complexity in regulating HMGA2 expression. PMID:21356192

  19. 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.

  20. An inducible translocation strategy to rapidly

    E-print Network

    Cai, Long

    trigger rapid plasma membrane translocation and engineering different enzymatic fusion constructs in the implementation of a rapamycin-triggered heterodimerization strategy. Using molecular engineering of different processes by using a small molecule­ dependent translocation of mutant Rho GTPases to the plasma membrane

  1. Antibody detection of translocations in Ewing sarcoma

    PubMed Central

    Luo, Wen; Milash, Brett; Dalley, Brian; Smith, Richard; Zhou, Holly; Dutrow, Natalie; Cairns, Bradley R; Lessnick, Stephen L

    2012-01-01

    The detection of chromosomal translocations has important implications in the diagnosis, prognosis and treatment of patients with cancer. Current approaches to translocation detection have significant shortcomings, including limited sensitivity and/or specificity, and difficulty in application to formalin-fixed paraffin-embedded (FFPE) clinical samples. We developed a new approach called antibody detection of translocations (ADOT) that avoids the shortcomings of current techniques. ADOT combines a transcriptional microarray-based approach with a novel antibody-based detection method. ADOT allows for the accurate and sensitive identification of translocations and provides exon-level information about the fusion transcript. ADOT can detect translocations in poor-quality unprocessed total ribonucleic acid (RNA). Furthermore, the technique is readily generalizable to detect any potential fusion transcript, including previously undescribed fusions. We demonstrate the feasibility of ADOT by examples in which both known and unknown Ewing sarcoma translocations are identified from cell lines, tumour xenografts and FFPE primary tumours. These results demonstrate that ADOT may be an effective approach for translocation analysis in clinical specimens with significant RNA degradation and may offer a novel diagnostic tool for translocation-based cancers. PMID:22419563

  2. Electrically facilitated translocation of protein through solid nanopore

    NASA Astrophysics Data System (ADS)

    Wu, Lingzhi; Liu, Hang; Zhao, Wenyuan; Wang, Lei; Hou, Chuanrong; Liu, Quanjun; Lu, Zuhong

    2014-03-01

    Nanopores have been proven as versatile single-molecule sensors for individual unlabeled biopolymer detection and characterization. In the present work, a relative large nanopore with a diameter of about 60 nm has been used to detect protein translocation driven by a series of applied voltages. Compared with previous studied small nanopores, a distinct profile of protein translocation through a larger nanopore has been characterized. First, a higher threshold voltage is required to drive proteins into the large nanopore. With the increase of voltages, the capture frequency of protein into the nanopore has been markedly enhanced. And the distribution of current blockage events is characterized as a function of biased voltages. Due to the large dimension of the nanopore, the adsorption and desorption phenomenon of proteins observed with a prolonged dwell time has been weakened in our work. Nevertheless, the protein can still be stretched into an unfolded state by increased electric forces at high voltages. In consideration of the high throughput of the large nanopore, a couple of proteins passing through the nanopore simultaneously occur at high voltage. As a new feature, the feasibility and specificity of a nanopore with distinct geometry have been demonstrated for sensing protein translocation, which broadly expand the application of nanopore devices.

  3. Counting and dynamic studies of the small unilamellar phospholipid vesicle translocation with single conical glass nanopores.

    PubMed

    Chen, Lizhen; He, Haili; Jin, Yongdong

    2015-01-01

    Phospholipid vesicles are ubiquitous cellular organelles that perform vital functions including materials transport and information transmission and have found promising biomedical applications. Although the transmembrane translocation (via nanopores) of phospholipid vesicles, especially small unilamellar phospholipid vesicles (SUVs), is recognized to be very important for these processes and applications, the details and dynamics remain not very clear. Herein, we use single conical glass nanopores as a model platform to systematically investigate the translocation dynamics of SUVs (?50-60 nm in diameter) through small nanopores with orifice diameters ranging from ?14 to 72 nm. Dynamic translocation of individual SUVs one by one through the nanopores was clearly observed and was analyzed by the occurrence of periodic oscillation in ionic current blockage signal under a negatively applied voltage. Translocation behaviors of the SUVs, in terms of magnitude and duration of ionic current blockage signal, varied and can be modulated by changing nanopore size, solution pH, vesicle concentration, applied voltage, and inner surface charge properties of the nanopores. The translocation rate of the SUVs through an ?72 nm nanopore is typically on a time scale of a few seconds (per SUV translocation event) and found nonlinearly proportional to the concentration of the SUVs. Moreover, the electrophoretic force has been verified as a main force to drive the SUVs through the nanopore since there is a nearly linear relationship between the current blockage frequency of SUVs translocation and the applied bias potentials ranging from -0.6 to -1 V. The findings provide fundamental insights into the translocation and interactions of SUVs with nanopores, and the reported nanopore platform may find potential useful bioapplications in single-cell and single-vesicle studies. PMID:25489990

  4. 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.

  5. Reverse Engineering of Proteasomal Translocation Rates

    E-print Network

    D. S. Goldobin; M. Mishto; K. Textoris-Taube; P. M. Kloetzel; A. Zaikin

    2008-07-28

    We address the problem of proteasomal protein translocation and introduce a new stochastic model of the proteasomal digestion (cleavage) of proteins. In this model we account for the protein translocation and the positioning of cleavage sites of a proteasome from first principles. We show by test examples and by processing experimental data that our model allows reconstruction of the translocation and cleavage rates from mass spectroscopy data on digestion patterns and can be used to investigate the properties of transport in different experimental set-ups. Detailed investigation with this model will enable theoretical quantitative prediction of the proteasomal activity.

  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. Recent Selection on the Y-to-Dot Translocation in Drosophila pseudoobscura

    PubMed Central

    Larracuente, Amanda M.; Clark, Andrew G.

    2014-01-01

    The Drosophila pseudoobscura dot chromosome acquired genes from the ancestral Drosophila Y chromosome in a Y-to-dot translocation event that occurred between 12.7 and 20.8 Ma. The formerly Y-linked genes mostly retained their testis-specific expression but shrank drastically in size, mostly through intron reduction, since becoming part of the dot chromosome in this species. We investigated the impact of this translocation on the evolution of the both the Y-to-dot translocated region and the original segments of the dot chromosome in D. pseudoobscura. Our survey of polymorphism and divergence across the chromosome reveals a reduction in variation, a deletion polymorphism segregating at high frequency, and a shift in the frequency spectra, all consistent with a history of recent selective sweeps in the Y-to-dot translocated region but not on the rest of the dot chromosome. We do find evidence for recombination primarily as gene conversion on the dot chromosome; however, predicted recombination events are restricted to the part of the dot chromosome outside the translocation. It therefore appears that recombination has resulted in a degree of decoupling between the ancestral Y region and the conserved region of the dot chromosome. PMID:24390701

  8. Cell Host & Microbe Translocation of Sickle Cell Erythrocyte MicroRNAs

    E-print Network

    Nicchitta, Chris

    a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria, including sickle cell diseases, occur at relatively high frequencies (Livincstone, 1971; Nagel and RothCell Host & Microbe Article Translocation of Sickle Cell Erythrocyte MicroRNAs into Plasmodium

  9. 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

  10. Translocation of imperiled species under changing climates.

    PubMed

    Schwartz, Mark W; Martin, Tara G

    2013-05-01

    Conservation translocation of species varies from restoring historic populations to managing the relocation of imperiled species to new locations. We review the literature in three areas--translocation, managed relocation, and conservation decision making--to inform conservation translocation under changing climates. First, climate change increases the potential for conflict over both the efficacy and the acceptability of conservation translocation. The emerging literature on managed relocation highlights this discourse. Second, conservation translocation works in concert with other strategies. The emerging literature in structured decision making provides a framework for prioritizing conservation actions--considering many possible alternatives that are evaluated based on expected benefit, risk, and social-political feasibility. Finally, the translocation literature has historically been primarily concerned with risks associated with the target species. In contrast, the managed relocation literature raises concerns about the ecological risk to the recipient ecosystem. Engaging in a structured decision process that explicitly focuses on stakeholder engagement, problem definition and specification of goals from the outset will allow creative solutions to be developed and evaluated based on their expected effectiveness. PMID:23574620

  11. Translocation of DNA across bacterial membranes.

    PubMed Central

    Dreiseikelmann, B

    1994-01-01

    DNA translocation across bacterial membranes occurs during the biological processes of infection by bacteriophages, conjugative DNA transfer of plasmids, T-DNA transfer, and genetic transformation. The mechanism of DNA translocation in these systems is not fully understood, but during the last few years extensive data about genes and gene products involved in the translocation processes have accumulated. One reason for the increasing interest in this topic is the discussion about horizontal gene transfer and transkingdom sex. Analyses of genes and gene products involved in DNA transfer suggest that DNA is transferred through a protein channel spanning the bacterial envelope. No common model exists for DNA translocation during phage infection. Perhaps various mechanisms are necessary as a result of the different morphologies of bacteriophages. The DNA translocation processes during conjugation, T-DNA transfer, and transformation are more consistent and may even be compared to the excretion of some proteins. On the basis of analogies and homologies between the proteins involved in DNA translocation and protein secretion, a common basic model for these processes is presented. PMID:7968916

  12. Translocation involving 1p and 17q is a recurrent genetic alteration of human neuroblastoma cells

    SciTech Connect

    Savelyeva, L.; Corvi, R.; Schwab, M. )

    1994-08-01

    Human neuroblastoma cells often are monosomic for the distal portion of 1p (1p36). The authors report that the deleted 1p material in cells of neuroblastoma lines is preferentially replaced by material from chromosome 17, resulting from an unbalanced 1;17 translocation. Chromosome 17 often acquires instability, followed by the integration of fragments into various marker chromosomes. As a consequence, 17q material can increase over 17p material. The nonrandom frequency of 1;17 translocations appears to indicate an as-yet-undefined contribution to neuroblastoma development. 35 refs., 4 figs., 1 tab.

  13. Theory of polymer translocation through a flickering nanopore under an alternating driving force.

    PubMed

    Sarabadani, Jalal; Ikonen, Timo; Ala-Nissila, Tapio

    2015-08-21

    We develop a theory for polymer translocation driven by a time-dependent force through an oscillating nanopore. To this end, we extend the iso-flux tension propagation theory [Sarabadani et al., J. Chem. Phys. 141, 214907 (2014)] for such a setup. We assume that the external driving force in the pore has a component oscillating in time, and the flickering pore is similarly described by an oscillating term in the pore friction. In addition to numerically solving the model, we derive analytical approximations that are in good agreement with the numerical simulations. Our results show that by controlling either the force or pore oscillations, the translocation process can be either sped up or slowed down depending on the frequency of the oscillations and the characteristic time scale of the process. We also show that while in the low and high frequency limits, the translocation time ? follows the established scaling relation with respect to chain length N0, in the intermediate frequency regime small periodic, fluctuations can have drastic effects on the dynamical scaling. The results can be easily generalized for non-periodic oscillations and elucidate the role of time dependent forces and pore oscillations in driven polymer translocation. PMID:26298154

  14. [Identification of the 1RS-7DS.7DL wheat-rye small segment translocation lines].

    PubMed

    Jun, Li; Xinguo, Zhu; Hongshen, Wan; Qin, Wang; Zongxiang, Tang; Shulan, Fu; Zujun, Yang; Manyu, Yang; Wuyun, Yang

    2015-06-01

    Rye (Secale cereale L., RR) is a valuable genetic resource for the improvement of common wheat (Triticum aestivum L., AABBDD). Transferring alien rye genes into wheat by distant hybridization and automatic chromosome doubling is an important and efficient method to boost agronomic traits, disease resistance and widening the gene pool in wheat. In this study, an octoploid triticale CD-13 (AABBDDRR) was obtained via automatic chromosome doubling by crossing landrace Penganbaimaizi (T. aestivum L., AABBDD) and rye "Qinling rye" (S. cereale cv. Qinling, RR). GISH and FISH analyses indicated that CD-13 contained a 1RS-7DS.7DL wheat-rye small segment translocation chromosome. In order to transfer the 1RS-7DS small segment translocation into hexaploid wheat, 58 lines of the F5 inbred population from the cross CD-13 x Chuanmai 42 were screened for rye chromosome segments by GISH and FISH analyses. The results showed that 13 lines contained the 1RS-7DS.7DL small segment translocation chromosome by reciprocal translocation between 1RS and 7DS. These translocation lines carrying 1RS small rye alien segment were tested for the translocation breakpoints and the presence of a storage protein locus Sec-1. The Sec-1 locus was absent in the line 811, a stable 1RS-7DS.7DL small segment translocation line. The translocation breakpoint of 1RS-7DS.7DL of this line was located in the interval of IB267-IAG95 around the telomere of 1RS chromosome. Thousand-kernel weight of the line 811 was much higher than the parent CD-13, but not significantly different from Chuanmai 42. This indicated that 1RS-7DS.7DL small segment translocation had no negative effect on thousand-kernel weight in the genetic background of Chuanmai 42. The line with 1RS-7DS.7DL translocation chromosomes can be used as a new genetic material for further studies of valuable genes and their genetic effect on 1RS small segment. PMID:26351056

  15. The persistence of stable translocations in mice following acute gamma irradiation

    SciTech Connect

    Spruill, M.D. |

    1994-12-31

    Animals, particularly the mouse, are important for estimating human risk from environmental exposure. Most cytogenetic studies have focused upon unstable events, i.e. dicentrics and fragments. Chromosome-specific composite DNA probes for the mouse have allowed the use of FISH (fluorescence in situ hybridization) to detect stable cytogenetic damage. THe specificity of FISH simplifies translocation detection and its sensitivity makes subtle translocations readily visible. C57BL/6 mice were acutely exposed to 0, 1, 2, 3 or 4 Gy {sup 137}Cs at 8 weeks of age. Peripheral blood and bone marrow were taken from four mice in each dose group at sampling times of 1, 8, 15 and 30 days. Probes specific for chromosomes 2 and 8 were used. The equivalent of 100 cells from each tissue was scored from each mouse. Preliminary results from bone marrow cells have shown that the percentage of reciprocal translocations remained constant up to one month. The frequency of non-reciprocal translocations decreased after a week, but then remained constant out to 30 days, while dicentrics decreased rapidly, with almost none remaining after 8 days. These data suggest that translocations will persist throughout the animal`s life span and be an adequate biodosimeter for radiation exposure.

  16. Factors predisposing to adjacent 2 and 3:1 disjunctions: study of 161 human reciprocal translocations.

    PubMed Central

    Jalbert, P; Sele, B

    1979-01-01

    Reciprocal translocations produce imbalances by three types of disjunction which are, in decreasing frequency, adjacent 1, 3:1, and adjacent 2. Adjacent 1 disjunction produces duplication deficiencies of inverse topography to those of adjacent 2. The imbalanced chromosome segments in one of these types are balanced in the other. The disjunction 3:1 produces pure trisomies and monosomies. The following situations predispose to adjacent 2 disjunction: translocations between the long arms of two acrocentric chromosomes or between one of these and that of a No 9 chromosome; centric segments, either short or carrying a heterochromatic zone (9qh); a balanced translocation in the mother. The factors predisposing to the disjunction adjacent 2 operate by selection, or directly on the meiotic configuration. Some of them (shortness of the interstitial segment, shortness of the short arms of translocation chromosomes) act in both these ways. Their influence is probably responsible for the repetitive and exclusive character of this disjunction. The conditions for the occurrence of the 3:1 disjunctions seem less strict than those for adjacent 2, although they should be of the same nature (involvement of acrocentrics or a chromosome 9 in the translocation, maternal origin). Images PMID:395305

  17. DNA nanopore translocation in glutamate solutions

    NASA Astrophysics Data System (ADS)

    Plesa, C.; van Loo, N.; Dekker, C.

    2015-08-01

    Nanopore experiments have traditionally been carried out with chloride-based solutions. Here we introduce silver/silver-glutamate-based electrochemistry as an alternative, and study the viscosity, conductivity, and nanopore translocation characteristics of potassium-, sodium-, and lithium-glutamate solutions. We show that it has a linear response at typical voltages and can be used to detect DNA translocations through a nanopore. The glutamate anion also acts as a redox-capable thickening agent, with high-viscosity solutions capable of slowing down the DNA translocation process by up to 11 times, with a corresponding 7 time reduction in signal. These results demonstrate that glutamate can replace chloride as the primary anion in nanopore resistive pulse sensing.

  18. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...used, and is recommended. (ii) Age. Healthy sexually mature animals shall be used. (iii) Number. (A) The number...for translocation heterozygosity. When males are sexually mature, testing for translocation heterozygosity shall begin....

  19. 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

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Single Stranded DNA Translocation Through a Fluctuating Nanopore

    E-print Network

    O. Flomenbom; J. Klafter

    2005-01-15

    We investigate the translocation of a single stranded DNA (ssDNA) through a pore, which fluctuates between two conformations, by using coupled master equations (ME). The probability density function (PDF) of the first passage times (FPT) of the translocation process is calculated, displaying a triple, double or mono-peaked behavior, depending on the system parameters. An analytical expression for the mean first passage time (MFPT) of the translocation process is derived, and provides an extensive characterization of the translocation process.

  2. Role of Denaturation in Maltose Binding Protein Translocation Marco Bacci,

    E-print Network

    Cecconi, Fabio

    Role of Denaturation in Maltose Binding Protein Translocation Dynamics Marco Bacci, Mauro Chinappi on voltage-driven transport of MBP across nanopores exploring the influence of denaturation on translocation blockades, associated to the translocation of denaturated and folded MBP conformations, respectively. We

  3. Slowing DNA Translocation in a Solid-State Nanopore

    E-print Network

    Li, Jiali

    Slowing DNA Translocation in a Solid-State Nanopore Daniel Fologea, James Uplinger, Brian Thomas ABSTRACT Reducing a DNA molecule's translocation speed in a solid-state nanopore is a key step toward rapid single molecule identification. Here we demonstrate that DNA translocation speeds can be reduced

  4. Translocations used to generate chromosome segment duplications in Neurospora can disrupt genes and create novel open reading frames.

    PubMed

    Singh, Parmit K; Iyer, Srividhya V; Sowjanya, T Naga; Raj, B Kranthi; Kasbekar, Durgadas P

    2010-12-01

    In Neurospora crassa, crosses between normal sequence strains and strains bearing some translocations can yield progeny bearing a duplication (Dp) of the translocated chromosome segment. Here, 30 breakpoint junction sequences of 12 Dp-generating translocations were determined. The breakpoints disrupted 13 genes (including predicted genes), and created 10 novel open reading frames. Insertion of sequences from LG III into LG I as translocation T(UK8-18) disrupts the eat-3 gene, which is the ortholog of the Podospora anserine gene ami1. Since ami1-homozygous Podospora crosses were reported to increase the frequency of repeat-induced point mutation (RIP), we performed crosses homozygous for a deficiency in eat-3 to test for a corresponding increase in RIP frequency. However, our results suggested that, unlike in Podospora, the eat-3 gene might be essential for ascus development in Neurospora. Duplication-heterozygous crosses are generally barren in Neurospora; however, by using molecular probes developed in this study, we could identify Dp segregants from two different translocation-heterozygous crosses, and using these we found that the barren phenotype of at least some duplication-heterozygous crosses was incompletely penetrant. PMID:21289436

  5. 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

  6. Financial costs of large carnivore translocations--accounting for conservation.

    PubMed

    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

  7. Introduction Background

    E-print Network

    Petta, Jason

    Research Conclusions #12;Background What is a hygrometer? VCSEL Chilled mirror hygrometer Why measure does a VCSEL hygrometer address these problems? 25Hz measurements Open source environment Low wind with chilled mirror hygrometer Pressure and Temperature effects #12;Calibration Techniques Removal of all

  8. Translocation in the nonpolytrichaceous moss grimmia laevigata

    SciTech Connect

    Alpert, P. )

    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.

  9. 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.

  10. Targeted Chromosomal Translocations and Essential Gene Knockout Using CRISPR/Cas9 Technology in Caenorhabditis elegans.

    PubMed

    Chen, Xiangyang; Li, Mu; Feng, Xuezhu; Guang, Shouhong

    2015-12-01

    Many genes play essential roles in development and fertility; their disruption leads to growth arrest or sterility. Genetic balancers have been widely used to study essential genes in many organisms. However, it is technically challenging and laborious to generate and maintain the loss-of-function mutations of essential genes. The CRISPR/Cas9 technology has been successfully applied for gene editing and chromosome engineering. Here, we have developed a method to induce chromosomal translocations and produce genetic balancers using the CRISPR/Cas9 technology and have applied this approach to edit essential genes in Caenorhabditis elegans. The co-injection of dual small guide RNA targeting genes on different chromosomes resulted in reciprocal translocation between nonhomologous chromosomes. These animals with chromosomal translocations were subsequently crossed with animals that contain normal sets of chromosomes. The F1 progeny were subjected to a second round of Cas9-mediated gene editing. Through this method, we successfully produced nematode strains with specified chromosomal translocations and generated a number of loss-of-function alleles of two essential genes (csr-1 and mes-6). Therefore, our method provides an easy and efficient approach to generate and maintain loss-of-function alleles of essential genes with detailed genetic background information. PMID:26482793

  11. 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

  12. Preimplantation genetic diagnosis for a known cryptic translocation: follow-up clinical report and implication of segregation products.

    PubMed

    McKenzie, L J; Cisneros, P L; Torsky, S; Bacino, C A; Buster, J E; Carson, S A; Simpson, J L; Bischoff, F

    2003-08-15

    This report describes preimplantation genetic diagnosis (PGD) of a couple with a known paternally-derived balanced cryptic translocation 46,XY.ish t(2q;17q)(210E14-,B37c1+;B37c1-,210E14+) in embryos from a couple who previously had a child with severe mental retardation and was previously described in this journal [Bacino et al., 2000]. This child inherited the unbalanced product of translocation from her father: 46,XX.ish der(2)t(2q;17q)pat(210E14-,B37c1+). The couple desired a normal offspring and sought PGD to avoid clinical pregnancy termination. They were treated three times with in vitro fertilization followed by PGD. Two sequential FISH hybridizations were performed. In the first hybridization, telomeric probes to 2q and 17q and a chromosome 17 centromere probe were employed. The second hybridization screened for maternal age-related aneuploidy (X,Y,13,18,21). Of the 18 informative embryos, only 4 (22%) were normal. The remaining 12 (67%) were abnormal; most with unbalanced products (10/12) from the paternally-derived rearrangement. The most frequent mode of segregation observed for this cryptic translocation was adjacent-1 (7/18, 39%). This suggests cryptic translocations are amenable to PGD and, as are traditional translocations, demonstrate higher frequencies of unbalanced segregants than the empiric risk of 10-15% observed at amniocentesis or chorionic villus sampling. Thus, cryptic translocations presumably behave like overt translocations, in that PGD must be performed on a relatively large number of embryos to assure even 2-3 transferable embryos. PMID:12900903

  13. Intestinal Microbiota, Microbial Translocation, and Systemic Inflammation in Chronic HIV Infection

    PubMed Central

    Dinh, Duy M.; Volpe, Gretchen E.; Duffalo, Chad; Bhalchandra, Seema; Tai, Albert K.; Kane, Anne V.; Wanke, Christine A.; Ward, Honorine D.

    2015-01-01

    Background.?Despite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation. Methods.?We profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls. Results.?The fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1? (IL-1?) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon ? level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-? level. There were negative correlations between endotoxin core IgM and IL-1? levels. Conclusions.?Patients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed. PMID:25057045

  14. 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

  15. No evidence for loss of genetic variation following sequential translocations in extant populations of a genetically depauperate species.

    PubMed

    Taylor, Sabrina S; Jamieson, Ian G

    2008-01-01

    Repeated population bottlenecks can lead to loss of genetic variation and normally should be avoided in threatened species to preserve evolutionary potential. We examined the effect of repeated bottlenecks, in the form of sequential translocations, on loss of genetic variation in a threatened passerine, the saddleback (Philesturnus carunculatus carunculatus), a species that has recovered from a remnant population with historically low levels of genetic variation. Although a slight but nonsignificant loss of alleles may have occurred between the first-order translocation and the extirpated source population, first-, second-, and third-order translocated populations had very similar levels of genetic variation to each other. The most obvious difference among the seven island populations appeared to lie in allele frequencies with little or no loss of alleles among extant populations. Although sequential translocations are known to cause loss of variation in genetically diverse species, our study indicates that genetically depauperate species may be less sensitive to loss of genetic variation through founder events presumably because the few remaining alleles are well represented in founding individuals. These results show that ancient bottlenecks may have a long-term effect on genetic variation, to the extent that contemporary population bottlenecks may leave no appreciable genetic signature. Our results suggest that subjecting genetically depauperate endangered species to sequential translocations could be used to rapidly establish new populations without further eroding genetic variation. PMID:17986194

  16. 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

  17. 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.

  18. Julia Frbel, Patrick Rose and Matthias Mller Twin-arginine Translocation

    E-print Network

    Just, Armin

    Julia Fröbel, Patrick Rose and Matthias Müller Twin-arginine Translocation and TatA TranslocaseA Translocase Component in Twin-arginine Translocation*S Received for publication,August 10, 2011 with twin-arginine precursors prior to the actual translocation event. Twin-arginine translocation (Tat

  19. Microbial Translocation Across the GI Tract*

    PubMed Central

    Brenchley, Jason M.; Douek, Daniel C.

    2012-01-01

    The lumen of the gastrointestinal (GI) tract is home to an enormous quantity of different bacterial species, our microbiota, that thrive in an often symbiotic relationship with the host. Given that the healthy host must regulate contact between the microbiota and its immune system to avoid overwhelming systemic immune activation, humans have evolved several mechanisms to attenuate systemic microbial translocation (MT) and its consequences. However, several diseases are associated with the failure of one or more of these mechanisms, with consequent immune activation and deleterious effects on health. Here, we discuss the mechanisms underlying MT, diseases associated with MT, and therapeutic interventions that aim to decrease it. PMID:22224779

  20. 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.

  1. Kinetics of Motor Protein Translocation on Single-Stranded DNA

    E-print Network

    Lohman, Timothy M.

    Chapter 4 Kinetics of Motor Protein Translocation on Single-Stranded DNA Christopher J. Fischer proteins along DNA or RNA can be studied in ensemble experiments by monitoring either the kinetics) or the kinetics of ATP hydrolysis by the motor protein during translocation. The pre-steady state kinetic data

  2. Polymer translocation through a long nanopore Elena Slonkina

    E-print Network

    Polymer translocation through a long nanopore Elena Slonkina Department of Chemistry, Moscow State, Texas 77005 Received 9 September 2002; accepted 23 January 2003 Polymer translocation through a nanopore through a nanopore indicate that the size and geometry of the pore are important factors in polymer

  3. Chaperone-assisted translocation of flexible polymers in three dimensions

    E-print Network

    Suhonen, P M

    2015-01-01

    Polymer translocation through a nanometer-scale pore assisted by chaperones binding to the polymer is a process encountered in vivo for proteins. Studying the relevant models by computer simulations is computationally demanding. Accordingly, previous studies are either for stiff polymers in three dimensions or flexible polymers in two dimensions. Here, we study chaperone-assisted translocation of flexible polymers in three dimensions using Langevin dynamics. We show that differences in binding mechanisms, more specifically, whether a chaperone can bind to a single or multiple sites on the polymer, lead to substantial differences in translocation dynamics in three dimensions. We show that the single-binding mode leads to dynamics that is very much like that in the constant-force driven translocation and accordingly mainly determined by tension propagation on the cis side. We obtain $\\beta \\approx 1.26$ for the exponent for the scaling of the translocation time with polymer length. This fairly low value can be ...

  4. Polypeptide translocation by the AAA+ ClpXP protease machine

    PubMed Central

    Barkow, Sarah R.; Levchenko, Igor; Baker, Tania A.; Sauer, Robert T.

    2009-01-01

    In the AAA+ ClpXP protease, ClpX uses repeated cycles of ATP hydrolysis to pull native proteins apart and to translocate the denatured polypeptide into ClpP for degradation. Here, we probe polypeptide features important for translocation. ClpXP degrades diverse synthetic peptide substrates despite major differences in side-chain chirality, size, and polarity. Moreover, translocation occurs without a peptide –NH and with 10 methylenes between successive peptide bonds. Pulling on homopolymeric tracts of glycine, proline, and lysine also allows efficient ClpXP degradation of a stably folded protein. Thus, minimal chemical features of a polypeptide chain are sufficient for translocation and protein unfolding by the ClpX machine. These results suggest that the translocation pore of ClpX is highly elastic, allowing interactions with a wide-range of chemical groups, a feature likely to be shared by many AAA+ unfoldases. PMID:19549599

  5. 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.

    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.

  6. 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.

  7. Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development

    PubMed Central

    Bhoj, Elizabeth J; Ramos, Purita; Baker, Linda A; Cost, Nicholas; Nordenskjöld, Agneta; Elder, Frederick F; Bleyl, Steven B; Bowles, Neil E; Arrington, Cammon B; Delhomme, Brigitte; Vanhoutteghem, Amandine; Djian, Philippe; Zinn, Andrew R

    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 fetus with unbalanced segregation of the translocation. The chromosome 13 breakpoint was ?400?kb away from the nearest gene, but the chromosome 9 breakpoint fell within an intron of Basonuclin 2 (BNC2), a gene that encodes an evolutionarily conserved nuclear zinc-finger protein. The BNC2/Bnc2 gene is abundantly expressed in developing mouse and human periurethral tissues. In all, 6 of 48 unrelated subjects with distal hypospadias had nine novel nonsynonymous substitutions in BNC2, five of which were computationally predicted to be deleterious. In comparison, two of 23 controls with normal penile urethra morphology, each had a novel nonsynonymous substitution in BNC2, one of which was predicted to be deleterious. Bnc2?/? mice of both sexes displayed a high frequency of distal urethral defects; heterozygotes showed similar defects with reduced penetrance. The association of BNC2 disruption with distal urethral defects and the gene's expression pattern indicate that it functions in urethral development. PMID:21368915

  8. Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development.

    PubMed

    Bhoj, Elizabeth J; Ramos, Purita; Baker, Linda A; Garg, Vidu; Cost, Nicholas; Nordenskjöld, Agneta; Elder, Frederick F; Bleyl, Steven B; Bowles, Neil E; Arrington, Cammon B; Delhomme, Brigitte; Vanhoutteghem, Amandine; Djian, Philippe; Zinn, Andrew R

    2011-05-01

    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 fetus with unbalanced segregation of the translocation. The chromosome 13 breakpoint was ?400 ?kb away from the nearest gene, but the chromosome 9 breakpoint fell within an intron of Basonuclin 2 (BNC2), a gene that encodes an evolutionarily conserved nuclear zinc-finger protein. The BNC2/Bnc2 gene is abundantly expressed in developing mouse and human periurethral tissues. In all, 6 of 48 unrelated subjects with distal hypospadias had nine novel nonsynonymous substitutions in BNC2, five of which were computationally predicted to be deleterious. In comparison, two of 23 controls with normal penile urethra morphology, each had a novel nonsynonymous substitution in BNC2, one of which was predicted to be deleterious. Bnc2(-/-) mice of both sexes displayed a high frequency of distal urethral defects; heterozygotes showed similar defects with reduced penetrance. The association of BNC2 disruption with distal urethral defects and the gene's expression pattern indicate that it functions in urethral development. PMID:21368915

  9. 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

  10. Characterization of Robertsonian translocations by using fluorescence in situ hybridization

    SciTech Connect

    Wolff, D.J.; Schwartz, S. )

    1992-01-01

    Fluorescence in situ hybridization with five biotin-labeled probes (three alphoid probes, a probe specific for beta-satellite sequences in all acrocentric chromosomes, and an rDNA probe) was used to characterize 30 different Robertsonian translocations, including three t(13;13); one t(15;15), four t(21;21), three t(13;14), two t(13;15), two (13;21), two t(13;22), one t(14;15), eight t(14;21), two t(14;22), two t(21;22). Of 8 de novo homologous translocations, only one t(13;13) chromosome was interpreted as dicentric, while 19 of 22 nonhomologous Robertsonian translocations were dicentric. The three monocentric nonhomologous translocations included both of the t(13;21) and one t(21;22). Two of 26 translocations studied using the beta-satellite probe showed a positive signal, while rDNA was undetectable in 10 cases studied. These results indicate that most homologous Robertsonian translocations appear monocentric, while the bulk of nonhomologous translocations show two alphoid signals. A majority of the breakpoints localized using this analysis seem to be distal to the centromere and just proximal to the beta-satellite and nuclear-organizing regions.

  11. Forced Translocation of Polymer through Nanopore: Deterministic Model and Simulations

    NASA Astrophysics Data System (ADS)

    Wang, Yanqian; Panyukov, Sergey; Liao, Qi; Rubinstein, Michael

    2012-02-01

    We propose a new theoretical model of forced translocation of a polymer chain through a nanopore. We assume that DNA translocation at high fields proceeds too fast for the chain to relax, and thus the chain unravels loop by loop in an almost deterministic way. So the distribution of translocation times of a given monomer is controlled by the initial conformation of the chain (the distribution of its loops). Our model predicts the translocation time of each monomer as an explicit function of initial polymer conformation. We refer to this concept as ``fingerprinting''. The width of the translocation time distribution is determined by the loop distribution in initial conformation as well as by the thermal fluctuations of the polymer chain during the translocation process. We show that the conformational broadening ?t of translocation times of m-th monomer ?tm^1.5 is stronger than the thermal broadening ?tm^1.25 The predictions of our deterministic model were verified by extensive molecular dynamics simulations

  12. 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.

  13. Translocation of gut flora and its role in sepsis.

    PubMed

    Vaishnavi, C

    2013-01-01

    Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. Sometimes instead of bacteria, inflammatory compounds are responsible for clinical symptoms as in systemic inflammatory response syndrome (SIRS). The difference between sepsis and SIRS is that pathogenic bacteria are isolated from patients with sepsis but not with those of SIRS. Bacterial translocation occurs more frequently in patients with intestinal obstruction and in immunocompromised patients and is the cause of subsequent sepsis. Factors that can trigger bacterial translocation from the gut are host immune deficiencies and immunosuppression, disturbances in normal ecological balance of gut, mucosal barrier permeability, obstructive jaundice, stress, etc. Bacterial translocation occurs through the transcellular and the paracellular pathways and can be measured both directly by culture of mesenteric lymph nodes and indirectly by using labeled bacteria, peripheral blood culture, detection of microbial DNA or endotoxin and urinary excretion of non-metabolisable sugars. Bacterial translocation may be a normal phenomenon occurring on frequent basis in healthy individuals without any deleterious consequences. But when the immune system is challenged extensively, it breaks down and results in septic complications at different sites away from the main focus. The factors released from the gut and carried in the mesenteric lymphatics but not in the portal blood are enough to cause multi-organ failure. Thus, bacterial translocation may be a promoter of sepsis but not the initiator. This paper reviews literature on the translocation of gut flora and its role in causing sepsis. PMID:24064638

  14. Improvement of the agronomic traits of a wheat-barley centric fusion by introgressing the 3HS.3BL translocation into a modern wheat cultivar.

    PubMed

    Türkösi, Edina; Farkas, András; Aranyi, Nikolett Réka; Hoffmann, Borbála; Tóth, Viola; Molnár-Láng, Márta

    2014-11-01

    The 3HS.3BL spontaneous Robertsonian translocation obtained from the progenies of wheat-barley (Chinese Spring × Betzes) hybrids backcrossed with wheat line Mv9kr1 was transferred into the modern Martonvásár wheat cultivar Mv Bodri. The translocation was identified with molecular cytogenetic methods. The inheritance of the translocation was traced using genomic in situ hybridization. Fluorescence in situ hybridization using barley subtelomeric (HvT01) and centromere-specific [(AGGGAG)4] repetitive DNA probes confirmed that the complete barley chromosome arm was involved in the Robertsonian translocation. The wheat-specific repetitive DNA probes identified the presence of the whole wheat genome, except the short arm of the 3B chromosome. Genotypes homozygous for the centric fusion were selected, after which morphological analysis was performed on the plants and the yield components were measured in the field during two consecutive vegetative seasons. The introgression of the 3HS.3BL translocation into the modern wheat cultivar Mv Bodri significantly reduced the plant height due to the incorporation of the dwarfing allele RhtD1b. The presence of the 3HS.3BL translocation in the Mv9kr1 and Mv Bodri wheat background improved tillering and seeds per plant productivity in field experiments carried out in Martonvásár and Keszthely, Hungary. PMID:25806585

  15. The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia

    PubMed Central

    Doyle, Orla M.; Bois, Catherine; Thomson, Pippa; Romaniuk, Liana; Whitcher, Brandon; Williams, Steven C.R.; Turkheimer, Federico E.; Stefansson, Hreinn; McIntosh, Andrew M.; Mehta, Mitul A.; Lawrie, Stephen M.

    2015-01-01

    BACKGROUND. The disrupted in schizophrenia 1 (DISC1) gene locus was originally identified in a Scottish pedigree with a high incidence of psychiatric disorders that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal translocation. Here, we investigated whether members of this family carrying the t(1;11)(q42.1;q14.3) translocation have a common brain-related phenotype and whether this phenotype is similar to that observed in schizophrenia (SCZ), using multivariate pattern recognition techniques. METHODS. We measured cortical thickness, cortical surface area, subcortical volumes, and regional cerebral blood flow (rCBF) in healthy controls (HC) (n = 24), patients diagnosed with SCZ (n = 24), patients diagnosed with bipolar disorder (BP) (n = 19), and members of the original Scottish family (n = 30) who were either carriers (T+) or noncarriers (T–) of the DISC1 translocation. Binary classification models were developed to assess the differences and similarities across groups. RESULTS. Based on cortical thickness, 72% of the T– group were assigned to the HC group, 83% of the T+ group were assigned to the SCZ group, and 45% of the BP group were classified as belonging to the SCZ group, suggesting high specificity of this measurement in predicting brain-related phenotypes. Shared brain-related phenotypes between SCZ and T+ individuals were found for cortical thickness only. Finally, a classification accuracy of 73% was achieved when directly comparing the pattern of cortical thickness of T+ and T– individuals. CONCLUSION. Together, the results of this study suggest that the DISC1 translocation may increase the risk of psychiatric disorders in this pedigree by affecting neurostructural phenotypes such as cortical thickness. FUNDING. This work was supported by the National Health Service Research Scotland, the Scottish Translational Medicine Research Collaboration, the Innovative Medicines Initiative (IMI), the Engineering and Physical Sciences Research Council (EPSRC), The Wellcome Trust, the National Institute of Health Research (NIHR), and Pfizer. PMID:26301809

  16. Correlations of telomere length, P53 mutation, and chromosomal translocation in soft tissue sarcomas

    PubMed Central

    Liu, Chunxia; Li, Bingcheng; Li, Li; Zhang, Haijun; Chen, Yunzhao; Cui, Xiaobin; Hu, Jianming; Jiang, Jingfang; Qi, Yan; Li, Feng

    2015-01-01

    Background: Soft tissue sarcomas (STSs) are a heterogeneous group of malignant tumors that can be divided into specific reciprocal translocation associated in STSs (SRTSs) and nonspecific reciprocal translocation associated in STSs (NRTSs). Telomeres play a key role in maintaining chromosomal stability; pathological telomere elongation is found in a number of cancers. In this study, we aimed to assess telomere lengths in the two types of sarcomas. Twenty formalin-fixed paraffin-embedded (FFPE) archival tissues, namely, 10 sarcomas with characteristic translocations and 10 without characteristic translocations, were included in this study. Expression levels of special fusion gene transcripts were detected in these tumors by reverse transcription polymerase chain reaction. Telomere lengths were assessed by fluorescence in situ hybridization. Results showed that in 10 of the 10 cases of SRTSs, telomere lengths were similar to or reduced compared with the surrounding normal cells. Telomere lengths were elongated in eight of 10 cases of NRTSs, but reduced in two cases. The difference in telomere length was statistically significant in the two types of sarcomas (P = 0.001). Upon combining the P53 mutation status, we found that the telomere length was short in eight cases, and only one case demonstrated p53 mutation. However, the telomere length was long in eight cases, and p53 mutation was observed in five cases. These data suggested that p53 mutation was accompanied with long telomeres, and telomeres possibly play an important role in NRTSs. Therefore, telomere-targeting therapy may lead to novel therapeutic strategies to improve treatment of NRTS patients. PMID:26191279

  17. Can hunting of translocated nuisance Canada geese reduce local conflicts?

    USGS Publications Warehouse

    Holevinski, R.A.; Malecki, R.A.; Curtis, P.D.

    2006-01-01

    Resident Canada geese (Branta canadensis) nest or reside in the temperate latitudes of North America. In past years, translocation-the capture and subsequent release of geese at distant locations-has been used to establish resident goose populations and to reduce nuisance problems. However, with new special hunting seasons designed to target resident Canada geese, we can now evaluate translocation as a management tool when hunting is allowed at release sites. We selected 2 study sites, representative of urban and suburban locations with nuisance resident geese, in central and western New York, USA. In June 2003, we translocated 80 neck-banded adult geese, 14 radiomarked adult females, and 83 juveniles 150 km east and southwest from urban and suburban problem sites in western New York to state-owned Wildlife Management Areas. At these same capture sites, we used 151 neck-banded adult geese, 12 radiomarked females, and 100 juveniles as controls to compare dispersal movements and harvest vulnerability to translocated geese. All observations (n = 45) of translocated radiomarked geese were <20 km from release sites, in areas where hunting was permitted. Only 25 of 538 observations (4.6%) of radiomarked geese at control sites were in areas open to hunting. The remainder of observations occurred at nonhunting locations within 10 km of control sites. More translocated adult geese (23.8%) were harvested than control geese (6.6%; ??2 = 72.98, P = 0.0009). More translocated juvenile geese were harvested (22.9%) than juvenile controls (5.0%; ??2 = 72.30, P = 0.0005). Only 7 (8.8%) translocated adult geese returned to the original capture sites during Canada goose hunting seasons. Translocation of adult and juvenile geese in family groups may alleviate nuisance problems at conflict sites through increased harvest, reducing the number of birds returning in subsequent years.

  18. De Novo microdeletion on an inherited Robertsonian translocation chromosome: A cause for dysmorphism in the apparently balanced translocation carrier

    SciTech Connect

    Bonthron, D.T.; Smith, S.J.L.; Fantes, J.; Gosden, C.M.

    1993-09-01

    Robertsonian translocations are usually ascertained through abnormal children, making proposed phenotypic effects of apparently balanced translocations difficult to study in an unbiased way. From molecular genetic studies, though, some apparently balanced rearrangments are now known to be associated with phenotypic abnormalities resulting from uniparental disomy. Molecular explanations for other cases in which abnormality is seen in a balanced translocation carrier are being sought. In the present paper, an infant is described who has retarded growth, developmental delay, gross muscular hypotonia, slender habitus, frontal bossing, micrognathia, hooked nose, abundant wispy hair, and blue sclerae. Cytogenetically, she appeared to be a carrier of a balanced, paternally derived 14;21 Robertsonian translocation. Analysis of DNA polymorphisms showed that she had no paternal allele at the D14S13 locus (14q32). Study of additional DNA markers within 14q32 revealed that her previously undescribed phenotype results from an interstitial microdeletion within 14q32. Fluorescent in situ hybridization was used to show that this microdeletion had occurred de novo on the Robertsonian translocation chromosome. These observations may reactivate old suspicions of a causal association between Robertsonian translocations and de novo rearrangements in offspring; a systematic search for similar subcytogentic rearrangements in other families, in which there are phenotypically abnormal children with apparently balanced translocations, may be fruitful. The clinical and molecular genetic data presented also define a new contiguous gene syndrome due to interstitial 14q32 deletion. 42 refs., 4 figs., 1 tab.

  19. DNA Translocations through Solid-State Plasmonic Nanopores

    PubMed Central

    2015-01-01

    Nanopores enable label-free detection and analysis of single biomolecules. Here, we investigate DNA translocations through a novel type of plasmonic nanopore based on a gold bowtie nanoantenna with a solid-state nanopore at the plasmonic hot spot. Plasmonic excitation of the nanopore is found to influence both the sensor signal (nanopore ionic conductance blockade during DNA translocation) and the process that captures DNA into the nanopore, without affecting the duration time of the translocations. Most striking is a strong plasmon-induced enhancement of the rate of DNA translocation events in lithium chloride (LiCl, already 10-fold enhancement at a few mW of laser power). This provides a means to utilize the excellent spatiotemporal resolution of DNA interrogations with nanopores in LiCl buffers, which is known to suffer from low event rates. We propose a mechanism based on plasmon-induced local heating and thermophoresis as explanation of our observations. PMID:25347403

  20. 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

  1. Bacterial Translocation – Impact on the Adipocyte Compartment

    PubMed Central

    Kruis, Tassilo; Batra, Arvind; Siegmund, Britta

    2013-01-01

    Over the last decade it became broadly recognized that adipokines and thus the fat tissue compartment exert a regulatory function on the immune system. Our own group described the pro-inflammatory function of the adipokine leptin within intestinal inflammation in a variety of animal models. Following-up on this initial work, the aim was to reveal stimuli and mechanisms involved in the activation of the fat tissue compartment and the subsequent release of adipokines and other mediators paralleled by the infiltration of immune cells. This review will summarize the current literature on the possible role of the mesenteric fat tissue in intestinal inflammation with a focus on Crohn’s disease (CD). CD is of particular interest in this context since the transmural intestinal inflammation has been associated with a characteristic hypertrophy of the mesenteric fat, a phenomenon called “creeping fat.” The review will address three consecutive questions: (i) What is inducing adipocyte activation, (ii) which factors are released after activation and what are the consequences for the local fat tissue compartment and infiltrating cells; (iii) do the answers generated before allow for an explanation of the role of the mesenteric fat tissue within intestinal inflammation? With this review we will provide a working model indicating a close interaction in between bacterial translocation, activation of the adipocytes, and subsequent direction of the infiltrating immune cells. In summary, the models system mesenteric fat indicates a unique way how adipocytes can directly interact with the immune system. PMID:24432024

  2. Controlled translocation of DNA segments through nanoelectrode gaps

    SciTech Connect

    Zhao, Xiongce; Payne, Christina M; Cummings, Peter T

    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.

  3. Effect of Sink Region Anoxia on Translocation Rate 1

    PubMed Central

    Geiger, D. R.; Christy, A. L.

    1971-01-01

    Translocation rate, ATP level, and CO2 production of a developing leaf (sink leaf) were studied in sugar beet (Beta vulgaris) plants prior to and during anaerobic treatment of the sink leaf. Within 3 to 5 minutes after onset of treatment with a N2 atmosphere, translocation into the sink leaf decreased to near zero and then recovered to a level of about 50% of the control over the next 2 hours. A decline in CO2 output and ATP levels coincided with the attainment of the new translocation rate. All three quantities returned to near control levels within 60 to 120 minutes after the sink leaf was returned to air. Swelling and ultrastructural changes in mitochondria coincided with the observed ATP level changes during inhibition and recovery periods. The first phase of marked inhibition of translocation did not coincide with low ATP level and appeared to be caused by decreased membrane permeability during the transition to anaerobic metabolism, possibly as a result of a temporary build up of toxic products. The correlation between ATP level and translocation rate suggests that ATP-dependent active transport in the sink leaf augments the driving force for translocation. Images PMID:16657588

  4. 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

  5. Protein kinase C translocation in human blood platelets

    SciTech Connect

    Wang, Hoauyan; Friedman, E. )

    1990-01-01

    Protein kinase C (PKC) activity and translocation in response to the phorbol ester, phorbol 12-myristate, 13-acetate (PMA), serotonin (5-HT) and thrombin was assessed in human platelets. Stimulation with PMA and 5-HT for 10 minutes or thrombin for 1 minute elicited platelet PKC translocation from cytosol to membrane. The catecholamines, norepinephrine or epinephrine at 10 {mu}M concentrations did not induce redistribution of platelet PKC. Serotonin and the specific 5-HT{sub 2} receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (DOI) but not the 5-HT{sub 1A} or 5-HT{sub 1B} agonists, ({plus minus}) 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT) or 5-methoxy-3-3-(1,2,3,6-tetrahydro-4-pyridin) 1H-indole succinate (RU 24969) induced dose-dependent PKC translocations. Serotonin-evoked PKC translocation was blocked by selective 5-HT{sub 2} receptor antagonists, ketanserin and spiroperidol. These results suggest that, in human platelets, PMA, thrombin and 5-HT can elicit PKC translocation from cytosol to membrane. Serotonin-induced PKC translocation in platelets is mediated via 5-HT{sub 2} receptors.

  6. 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

  7. 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.

  8. 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.

  9. Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations.

    PubMed

    Branco, Miguel R; Pombo, Ana

    2006-05-01

    After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability. PMID:16623600

  10. Conflict Bear Translocation: Investigating Population Genetics and Fate of Bear Translocation in Dachigam National Park, Jammu and Kashmir, India.

    PubMed

    Mukesh; Sharma, Lalit Kumar; Charoo, Samina Amin; Sathyakumar, Sambandam

    2015-01-01

    The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape. PMID:26267280

  11. Conflict Bear Translocation: Investigating Population Genetics and Fate of Bear Translocation in Dachigam National Park, Jammu and Kashmir, India

    PubMed Central

    Mukesh; Sharma, Lalit Kumar; Charoo, Samina Amin; Sathyakumar, Sambandam

    2015-01-01

    The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth ‘conflict bears’ from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape. PMID:26267280

  12. 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.

  13. Understanding publication bias in reintroduction biology by assessing translocations of New Zealand's herpetofauna.

    PubMed

    Miller, Kimberly A; Bell, Trent P; Germano, Jennifer M

    2014-08-01

    The intentional translocation of animals is an important tool for species conservation and ecosystem restoration, but reported success rates are low, particularly for threatened and endangered species. Publication bias further distorts success rates because the results of successful translocations may be more likely to be published than failed translocations. We conducted the first comprehensive review of all published and unpublished translocations of herpetofauna in New Zealand to assess publication bias. Of 74 translocations of 29 species in 25 years, 35 have been reported in the published literature, and the outcomes of 12 have been published. Using a traditional definition of success, publication bias resulted in a gross overestimate of translocation success rates (41.7% and 8.1% for published and all translocations, respectively), but bias against failed translocations was minimal (8.3% and 6.8%, respectively). Publication bias against translocations with uncertain outcomes, the vast majority of projects, was also strong (50.0% and 85.1% for published and all translocations, respectively). Recent translocations were less likely to be published than older translocations. The reasons behind translocations were related to publication. A greater percentage of translocations for conservation and research were published (63.3% and 40.0%, respectively) than translocations for mitigation during land development (10.0%). Translocations conducted in collaboration with a university were more frequently published (82.7% and 24.4%, respectively). To account for some of this publication bias, we reassessed the outcome of each translocation using a standardized definition of success, which takes into consideration the species' life history and the time since release. Our standardized definition of translocation success provided a more accurate summary of success rates and allows for a more rigorous evaluation of the causes of translocation success and failure in large-scale reviews. PMID:24606604

  14. Identification of chromosomal translocation hotspots via scan statistics

    PubMed Central

    Silva, Israel T.; Rosales, Rafael A.; Holanda, Adriano J.; Nussenzweig, Michel C.; Jankovic, Mila

    2014-01-01

    Motivation: The detection of genomic regions unusually rich in a given pattern is an important undertaking in the analysis of next-generation sequencing data. Recent studies of chromosomal translocations in activated B lymphocytes have identified regions that are frequently translocated to c-myc oncogene. A quantitative method for the identification of translocation hotspots was crucial to this study. Here we improve this analysis by using a simple probabilistic model and the framework provided by scan statistics to define the number and location of translocation breakpoint hotspots. A key feature of our method is that it provides a global chromosome-wide nominal control level to clustering, as opposed to previous methods based on local criteria. While being motivated by a specific application, the detection of unusual clusters is a widespread problem in bioinformatics. We expect our method to be useful in the analysis of data from other experimental approaches such as of ChIP-seq and 4C-seq. Results: The analysis of translocations from B lymphocytes with the method described here reveals the presence of longer hotspots when compared with those defined previously. Further, we show that the hotspot size changes substantially in the absence of DNA repair protein 53BP1. When 53BP1 deficiency is combined with overexpression of activation-induced cytidine deaminase, the hotspot length increases even further. These changes are not detected by previous methods that use local significance criteria for clustering. Our method is also able to identify several exclusive translocation hotspots located in genes of known tumor supressors. Availability and implementation: The detection of translocation hotspots is done with hot_scan, a program implemented in R and Perl. Source code and documentation are freely available for download at https://github.com/itojal/hot_scan. Contact: isilva@rockefeller.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24860160

  15. Low processivity for DNA translocation by the ISWI molecular motor.

    PubMed

    Eastlund, Allen; Al-Ani, Gada; Fischer, Christopher J

    2015-10-01

    The motor protein ISWI (Imitation SWItch) is the conserved catalytic ATPase domain of the ISWI family of chromatin remodelers. Members of the ISWI family are involved in regulating the structure of cellular chromatin during times of transcription, translation, and repair. Current models for the nucleosome repositioning activity of ISWI and other chromatin remodelers require the translocation of the remodeling protein along double-stranded DNA through an ATP-dependent mechanism. Here we report results from spectrofluorometric stopped-flow experiments which demonstrate that ISWI displays very low processivity for free DNA translocation. By combining these results with those from experiments monitoring the DNA stimulated ATPase activity of ISWI we further demonstrate that the DNA translocation by ISWI is tightly coupled to ATP hydrolysis. The calculated coupling efficiency of 0.067±0.018 ATP/ISWI/bp is seemingly quite low in comparison to similar DNA translocases and we present potential models to account for this. Nevertheless, the tight coupling of ATP hydrolysis to DNA translocation suggests that DNA translocation is not energetically rate limiting for nucleosome repositioning by ISWI. PMID:26116984

  16. A somatic origin of homologous Robertsonian translocations and isochromosomes

    SciTech Connect

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A. ); Basaran, S.; Yueksel-Apak, M. ); Neri, G. ); Serville, F. ); Balicek, P.; Haluza, R. ); Farah, L.M.S. )

    1994-02-01

    One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.

  17. A Somatic Origin of Homologous Robertsonian Translocations and Isochromosomes

    PubMed Central

    Robinson, W. P.; Bernasconi, F.; Basaran, S.; Yüksel-Apak, M.; Neri, G.; Serville, F.; Balicek, P.; Haluza, R.; Farah, L. M. S.; Lüleci, G.; Schinzel, A. A.

    1994-01-01

    One t(14q14q), three t(15q15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. ImagesFigure 1 PMID:8304346

  18. Translocation and Endocytosis for Cell-penetrating Peptide Internalization

    PubMed Central

    Jiao, Chen-Yu; Delaroche, Diane; Burlina, Fabienne; Alves, Isabel D.; Chassaing, Gérard; Sagan, Sandrine

    2009-01-01

    Cell-penetrating peptides (CPPs) share the property of cellular internalization. The question of how these peptides reach the cytoplasm of cells is still widely debated. Herein, we have used a mass spectrometry-based method that enables quantification of internalized and membrane-bound peptides. Internalization of the most used CPP was studied at 37 °C (endocytosis and translocation) and 4 °C (translocation) in wild type and proteoglycan-deficient Chinese hamster ovary cells. Both translocation and endocytosis are internalization pathways used by CPP. The choice of one pathway versus the other depends on the peptide sequence (not the number of positive changes), the extracellular peptide concentration, and the membrane components. There is no relationship between the high affinity of these peptides for the cell membrane and their internalization efficacy. Translocation occurs at low extracellular peptide concentration, whereas endocytosis, a saturable and cooperative phenomenon, is activated at higher concentrations. Translocation operates in a narrow time window, which implies a specific lipid/peptide co-import in cells. PMID:19833724

  19. Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics

    PubMed Central

    2014-01-01

    Background The liver is the first line of defence against continuously occurring influx of microbial-derived products and bacteria from the gut. Intestinal bacteria have been implicated in the pathogenesis of alcoholic liver cirrhosis. Escape of intestinal bacteria into the ascites is involved in the pathogenesis of spontaneous bacterial peritonitis, which is a common complication of liver cirrhosis. The association between faecal bacterial populations and alcoholic liver cirrhosis has not been resolved. Methods Relative ratios of major commensal bacterial communities (Bacteroides spp., Bifidobacterium spp., Clostridium leptum group, Enterobactericaea and Lactobacillus spp.) were determined in faecal samples from post mortem examinations performed on 42 males, including cirrhotic alcoholics (n?=?13), non-cirrhotic alcoholics (n?=?15), non-alcoholic controls (n?=?14) and in 7 healthy male volunteers using real-time quantitative PCR (RT-qPCR). Translocation of bacteria into liver in the autopsy cases and into the ascites of 12 volunteers with liver cirrhosis was also studied with RT-qPCR. CD14 immunostaining was performed for the autopsy liver samples. Results Relative ratios of faecal bacteria in autopsy controls were comparable to those of healthy volunteers. Cirrhotics had in median 27 times more bacterial DNA of Enterobactericaea in faeces compared to the healthy volunteers (p?=?0.011). Enterobactericaea were also the most common bacteria translocated into cirrhotic liver, although there were no statistically significant differences between the study groups. Of the ascites samples from the volunteers with liver cirrhosis, 50% contained bacterial DNA from Enterobactericaea, Clostridium leptum group or Lactobacillus spp.. The total bacterial DNA in autopsy liver was associated with the percentage of CD14 expression (p?=?0.045). CD14 expression percentage in cirrhotics was significantly higher than in the autopsy controls (p?=?0.004). Conclusions Our results suggest that translocation of intestinal bacteria into liver may be involved as a one factor in the pathogenesis of alcoholic liver cirrhosis. PMID:24564202

  20. Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations.

    PubMed

    Adams, Julia; Nassiri, Mehdi

    2015-10-01

    The majority of patients with acute promyelocytic leukemia (APL) manifest the t(15;17)(q24.1;q21.2) translocation; however, a minor but significant proportion of patients with APL harbor complex, cryptic, or variant translocations, which typically involve RARA. With the exception of ZBTB16/RARA, these variants have similar morphologic and immunophenotypic features as classic APL. Study of the variant forms of APL not only gives insight into the pathogenesis of APL but also allows us to understand the mechanism of retinoid therapy. It is important to identify these cryptic and variant translocations because certain variants, including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans retinoic acid, arsenic trioxide, and anthracyclines. PMID:26414475

  1. Uptake and translocation of hexachlorobenzene: Oilpumpkin and sunflower

    SciTech Connect

    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.

  2. Translocation of polymers into crowded media with dynamic attractive nanoparticles

    NASA Astrophysics Data System (ADS)

    Cao, Wei-Ping; Ren, Qing-Bao; Luo, Meng-Bo

    2015-07-01

    The translocation of polymers through a small pore into crowded media with dynamic attractive nanoparticles is simulated. Results show that the nanoparticles at the trans side can affect the translocation by influencing the free-energy landscape and the diffusion of polymers. Thus the translocation time ? is dependent on the polymer-nanoparticle attraction strength ? and the mobility of nanoparticles V . We observe a power-law relation of ? with V , but the exponent is dependent on ? and nanoparticle concentration. In addition, we find that the effect of attractive dynamic nanoparticles on the dynamics of polymers is dependent on the time scale. At a short time scale, subnormal diffusion is observed at strong attraction and the diffusion is slowed down by the dynamic nanoparticles. However, the diffusion of polymers is normal at a long time scale and the diffusion constant increases with the increase in V .

  3. Translocation of polymers into crowded media with dynamic attractive nanoparticles.

    PubMed

    Cao, Wei-Ping; Ren, Qing-Bao; Luo, Meng-Bo

    2015-07-01

    The translocation of polymers through a small pore into crowded media with dynamic attractive nanoparticles is simulated. Results show that the nanoparticles at the trans side can affect the translocation by influencing the free-energy landscape and the diffusion of polymers. Thus the translocation time ? is dependent on the polymer-nanoparticle attraction strength ? and the mobility of nanoparticles V. We observe a power-law relation of ? with V, but the exponent is dependent on ? and nanoparticle concentration. In addition, we find that the effect of attractive dynamic nanoparticles on the dynamics of polymers is dependent on the time scale. At a short time scale, subnormal diffusion is observed at strong attraction and the diffusion is slowed down by the dynamic nanoparticles. However, the diffusion of polymers is normal at a long time scale and the diffusion constant increases with the increase in V. PMID:26274196

  4. A Tat ménage à trois--The role of Bacillus subtilis TatAc in twin-arginine protein translocation.

    PubMed

    Goosens, Vivianne J; De-San-Eustaquio-Campillo, Alba; Carballido-López, Rut; van Dijl, Jan Maarten

    2015-10-01

    The twin-arginine translocation system (Tat) is a protein transport system that moves fully folded and cofactor-containing proteins across membranes of bacteria, archaea and thylakoids. The minimal Tat pathway is composed of two subunits, TatA and TatC. In some organisms TatA has been duplicated and evolved to form a third specialized subunit, TatB. The Bacillus subtilis genome encodes two TatC subunits (TatCd and TatCy) and three TatA subunits (TatAd, TatAy and TatAc). These subunits combine to form two parallel minimal pathways, TatAy-TatCy and TatAd-TatCd. The purpose and role of the third TatA component, TatAc, has remained ambiguous. In this study we examined the translocation of two natively expressed TatAy-TatCy-dependent substrates, EfeB and QcrA, in various Tat-deficient genetic backgrounds. More specifically, we examined the ability of different mutated TatAy subunits to complement for the absence of wild-type TatAy. We further detailed a graded growth phenotype associated with the functional translocation of EfeB. We found that in various instances where specific amino acid substitutions were made in TatAy, a definite TatAc-associated growth phenotype occurred in genetic backgrounds lacking TatAc. Altogether, our findings show that TatAy and TatAc interact and that this TatAy-TatAc interaction, although not essential, supports the translocation of the Tat substrate EfeB when TatAy function is compromised. This implies that the third TatA-like protein in B. subtilis could represent an intermediate evolutionary step in TatA-TatB specialization. PMID:26239117

  5. Effect of Zinc on Translocation of Iron in Soybean Plants

    PubMed Central

    Ambler, J. E.; Brown, J. C.; Gauch, H. G.

    1970-01-01

    Zinc interfered with translocation of iron from roots to above ground parts of Glycine max. (L.) Merrill var. Hawkeye. During periods in which zinc impeded iron translocation, it also suppressed the production of reductant by roots. Addition of iron, as a ferric metal chelate (iron ethylenediaminedihydroxyphenylacetic acid), to the growth medium overcame the interference of zinc. In the root epidermis, potassium ferricyanide formed a precipitate (Prussian blue) with ferrous iron derived from the previously supplied iron ethylenediaminedihydroxyphenylacetic acid. The reduction of ferric iron was suppressed by zinc. Images PMID:16657457

  6. [Elbow dislocation in children associated with proximal radioulnar translocation].

    PubMed

    Wodecki, P; Maiza, D; Rozenblum, B

    2007-04-01

    We report a unique case of posterior elbow dislocation with proximal radioulnar translocation in a six-year-old child with 3D reconstruction CT images. Five other cases of this type of association have been reported in the literature. Diagnosis is often established late. Our case illustrates the diagnostic and therapeutic difficulties. The CT scan demonstrated the presence of the proximal radioulnar translocation and contributed greatly to understanding the pathogenic mechanism: the radius crossed over the ulna anteriorly. The CT-scan can reveal associated lesions missed on the plain x-rays. Surgical reduction is generally needed, preferably via a medial approach. PMID:17401294

  7. Cosmic microwave background theory.

    PubMed

    Bond, J R

    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 DeltaT flat in frequency and broadly follow inflation-based expectations. That the levels are approximately (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 Lambda 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 Lambda and moderate constraints on Omegatot, 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

  8. 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...

  9. PERSPECTIVE Exploring translocation of proteins on DNA by NMR

    E-print Network

    Clore, G. Marius

    PERSPECTIVE Exploring translocation of proteins on DNA by NMR G. Marius Clore Received: 19 May 2011 of transcription factors, DNA and their complexes from both NMR and crystal- lography, much less is known-dimensional sliding. In this brief per- spective I summarize recent NMR developments from our laboratory that have

  10. An intergenomic reciprocal translocation associated with oat winterhardiness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The reciprocal intergenomic translocation between hexaploid oat (Avena sp.) chromosomes 7C and 17 (T7C-17) has been associated with the division of cultivated oat into A. sativa (L.) and A. byzantina (C. Koch) species as well as fall and spring growth habit. The objective of this experiment was to ...

  11. Mechanistic stoichiometry of proton translocation by cytochrome cbb3

    PubMed Central

    Rauhamäki, Virve; Bloch, Dmitry A.; Wikström, Mårten

    2012-01-01

    Cytochrome cbb3 belongs to the superfamily of respiratory heme-copper oxidases that couple the reduction of molecular oxygen to proton translocation across the bacterial or mitochondrial membrane. The cbb3-type enzymes are found only in bacteria, and are both structurally and functionally the most distant from their mitochondrial counterparts. The mechanistic H+/e? stoichiometry of proton translocation in these cbb3-type cytochrome c oxidases has remained controversial. A stoichiometric efficiency of only one-half that of the mitochondrial aa3-type enzyme was recently proposed to be related to adaptation of the organism to microaerobic environments. Here, proton translocation by the Rhodobacter sphaeroides enzyme was studied using purified cytochrome cbb3 reconstituted into liposomes. An H+/e? stoichiometry of proton translocation close to unity was observed using the oxygen pulse method, but solely in conditions in which the vast majority of the enzyme was fully reduced in the anaerobic state before the O2 pulse. These data were compared with results using whole cells or spheroplasts, and the discrepancies in the literature data were discussed. Our results suggest that a proton-pumping efficiency of 1 H+/e? may be achieved using the single-proton uptake pathway identified in the structure of cytochrome cbb3. The mechanism of proton pumping thus differs from that of the aa3-type oxidases of mitochondria and bacteria. PMID:22529361

  12. Autosomal Translocation Patient Who Experienced Premature Menopause: A Case Report

    PubMed Central

    Kim, Yesol; Jeong, Do-won; Lee, Eun-gyeong; Jeon, Dong-Su; Kim, Jun-Mo

    2015-01-01

    Premature ovarian failure (POF) is a condition in which the ovarian functions of hormone production and oocyte development become impaired before the typical age for menopause. POF and early menopause are present in a broad spectrum of gonad dysgenesis, from a complete cessation of ovarian function to an intermittent follicle maturation failure. Actually POF has been identified as a genetic entity (especially chromosome X), but data on genetic factors of premature menopause are limited. Until now, several cases revealed that inactivation of X chromosomes has an effect on ages of premature menopause and females with balanced or unbalanced X-autosome translocations can have several reproductive problems. On the other hand, there have been a few data that was caused by autosome-autosome translocation can lead. Therefore we report a relevant case of POF with translocation between chromosomes 1 and 4. She had her first menstrual period at the age of 12, and after 7 years she stopped menstruation. Chromosomal analysis showed 46, XX, t (1;4) (p22.3;q31.3). While evaluating this rare case, we could review various causes (especially genetic factors) of POF. To remind clinicians about this disease, we report a case of POF caused by autosome-autosome translocation with a literature review. PMID:26356509

  13. Translocation and Absorption of Glyphosate in Flowering Sicklepod (Senna obtusifolia)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sicklepod is a competitive and prolific weed that emerges throughout the crop season. Glyphosate applications at sicklepod flowering have been shown to greatly reduce seed production, although there is limited information on glyphosate translocation in flowering weeds. Therefore, a laboratory stud...

  14. 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.

  15. DNA Translocation and Unzipping through a Nanopore: Some Geometrical Effects

    PubMed Central

    Muzard, J.; Martinho, M.; Mathé, J.; Bockelmann, U.; Viasnoff, V.

    2010-01-01

    Abstract This article explores the role of some geometrical factors on the electrophoretically driven translocations of macromolecules through nanopores. In the case of asymmetric pores, we show how the entry requirements and the direction of translocation can modify the information content of the blocked ionic current as well as the transduction of the electrophoretic drive into a mechanical force. To address these effects we studied the translocation of single-stranded DNA through an asymmetric ?-hemolysin pore. Depending on the direction of the translocation, we measure the capacity of the pore to discriminate between both DNA orientations. By unzipping DNA hairpins from both sides of the pores we show that the presence of single strand or double strand in the pore can be discriminated based on ionic current levels. We also show that the transduction of the electrophoretic drive into a denaturing mechanical force depends on the local geometry of the pore entrance. Eventually we discuss the application of this work to the measurement of energy barriers for DNA unzipping as well as for protein binding and unfolding. PMID:20483325

  16. UPTAKE, TRANSLOCATION AND RELEASE OF PHOSPHORUS BY 'ELODEA DENSA'

    EPA Science Inventory

    Short-term (16h) laboratory studies of 32p uptake by Elodea densa rooted in sediment demonstrated both foliar and root uptake, and that translocation occurred acropetally and basipetally. Root absorption is projected to provide 83-85% of total phosphorus uptake during 12-16th pho...

  17. 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 12 March 1999 Abstract ATP synthase is conceived as a rotatory engine with two reversible drives that the hydrolysis of three molecules of ATP in FI drives the shaft over a full circle in three steps of 120³ each

  18. Promiscuous archaeal ATP synthase concurrently coupled to Na+ translocation

    E-print Network

    Huang, Ching-Tsan

    Promiscuous archaeal ATP synthase concurrently coupled to Na+ and H+ translocation Katharina98B02057 Chii-Shen Yang, PhD December 25, 2012 The 6th Classroom ATP (adenosine triphosphate) synthase ATP ATP ATP synthase ATP synthase ATP synthase ATP synthase Methanosarcina acetivorans

  19. Translocation of structured polynucleotides through nanopores Ulrich Gerland

    E-print Network

    Bundschuh, Ralf

    experiments studied the transloca- tion of DNA and RNA molecules through narrow pores, which allow single. In the experiments so far, a membrane protein, -hemolysin, was used as the pore. An electric field acting on the negatively charged DNA/RNA backbone drives the molecules through the pore, and translocation is monitored

  20. 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.

  1. Soil translocation estimates calibrated for moldboard plow depth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over the past century, one of the biggest culprits of tillage-induced soil erosion and translocation has been the moldboard plow. The distance soil will move by moldboard plow tillage has been shown to be correlated with slope gradient. Lindstrom et al. (1992) developed regression equations describi...

  2. Computer simulation study of fullerene translocation through lipid membranes

    E-print Network

    Wong-Ekkabut, Jirasak

    Computer simulation study of fullerene translocation through lipid membranes JIRASAK WONG-EKKABUT1 aggregates of fullerene molecules can enter cells and alter their functions, and also cross the blood­brain barrier. However, the mechanisms by which fullerenes penetrate and disrupt cell membranes are still poorly

  3. ORIGINAL ARTICLE Translocator Protein PET Imaging for Glial Activation

    E-print Network

    Pike, Victor W.

    ORIGINAL ARTICLE Translocator Protein PET Imaging for Glial Activation in Multiple Sclerosis Unsong of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has further define TSPO as an informative marker of glial activation in MS. Keywords Multiple sclerosis

  4. 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

  5. A Gatekeeper Chaperone Complex Directs Translocator Secretion during Type Three Secretion

    PubMed Central

    Archuleta, Tara L.; Spiller, Benjamin W.

    2014-01-01

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ?20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors. PMID:25375170

  6. A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

    SciTech Connect

    Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko

    2014-11-06

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components that form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.

  7. A gatekeeper chaperone complex directs translocator secretion during Type Three Secretion

    DOE PAGESBeta

    Archuleta, Tara L.; Spiller, Benjamin W.; Kubori, Tomoko

    2014-11-06

    Many Gram-negative bacteria use Type Three Secretion Systems (T3SS) to deliver effector proteins into host cells. These protein delivery machines are composed of cytosolic components that recognize substrates and generate the force needed for translocation, the secretion conduit, formed by a needle complex and associated membrane spanning basal body, and translocators that form the pore in the target cell. A defined order of secretion in which needle component proteins are secreted first, followed by translocators, and finally effectors, is necessary for this system to be effective. While the secreted effectors vary significantly between organisms, the ~20 individual protein components thatmore »form the T3SS are conserved in many pathogenic bacteria. One such conserved protein, referred to as either a plug or gatekeeper, is necessary to prevent unregulated effector release and to allow efficient translocator secretion. The mechanism by which translocator secretion is promoted while effector release is inhibited by gatekeepers is unknown. We present the structure of the Chlamydial gatekeeper, CopN, bound to a translocator-specific chaperone. The structure identifies a previously unknown interface between gatekeepers and translocator chaperones and reveals that in the gatekeeper-chaperone complex the canonical translocator-binding groove is free to bind translocators. Thus, structure-based mutagenesis of the homologous complex in Shigella reveals that the gatekeeper-chaperone-translocator complex is essential for translocator secretion and for the ordered secretion of translocators prior to effectors.« less

  8. Initiation of translocation by Type I restriction-modification enzymes is associated with a

    E-print Network

    Dekker, Cees

    Initiation of translocation by Type I restriction- modification enzymes is associated with a short involves DNA translocation by the restriction subunit HsdR. Type I R-M enzymes are composed of three (Hsd the recognition-translocation switch of Type I restriction enzymes forms an important first step in resolving

  9. 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.

  10. The Interplay Between Host Genetic Variation, Viral Replication, and Microbial Translocation in Untreated HIV-Infected Individuals.

    PubMed

    Perkins, Molly R; Bartha, Istvan; Timmer, J Katherina; Liebner, Julia C; Wollinsky, David; Günthard, Huldrych F; Hauser, Christoph; Bernasconi, Enos; Hoffmann, Matthias; Calmy, Alexandra; Battegay, Manuel; Telenti, Amalio; Douek, Daniel C; Fellay, Jacques

    2015-08-15

    Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid-binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection. PMID:25701868

  11. Molecular analysis of DiGeorge Syndrome-related translocation breakpoints in 22q11.2

    SciTech Connect

    Chieffo, C.; Barnoski, B.L.; Emanuel, B.S.

    1994-09-01

    22q11 demonstrates a high frequency of disease-specific rearrangements. Several of the rearrangements are associated with developmental abnormalities such as DiGeorge Syndrome (DGS), Velocardiofacial Syndrome (VCFS), Cat Eye Syndrome (CES) and Supernumerary der(22)t(11;22) Syndrome. DGS and VCFS involve deletions of 22q11.2 resulting from unbalanced translocations or microdeletions. In contrast, CES and Supernumerary der(22)t(11;22) Syndrome result from duplications of this region via inter- or intra- chromosomal exchange. Although the molecular mechanism giving rise to these rearrangements has yet to be elucidated, the presence of known 22q11 repetitive elements are likely to be involved. GM5878 is a 46,XY,t(10;22) cell line from a balanced translocation carrier father of an unbalanced DGS patient. GM0980 is a cell line from a patient with features of DGS/VCFS with an unbalanced karyotype. Using FISH cosmids, we have localized these translocation breakpoints near pH160b (D22S66) which maps to the center of the DiGeorge chromosomal region (DGCR). To further localize the breakpoint of GM5878, overlapping cosmids spanning this region were used as probes for FISH. Use of additional overlapping cosmids allowed the sublocalization of the breakpoint to a 10kb region. A 4.8 kb BglII fragment predicted to cross the breakpoint was isolated. When this fragment was used as a probe to normal and GM5878 DNA, novel bands were detected in GM5878 DNA digested with EcoRI and BglII. Similar analysis of the GM0980 breakpoint is being pursued. Full molecular characterization of these translocations is in progress using inverse PCR to clone the junctional fragments for sequencing. Detailed analysis of the region may reveal molecular features which make this a rearrangement prone area of the genome and help elucidate its relationship to human cytogenetic disease.

  12. Voltage-driven translocation behaviors of IgG molecule through nanopore arrays

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Wang, Bing; Sha, Jingjie; Yang, Yue; Hou, Yaozong; Ni, Zhonghua; Chen, Yunfei

    2013-05-01

    Nanopore-based biosensing has attracted more and more interests in the past years, which is also regarded as an emerging field with major impact on bio-analysis and fundamental understanding of nanoscale interactions down to single-molecule level. In this work, the voltage-driven translocation properties of goat antibody to human immunoglobulin G (IgG) are investigated using nanopore arrays in polycarbonate membranes. Obviously, the background ionic currents are modulated by IgG molecules for their physical place-holding effect. However, the detected ionic currents do `not' continuously decrease as conceived; the currents first decrease, then increase, and finally stabilize with increasing IgG concentration. To understand this phenomenon, a simplified model is suggested, and the calculated results contribute to the understanding of the abnormal phenomenon in the actual ionic current changing tendency.

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

    PubMed Central

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

    2012-01-01

    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 and for genetic susceptibility using an in vitro bleomycin challenge assay. Spontaneous translocation frequencies in both maternal and newborn lymphocytes were not associated with cigarette smoking, socio-economic 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: p ? 0.0007 for dicentrics and fragments, and p ? 0.002 for translocations. Caucasian American newborns demonstrated a significant association between dicentrics and fragments as measured by painting, and bleomycin sensitivity (p ? 0.0002), but no such association was observed for African American newborns. The results of this study indicate that while differences were observed between African Americans and Caucasian Americans, race does not appear to be a major contributor to chromosome damage in newborns or their mothers. However, peripheral lymphocytes in pregnant women are more susceptible to genetic damage than peripheral lymphocytes in newborns. PMID:20060061

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

    SciTech Connect

    Jordan, R.; Schwartz, J.L. )

    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.

  15. 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.

  16. 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.

  17. Methylation of CpG sites in BCL2 major breakpoint region and the increase of BCL2/JH translocation with aging.

    PubMed

    Martin-Guerrero, Idoia; de Prado, Elena; Ardanaz, Maite; Martin-Arruti, Maialen; Garcia-Orad, Cristina; Guerra, Isabel; Ruiz, Irune; Zabalza, Iñaki; Garcia-Orad, Africa

    2015-10-01

    The BCL2 breakage mechanism has been shown to be highly dependent on DNA methylation at the major breakpoint region (MBR) CpG sites. We recently described an increased frequency of BCL2/ JH translocation with aging. It is known that methylation levels change with aging. The present study aimed to determine whether methylation alterations at CpG sites of BCL2 MBR were the cause of increased breakages with aging. We analyzed the methylation levels of three CpG sites on the region by pyrosequencing and studied if methylation levels and/or polymorphisms affecting CpG sites were associated with an increase of translocations. We observed that although the methylation levels of MBR CpG sites were higher in individuals with BCL2/JH translocation, in contrast to our expectations, these levels decreased with the age. Moreover, we show that polymorphisms at those CpG sites leading to absence of methylation seem to be a protective factor for the apparition of translocations. PMID:26335622

  18. Uptake, internalization and nuclear translocation of radioimmunotherapeutic agents.

    PubMed

    Hillyar, Christopher R T; Cornelissen, Bart; Vallis, Katherine A

    2014-03-01

    Radioimmunotherapy (RIT) agents that incorporate short-range particle-emitting radionuclides exploit the high linear energy transfer of ?-particles and Auger electrons. Both are densely ionizing, generate complex DNA double-strand breaks and so are profoundly cytotoxic. Internalizing RIT agents enter tumor cells through receptor-mediated endocytosis and by incorporation of cell-penetrating peptides. Once internalized, some RIT agents mediate escape from endosomes and/or translocate to the nucleus. In the classical nuclear import pathway, ?/?-importins recognize nuclear localization sequences in RIT agents. Translocation through nuclear pores enables RIT agents to bind to nuclear targets induced by, for example, cellular stress, growth factors or anticancer therapy, such as ?H2AX or p27(KIP-1). This review discusses RIT agents designed to exploit the mechanisms underlying these complex processes and compares them with noninternalizing RIT agents. PMID:24592956

  19. Realistic extensions of a Brownian ratchet for protein translocation

    E-print Network

    A. Depperschmidt; N. Ketterer; P. Pfaffelhuber

    2011-07-26

    We study a model for the translocation of proteins across membranes through a nanopore using a ratcheting mechanism. When the protein enters the nanopore it diffuses in and out of the pore according to a Brownian motion. Moreover, it is bound by ratcheting molecules which hinder the diffusion of the protein out of the nanopore, i.e. the Brownian motion is reflected such that no ratcheting molecule exits the pore. New ratcheting molecules bind at rate gamma. Extending our previous approach (Depperschmidt and Pfaffelhuber, 2010) we allow the ratcheting molecules to dissociate (at rate delta) from the protein (Model I). We also provide an approximate model (Model II) which assumes a Poisson equilibrium of ratcheting molecules on one side of the current reflection boundary. Using analytical methods and simulations we show that the speed of both models are approximately the same. Our analytical results on Model II give the speed of translocation by means of a solution of an ordinary differential equation.

  20. 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.

  1. Conductivity in the anisotropic background

    E-print Network

    Bum-Hoon Lee; Siyoung Nam; Da-Wei Pang; Chanyong Park

    2011-02-28

    By using the gauge/gravity duality, we investigate the dual field theories of the anisotropic backgrounds, which are exact solutions of Einstein-Maxwell-dilaton theory with a Liouville potential. When we turn on the bulk gauge field fluctuation $A_x$ with a non-trivial dilaton coupling, the AC conductivity of this dual field theory is proportional to the frequency with an exponent depending on parameters of the anisotropic background. In some parameter regions, we find that this conductivity can have the negative exponent like the strange metal. In addition, we also investigate another U(1) gauge field fluctuation, which is not coupled with a dilaton field. We classify all possible conductivities of this system and find that the exponent of the conductivity is always positive.

  2. Physical Background OfPhysical Background Of Nuclear Magnetic ResonanceNuclear Magnetic Resonance

    E-print Network

    Olszewski Jr., Edward A.

    with the external field The magnetic moment rotates around B0 at the Larmor frequency, : 00 2 BB m ge p p == #12Physical Background OfPhysical Background Of Nuclear Magnetic ResonanceNuclear Magnetic Resonance In 1924, Wolfgang Pauli postulated a new degree of freedom for subatomic particles Cause magnetic moments

  3. Subcellular distribution and translocation of radionuclides in plants

    SciTech Connect

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

    1999-09-01

    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{sup {minus}83}, Sr{sup {minus}85}, Mn{sup {minus}54}, Nb{sup {minus}95}, and Se{sup {minus}75} remained in the supernatant fraction; 55% and 20% of Cr{sup {minus}51} was bound to soybean and cucumber cell wall fractions, respectively; 70% or more of Be{sup {minus}7}, Y{sup {minus}88}, and Fe{sup {minus}59} was fixed in the chloroplast fraction; and approx. 10% of Sc{sup {minus}46}, Fe{sup {minus}59}, V{sup {minus}48}, and As were fixed in the mitochondrial fraction. Translocation of nuclides within the soybean plant at different stages of growth has been determined. Vanadium, Y{sup {minus}88}, Be{sup {minus}7}, Se{sup {minus}75}, Nb{sup {minus}95}, Sc{sup {minus}46}, Cr{sup {minus}51}, and Zr{sup {minus}88} were predominantly accumulated in the root. Although the total percentage of plant uptake of Sc{sup {minus}46}, Zr{sup {minus}88}, Nb{sup {minus}95}, Sc{sup {minus}46}, and Cr{sup {minus}51} was high, because of low mobility and translocation to shoot, their accumulation in the fruit fraction was negligible. The translocation of mobile nuclides in plants was demonstrated clearly by Rb{sup {minus}83}, Zn{sup {minus}65}, and Fe{sup {minus}59}. Data on the nuclide fraction mobilized from vegetative parts into edible parts was used to assess the percentage of accumulated radionuclides in plants that may reach humans through beans.

  4. Repetitive telomeric sequences in chromosomal translocations involving chromosome 21

    SciTech Connect

    Qu, J.; Dallaire, L.; Fetni, R.

    1994-09-01

    Telomeres perform key functions in maintaining chromosome integrity. In some structural rearrangements the structure and polymorphism in human telomeres may play a significant role. However, of all the telomeric and subtelomeric sequences, only the terminal TTAGGG repeats are believed essential for telomere function. During the course of a study on the role of telomere structure and polymorphism in chromosomal rearrangements observed in families referred for prenatal diagnosis, we studied three cases in which chromosome 21 was involved. Repetitive TTAGGG sequences for all human chromosomes were used as probes (Oncor). Case 1, a de novo cryptic translocation (2;21) was initially identified as monosomy 21 in a child with psychomotor delay and mild dysmorphism. Using a cosmid probe specific for region 21q22.3 and whole chromosome 21 specific painting probe, the long arm of 21 was found on the short arm of chromosome 2 with an interstitial telomere at the breakpoint junction. All the cells were monosomic for 21pter{yields}q21. Case 2 is a familial (19;21) translocation. GTG-banding and FISH with a satellite probe showed no apparent loss of material at the end of either 19q or 21q, with an interstitial telomere at the fusion site of the two intact chromosomes. In case 3, a four generation reciprocal (20;21) translocation, there was no interstitial telomere. The persistence of an interstitial telomere is a relatively rare event which can now be observed with in situ hybridization. Its study may lead to a better understanding of the dynamics of translocations and of chromosome imbalance.

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

    SciTech Connect

    Maround, C.; Schmerler, S.; Hutcheon, R.G.

    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.

  6. Translocation of Sulfate in Soybean (Glycine max L. Merr) 1

    PubMed Central

    Smith, Ivan K.; Lang, A. Lee

    1988-01-01

    Sulfate translocation in soybean (Glycine max L. Merr) was investigated. More than 90% of the sulfate entering the shoot system was recoverable in one or two developing trifoliate leaves. In young plants, the first trifoliate leaf contained between 10 to 20 times as much sulfate as the primary leaves, even though both types of leaf had similar rates of transpiration and photosynthesis. We conclude that most of the sulfate entering mature leaves is rapidly loaded into the phloem and translocated to sinks elsewhere in the plant. This loading was inhibited by carbonylcyanide m-chlorophenylhydrazone and selenate. At sulfate concentrations below 0.1 millimolar, more than 95% of the sulfate entering primary leaves was exported. At higher concentrations the rate of export increased but so did the amount of sulfate remaining in the leaves. Removal of the first trifoliate leaf increased two-fold the transport of sulfate to the apex, indicating that these are competing sinks for sulfate translocated from the primary leaves. The small amount of sulfate transported into the mesophyll cells of primary leaves is a result of feedback regulation by the intracellular sulfate pool, not a consequence of their metabolic inactivity. For example, treatment of plants with 2 millimolar aminotriazole caused a 700 nanomoles per gram fresh weight increase in the glutathione content of primary leaves, but had no effect on sulfate aquisition. PMID:16665991

  7. Detection of Kinase Translocation Using Microfluidic Electroporative Flow Cytometry

    NASA Astrophysics Data System (ADS)

    Lu, Chang; Wang, Jun; Bao, Ning; Paris, Leela; Wang, Hsiang-Yu; Geahlen, Robert

    2008-03-01

    Translocation of a protein between different subcellular compartments is a common event during signal transduction in living cells. Detection of these events has been largely carried out based on imaging of a low number of cells and subcellular fractionation/Western blotting. These conventional techniques either lack the high throughput desired for probing an entire cell population or provide only the average behaviors of cell populations without information from single cells. Here we demonstrate a new tool, referred to as microfluidic electroporative flow cytometry, to detect the translocation of an EGFP-tagged tyrosine kinase, Syk, to the plasma membrane in B cells at the level of the cell population. We combine electroporation with flow cytometry and observe the release of intracellular kinase out of the cells during electroporation. We found that the release of the kinase was strongly influenced by its subcellular localization. Cells stimulated through the antigen receptor have a fraction of the kinase at the plasma membrane and retain more kinase after electroporation than do cells without stimulation and translocation. This tool will have utility for kinase-related drug discovery and tumor diagnosis and staging.

  8. Single-molecule studies of bacterial protein translocation.

    PubMed

    Kedrov, Alexej; Kusters, Ilja; Driessen, Arnold J M

    2013-10-01

    In prokaryotes, a large share of the proteins are secreted from the cell through a process that requires their translocation across the cytoplasmic membrane. This process is mediated by the universally conserved Sec system with homologues in the endoplasmic reticulum and thylakoid membranes of eukaryotes. The Sec system also facilitates the membrane insertion of integral membrane proteins, an essential step along their folding pathway. In bacteria, the Sec system consists of the protein-conducting channel (SecYEG) that associates with soluble components, such as the motor protein SecA or translating ribosomes, and with integral membrane proteins, such as the heterotrimeric complex termed SecDFyajC and the YidC insertase. Over the past three decades, biochemical and structural studies have provided a comprehensive view of protein translocation, but the exact mechanistic details of this process remain to be resolved. For a number of other biomolecular systems, single-molecule biophysical analysis has efficiently complemented the conventional biochemical studies conducted in bulk, with high-sensitivity measurements probing the structure and dynamics of individual molecules in vitro and in vivo. Here, we review recent advances in studies of protein translocation employing single-molecule techniques with the aim of resolving molecular mechanisms, thereby providing a new and detailed view of the process. PMID:24024480

  9. Compositions and methods for detecting gene rearrangements and translocations

    DOEpatents

    Rowley, Janet D. (Chicago, IL); Diaz, Manuel O. (Chicago, IL)

    2000-01-01

    Disclosed is a series of nucleic acid probes for use in diagnosing and monitoring certain types of leukemia using, e.g., Southern and Northern blot analyses and fluorescence in situ hybridization (FISH). These probes detect rearrangements, such as translocations involving chromosome band 11q23 with other chromosomes bands, including 4q21, 6q27, 9p22, 19p13.3, in both dividing leukemic cells and interphase nuclei. The breakpoints in all such translocations are clustered within an 8.3 kb BamHI genomic region of the MLL gene. A novel 0.7 kb BamH1 cDNA fragment derived from this gene detects rearrangements on Southern blot analysis with a single BamHI restriction digest in all patients with the common 11q23 translocations and in patients with other 11q23 anomalies. Northern blot analyses are presented demonstrating that the MLL gene has multiple transcripts and that transcript size differentiates leukemic cells from normal cells. Also disclosed are MLL fusion proteins, MLL protein domains and anti-MLL antibodies.

  10. Dominant-lethal mutations and heritable translocations in mice

    SciTech Connect

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

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

    SciTech Connect

    Park, V.M.; Gross, S.J.; Tharapel, A.T.

    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.

  12. Effects of antibiotics and other inhibitors on ATP-dependent protein translocation into membrane vesicles.

    PubMed Central

    Chen, L; Tai, P C

    1987-01-01

    The effects of several membrane antibiotics and other agents on ATP-dependent protein translocation were examined in membrane vesicles under conditions where no significant proton motive force was present. The membrane perturbants ethanol and procaine abolished ATP-dependent protein translocation. Phenethyl alcohol at low concentrations abolished translocation, whereas at high concentrations it allowed precursors to be translocated but inhibited their processing. Translocation of precursors promoted by phenethyl alcohol was temperature dependent and occurred without an added energy source but was enhanced by ATP. However, such precursors could not be further processed to mature forms upon removal of the alcohol. The membrane-active antibiotics polymyxin B and gramicidin S were strong inhibitors of translocation, whereas gramicidin D, cerulenin, and mycobacillin had no effect even at higher concentrations, indicating some specificity in interference with protein translocation. Duramycin, an antibiotic previously shown to affect protein-lipid interaction, severely impaired protein translocation. These results showed that membrane structures play important roles, either directly or indirectly, in protein translocation. Chelating agents 1,10-phenanthroline and EDTA, but not EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], also abolished protein translocation. Images PMID:2438267

  13. Effect of family support on the success of translocated black-tailed prairie dogs.

    PubMed

    Shier, D M

    2006-12-01

    Translocation has become a widely used conservation tool but remains only marginally successful. High mortality is often attributed to predation, but for highly social species, founder group composition may also play a critical role in postrelease survival. I compared the fitness of black-tailed prairie dogs translocated with or without their family groups. Animals in the family translocated groups were individually marked and observed until coterie membership was determined. Nonfamily translocated animals were trapped without regard to family membership. I measured fitness by retrapping all marked animals remaining at release sites in the summer following release. Family translocated animals were five times more likely to survive and had significantly higher reproductive success than those translocated without families. Predation was an important impediment of translocation success, but family translocation significantly reduced the success of predators on newly established prairie dog colonies. Postrelease survival was also affected by the timing of release, but appeared to be more important for juveniles than adults. These results demonstrate the importance of considering familiarity when translocations are required. More broadly, these results illustrate the value of applying animal behavior to conservation efforts and suggest that other species dependent on social interactions for survival and reproduction may benefit substantially from the maintenance of social groups during translocations. PMID:17181813

  14. 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

  15. Force-induced calcium concentration change and focal adhesion translocation : effects of force amplitude and frequency

    E-print Network

    Mack, Peter J. (Peter Joseph), 1980-

    2004-01-01

    Vascular endothelial cells rapidly sense and transduce external forces into biological signals through a process known as mechanotransduction. Numerous biological processes are involved in mechanotransduction, including ...

  16. 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).

  17. 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)

  18. Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, ?-arrestin translocation and chemotaxis assays

    PubMed Central

    Gilchrist, A; Gauntner, T D; Fazzini, A; Alley, K M; Pyen, D S; Ahn, J; Ha, S J; Willett, A; Sansom, S E; Yarfi, J L; Bachovchin, K A; Mazzoni, M R; Merritt, J R

    2014-01-01

    Background and Purpose Investigators have suggested that the chemokine receptor CCR1 plays a role in multiple myeloma. Studies using antisense and neutralizing antibodies to CCR1 showed that down-regulation of the receptor altered disease progression in a mouse model. More recently, experiments utilizing scid mice injected with human myeloma cells demonstrated that the CCR1 antagonist BX471 reduced osteolytic lesions, while the CCR1 antagonist MLN-3897 prevented myeloma cell adhesion to osteoclasts. However, information is limited regarding the pharmacology of CCR1 antagonists in myeloma cells. Experimental Approach We compared several well-studied CCR1 antagonists including AZD4818, BX471, CCX354, CP-481715, MLN-3897 and PS899877 for their ability to inhibit binding of [125I]-CCL3 in vitro using membranes prepared from RPMI 8226 cells, a human multiple myeloma cell line that endogenously expresses CCR1. In addition, antagonists were assessed for their ability to modulate CCL3-mediated internalization of CCR1 and CCL3-mediated cell migration using RPMI 8226 cells. As many GPCRs signal through ?–arrestin-dependent pathways that are separate and distinct from those driven by G-proteins, we also evaluated the compounds for their ability to alter ?-arrestin translocation. Key Results There were clear differences between the CCR1 antagonists in their ability to inhibit CCL3 binding to myeloma cells, as well as in their ability to inhibit G–protein-dependent and -independent functional responses. Conclusions and Implications Our studies demonstrate that tissue phenotype seems to be relevant with regards to CCR1. Moreover, it appears that for CCR1 antagonists, inhibition of ?-arrestin translocation is not necessarily linked to chemotaxis or receptor internalization. PMID:24990525

  19. 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

  20. 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.

  1. 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.

  2. Simulation on the translocation of homopolymers through sandwich-like compound channels.

    PubMed

    Wang, Chao; Chen, Ying-Cai; Wu, Fan; Luo, Meng-Bo

    2015-12-21

    The forced translocation of homopolymers through ??? sandwich-like compound channels was investigated by Monte Carlo simulation. The interaction between polymer and part ? is strongly attractive, whereas that between polymer and part ? is purely repulsive. Simulation results show that the translocation is influenced obviously by the length of part ? (L?) and the starting position of part ? (L?1). For small L?, the translocation is mainly governed by the escaping process, and polymer is trapped near the exit of the channel. However, the translocation time can be tuned by varying L?1 and the fastest translocation can be achieved at relatively large L?1. Whereas for large L? and small L?1, the translocation is mainly controlled by the filling process. It is difficult for polymer to enter the channel, and polymer is trapped at the first ?? interface. Finally, the dynamics for the filling process and the escaping process are discussed from the view of free-energy landscape, respectively. PMID:26696074

  3. 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 ...

  4. INDIAN BACKGROUNDS Patuxent Wildlife

    E-print Network

    INDIAN BACKGROUNDS of the Patuxent Wildlife Research Center |./«arine'a(Megical Laboratory NOV 19 of Sport Fisheries and Wildlife Circular 138 #12;#12;INDIAN BACKGROUNDS of the Patuxent Wildlife Research of Indian Relics The Indian artifacts on display in the C. Hart Merriam Laboratory were collected

  5. 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.

  6. Correlators in nontrivial backgrounds

    SciTech Connect

    Mello Koch, Robert de; Ives, Norman; Stephanou, Michael

    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.

  7. 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

  8. Settlement of humpback chub (Gila cypha) into novel food webs following translocation: considering open niche space in translocation of large-river fishes

    USGS Publications Warehouse

    Paukert, Craig P.; Spurgeon, Jonathan J.; Healy, Brian D.; Trammell, Melissa; Speas, Dave; Smith, Emily Omana

    2015-01-01

    The Humpback Chub Gila cypha, a large-bodied, endangered cyprinid endemic to the Colorado River basin, is in decline throughout most of its range due largely to anthropogenic factors. Translocation of Humpback Chub into tributaries of the Colorado River is one conservation activity that may contribute to the expansion of the species’ current range and eventually provide population redundancy. We evaluated growth, survival, and dispersal following translocation of approximately 900 Humpback Chub over a period of 3 years (2009, 2010, and 2011) into Shinumo Creek, a tributary stream of the Colorado River within Grand Canyon National Park. Growth and condition of Humpback Chub in Shinumo Creek were consistent among year-classes and equaled or surpassed growth estimates from both the main-stem Colorado River and the Little Colorado River, where the largest (and most stable) Humpback Chub aggregation remains. Based on passive integrated tag recoveries, 53% ( = 483/902) of translocated Humpback Chub dispersed from Shinumo Creek into the main-stem Colorado River as of January 2013, 35% leaving within 25 d following translocation. Annual apparent survival estimates within Shinumo Creek ranged from 0.22 to 0.41, but were strongly influenced by emigration. Results indicate that Shinumo Creek provides favorable conditions for growth and survival of translocated Humpback Chub and could support a new population if reproduction and recruitment occur in the future. Adaptation of translocation strategies of Humpback Chub into tributary streams ultimately may refine the role translocation plays in recovery of the species.

  9. 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

  10. Health protocol for translocation of free-ranging elk.

    PubMed

    Corn, J L; Nettles, V F

    2001-07-01

    When considering an elk (Cervus elaphus) restoration program, wildlife managers must evaluate the positive and negative elements of translocation. We prepared this protocol to give an overview of health considerations associated with translocation of elk, with an emphasis on movement of free-ranging elk from western North America to the southeastern USA. We evaluated infectious agents and ectoparasites reported in elk from two perspectives. First, we made a qualitative estimate of the ability of the agent to be introduced and to become established. This was done using a selected set of epidemiologic factors. Second, if there was a good possibility that the organism could become established in the release area, the potential pathological consequences for elk and other wildlife, domestic animals, and humans were assessed via examination of the literature and consultation with other animal health specialists. The results of these evaluations were used to classify infectious agents and ectoparasites as low risk (n = 174), unknown risk (n = 10), and high risk (n = 9). We classified Anaplasma marginale, Anaplasma ovis, Mycobacterium paratuberculosis, Pasteurella multocida serotype 3, Elaphostrongylus cervi, Dicrocoelium dendriticum, Fascioloides magna, Echinococcus granulosus, Dermacentor albipictus, and Otobius megnini as unknown risks. High risk infectious agents and ectoparasites were the agent of chronic wasting disease, Brucella abortus, Mycobacterium bovis, Dermacentor andersoni, Ixodes pacificus, and Psoroptes sp. Parelaphostrongylus tennis, Elaeophora schneideri, and a Babesia sp. are parasites endemic in the southeastern USA that may present a "reverse risk" and adversely affect elk if released in some parts of the region. We developed a five-component protocol to reduce the risk of introduction of high risk infectious agents and ectoparasites that included: (1) evaluation of the health status of source populations, (2) quarantines, (3) physical examination and diagnostic testing, (4) restrictions on translocation of animals from certain geographic areas or populations, and (5) prophylactic treatment. PMID:11504216

  11. Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

    PubMed Central

    Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

    2012-01-01

    Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ?100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

  12. 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.

  13. Protein translocation without specific quality control in a computational model of the Tat system

    NASA Astrophysics Data System (ADS)

    Nayak, Chitra R.; Brown, Aidan I.; Rutenberg, Andrew D.

    2014-10-01

    The twin-arginine translocation (Tat) system transports folded proteins of various sizes across both bacterial and plant thylakoid membranes. The membrane-associated TatA protein is an essential component of the Tat translocon, and a broad distribution of different sized TatA-clusters is observed in bacterial membranes. We assume that the size dynamics of TatA clusters are affected by substrate binding, unbinding, and translocation to associated TatBC clusters, where clusters with bound translocation substrates favour growth and those without associated substrates favour shrinkage. With a stochastic model of substrate binding and cluster dynamics, we numerically determine the TatA cluster size distribution. We include a proportion of targeted but non-translocatable (NT) substrates, with the simplifying hypothesis that the substrate translocatability does not directly affect cluster dynamical rate constants or substrate binding or unbinding rates. This amounts to a translocation model without specific quality control. Nevertheless, NT substrates will remain associated with TatA clusters until unbound and so will affect cluster sizes and translocation rates. We find that the number of larger TatA clusters depends on the NT fraction f. The translocation rate can be optimized by tuning the rate of spontaneous substrate unbinding, {{\\Gamma }_{U}}. We present an analytically solvable three-state model of substrate translocation without cluster size dynamics that follows our computed translocation rates, and that is consistent with in vitro Tat-translocation data in the presence of NT substrates.

  14. Protein translocation without specific quality control in a computational model of the Tat system

    E-print Network

    Chitra R. Nayak; Aidan I. Brown; Andrew D. Rutenberg

    2014-08-20

    The twin-arginine translocation (Tat) system transports folded proteins of various sizes across both bacterial and plant thylakoid membranes. The membrane-associated TatA protein is an essential component of the Tat translocon, and a broad distribution of different sized TatA-clusters is observed in bacterial membranes. We assume that the size dynamics of TatA clusters are affected by substrate binding, unbinding, and translocation to associated TatBC clusters, where clusters with bound translocation substrates favour growth and those without associated substrates favour shrinkage. With a stochastic model of substrate binding and cluster dynamics, we numerically determine the TatA cluster size distribution. We include a proportion of targeted but non-translocatable (NT) substrates, with the simplifying hypothesis that the substrate translocatability does not directly affect cluster dynamical rate constants or substrate binding or unbinding rates. This amounts to a translocation model without specific quality control. Nevertheless, NT substrates will remain associated with TatA clusters until unbound and so will affect cluster sizes and translocation rates. We find that the number of larger TatA clusters depends on the NT fraction $f$. The translocation rate can be optimized by tuning the rate of spontaneous substrate unbinding, $\\Gamma_U$. We present an analytically solvable three-state model of substrate translocation without cluster size dynamics that follows our computed translocation rates, and that is consistent with {\\em in vitro} Tat-translocation data in the presence of NT substrates.

  15. 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

  16. Modeling the mechanochemistry of the ?29 DNA translocation motor

    NASA Astrophysics Data System (ADS)

    Perez-Carrasco, R.; Fiasconaro, A.; Falo, F.; Sancho, J. M.

    2013-03-01

    We present a study of the DNA translocation of the bacteriophage ?29 packaging molecular motor. From the available experimental information we present a model system based on a stochastic flashing potential, which reproduces the experimental observations such as detailed trajectories, steps and substeps, spatial correlation, and velocity. Moreover, the model allows the evaluation of the power and efficiency of this motor. We have found that the maximum power regime does not correspond with that of the maximum efficiency. This information can stimulate further experiments.

  17. Translocation properties of novel cell penetrating transportan and penetratin analogues.

    PubMed

    Lindgren, M; Gallet, X; Soomets, U; Hällbrink, M; Bråkenhielm, E; Pooga, M; Brasseur, R; Langel, U

    2000-01-01

    Novel analogues of the cell-penetrating peptides penetratin and transportan were synthesized. The distribution of the biotin-labeled peptides in Bowes melanoma cell line has been investigated by indirect fluorescence with fluorescein-streptavidin detection. The time course of uptake of (125)I-labeled transportan analogues has been characterized in the same cell line. Molecular modeling was used to analyze the penetration and the orientation of molecules in a simulated biological membrane. The results, both from molecular modeling and fluorescence studies, imply that penetratin and transportan do not enter the cells by related mechanisms and that they do not belong to the same family of translocating peptides. PMID:10995204

  18. Yerkes Summer Institute 2002 Introduction & Background

    E-print Network

    Collar, Juan I.

    a Short Wave (SW) radio signal? What role does wave propagation (the movement of radio waves through don't already know the answers. Background Radio waves are electromagnetic waves and as such are just is broken into various frequencies. Radio waves are found in the Kilohertz (103 Hz) to Megahertz (106 Hz

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

    SciTech Connect

    Schwartz, P.E. )

    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.

  20. The Cosmic Background Radiation

    E-print Network

    George Smoot; Douglas Scott

    1997-11-08

    We summarise the current status of cosmic microwave background spectrum and anisotropy measurements, and their theoretical interpretation. This is the update of the mini-review for the 1997 web-version of the Review of Particle Properties.

  1. Introduction Biological Background

    E-print Network

    Mahaffy, Joseph M.

    @mail.sdsu.eduUBC Biomath Seminar -- (1/39) #12;Introduction Biological Background Mathematical Models Conclusions Tunicate ­ Ciona intestinalis Ciona intestinalis ­ Tunicate ­ Sea Squirt Joseph M. Mahaffy, jmahaffy

  2. Proteomics: General Background

    E-print Network

    Grosu, Radu

    Proteomics: General Background Michael Hadjiargyrou Department of Biomedical Engineering #12;What is proteomics? · Study of the Proteome: Field that utilizes protein sequences, expression and structure, large scale manner · may also involve bioinformatic analysis and storage of data #12;Proteomics

  3. The Cosmic Microwave Background

    E-print Network

    Joseph Silk

    2002-12-12

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

  4. Role of the Twin-Arginine Translocation Pathway in Staphylococcus? †

    PubMed Central

    Biswas, Lalitha; Biswas, Raja; Nerz, Christiane; Ohlsen, Knut; Schlag, Martin; Schäfer, Tina; Lamkemeyer, Tobias; Ziebandt, Anne-Kathrin; Hantke, Klaus; Rosenstein, Ralf; Götz, Friedrich

    2009-01-01

    In Staphylococcus, the twin-arginine translocation (Tat) pathway is present only in some species and is composed of TatA and TatC. The tatAC operon is associated with the fepABC operon, which encodes homologs to an iron-binding lipoprotein, an iron-dependent peroxidase (FepB), and a high-affinity iron permease. The FepB protein has a typical twin-arginine (RR) signal peptide. The tat and fep operons constitute an entity that is not present in all staphylococcal species. Our analysis was focused on Staphylococcus aureus and S. carnosus strains. Tat deletion mutants (?tatAC) were unable to export active FepB, indicating that this enzyme is a Tat substrate. When the RR signal sequence from FepB was fused to prolipase and protein A, their export became Tat dependent. Since no other protein with a Tat signal could be detected, the fepABC-tatAC genes comprise not only a genetic but also a functional unit. We demonstrated that FepABC drives iron import, and in a mouse kidney abscess model, the bacterial loads of ?tatAC and ?tat-fep mutants were decreased. For the first time, we show that the Tat pathway in S. aureus is functional and serves to translocate the iron-dependent peroxidase FepB. PMID:19633084

  5. Role of the twin-arginine translocation pathway in Staphylococcus.

    PubMed

    Biswas, Lalitha; Biswas, Raja; Nerz, Christiane; Ohlsen, Knut; Schlag, Martin; Schäfer, Tina; Lamkemeyer, Tobias; Ziebandt, Anne-Kathrin; Hantke, Klaus; Rosenstein, Ralf; Götz, Friedrich

    2009-10-01

    In Staphylococcus, the twin-arginine translocation (Tat) pathway is present only in some species and is composed of TatA and TatC. The tatAC operon is associated with the fepABC operon, which encodes homologs to an iron-binding lipoprotein, an iron-dependent peroxidase (FepB), and a high-affinity iron permease. The FepB protein has a typical twin-arginine (RR) signal peptide. The tat and fep operons constitute an entity that is not present in all staphylococcal species. Our analysis was focused on Staphylococcus aureus and S. carnosus strains. Tat deletion mutants (DeltatatAC) were unable to export active FepB, indicating that this enzyme is a Tat substrate. When the RR signal sequence from FepB was fused to prolipase and protein A, their export became Tat dependent. Since no other protein with a Tat signal could be detected, the fepABC-tatAC genes comprise not only a genetic but also a functional unit. We demonstrated that FepABC drives iron import, and in a mouse kidney abscess model, the bacterial loads of DeltatatAC and Deltatat-fep mutants were decreased. For the first time, we show that the Tat pathway in S. aureus is functional and serves to translocate the iron-dependent peroxidase FepB. PMID:19633084

  6. 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

  7. 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

  8. Novel translocation in acute megakaryoblastic leukemia (AML-M7).

    PubMed

    Toretsky, Jeffrey A; Everly, Eileen M; Padilla-Nash, Hesed M; Chen, Allen; Abruzzo, Lynne V; Eskenazi, Allen E; Frantz, Chris; Ried, Thomas; Stamberg, Judith

    2003-05-01

    The authors report a unique translocation in a patient with M7 acute myeloid leukemia and review the literature. A 22-month-old girl without Down syndrome was diagnosed with acute myeloid leukemia, subtype M7 (AML-M7), and died with relapsed disease following bone marrow transplantation. Tumor cells were evaluated using cytogenetics (including spectral karyotyping), immunohistochemistry, and flow cytometry. The patient was found to have a previously unreported complex translocation as follows: 50,XX,der(1)t(1;5)(p36?.1;p15?.1),del(5)(p15?.1), +6,+der(6;7)(?;?),der(7)t(6;7)(?;p22)[2],der(9)t(6;9) (?;p21)t(9;14)(q34;q11.2-q13),+10,t(12;16)(p13;q24),-14[2], del(14)(q13)[2],+der(19)t(1;19)(?;p13.3),+22[cp 4]. AML-M7 in non-Down syndrome patients is a rare disease that requires improved prognostic markers. PMID:12759627

  9. Deconvoluting chain heterogeneity from driven translocation through a nanopore

    NASA Astrophysics Data System (ADS)

    Adhikari, Ramesh; Bhattacharya, Aniket

    2015-02-01

    We study translocation dynamics of a driven compressible semi-flexible chain consisting of alternate blocks of stiff (S) and flexible (F) segments of size m and n, respectively, for different chain length N in two dimensions (2D). The free parameters in the model are the bending rigidity ?b which controls the three-body interaction term, the elastic constant kF in the FENE (bond) potential between successive monomers, as well as the segmental lengths m and n and the repeat unit p (N=m_pn_p) and the solvent viscosity ?. We demonstrate that due to the change in entropic barrier and the inhomogeneous viscous drag on the chain backbone a variety of scenarios are possible, amply manifested in the waiting time distribution of the translocating chain. This information can be deconvoluted to extract the mechanical properties of the chain at various length scales and thus can be used to nanopore based methods to probe bio-molecules, such as DNA, RNA and proteins.

  10. Molecular determinants of nucleolar translocation of RNA helicase A

    SciTech Connect

    Liu Zhe; Kenworthy, Rachael; Green, Christopher; Tang, Hengli

    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.

  11. Novel Class of Potential Therapeutics that Target Ricin Retrograde Translocation

    PubMed Central

    Redmann, Veronika; Gardner, Thomas; Lau, Zerlina; Morohashi, Keita; Felsenfeld, Dan; Tortorella, Domenico

    2013-01-01

    Ricin toxin, an A-B toxin from Ricinus communis, induces cell death through the inhibition of protein synthesis. The toxin binds to the cell surface via its B chain (RTB) followed by its retrograde trafficking through intracellular compartments to the ER where the A chain (RTA) is transported across the membrane and into the cytosol. Ricin A chain is transported across the ER membrane utilizing cellular proteins involved in the disposal of aberrant ER proteins by a process referred to as retrograde translocation. Given the current lack of therapeutics against ricin intoxication, we developed a high-content screen using an enzymatically attenuated RTA chimera engineered with a carboxy-terminal enhanced green fluorescent protein (RTAE177Qegfp) to identify compounds that target RTA retrograde translocation. Stabilizing RTAE177Qegfp through the inclusion of proteasome inhibitor produced fluorescent peri-nuclear granules. Quantitative analysis of the fluorescent granules provided the basis to discover compounds from a small chemical library (2080 compounds) with known bioactive properties. Strikingly, the screen found compounds that stabilized RTA molecules within the cell and several compounds limited the ability of wild type RTA to suppress protein synthesis. Collectively, a robust high-content screen was developed to discover novel compounds that stabilize intracellular ricin and limit ricin intoxication. PMID:24366208

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

    E-print Network

    Dekker, Nynke

    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 conductance shows a three-order-of-magnitude decrease with decreasing salt concentrations from 1 M to 1 µ

  13. Export Pathway Selectivity of Escherichia coli Twin Arginine Translocation Signal Peptides*S

    E-print Network

    Georgiou, George

    Export Pathway Selectivity of Escherichia coli Twin Arginine Translocation Signal Peptides encodes at least 29 putative sig- nal peptides containing a twin arginine motif characteristic of proteins exported via the twin arginine translocation (Tat) path- way. Fusions of the putative Tat signal peptides

  14. Mating system in a gopher tortoise population established through multiple translocations: Apparent advantage of prior residence

    E-print Network

    Georgia, University of

    -sustaining population (Griffith et al., 1989; but see Seddon, 1999), but this definition falls short of elaboratingMating system in a gopher tortoise population established through multiple translocations: Apparent a b s t r a c t Population manipulations such as translocation are becoming increasingly important

  15. De Novo nonreciprocal translocation 1;8 confirmed by fluorescent in situ hybridization

    SciTech Connect

    Wiley, J.E.; Stout, C.; Palmer, S.M.

    1995-07-17

    Constitutional nonreciprocal translocations are extremely rare, and even their existence is controversial. We report on a newborn infant with a de novo nonreciprocal translocation between chromosomes 1 and 8 resulting in 1q42.3 deletion syndrome. Fluorescent in situ hybridization with whole chromosome paints confirmed the conventional cytogenetic diagnosis. 3 refs., 2 figs., 1 tab.

  16. Optimality of the Munch mechanism for translocation of sugars in plants

    E-print Network

    the physical principles governing the morphological diversity of plants. Keywords: phloem transport; sugar translocation velocity by providing plants with the ability to respond rapidly to environ- mental perturbationsOptimality of the Mu¨nch mechanism for translocation of sugars in plants K. H. Jensen1,, J. Lee2

  17. Sec-Independent Protein Translocation by the Maize Hcf106 Protein

    E-print Network

    plant chloroplasts. A third translocation mechanism in chloroplasts [the proton concentration difference the endo- symbiotic origin of chloroplasts. Thus, the third protein translocation pathway, of which HCF106 triphosphate (ATP) and is inhibited by NaN3 (2), whereas sig- nal recognition particle (SRP) substrates require

  18. Xylem exudate composition and root-to-shoot nickel translocation in Alyssum species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An improved understanding of Ni root-to-shoot translocation mechanism in hyperaccumulators is necessary to increase Ni uptake efficiency for phytoextraction technologies. It is presumed that an important aspect of Ni translocation and storage involves chelation with organic ligands. It has been re...

  19. Role of JNK Activation and Mitochondrial Bax Translocation in Allicin-Induced Apoptosis in Human Ovarian Cancer SKOV3 Cells

    PubMed Central

    Xu, Ling; Yu, Jin; Zhai, Dongxia; Zhang, Danying; Shen, Wei; Bai, Lingling; Cai, Zailong; Yu, Chaoqin

    2014-01-01

    Background. Allicin, the major component of freshly crushed garlic, is one of the most biologically active compounds of garlic; it has been reported to induce apoptosis in cancer cells; however, the mechanism by which allicin exerts its apoptotic effects is not fully understood. The aim of the present study was to further elucidate the apoptotic pathways induced by allicin in the human ovarian cancer cell line SKOV3. Methods. Cell proliferation and apoptosis were measured by cell-counting assay and flow cytometry analysis. Activation of the signaling pathway was screened by human phospho-kinase array analysis, and the activated pathway and its related proteins were further confirmed by western blot analysis. Results. Allicin induced SKOV3 cell apoptosis and JNK phosphorylation in a time- and dose-dependent manner, but these were significantly blocked by SP600125 (an inhibitor of JNK). The findings suggest that JNK phosphorylation is related to the action of allicin on SKOV3 cells. Furthermore, JNK activation induced Bcl-2 family activation, triggered mitochondria-mediated signaling pathways, and led to the translocation of a considerable amount of Bax and cytochrome c release. Conclusions. JNK activation and mitochondrial Bax translocation are involved in allicin-induced apoptosis in SKOV3 cells. Our data input new insights to the literature of allicin-induced apoptosis. PMID:25097657

  20. Role of JNK Activation and Mitochondrial Bax Translocation in Allicin-Induced Apoptosis in Human Ovarian Cancer SKOV3 Cells.

    PubMed

    Xu, Ling; Yu, Jin; Zhai, Dongxia; Zhang, Danying; Shen, Wei; Bai, Lingling; Cai, Zailong; Yu, Chaoqin

    2014-01-01

    Background. Allicin, the major component of freshly crushed garlic, is one of the most biologically active compounds of garlic; it has been reported to induce apoptosis in cancer cells; however, the mechanism by which allicin exerts its apoptotic effects is not fully understood. The aim of the present study was to further elucidate the apoptotic pathways induced by allicin in the human ovarian cancer cell line SKOV3. Methods. Cell proliferation and apoptosis were measured by cell-counting assay and flow cytometry analysis. Activation of the signaling pathway was screened by human phospho-kinase array analysis, and the activated pathway and its related proteins were further confirmed by western blot analysis. Results. Allicin induced SKOV3 cell apoptosis and JNK phosphorylation in a time- and dose-dependent manner, but these were significantly blocked by SP600125 (an inhibitor of JNK). The findings suggest that JNK phosphorylation is related to the action of allicin on SKOV3 cells. Furthermore, JNK activation induced Bcl-2 family activation, triggered mitochondria-mediated signaling pathways, and led to the translocation of a considerable amount of Bax and cytochrome c release. Conclusions. JNK activation and mitochondrial Bax translocation are involved in allicin-induced apoptosis in SKOV3 cells. Our data input new insights to the literature of allicin-induced apoptosis. PMID:25097657

  1. 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.

  2. Defective mutations within the translocation domain of Clostridium difficile toxin B impair disease pathogenesis.

    PubMed

    Hamza, Therwa; Zhang, Zhifen; Melnyk, Roman A; Feng, Hanping

    2016-02-01

    The Clostridium difficile toxin B is one of the main virulence factors and plays an important role in the pathogenesis of C. difficile infection (CDI). We recently revealed crucial residues in the translocation domain of TcdB for the pore formation and toxin translocation. In this study, we investigated the effects of mutating a critical site involved in pore formation, Leu-1106, to residues that differ in size and polarity (Phe, Ala, Cys, Asp). We observed a broad range of effects on TcdB function in vitro consistent with the role of this site in pore formation and translocation. We show that mice challenged systemically with a lethal dose (LD100) of the most defective mutant (L1106K) showed no symptoms of disease highlighting the importance of this residue and the translocation domain in disease pathogenesis. These findings offer insights into the structure function of the toxin translocation pore, and inform novel therapeutic strategies against CDI. PMID:26507679

  3. Translocation of stiff polymers through a nanopore driven by binding particles

    E-print Network

    Yu, Wancheng; Luo, Kaifu

    2012-01-01

    We investigate the translocation of stiff polymers in the presence of binding particles through a nanopore by two-dimensional Langevin dynamics simulations. We find that the mean translocation time shows a minimum as a function of the binding energy $\\epsilon$ and the particle concentration $\\phi$, due to the interplay of the force from binding and the frictional force. Particularly, for the strong binding the translocation proceeds with a decreasing translocation velocity induced by a significant increase of the frictional force. In addition, both $\\epsilon$ and $\\phi$ have an notable impact on the distribution of the translocation time. With increasing $\\epsilon$ and $\\phi$, it undergoes a transition from an asymmetric and broad distribution under the weak binding to a nearly Gaussian one under the strong binding, and its width becomes gradually narrower.

  4. Transducin translocation contributes to rod survival and enhances synaptic transmission from rods to rod bipolar cells.

    PubMed

    Majumder, Anurima; Pahlberg, Johan; Boyd, Kimberly K; Kerov, Vasily; Kolandaivelu, Saravanan; Ramamurthy, Visvanathan; Sampath, Alapakkam P; Artemyev, Nikolai O

    2013-07-23

    In rod photoreceptors, several phototransduction components display light-dependent translocation between cellular compartments. Notably, the G protein transducin translocates from rod outer segments to inner segments/spherules in bright light, but the functional consequences of translocation remain unclear. We generated transgenic mice where light-induced transducin translocation is impaired. These mice exhibited slow photoreceptor degeneration, which was prevented if they were dark-reared. Physiological recordings showed that control and transgenic rods and rod bipolar cells displayed similar sensitivity in darkness. After bright light exposure, control rods were more strongly desensitized than transgenic rods. However, in rod bipolar cells, this effect was reversed; transgenic rod bipolar cells were more strongly desensitized than control. This sensitivity reversal indicates that transducin translocation in rods enhances signaling to rod bipolar cells. The enhancement could not be explained by modulation of inner segment conductances or the voltage sensitivity of the synaptic Ca(2+) current, suggesting interactions of transducin with the synaptic machinery. PMID:23836670

  5. 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

  6. Overwintering of Gopher Tortoises (Gopherus polyphemus) Translocated to the Northern Limit of Their Geographic Range: Temperatures, Timing, and Survival

    E-print Network

    Georgia, University of

    Overwintering of Gopher Tortoises (Gopherus polyphemus) Translocated to the Northern Limit in gopher tortoises (Gopherus polyphemus) translocated to the northern periphery of their geographic range by using miniature temperature data loggers during 2 winters. All adult and juvenile tortoises monitored

  7. Stochastic Gravitational Wave Background from Exoplanets

    E-print Network

    Ain, Anirban; Mitra, Sanjit

    2015-01-01

    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 totalling about two hundred billion. These surveys, based on electro-magnetic observations, are limited to a very small neighbourhood 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 electro-magnetic astronomy. The cumulative effect of the planets, with periods ranging from 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 or less than the galactic background at different frequencies. Our estimate shows that the net backg...

  8. Translocation of cationic amphipathic peptides across the membranes of pure phospholipid giant vesicles.

    PubMed

    Wheaten, Sterling A; Ablan, Francis D O; Spaller, B Logan; Trieu, Julie M; Almeida, Paulo F

    2013-11-01

    The ability of amphipathic polypeptides with substantial net positive charges to translocate across lipid membranes is a fundamental problem in physical biochemistry. These peptides should not passively cross the bilayer nonpolar region, but they do. Here we present a method to measure peptide translocation and test it on three representative membrane-active peptides. In samples of giant unilamellar vesicles (GUVs) prepared by electroformation, some GUVs enclose inner vesicles. When these GUVs are added to a peptide solution containing a membrane-impermeant fluorescent dye (carboxyfluorescein), the peptide permeabilizes the outer membrane, and dye enters the outer GUV, which then exhibits green fluorescence. The inner vesicles remain dark if the peptide does not cross the outer membrane. However, if the peptide translocates, it permeabilizes the inner vesicles as well, which then show fluorescence. We also measure translocation, simultaneously on the same GUV, by the appearance of fluorescently labeled peptides on the inner vesicle membranes. All three peptides examined are able to translocate, but to different extents. Peptides with smaller Gibbs energies of insertion into the membrane translocate more easily. Further, translocation and influx occur broadly over the same period, but with very different kinetics. Translocation across the outer membrane follows approximately an exponential rise, with a characteristic time of 10 min. Influx occurs more abruptly. In the outer vesicle, influx happens before most of the translocation. However, some peptides cross the membrane before any influx is observed. In the inner vesicles, influx occurs abruptly sometime during peptide translocation across the membrane of the outer vesicle. PMID:24152283

  9. 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

  10. BACKGROUND RESEARCH SAMPLE CODE

    E-print Network

    Gray, Jeffrey G.

    . This type of diabetes is normally seen in children at a very young age. Type II diabetes, on the other handBACKGROUND RESEARCH SAMPLE CODE INTRODUCTION APPLICATION MATERIALS ABSTRACT PURPOSE Diabetes is when the body does not properly use or store the glucose (Mayoclinic). There are two types of diabetes

  11. China: Background Notes Series.

    ERIC Educational Resources Information Center

    Reams, Joanne Reppert

    Concise background information on the People's Republic of China is provided. The publication begins with a profile of the country, outlining the people, geography, economy, and membership in international organizations. The bulk of the document then discusses in more detail China's people, geography, history, government, education, economy, and…

  12. Monitored background radiometer

    NASA Technical Reports Server (NTRS)

    Ruel, C.; Larouche, M.; Donato, M.

    1986-01-01

    The infrared (IR) testing of the Olympus thermal model has provided a capability to perform cost effective thermal balance testing of satellites and satellite components. A high-accuracy monitored background radiometer was developed for the measurement of absorbed radiation heat flux encountered during IR thermal vacuum testing of spacecraft. The design, development, and calibration of this radiometer is described.

  13. Berkeley Low Background Facility

    NASA Astrophysics Data System (ADS)

    Thomas, K. J.; Smith, A. R.; Poon, A. W. P.; Chan, Y. D.; Norman, E. B.; Lesko, K. T.

    2015-08-01

    The Berkeley Low Background Facility (BLBF) at Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background laboratory on the surface at LBNL and at the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products; active screening via neutron activation analysis for U,Th, and K as well as a variety of stable isotopes; and neutron flux/beam characterization measurements through the use of monitors. A general overview of the facilities, services, and sensitivities will be presented. Recent activities and upgrades will also be described including an overview of the recently installed counting system at SURF (recently relocated from Oroville, CA in 2014), the installation of a second underground counting station at SURF in 2015, and future plans. The BLBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  14. 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

  15. EBSD Images Theoretical Background

    E-print Network

    Psaltis, Demetri

    /s assuming a constant growth rate on the 20 first seconds. Bad quality welds were produced by adding grease-tomography. Figure 8 Transverse slice of the bad quality weld observed through X-ray micro- tomography. The poresMotivation EBSD Images Theoretical Background Defects in the Weld Grain Growth Low Speed Welding

  16. Building Background Knowledge

    ERIC Educational Resources Information Center

    Fisher, Douglas; Ross, Donna; Grant, Maria

    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 their ability to ask questions and wonder--both key components of inquiry. In this article,…

  17. Gravitational wave background from binary systems

    SciTech Connect

    Rosado, Pablo A.

    2011-10-15

    Basic aspects of the background of gravitational waves and its mathematical characterization are reviewed. The spectral energy density parameter {Omega}(f), commonly used as a quantifier of the background, is derived for an ensemble of many identical sources emitting at different times and locations. For such an ensemble, {Omega}(f) is generalized to account for the duration of the signals and of the observation, so that one can distinguish the resolvable and unresolvable parts of the background. The unresolvable part, often called confusion noise or stochastic background, is made by signals that cannot be either individually identified or subtracted out of the data. To account for the resolvability of the background, the overlap function is introduced. This function is a generalization of the duty cycle, which has been commonly used in the literature, in some cases leading to incorrect results. The spectra produced by binary systems (stellar binaries and massive black hole binaries) are presented over the frequencies of all existing and planned detectors. A semi-analytical formula for {Omega}(f) is derived in the case of stellar binaries (containing white dwarfs, neutron stars or stellar-mass black holes). Besides a realistic expectation of the level of background, upper and lower limits are given, to account for the uncertainties in some astrophysical parameters such as binary coalescence rates. One interesting result concerns all current and planned ground-based detectors (including the Einstein Telescope). In their frequency range, the background of binaries is resolvable and only sporadically present. In other words, there is no stochastic background of binaries for ground-based detectors.

  18. Novel Bread Wheat Lines Enriched in Carotenoids Carrying Hordeum chilense Chromosome Arms in the ph1b Background

    PubMed Central

    Rey, María-Dolores; Calderón, María-Carmen; Rodrigo, María Jesús; Zacarías, Lorenzo; Alós, Enriqueta; Prieto, Pilar

    2015-01-01

    The use of crop wild relative species to improve major crops performance is well established. Hordeum chilense has a high potential as a genetic donor to increase the carotenoid content of wheat. Crosses between the 7Hch H. chilense substitution lines in wheat and the wheat pairing homoeologous1b (ph1b) mutant allowed the development of wheat-H. chilense translocation lines for both 7Hch? and 7Hch? chromosome arms in the wheat background. These translocation lines were characterized by in situ hybridization and using molecular markers. In addition, reverse phase chromatography (HPLC) analysis was carried out to evaluate the carotenoid content and both 7Hch??7AL and 7AS?7Hch? disomic translocation lines. The carotenoid content in 7Hch??7AL and 7AS?7Hch? disomic translocation lines was higher than the wheat-7Hch addition line and double amount of carotenoids than the wheat itself. A proteomic analysis confirmed that the presence of chromosome 7Hch introgressions in wheat scarcely altered the proteomic profile of the wheat flour. The Psy1 (Phytoene Synthase1) gene, which is the first committed step in the carotenoid biosynthetic pathway, was also cytogenetically mapped on the 7Hch? chromosome arm. These new wheat-H. chilense translocation lines can be used as a powerful tool in wheat breeding programs to enrich the diet in bioactive compounds. PMID:26241856

  19. Cis-Trans Dynamical Asymmetry in Driven Polymer Translocation

    E-print Network

    Takuya Saito; Takahiro Sakaue

    2013-06-25

    During polymer translocation driven by e.g. voltage drop across a nanopore, the segments in the cis-side is incessantly pulled into the pore, which are then pushed out of it into the trans-side. This pulling and pushing polymer segments are described in the continuum level by nonlinear transport processes known, respectively, as fast and slow diffusions. By matching solutions of both sides through the mass conservation across the pore, we provide a physical basis for the cis and trans dynamical asymmetry, a feature repeatedly reported in recent numerical simulations. We then predict how the total driving force is dynamically allocated between cis (pulling) and trans (pushing) sides, demonstrating that the trans-side event adds a finite-chain length effect to the dynamical scaling, which may become substantial for weak force and/or high pore friction cases.

  20. 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

  1. 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.

  2. Translocation of double strand DNA into a biological nanopore

    NASA Astrophysics Data System (ADS)

    Chatkaew, Sunita; Mlayeh, Lamia; Leonetti, Marc; Homble, Fabrice

    2009-03-01

    Translocation of double strand DNA across a unique mitochondrial biological nanopore (VDAC) is observed by an electrophysiological method. Characteristics of opened and sub-conductance states of VDAC are studied. When the applied electric potential is beyond ± 20 mV, VDAC transits to a sub-conductance state. Plasmids (circular double strand DNA) with a diameter greater than that of the channel shows the current reduction into the channel during the interaction but the state with zero-current is not observed. On the contrary, the interaction of linear double strand DNA with the channel shows the current reduction along with the zero-current state. These show the passages of linear double strand DNA across the channel and the electrostatic effect due to the surface charges of double strand DNA and channel for circular and linear double strand DNA.

  3. Complex karyotype with novel translocation in pure erythroid leukemia patient.

    PubMed

    Aljabry, Mansour

    2015-02-24

    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. 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

  5. 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

  6. Phosphorylation of Phosducin Accelerates Rod Recovery from Transducin Translocation

    PubMed Central

    Belcastro, Marycharmain; Song, Hongman; Sinha, Satyabrata; Song, Chunyan; Mathers, Peter H; Sokolov, Maxim

    2012-01-01

    Purpose. In rods saturated by light, the G protein transducin undergoes translocation from the outer segment compartment, which results in the uncoupling of transducin from its innate receptor, rhodopsin. We measured the kinetics of recovery from this adaptive cellular response, while also investigating the role of phosducin, a phosphoprotein binding transducin ?? subunits in its de-phosphorylated state, in regulating this process. Methods. Mice were exposed to a moderate rod-saturating light triggering transducin translocation, and then allowed to recover in the dark while free running. The kinetics of the return of the transducin subunits to the outer segments were compared in transgenic mouse models expressing full-length phosducin, and phosducin lacking phosphorylation sites serine 54 and 71, using Western blot analysis of serial tangential sections of the retina. Results. In mice expressing normal phosducin, transducin ? and ?? subunits returned to the outer segments with a half-time (t1/2) of ?24 and 29 minutes, respectively. In the phosducin phosphorylation mutants, the transducin ? subunit moved four times slower, with t1/2 ?95 minutes, while the movement of transducin ?? was less affected. Conclusions. We demonstrate that the recovery of rod photoreceptors from the ambient saturating levels of illumination, in terms of the return of the light-dispersed transducin subunits to the rod outer segments, occurs six times faster than reported previously. Our data also support the notion that the accumulation of transducin ? subunit in the outer segment is driven by its re-binding to the transducin ?? dimer, because this process is accelerated significantly by phosducin phosphorylation. PMID:22491418

  7. DNA translocation through an array of kinked nanopores

    SciTech Connect

    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

    2010-08-06

    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.

  8. DNA translocation through an array of kinked nanopores

    NASA Astrophysics Data System (ADS)

    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.; Jeffrey Brinker, C.

    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.

  9. DNA translocation through an array of kinked nanopores

    NASA Astrophysics Data System (ADS)

    Chen, Zhu

    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 behaviors in more robust synthetic materials that are more readily integrated into practical devices. To date, 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-nanometer 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 to 'straight-through' proteinaceous nanopores of comparable dimensions, kinked nanopores exhibit a factor of up to 5x 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 major functional behaviors of protein pores in our solid-state nanopore system.

  10. THE GENETIC ANALYSIS OF A RECIPROCAL TRANSLOCATION, eTI(I1I; V), IN CAENORHABDITIS ELEGANS

    E-print Network

    Baillie, David

    THE GENETIC ANALYSIS OF A RECIPROCAL TRANSLOCATION, eTI(I1I; V), IN CAENORHABDITIS ELEGANS RAJA E 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 a dominant crossover suppressor for both the right half

  11. THE JOURNAL OF CHEMICAL PHYSICS 137, 144903 (2012) Translocation dynamics of freely jointed Lennard-Jones chains

    E-print Network

    Muzzio, Fernando J.

    2012-01-01

    the incre- mental gauge cell method. The free energy profile of a translocating chain was found by combining adsorption and repulsive steric hindrance contributions to the free energy. Translocation times fell into two of translocation times with increasing adsorption strength, with sharp peak associated with local free energy

  12. Stochastic Gravitational Wave Background from Exoplanets

    E-print Network

    Anirban Ain; Shilpa Kastha; Sanjit Mitra

    2015-04-09

    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 totalling about two hundred billion. These surveys, based on electro-magnetic observations, are limited to a very small neighbourhood 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 electro-magnetic astronomy. The cumulative effect of the planets, with periods ranging from 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 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.

  13. 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.

  14. Cosmology and the Cosmic Background Explorer (COBE)

    NASA Technical Reports Server (NTRS)

    Boggess, Nancy W.

    1989-01-01

    COBE, planned for launch aboard a Delta rocket, is NASA's first space mission specifically designed to study the diffuse IR and microwave background radiation. COBE has three instruments for performing precision measurements of the spectrum and angular distribution of the 3 K cosmic background radiation and for making an all-sky survey of the diffuse IR emission at wavelengths of 1-300 microns. COBE will carry differential microwave radiameters to search for anisotropies to a sensitivity per 7-deg pixel of 0.15 mK at frequencies of 53 and 90 GHz and of 0.3 mK at 32 GHz.

  15. 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.

    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.

  16. 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.

  17. Antiscalar cosmological background

    E-print Network

    Eduard G. Mychelkin; Maxim A. Makukov

    2015-06-11

    It is shown that the antiscalar approach to dark energy, whereby the energy-momentum tensor of the scalar field has the sign opposite to that of the rest of the matter, follows from the considerations of thermodynamic stability, as well as from the static limit of the Einstein-Maxwell equations. The same limit also demonstrates that the resulting background antiscalar field proves to be of quasi-electrostatic origin.

  18. Slow CCL2-dependent translocation of biopersistent particles from muscle to brain

    PubMed Central

    2013-01-01

    Background Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micron/submicron-sized agglomerates. Although generally well tolerated, alum is occasionally detected within monocyte-lineage cells long after immunization in presumably susceptible individuals with systemic/neurologic manifestations or autoimmune (inflammatory) syndrome induced by adjuvants (ASIA). Methods On the grounds of preliminary investigations in 252 patients with alum-associated ASIA showing both a selective increase of circulating CCL2, the major monocyte chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments to assess biodistribution of vaccine-derived aluminum and of alum-particle fluorescent surrogates injected in muscle. Aluminum was detected in tissues by Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used. Results Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection. Both fluorescent materials injected into muscle translocated to draining lymph nodes (DLNs) and thereafter were detected associated with phagocytes in blood and spleen. Particles linearly accumulated in the brain up to the six-month endpoint; they were first found in perivascular CD11b+ cells and then in microglia and other neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier. Loss/gain-of-function experiments consistently implicated CCL2 in systemic diffusion of Al-Rho particles captured by monocyte-lineage cells and in their subsequent neurodelivery. Stereotactic particle injection pointed out brain retention as a factor of progressive particle accumulation. Conclusion Nanomaterials can be transported by monocyte-lineage cells to DLNs, blood and spleen, and, similarly to HIV, may use CCL2-dependent mechanisms to penetrate the brain. This occurs at a very low rate in normal conditions explaining good overall tolerance of alum despite its strong neurotoxic potential. However, continuously escalating doses of this poorly biodegradable adjuvant in the population may become insidiously unsafe, especially in the case of overimmunization or immature/altered blood brain barrier or high constitutive CCL-2 production. PMID:23557144

  19. Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat

    PubMed Central

    2014-01-01

    Background There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2. transcellular transport across amniotic membranes 3. transport through ~20 nm wide transtrophoblastic channels in a size dependent manner. The three AuNP sizes used to test this hypothesis are either well below, or of similar size or well above the diameters of the transtrophoblastic channels. Methods We intravenously injected monodisperse, negatively charged, radio-labelled 1.4 nm, 18 nm and 80 nm 198AuNP at a mass dose of 5, 3 and 27 ?g/rat, respectively, into pregnant rats on day 18 of gestation and in non-pregnant control rats and studied the biodistribution in a quantitative manner based on the radio-analysis of the stably labelled 198AuNP after 24 hours. Results We observed significant biokinetic differences between pregnant and non-pregnant rats. AuNP fractions in the uterus of pregnant rats were at least one order of magnitude higher for each particle size roughly proportional to the enlarged size and weight of the pregnant uterus. All three sizes of 198AuNP were found in the placentas and amniotic fluids with 1.4 nm AuNP fractions being two orders of magnitude higher than those of the larger AuNP on a mass base. In the fetuses, only fractions of 0.0006 (30 ng) and 0.00004 (0.1 ng) of 1.4 nm and 18 nm AuNP, respectively, were detected, but no 80 nm AuNP (<0.000004 (<0.1 ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24 hours but indicate that AuNP translocation occurs across the placental tissues either through transtrophoblastic channels and/or via transcellular processes. Conclusion Our data suggest that the translocation of AuNP from maternal blood into the fetus is NP-size dependent which is due to mechanisms involving (1) transport through transtrophoblastic channels ¿ also present in the human placenta ¿ and/or (2) endocytotic and diffusive processes across the placental barrier. PMID:25928666

  20. Adhesins and Host Serum Factors Drive Yop Translocation by Yersinia into Professional Phagocytes during Animal Infection

    PubMed Central

    Maldonado-Arocho, Francisco J.; Green, Carlos; Fisher, Michael L.; Paczosa, Michelle K.; Mecsas, Joan

    2013-01-01

    Yersinia delivers Yops into numerous types of cultured cells, but predominantly into professional phagocytes and B cells during animal infection. The basis for this cellular tropism during animal infection is not understood. This work demonstrates that efficient and specific Yop translocation into phagocytes by Yersinia pseudotuberculosis (Yptb) is a multi-factorial process requiring several adhesins and host complement. When WT Yptb or a multiple adhesin mutant strain, ?ail?inv?yadA, colonized tissues to comparable levels, ?ail?inv?yadA translocated Yops into significantly fewer cells, demonstrating that these adhesins are critical for translocation into high numbers of cells. However, phagocytes were still selectively targeted for translocation, indicating that other bacterial and/or host factors contribute to this function. Complement depletion showed that complement-restricted infection by ?ail?inv?yadA but not WT, indicating that adhesins disarm complement in mice either by prevention of opsonophagocytosis or by suppressing production of pro-inflammatory cytokines. Furthermore, in the absence of the three adhesins and complement, the spectrum of cells targeted for translocation was significantly altered, indicating that Yersinia adhesins and complement direct Yop translocation into neutrophils during animal infection. In summary, these findings demonstrate that in infected tissues, Yersinia uses adhesins both to disarm complement-dependent killing and to efficiently translocate Yops into phagocytes. PMID:23818844

  1. Genetic variation in natural and translocated populations of the endangered Delmarva fox squirrel (Sciurus niger cinereus)

    USGS Publications Warehouse

    Lance, S.L.; Maldonado, J.E.; Bocetti, C.I.; Pattee, O.H.; Ballou, J.D.; Fleischer, R.C.

    2003-01-01

    The Delmarva fox squirrel, Sciurus niger cinereus, is a federally listed endangered subspecies whose range has been reduced by 90%. In an attempt to increase both population size and range, translocation sites were established beginning in the 1960's by moving squirrels from the natural range to sites outside the current range. Although translocations have served as the primary component of the DFS recovery program, there has been very little post-release examination of the genetics of the translocation sites. In this study, we developed ten microsatellite loci, screened the three polymorphic loci, and sequenced a 330 bp fragment of the mitochondrial control region in order to assess levels of genetic variation in natural and translocated regions of Delmarva fox squirrels and to compare them to Southeastern fox squirrels (S. n. niger). Although we found low levels of microsatellite polymorphism, there were no differences in heterozygosity between natural and translocated regions, or between Delmarva and Southeastern fox squirrels. We found high levels of polymorphism in the mitochondrial control region. Our patterns of haplotype diversity suggest incomplete lineage sorting of the two subspecies. In general, our data suggest that the current levels of genetic variation in the translocated sites are representative of those found in the natural population, and we encourage the continued use of translocations as a major component of Delmarva fox squirrel recovery.

  2. Leading tip drives soma translocation via forward F-actin flow during neuronal migration.

    PubMed

    He, Min; Zhang, Zheng-hong; Guan, Chen-bing; Xia, Di; Yuan, Xiao-bing

    2010-08-11

    Neuronal migration involves coordinated extension of the leading process and translocation of the soma, but the relative contribution of different subcellular regions, including the leading process and cell rear, in driving soma translocation remains unclear. By local manipulation of cytoskeletal components in restricted regions of cultured neurons, we examined the molecular machinery underlying the generation of traction force for soma translocation during neuronal migration. In actively migrating cerebellar granule cells in culture, a growth cone (GC)-like structure at the leading tip exhibits high dynamics, and severing the tip or disrupting its dynamics suppressed soma translocation within minutes. Soma translocation was also suppressed by local disruption of F-actin along the leading process but not at the soma, whereas disrupting microtubules along the leading process or at the soma accelerated soma translocation. Fluorescent speckle microscopy using GFP-alpha-actinin showed that a forward F-actin flow along the leading process correlated with and was required for soma translocation, and such F-actin flow depended on myosin II activity. In migrating neurons, myosin II activity was high at the leading tip but low at the soma, and increasing or decreasing this front-to-rear difference accelerated or impeded soma advance. Thus, the tip of the leading process actively pulls the soma forward during neuronal migration through a myosin II-dependent forward F-actin flow along the leading process. PMID:20702717

  3. 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.

  4. Translocation of a semiflexible polymer through a nanopore in the presence of attractive binding particles

    NASA Astrophysics Data System (ADS)

    Adhikari, Ramesh; Bhattacharya, Aniket

    2015-09-01

    We study the translocation dynamics of a semiflexible polymer through a nanopore from the cis into the trans compartment containing attractive binding particles (BPs) using the Langevin dynamics simulation in two dimensions. The binding particles accelerate the threading process in two ways: (i) reducing the back-sliding of the translocated monomer, and (ii) providing the pulling force toward the translocation direction. We observe that for certain binding strength (?c) and concentration (? ) of the BPs, the translocation is faster than the ideal ratcheting condition as elucidated by Simon, Peskin, and Oster [M. Simon, C. S. Peskin, and G. F. Oster, Proc. Natl. Acad. Sci. USA 89, 3770 (1992), 10.1073/pnas.89.9.3770]. The asymmetry produced by the BPs at the trans-side leads to similarities of this process to that of a driven translocation with an applied force inside the pore manifested in various physical quantities. Furthermore, we provide an analytic expression for the force experienced by the translocating chain as well as for the scaled mean first passage time (MFPT), for which we observe that for various combinations of N , ? , and ? the scaled MFPT ( /N1.5?0.8) collapses onto the same master plot. Based on the analysis of our simulation data, we provide plausible arguments with regard to how the scaling theory of driven translocation can be generalized for such a directed diffusion process by replacing the externally applied force with an effective force.

  5. Domain Organization in Clostridium botulinum Neurotoxin Type E is Unique: Its Implication in Faster Translocation

    SciTech Connect

    Kumaran, D.; Eswaramoorthy, S; Furey, W; Navaza, J; Sax, M; Swaminathan, S

    2009-01-01

    Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.

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

    SciTech Connect

    Cunningham, K.; Wickner, W.T. )

    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.

  7. Dermatoglyphics and Reproductive Risk in a Family with Robertsonian Translocation 14q;21q

    PubMed Central

    Kolgeci, Selim; Kolgeci, Jehona; Azemi, Mehmedali; Daka, Aferdita; Shala-Beqiraj, Ruke; Kurtishi, Ilir; Sopjani, Mentor

    2015-01-01

    Aim: The present study is carried out to evaluate the risk of giving birth to children with Down syndrome in a family with Robertsonian translocation 14q;21q, and to find the dermatoglyphic changes present in carriers of this translocation. Methods: Cytogenetics diagnosis has been made according to Moorhead and Seabright method, while the analysis of prints (dermatoglyphics analysis) was made with the Cummins and Midlo method. Results: Cytogenetic diagnosis has been made in a couple who suffered the spontaneous miscarriages and children with Down syndrome. Robertsonian translocation between chromosomes 14 and 21 (45, XX, der (14; 21) (q10; q10)) was found in a female partner who had four pregnancies, in two of which was found fetus karyotype with trisomy in chromosome 21 and pregnancies were terminated. The outcome of fourth pregnancy was twin birth, one of them with normal karyotype and another with Down syndrome due to Robertsonian translocation inherited by mother side. Specific dermatoglyphics traits are found in the child carrying Down syndrome, whereas several traits of dermatoglyphics characteristic of Down syndrome have been displayed among the silent carriers of Robertsonian translocation 14q;21q. Conclusion: Robertsonian translocation found in female partner was the cause of spontaneous miscarriages, of giving birth to a child with Down syndrome, and of trisomy of chromosome 21 due to translocation in two pregnancies. PMID:26236088

  8. Translocation Down syndrome in Ohio 1970-1981: epidemiologic and cytogenetic factors and mutation rate estimates.

    PubMed Central

    Pulliam, L H; Huether, C A

    1986-01-01

    Sixteen hundred eighty-eight Down syndrome live births, including 65 (5.2%) translocations, were ascertained in Ohio between 1970 and 1981. Translocations of known origin were 24.4% maternal, 2.2% paternal, and 73.3% de novo. Translocation subtypes were 14/21 (45.7%), 15/21 (2.9%), 21/21 (40.0%), 21/22 (2.9%), and other (8.5%). Among 14/21 translocations, 33.3% were maternal in origin and 66.7% were de novo, while 100% of 21/21 translocations were de novo. No differences were found when the maternal- and paternal-age distributions of all translocations or various translocation subsets were compared with the live-birth control distributions. However, mean maternal and paternal ages of de novo translocations were significantly lower than that of the live-birth controls. Ohio data showed the average maternal age of de novo D/21 cases to be significantly lower than the control. Ages of both parents of de novo G/21 cases and paternal age of D/21 cases were not different from the control. De novo translocation mutation rate estimates were 0.8 X 10(-5) for 14/21, 1.2 X 10(-5) for 21/21, and 2.2 X 10(-5) overall. Ohio estimates (3.2 X 10(-5) for 1970-1972 and 1.4 X 10(-5) for 1973-1975) did not reflect the increase in mutation rate previously found in New York during 1973-1977. PMID:2945428

  9. 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

  10. A voltage-gated pore for translocation of tRNA

    SciTech Connect

    Koley, Sandip; Adhya, Samit

    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.

  11. 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 $\

  12. Poly-L-arginine-hydroxyapatite nanoparticle complexes translocate through lipid bilayer membranes.

    PubMed

    Ueno, Satoru; Shimabayashi, Saburo

    2009-01-01

    Certain molecules, which are able to directly translocate across phospholipid bilayer membranes (cell or endosormal membrane), can be useful as carriers (vectors) for drags (especially polymeric drags). We have studied the translocationability of the hydroxyapatite nanoparticle-poly-L-arginine complex through the negatively charged phospholipid bilayer membranes by using several instruments. It was confirmed by means of a confocal laser scanning microscopy (CLSM) not only the fact that the complex can translocate through the membranes but also the fact that the complexes were still retained in the inner water layer of the liposome even after the translocation. PMID:19581704

  13. Quantifying the role of chaperones in protein translocation by computational modeling.

    PubMed

    Assenza, Salvatore; De Los Rios, Paolo; Barducci, Alessandro

    2015-01-01

    The molecular chaperone Hsp70 plays a central role in the import of cytoplasmic proteins into organelles, driving their translocation by binding them from the organellar interior. Starting from the experimentally-determined structure of the E. coli Hsp70, we computed, by means of molecular simulations, the effective free-energy profile for substrate translocation upon chaperone binding. We then used the resulting free energy to quantitatively characterize the kinetics of the import process, whose comparison with unassisted translocation highlights the essential role played by Hsp70 in importing cytoplasmic proteins. PMID:25988176

  14. Quantifying the role of chaperones in protein translocation by computational modelling

    E-print Network

    Salvatore Assenza; Paolo De Los Rios; Alessandro Barducci

    2014-11-25

    The molecular chaperone Hsp70 plays a central role in the import of cytoplasmic proteins into organelles, driving their translocation by binding them from the organellar interior. Starting from the experimentally-determined structure of the \\textit{E. coli} Hsp70, we computed, by means of molecular simulations, the effective free-energy profile for substrate translocation upon chaperone binding. We then used the resulting free energy to quantitatively characterize the kinetics of the import process, whose comparison with unassisted translocation highlights the essential role played by Hsp70 in importing cytoplasmic proteins.

  15. Single Stranded DNA Translocation Through A Nanopore: A Master Equation Approach

    E-print Network

    O. Flomenbom; J. Klafter

    2003-07-17

    We study voltage driven translocation of a single stranded (ss) DNA through a membrane channel. Our model, based on a master equation (ME) approach, investigates the probability density function (pdf) of the translocation times, and shows that it can be either double or mono-peaked, depending on the system parameters. We show that the most probable translocation time is proportional to the polymer length, and inversely proportional to the first or second power of the voltage, depending on the initial conditions. The model recovers experimental observations on hetro-polymers when using their properties inside the pore, such as stiffness and polymer-pore interaction.

  16. Quantifying the role of chaperones in protein translocation by computational modeling

    PubMed Central

    Assenza, Salvatore; De Los Rios, Paolo; Barducci, Alessandro

    2015-01-01

    The molecular chaperone Hsp70 plays a central role in the import of cytoplasmic proteins into organelles, driving their translocation by binding them from the organellar interior. Starting from the experimentally-determined structure of the E. coli Hsp70, we computed, by means of molecular simulations, the effective free-energy profile for substrate translocation upon chaperone binding. We then used the resulting free energy to quantitatively characterize the kinetics of the import process, whose comparison with unassisted translocation highlights the essential role played by Hsp70 in importing cytoplasmic proteins. PMID:25988176

  17. Tourette syndrome in a pedigree with a 7;18 translocation: Identification of a YAC spanning the translocation breakpoint at 18q22.3

    SciTech Connect

    Boghosian-Sell, L.; Overhauser, J.; Comings, D.E.

    1996-11-01

    Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pathologies include attention deficit disorder and obsessive-compulsive disorder (OCD). Extensive linkage analysis based on an autosomal dominant mode of transmission with reduced penetrance has failed to show linkage with polymorphic markers, suggesting either locus heterogeneity or a polygenic origin for Tourette syndrome. An individual diagnosed with Tourette syndrome has been described carrying a constitutional chromosome translocation. Other family members carrying the translocation exhibit features seen in Tourette syndrome including motor tics, vocal tics, and OCD. Since the disruption of specific genes by a chromosomal rearrangement can elicit a particular phenotype, we have undertaken the physical mapping of the 7;18 translocation such that genes mapping at the site of the breakpoint can be identified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18), a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventual identification of genes that map to chromosomes 7 and 18 at the site of the translocation. 41 refs., 3 figs., 1 tab.

  18. 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

  19. 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

  20. SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

    SciTech Connect

    Joo, Hyun-Yoo; Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 ; 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; Cho, Myung-Haing; Kim, Joon; Lee, Kee-Ho

    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.

  1. The Extragalactic Radio Background

    NASA Technical Reports Server (NTRS)

    Kogut, A.; Fixsen, D. J.; Levin, S. M.; Limon, M.; Lubin, P. M.; Seiffert, M.; Singal, J.; Villela, T.; Wollack, E.; Wuensche, C. A.

    2011-01-01

    The existence of an isotropic component of the high-latitude radio sky has been recognized for nearly fifty years, but has typically been assumed to be Galactic in origin. We use recent radio observations to test whether the observed high-latitude component could originate within either an extended Galactic halo or a more local "bubble" structure. The lack of significant polarization from the isotropic component, combined with the lack of significant correlation with the Galactic far-infrared emission, rule out an origin within the Galaxy. We conclude that an extragalactic origin is the only viable alternative for the bulk of the isotropic high-latitude emission. The extragalactic component is 2-3 times brighter than local (Galactic) emission towards the Galactic poles and is consistent with a power law in frequency with amplitude T(sub r) = 24.1 plus or minus 2.1 K and spectral index beta = -2.599 plus or minus 0.036 evaluated at reference frequency 310 MHz.

  2. 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.

  3. Muscle contraction increases carnitine uptake via translocation of OCTN2

    SciTech Connect

    Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

    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.

  4. 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.

  5. APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma

    PubMed Central

    Walker, Brian A; Wardell, Christopher P; Murison, Alex; Boyle, Eileen M; Begum, Dil B; Dahir, Nasrin M; Proszek, Paula Z; Melchor, Lorenzo; Pawlyn, Charlotte; Kaiser, Martin F; Johnson, David C; Qiang, Ya-Wei; Jones, John R; Cairns, David A; Gregory, Walter M; Owen, Roger G; Cook, Gordon; Drayson, Mark T; Jackson, Graham H; Davies, Faith E; Morgan, Gareth J

    2015-01-01

    We have sequenced 463 presenting cases of myeloma entered into the UK Myeloma XI study using whole exome sequencing. Here we identify mutations induced as a consequence of misdirected AID in the partner oncogenes of IGH translocations, which are activating and associated with impaired clinical outcome. An APOBEC mutational signature is seen in 3.8% of cases and is linked to the translocation mediated deregulation of MAF and MAFB, a known poor prognostic factor. Patients with this signature have an increased mutational load and a poor prognosis. Loss of MAF or MAFB expression results in decreased APOBEC3B and APOBEC4 expression, indicating a transcriptional control mechanism. Kataegis, a further mutational pattern associated with APOBEC deregulation, is seen at the sites of the MYC translocation. The APOBEC mutational signature seen in myeloma is, therefore, associated with poor prognosis primary and secondary translocations and the molecular mechanisms involved in generating them. PMID:25904160

  6. INFLUENCE OF ANTIBIOTICS ON THE INTESTINAL TRACT SURVIVAL AND TRANSLOCATION OF ENVIRONMENTAL PSEUDOMONAS SPECIES

    EPA Science Inventory

    The environmental release of microorganisms has prompted the investigation of potential health effects associated with their release. n this study, survival and translocation to the spleen and liver of several environmental Pseudomonas spp. was investigated in antibiotic-treated ...

  7. Kinesin-1 Translocation along Human Breast Cancer Cell Microtubules in Vitro

    NASA Astrophysics Data System (ADS)

    Shojania Feizabadi, Mitra; Jun, Yonggun

    2015-03-01

    A principle approach to better understand intra-cellular microtubule based transport is to study such it in vitro. Such in vitro examinations have predominantly used microtubules polymerized from bovine brain tubulin, but motor function can also in principle be affected by the specific tubulin isotypes present in different cells. The human breast cancer cells carry different beta tubulin isotype distribution. However, it is entirely unknown whether transport along the microtubules is different in these cells. In this work we have characterized, for the first time, the translocation specifications of kinesin-1 along human breast cancer cell microtubules polymerized in vitro. We found that as compared with the translocation along bovine brain microtubules, kinesin-1 shows a fifty percent shorter processive run length and slightly slower velocity under similar experimental conditions. These first time results support the regulatory role of tubulin isotypes in regards to motor protein translocations, and quantify the translocation specifications of kinesin-1 along microtubules of human breast cancer cells.

  8. Tea plant uptake and translocation of polycyclic aromatic hydrocarbons from water and around air.

    PubMed

    Lin, Daohui; Zhu, Lizhong; He, Wei; Tu, Youying

    2006-05-17

    This study, which aimed to investigate the capacity of tea plant uptake and translocation of polycyclic aromatic hydrocarbons (PAHs), was divided into two sections. One was to study tea plant root uptake of PAHs from water and translocation to leaves. The other was to research tea plant leaf uptake of PAHs from air. It was observed that tea plant roots and leaves could strongly accumulate PAHs from around the environment. The capacity of tea plant uptake and translocation of PAHs were found to be closely relative to the physical-chemical properties of PAHs. With the increase of IgK(ow) (octanol-water partition coefficient) of the PAHs, both root concentration factors and leaf concentration factors increased exponentially, while translocation factors from roots to leaves decreased exponentially. PMID:19127741

  9. Single-Molecule Protein Unfolding and Translocation by an ATP-Fueled Proteolytic Machine

    E-print Network

    Aubin-Tam, Marie-Eve

    All cells employ ATP-powered proteases for protein-quality control and regulation. In the ClpXP protease, ClpX is a AAA+ machine that recognizes specific protein substrates, unfolds these molecules, and then translocates ...

  10. Polymer translocation in solid-state nanopores: Dependence on hydrodynamic interactions and polymer configuration

    NASA Astrophysics Data System (ADS)

    Edmonds, Christopher M.; Hesketh, Peter J.; Nair, Sankar

    2013-11-01

    We present a Brownian dynamics investigation of 3-D Rouse and Zimm polymer translocation through solid-state nanopores. We obtain different scaling exponents ? for both polymers using two initial configurations: minimum energy, and 'steady-state'. For forced translocation, Rouse polymers (no hydrodynamic interactions), shows a large dependence of ? on initial configuration and voltage. Higher voltages result in crowding at the nanopore exit and reduced ?. When the radius of gyration is in equilibrium at the beginning and end of translocation, ? = 1 + ? where ? is the Flory exponent. For Zimm polymers (including hydrodynamic interactions), crowding is reduced and ? = 2?. Increased pore diameter does not affect ? at moderate voltages that reduce diffusion effects. For unforced translocation using narrow pores, both polymers give ? = 1 + 2?. Due to increased polymer-pore interactions in the narrow pore, hydrodynamic drag effects are reduced, resulting in identical scaling.

  11. Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma

    SciTech Connect

    Turc-Carel, C.; Cin, P.D.; Limon, J.; Rao, U.; Li, F.P.; Corson, J.M.; Zimmerman, R.; Parry, D.M.; Cowan, J.M.; Sandberg, A.A.

    1987-04-01

    A translocation that involves chromosome X (band p11.2) and chromosome 18 (band q11.2) was observed in short-term in vitro cultures of cells from five synovial sarcomas and one malignant fibrous histiocytoma. In four of these tumors, the translocation t(X;18)(p11.2;q11.2) was reciprocal. The two other tumors had complex translocations: t(X;18;21)(p11.2;q11.2;p13) and t(X;15;18)(p11.2;q23;q11.2). A translocation between chromosomes X and 18 was not detected in other histological types of soft tissue sarcoma. The X;18 rearrangement appears to characterize the synovial sarcoma and is the first description of a primary, nonrandom change in the sex chromosome of a human solid tumor.

  12. SYSTEMIC TRANSLOCATION OF PARTICULATE MATTER-ASSOCIATED METALS FOLLOWING A SINGLE INTRATRACHEAL INSTILLATION IN RATS

    EPA Science Inventory

    Respirable ambient particulate matter (PM) exposure has been associated with an increased risk of cardiovascular disease. Direct translocation of PM associated metals from the lungs into systemic circulation may be partly responsible. We measured elemental content of lungs, pla...

  13. Three-Dimensional Genome Architecture Influences Partner Selection for Chromosomal Translocations in Human Disease

    E-print Network

    Engreitz, Jesse Michael

    Chromosomal translocations are frequent features of cancer genomes that contribute to disease progression. These rearrangements result from formation and illegitimate repair of DNA double-strand breaks (DSBs), a process ...

  14. Effect of charge patterns along a solid-state nanopore on polyelectrolyte translocation.

    PubMed

    Katkar, H H; Muthukumar, M

    2014-04-01

    We investigate the effectiveness of charge patterns along a nanopore on translocation dynamics of a flexible polyelectrolyte. We perform a three dimensional Langevin dynamics simulation of a uniformly charged flexible polyelectrolyte translocating under uniform external electric field through a solid-state nanopore. We maintain the total charge along the pore to be constant, while varying its distribution by placing alternate charged and uncharged sections of different lengths along the pore length. Longest average translocation time is observed for a pattern corresponding to an optimum section length, with a major delay in the translocation time during the pore ejection stage. This optimum section length is independent of lengths of polyelectrolyte and pore within the range studied. A theory based on the Fokker-Planck formalism is found to successfully describe the observed trends with reasonable quantitative agreement. PMID:24712816

  15. 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

  16. High-performance analysis of single interphase cells with custom DNA probes spanning translocation break points

    NASA Astrophysics Data System (ADS)

    Weier, Heinz-Ulli G.; Munne, S.; Lersch, Robert A.; Marquez, C.; Wu, J.; Pedersen, Roger A.; Fung, Jingly

    1999-06-01

    The chromatin organization of interphase cell nuclei, albeit an object of intense investigation, is only poorly understood. In the past, this has hampered the cytogenetic analysis of tissues derived from specimens where only few cells were actively proliferating or a significant number of metaphase cells could be obtained by induction of growth. Typical examples of such hard to analyze cell systems are solid tumors, germ cells and, to a certain extent, fetal cells such as amniocytes, blastomeres or cytotrophoblasts. Balanced reciprocal translocations that do not disrupt essential genes and thus do not led to disease symptoms exit in less than one percent of the general population. Since the presence of translocations interferes with homologue pairing in meiosis, many of these individuals experience problems in their reproduction, such as reduced fertility, infertility or a history of spontaneous abortions. The majority of translocation carriers enrolled in our in vitro fertilization (IVF) programs carry simple translocations involving only two autosomes. While most translocations are relatively easy to spot in metaphase cells, the majority of cells biopsied from embryos produced by IVF are in interphase and thus unsuitable for analysis by chromosome banding or FISH-painting. We therefore set out to analyze single interphase cells for presence or absence of specific translocations. Our assay, based on fluorescence in situ hybridization (FISH) of breakpoint-spanning DNA probes, detects translocations in interphase by visual microscopic inspection of hybridization domains. Probes are prepared so that they span a breakpoint and cover several hundred kb of DNA adjacent to the breakpoint. On normal chromosomes, such probes label a contiguous stretch of DNA and produce a single hybridization domain per chromosome in interphase cells. The translocation disrupts the hybridization domain and the resulting two fragments appear as physically separated hybridization domains in the nucleus. To facilitate the detection, DNA probes for breakpoints on different chromosomes are labeled in different colors, so the translocation event can be detected as a fusion of red and green hybridization domains. We applied this scheme successfully for the analysis of somatic and germ cells from more than 20 translocation patients, each with individual breakpoints, and provide summaries of our experience as well as strategies, cost and time frames to prepare case-specific translocation probes.

  17. Markers of bacterial translocation in end-stage liver disease

    PubMed Central

    Koutsounas, Ioannis; Kaltsa, Garyfallia; Siakavellas, Spyros I; Bamias, Giorgos

    2015-01-01

    Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT. PMID:26380651

  18. 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

  19. TRPC6 channel translocation into phagosomal membrane augments phagosomal function.

    PubMed

    Riazanski, Vladimir; Gabdoulkhakova, Aida G; Boynton, Lin S; Eguchi, Raphael R; Deriy, Ludmila V; Hogarth, D Kyle; Loaëc, Nadège; Oumata, Nassima; Galons, Hervé; Brown, Mary E; Shevchenko, Pavel; Gallan, Alexander J; Yoo, Sang Gune; Naren, Anjaparavanda P; Villereal, Mitchel L; Beacham, Daniel W; Bindokas, Vytautas P; Birnbaumer, Lutz; Meijer, Laurent; Nelson, Deborah J

    2015-11-24

    Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H(+) into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired. PMID:26604306

  20. DNA Translocation through Hydrophilic Nanopore in Hexagonal Boron Nitride

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi; Hu, Ying; Wang, Hao; Xu, Zhi; Wang, Wenlong; Bai, Xuedong; Shan, Xinyan; Lu, Xinghua

    2013-11-01

    Ultra-thin solid-state nanopore with good wetting property is strongly desired to achieve high spatial resolution for DNA sequencing applications. Atomic thick hexagonal boron nitride (h-BN) layer provides a promising two-dimensional material for fabricating solid-state nanopores. Due to its good oxidation resistance, the hydrophilicity of h-BN nanopore device can be significantly improved by UV-Ozone treatment. The contact angle of a KCl-TE droplet on h-BN layer can be reduced from 57° to 26° after the treatment. Abundant DNA translocation events have been observed in such devices, and strong DNA-nanopore interaction has been revealed in pores smaller than 10 nm in diameter. The 1/f noise level is closely related to the area of suspended h-BN layer, and it is significantly reduced in smaller supporting window. The demonstrated performance in h-BN nanopore paves the way towards base discrimination in a single DNA molecule.

  1. Bacterial Na+-translocating ferredoxin:NAD+ oxidoreductase

    PubMed Central

    Biegel, Eva; Müller, Volker

    2010-01-01

    The anaerobic acetogenic bacterium Acetobacterium woodii carries out a unique type of Na+-motive, anaerobic respiration with caffeate as electron acceptor, termed “caffeate respiration.” Central, and so far the only identified membrane-bound reaction in this respiration pathway, is a ferredoxin:NAD+ oxidoreductase (Fno) activity. Here we show that inverted membrane vesicles of A. woodii couple electron transfer from reduced ferredoxin to NAD+ with the transport of Na+ from the outside into the lumen of the vesicles. Na+ transport was electrogenic, and accumulation was inhibited by sodium ionophores but not protonophores, demonstrating a direct coupling of Fno activity to Na+ transport. Results from inhibitor studies are consistent with the hypothesis that Fno activity coupled to Na+ translocation is catalyzed by the Rnf complex, a membrane-bound, iron–sulfur and flavin-containing electron transport complex encoded by many bacterial and some archaeal genomes. Fno is a unique type of primary Na+ pump and represents an early evolutionary mechanism of energy conservation that expands the redox range known to support life. In addition, it explains the lifestyle of many anaerobic bacteria and gives a mechanistic explanation for the enigma of the energetic driving force for the endergonic reduction of ferredoxin with NADH plus H+ as reductant in a number of aerobic bacteria. PMID:20921383

  2. Successive site translocating inoculation potentiates DNA/recombinant vaccinia vaccination

    PubMed Central

    Ren, Yanqin; Wang, Na; Hu, Weiguo; Zhang, Xiaoyan; Xu, Jianqing; Wan, Yanmin

    2015-01-01

    DNA vaccines have advantages over traditional vaccine modalities; however the relatively low immunogenicity restrains its translation into clinical use. Further optimizations are needed to get the immunogenicity of DNA vaccine closer to the level required for human use. Here we show that intramuscularly inoculating into a different limb each time significantly improves the immunogenicities of both DNA and recombinant vaccinia vaccines during multiple vaccinations, compared to repeated vaccination on the same limb. We term this strategy successive site translocating inoculation (SSTI). SSTI could work in synergy with genetic adjuvant and DNA prime-recombinant vaccinia boost regimen. By comparing in vivo antigen expression, we found that SSTI avoided the specific inhibition of in vivo antigen expression, which was observed in the limbs being repeatedly inoculated. Employing in vivo T cell depletion and passive IgG transfer, we delineated that the inhibition was not mediated by CD8+ T cells but by specific antibodies. Finally, by using C3?/? mouse model and in vivo NK cells depletion, we identified that specific antibodies negatively regulated the in vivo antigen expression primarily in a complement depended way. PMID:26667202

  3. 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.

  4. Evolving understanding of translocator protein 18 kDa (TSPO).

    PubMed

    Li, Fei; Liu, Jian; Garavito, R Michael; Ferguson-Miller, Shelagh

    2015-09-01

    The translocator protein 18 kDa (TSPO) has been the focus of intense research by the biomedical community and the pharmaceutical industry because of its apparent involvement in many disease-related processes. These include steroidogenesis, apoptosis, inflammation, neurological disease and cancer, resulting in the use of TSPO as a biomarker and its potential as a drug target. Despite more than 30 years of study, the precise function of TSPO remains elusive. A recent breakthrough in determining the high-resolution crystal structures of bacterial homologs of mitochondrial TSPO provides new insight into the structural and functional properties at a molecular level and new opportunities for investigating the significance of this ancient and highly conserved protein family. The availability of atomic level structural information from different species also provides a platform for structure-based drug development. Here we briefly review current knowledge regarding TSPO and the implications of the new structures with respect to hypotheses and controversies in the field. PMID:25882248

  5. 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. Work supported by NSF-OCI-0749360 and NSF-IOS-125317.

  6. TRPC6 channel translocation into phagosomal membrane augments phagosomal function

    PubMed Central

    Riazanski, Vladimir; Gabdoulkhakova, Aida G.; Boynton, Lin S.; Eguchi, Raphael R.; Deriy, Ludmila V.; Hogarth, D. Kyle; Loaëc, Nadège; Oumata, Nassima; Galons, Hervé; Brown, Mary E.; Shevchenko, Pavel; Gallan, Alexander J.; Yoo, Sang Gune; Naren, Anjaparavanda P.; Villereal, Mitchel L.; Beacham, Daniel W.; Bindokas, Vytautas P.; Birnbaumer, Lutz; Meijer, Laurent; Nelson, Deborah J.

    2015-01-01

    Defects in the innate immune system in the lung with attendant bacterial infections contribute to lung tissue damage, respiratory insufficiency, and ultimately death in the pathogenesis of cystic fibrosis (CF). Professional phagocytes, including alveolar macrophages (AMs), have specialized pathways that ensure efficient killing of pathogens in phagosomes. Phagosomal acidification facilitates the optimal functioning of degradative enzymes, ultimately contributing to bacterial killing. Generation of low organellar pH is primarily driven by the V-ATPases, proton pumps that use cytoplasmic ATP to load H+ into the organelle. Critical to phagosomal acidification are various channels derived from the plasma membrane, including the anion channel cystic fibrosis transmembrane conductance regulator, which shunt the transmembrane potential generated by movement of protons. Here we show that the transient receptor potential canonical-6 (TRPC6) calcium-permeable channel in the AM also functions to shunt the transmembrane potential generated by proton pumping and is capable of restoring microbicidal function to compromised AMs in CF and enhancement of function in non-CF cells. TRPC6 channel activity is enhanced via translocation to the cell surface (and then ultimately to the phagosome during phagocytosis) in response to G-protein signaling activated by the small molecule (R)-roscovitine and its derivatives. These data show that enhancing vesicular insertion of the TRPC6 channel to the plasma membrane may represent a general mechanism for restoring phagosome activity in conditions, where it is lost or impaired. PMID:26604306

  7. Microscopic Mechanics of Hairpin DNA Translocation through Synthetic Nanopores

    PubMed Central

    Comer, Jeffrey; Dimitrov, Valentin; Zhao, Qian; Timp, Gregory; Aksimentiev, Aleksei

    2009-01-01

    Abstract Nanoscale pores have proved useful as a means to assay DNA and are actively being developed as the basis of genome sequencing methods. Hairpin DNA (hpDNA), having both double-helical and overhanging coil portions, can be trapped in a nanopore, giving ample time to execute a sequence measurement. In this article, we provide a detailed account of hpDNA interaction with a synthetic nanopore obtained through extensive all-atom molecular dynamics simulations. For synthetic pores with minimum diameters from 1.3 to 2.2 nm, we find that hpDNA can translocate by three modes: unzipping of the double helix and—in two distinct orientations—stretching/distortion of the double helix. Furthermore, each of these modes can be selected by an appropriate choice of the pore size and voltage applied transverse to the membrane. We demonstrate that the presence of hpDNA can dramatically alter the distribution of ions within the pore, substantially affecting the ionic current through it. In experiments and simulations, the ionic current relative to that in the absence of DNA can drop below 10% and rise beyond 200%. Simulations associate the former with the double helix occupying the constriction and the latter with accumulation of DNA that has passed through the constriction. PMID:19167307

  8. Estimating Stochastic Gravitational Wave Backgrounds with Sagnac Calibration

    E-print Network

    Hogan, C J; Hogan, Craig J.; Bender, Peter L.

    2001-01-01

    Armstrong et al. have recently presented new ways of combining signals to precisely cancel laser frequency noise in spaceborne interferometric gravitational wave detectors such as LISA. One of these combinations, the symmetrized Sagnac observable, is much less sensitive to external signals at low frequencies than other combinations, and thus can be used to determine the instrumental noise level. We note here that this calibration of the instrumental noise permits smoothed versions of the power spectral density of stochastic gravitational wave backgrounds to be determined with considerably higher accuracy than earlier estimates, at frequencies where one type of noise strongly dominates and is not substantially correlated between the six main signals generated by the antenna. We illustrate this technique by analyzing simple estimators of gravitational wave background power, and show that the instrumental sensitivity to broad-band backgrounds at some frequencies can be improved by more than an order of magnitude...

  9. Follow-up of a familial translocation t(10;16) with an unusual segregation pattern

    SciTech Connect

    Resta, R.G.; Luthardt, F.; Kapur, R.

    1996-05-17

    Bofinger et al. reported on a four-generation family with an unusual segregation pattern involving a translocation t(10;16)(q26.3;p13.1). All relatives either had a balanced or unbalanced translocation. We report on five additional relatives, none of whom have a normal karyotype. This unusual segregation pattern may be due to chance or be the result of meiotic drive. 17 refs., 1 fig., 1 tab.

  10. Evaluating the applicability of the Fokker-Planck equation in polymer translocation: A Brownian dynamics study

    NASA Astrophysics Data System (ADS)

    Polson, James M.; Dunn, Taylor R.

    2014-05-01

    Brownian dynamics (BD) simulations are used to study the translocation dynamics of a coarse-grained polymer through a cylindrical nanopore. We consider the case of short polymers, with a polymer length, N, in the range N = 21-61. The rate of translocation is controlled by a tunable friction coefficient, ?0p, for monomers inside the nanopore. In the case of unforced translocation, the mean translocation time scales with polymer length as ??1? ˜ (N - Np)?, where Np is the average number of monomers in the nanopore. The exponent approaches the value ? = 2 when the pore friction is sufficiently high, in accord with the prediction for the case of the quasi-static regime where pore friction dominates. In the case of forced translocation, the polymer chain is stretched and compressed on the cis and trans sides, respectively, for low ?0p. However, the chain approaches conformational quasi-equilibrium for sufficiently large ?0p. In this limit the observed scaling of ??1? with driving force and chain length supports the Fokker-Planck (FP) prediction that ??? ? N/fd for sufficiently strong driving force. Monte Carlo simulations are used to calculate translocation free energy functions for the system. The free energies are used with the FP equation to calculate translocation time distributions. At sufficiently high ?0p, the predicted distributions are in excellent agreement with those calculated from the BD simulations. Thus, the FP equation provides a valid description of translocation dynamics for sufficiently high pore friction for the range of polymer lengths considered here. Increasing N will require a corresponding increase in pore friction to maintain the validity of the FP approach. Outside the regime of low N and high pore friction, the polymer is out of equilibrium, and the FP approach is not valid.

  11. Role of the ? Clamp in the Protein Translocation Mechanism of Anthrax Toxin.

    PubMed

    Brown, Michael J; Thoren, Katie L; Krantz, Bryan A

    2015-10-01

    Membrane-embedded molecular machines are utilized to move water-soluble proteins across these barriers. Anthrax toxin forms one such machine through the self-assembly of its three component proteins--protective antigen (PA), lethal factor, and edema factor. Upon endocytosis into host cells, acidification of the endosome induces PA to form a membrane-inserted channel, which unfolds lethal factor and edema factor and translocates them into the host cytosol. Translocation is driven by the proton motive force, composed of the chemical potential, the proton gradient (?pH), and the membrane potential (??). A crystal structure of the lethal toxin core complex revealed an "? clamp" structure that binds to substrate helices nonspecifically. Here, we test the hypothesis that, through the recognition of unfolding helical structure, the ? clamp can accelerate the rate of translocation. We produced a synthetic PA mutant in which an ? helix was crosslinked into the ? clamp to block its function. This synthetic construct impairs translocation by raising a yet uncharacterized translocation barrier shown to be much less force dependent than the known unfolding barrier. We also report that the ? clamp more stably binds substrates that can form helices than those, such as polyproline, that cannot. Hence, the ? clamp recognizes substrates by a general shape-complementarity mechanism. Substrates that are incapable of forming compact secondary structure (due to the introduction of a polyproline track) are severely deficient for translocation. Therefore, the ? clamp and its recognition of helical structure in the translocating substrate play key roles in the molecular mechanism of protein translocation. PMID:26344833

  12. In vitro translocation of quantum dots and influence of oxidative stress.

    PubMed

    Geys, Jorina; De Vos, Rita; Nemery, Benoit; Hoet, Peter H M

    2009-11-01

    In vivo, translocation of inhaled nanoparticles to the circulation has been demonstrated. However, the interaction of nanoparticles with the lung epithelium is not understood. In this study, we investigated, in vitro, the translocation of nano-sized quantum dots (QDs; 25 pmol/ml) through a tight monolayer of primary isolated rat alveolar epithelial cells. The influence of surface charge on translocation was examined using nonfunctionalized QDs, amine-QDs, and carboxyl-QDs. The interaction between nanoparticles and the lung epithelium was monitored by repeatedly measuring the transepithelial electrical resistance (TEER) and by examining the cell layer with confocal microscopy. The effect of oxidative stress was tested by incubating the cells with tert-butyl hydroperoxide (t-BOOH; 75 microM or 1 or 10 mM); the antioxidant N-acetyl-L-cysteine was also used to assess the role of particle-mediated oxidative stress. No translocation through a tight monolayer of primary rat alveolar epithelial cells was observed for any of the different types of QDs. In general, an increase in TEER was found after incubation with QDs. A condition of low oxidative stress did not enhance translocation. In contrast, conditions of high stress (1 or 10 mM t-BOOH or due to QDs toxicity) with disruption of the cell layer, as shown in a decreased TEER, resulted in substantial translocation. In conclusion, no translocation of QDs was found through a tight monolayer of primary rat alveolar epithelial cells, regardless of the QDs surface charge. QDs did not impair the barrier function of the epithelial cells. In conditions with disruption of the cell-cell barrier, translocation was demonstrated. PMID:19734320

  13. Short-Term Space-Use Patterns of Translocated Mojave Desert Tortoise in Southern California

    PubMed Central

    Farnsworth, Matthew L.; Dickson, Brett G.; Zachmann, Luke J.; Hegeman, Ericka E.; Cangelosi, Amanda R.; Jackson, Thomas G.; Scheib, Amanda F.

    2015-01-01

    Increasingly, renewable energy comprises a larger share of global energy production. Across the western United States, public lands are being developed to support renewable energy production. Where there are conflicts with threatened or endangered species, translocation can be used in an attempt to mitigate negative effects. For the threatened Mojave desert tortoise (Gopherus agassizii), we sought to compare habitat- and space-use patterns between short-distance translocated, resident, and control groups. We tested for differences in home range size based on utilization distributions and used linear mixed-effects models to compare space-use intensity, while controlling for demographic and environmental variables. In addition, we examined mean movement distances as well as home range overlap between years and for male and female tortoises in each study group. During the first active season post-translocation, home range size was greater and space-use intensity was lower for translocated tortoises than resident and control groups. These patterns were not present in the second season. In both years, there was no difference in home range size or space-use intensity between control and resident groups. Translocation typically resulted in one active season of questing followed by a second active season characterized by space-use patterns that were indistinguishable from control tortoises. Across both years, the number of times a tortoise was found in a burrow was positively related to greater space-use intensity. Minimizing the time required for translocated tortoises to exhibit patterns similar to non-translocated individuals may have strong implications for conservation by reducing exposure to adverse environmental conditions and predation. With ongoing development, our results can be used to guide future efforts aimed at understanding how translocation strategies influence patterns of animal space use. PMID:26352691

  14. Prenatal Diagnosis of Rare Familial Unbalanced Translocation of Chromosomes 7 and 12

    PubMed Central

    Tezcan, Berrin; Bredaki, Foteini Emmanouella

    2015-01-01

    Case Details. We report rare familial unbalanced translocation of chromosomes 7 and 12, which was diagnosed prenatally at 20+3 weeks of gestation. Woman's partner had been tested in the past and was found to be a carrier of a balanced translocation; his karyotype showed a balanced reciprocal translocation of 46, XY, t(7;12)(q34;q24,32). Partner's brother had an unbalanced form of the translocation with severe learning disability. The diagnosis of the anomaly was based on two- and three-dimensional ultrasound and microarray analysis. Ultrasonography findings included fetal microcephaly and alobar holoprosencephaly, dysmorphic face (flat occiput, absent nasal bone, microphthalmia, hypotelorism, and single nostril), and hyperechogenic bowel. Genome-wide array analysis and cytogenetic results from the amniotic fluid showed unbalanced translocation in chromosomes 7 and 12 with deletion of an approximately 16.5?Mb and a duplication of 6.1?Mb, respectively, Arr 7q34q36.3(142,668,576-159,161,648)x1,12q24.32q24.33(127,708,720-133,777,560)x3, karyotype (der (7) t(7;12) (q34;q24)pat). This unbalanced translocation was due to the segregation of the father's balanced translocation. In this particular case, the recurrence of an unbalanced translocation in the subsequent pregnancies is estimated to be 20%. Understanding the individuals' phenotype in association with the gain and loss of copy number is important and can further provide us with information on that particular region of the named chromosomes. PMID:26294991

  15. 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.

  16. The Relationship of Rhythmic and Melodic Perception with Background Music Distraction in College Level Students

    E-print Network

    Dove, Michael Karl

    2009-04-27

    This study investigated relationships among the ability to audiate musical stimuli, background music condition, familiarity, gender, general academic achievement, age, and frequency of use on the level of distraction caused by background music...

  17. Breakpoints in Robertsonian translocations are localized to satellite III DNA by fluorescence in situ hybridization

    SciTech Connect

    Gravholt, C.H.; Friedrich, U.; Caprani, M.; Jorgensen, A.L. )

    1992-12-01

    The authors characterized 21 t(13;14) and 3 t(14;21) Robertsonian translocations for the presence of DNA derived from the short arms of the translocated acrocentric chromosomes and identified their centromeres. Nineteen of these 24 translocation carriers were unrelated. Using centromeric [alpha]-repeat DNA as chromosome-specific probe, they found by in situ hybridization that all 24 translocation chromosomes were dicentric. The chromatin between the two centromeres did not stain with silver, and no hybridization signal was detected with probes for rDNA or [beta]-satellite DNA that flank the distal and proximal ends of the rDNA region on the short arm of the acrocentrics. By contrast, all 24 translocation chromosomes gave a distinct hybridization signal when satellite III DNA was used as probe. This result strongly suggests that the chromosomal rearrangements leading to Robertsonian translocations occur preferentially in satellite III DNA. The authors hypothesize that guanine-rich satellite III repeats may promote chromosomal recombination by formation of tetraplex structures. The findings localize satellite III DNA to the short arm of the acrocentric chromosomes distal to centromeric [alpha]-repeat DNA and proximal to [beta]-satellite DNA. 32 refs., 4 figs., 2 tabs.

  18. Clinicopathological features of Xp11.2 translocation renal cell carcinoma

    PubMed Central

    Lim, Bumjin; You, Dalsan; Jeong, In Gab; Kwon, Taekmin; Hong, Sungwoo; Song, Cheryn; Cho, Yong Mee; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong

    2015-01-01

    Purpose Xp11.2 translocation renal cell carcinoma (RCC) is characterized by various translocations of the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults. Here, we review the clinicopathological features of Xp11.2 translocation RCC. Materials and Methods We identified 21 patients with Xp11.2 translocation RCC. We retrospectively analyzed patient characteristics, clinical manifestations, and specific pathological features to assess definitive diagnosis, surgical and systemic treatments, and clinical outcomes. Results The mean age at diagnosis was 43.4±20.0 years (range, 8-80 years; 8 males and 13 females). Eleven patients were incidentally diagnosed, nine patients presented with local symptoms, and one patient presented with systemic symptoms. The mean tumor size was 6.2±3.8 cm (range, 1.9-14 cm). At the time of diagnosis, 11, 1, and 5 patients showed stage I, II, and III, respectively. Four patients showed distant metastasis. At analysis, 15 patients were disease-free after a median follow-up period of 30.0 months. Four patients received target therapy but not effectively. Conclusions Xp11 translocation RCC tends to develop in young patients with lymph node metastasis. Targeted therapy did not effectively treat our patients. Surgery is the only effective therapy for Xp11 translocation RCC, and further studies are needed to assess systemic therapy and long-term prognosis. PMID:25763125

  19. An interaction between the SRP receptor and the translocon is critical during cotranslational protein translocation

    PubMed Central

    Jiang, Ying; Cheng, Zhiliang; Mandon, Elisabet C.; Gilmore, Reid

    2008-01-01

    The signal recognition particle (SRP)–dependent targeting pathway facilitates rapid, efficient delivery of the ribosome–nascent chain complex (RNC) to the protein translocation channel. We test whether the SRP receptor (SR) locates a vacant protein translocation channel by interacting with the yeast Sec61 and Ssh1 translocons. Surprisingly, the slow growth and cotranslational translocation defects caused by deletion of the transmembrane (TM) span of yeast SR? (SR?-?TM) are exaggerated when the SSH1 gene is disrupted. Disruption of the SBH2 gene, which encodes the ? subunit of the Ssh1p complex, likewise causes a growth defect when combined with SR?-?TM. Cotranslational translocation defects in the ssh1?SR?-?TM mutant are explained by slow and inefficient in vivo gating of translocons by RNCs. A critical function for translocation channel ? subunits in the SR–channel interaction is supported by the observation that simultaneous deletion of Sbh1p and Sbh2p causes a defect in the cotranslational targeting pathway that is similar to the translocation defect caused by deletion of either subunit of the SR. PMID:18347066

  20. Beta-like importins mediate the nuclear translocation of mitogen-activated protein kinases.

    PubMed

    Zehorai, Eldar; Seger, Rony

    2014-01-01

    The rapid nuclear translocation of signaling proteins upon stimulation is important for the regulation of de novo gene expression. We have studied the stimulated nuclear shuttling of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) and found that they translocate into the nucleus in a Ran-dependent, but NLS- or NTS-independent, manner, unrelated to their catalytic activity. We show that this translocation involves three ?-like importins, importins 3, 7, and 9 (Imp3/7/9). Knockdown of these importins inhibits the nuclear translocation of the MAPKs and, thereby, activation of their transcription factor targets. We further demonstrate that the translocation requires the stimulated formation of heterotrimers composed of Imp3/Imp7/MAPK or Imp3/Imp9/MAPK. JNK1/2 and p38?/? bind to either Imp7 or Imp9 upon stimulated posttranslational modification of the two Imps, while Imp3 joins the complex after its stimulation-induced phosphorylation. Once formed, these heterotrimers move to the nuclear envelope, where importin 3 remains, while importins 7 and 9 escort the MAPKs into the nucleus. These results suggest that ?-like importins are central mediators of stimulated nuclear translocation of signaling proteins and therefore add a central level of regulation to stimulated transcription. PMID:24216760

  1. Translocation of Non-Canonical Polypeptides into Cells Using Protective Antigen.

    PubMed

    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

  2. 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

  3. NODAL DIFFUSE LARGE B-CELL LYMPHOMAS IN CHILDREN AND ADOLESCENTS: IMMUNOHISTOCHEMICAL EXPRESSION PATTERNS AND C-MYC TRANSLOCATION IN RELATION TO CLINICAL OUTCOME

    PubMed Central

    Gualco, Gabriela; Weiss, Lawrence M.; Harrington, William J.; Bacchi, Carlos E.

    2009-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a very infrequent neoplasm in the pediatric age group; therefore there are very few studies on the immunophenotype or genetics of these cases. We studied a series of 16 patients with nodal DLBCL occurring in patients between 10 and 18 years of age. The cases were classified according to the 2008 World Health Organization classification criteria, with application of immunohistochemistry for the detection of CD10, BCL-6 and MUM1 proteins to divide the lymphomas into germinal center and non-germinal center types. In addition, TCL1, BCL-2 expression, and the Ki-67 proliferation index were evaluated by immunohistochemistry, and c-MYC and BCL-2 translocations were evaluated by FISH. All these parameters were correlated with clinical features and outcome. Our study revealed that centroblastic morphology and the germinal center type of DLBCL are more prevalent in these young patients (63%), with 37% containing a c-MYC translocation. Only one case showed a BCL-2 translocation, reflecting a double-hit case with features intermediate between DLBCL and Burkitt lymphoma. We found a higher frequency of BCL-2 expression than previously reported, with no direct influence on the outcome of the disease in univariate or multivariate analysis. The expression of TCL1 has not been specifically studied in nodal pediatric DLBCL before; we found a 31% incidence of TCL1 expression. MUM1 expression was observed in 44% of the cases and these positive cases showed a significant negative impact on clinical outcome. TCL1 is directly and significantly associated with the presence of c-MYC and a high proliferative index. The germinal center and non-germinal center subtypes showed significant differences for both overall survival and disease-free interval. C-MYC translocation was found in 37% of patients, and had a favorable impact on clinical outcome. We conclude that nodal pediatric and adolescent DLBCL are mainly of the germinal center type, with a generally good outcome in spite of the frequent expression of BCL-2 and the presence of c-MYC translocation. TCL1 expression seems to be associated with a good clinical outcome, while MUM1 expression predicts a poor clinical outcome. PMID:19816150

  4. Modeling of the Human Alveolar Rhabdomyosarcoma Pax3-Foxo1 Chromosome Translocation in Mouse Myoblasts Using CRISPR-Cas9 Nuclease

    PubMed Central

    Lagutina, Irina V.; Valentine, Virginia; Picchione, Fabrizio; Harwood, Frank; Valentine, Marcus B.; Villarejo-Balcells, Barbara; Carvajal, Jaime J.; Grosveld, Gerard C.

    2015-01-01

    Many recurrent chromosome translocations in cancer result in the generation of fusion genes that are directly implicated in the tumorigenic process. Precise modeling of the effects of cancer fusion genes in mice has been inaccurate, as constructs of fusion genes often completely or partially lack the correct regulatory sequences. The reciprocal t(2;13)(q36.1;q14.1) in human alveolar rhabdomyosarcoma (A-RMS) creates a pathognomonic PAX3-FOXO1 fusion gene. In vivo mimicking of this translocation in mice is complicated by the fact that Pax3 and Foxo1 are in opposite orientation on their respective chromosomes, precluding formation of a functional Pax3-Foxo1 fusion via a simple translocation. To circumvent this problem, we irreversibly inverted the orientation of a 4.9 Mb syntenic fragment on chromosome 3, encompassing Foxo1, by using Cre-mediated recombination of two pairs of unrelated oppositely oriented LoxP sites situated at the borders of the syntenic region. We tested if spatial proximity of the Pax3 and Foxo1 loci in myoblasts of mice homozygous for the inversion facilitated Pax3-Foxo1 fusion gene formation upon induction of targeted CRISPR-Cas9 nuclease-induced DNA double strand breaks in Pax3 and Foxo1. Fluorescent in situ hybridization indicated that fore limb myoblasts show a higher frequency of Pax3/Foxo1 co-localization than hind limb myoblasts. Indeed, more fusion genes were generated in fore limb myoblasts via a reciprocal t(1;3), which expressed correctly spliced Pax3-Foxo1 mRNA encoding Pax3-Foxo1 fusion protein. We conclude that locus proximity facilitates chromosome translocation upon induction of DNA double strand breaks. Given that the Pax3-Foxo1 fusion gene will contain all the regulatory sequences necessary for precise regulation of its expression, we propose that CRISPR-Cas9 provides a novel means to faithfully model human diseases caused by chromosome translocation in mice. PMID:25659124

  5. 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

  6. Signal detection: historical background.

    PubMed

    Egberts, Toine C G

    2007-01-01

    A primary aim in pharmacovigilance is the timely detection of either new adverse drug reactions (ADRs) or a relevant change of the frequency of ADRs that are already known to be associated with the drugs involved, i.e. signal detection. Adequate signal detection solely based on the human intellect (case-by-case analysis or qualitative signal detection) has proven its value. However, it is becoming increasingly time consuming given the growing volume of data, as well as less effective, especially in more complex associations, such as drug-drug interactions, syndromes and when various covariates are involved. In quantitative signal detection, measures that express the extent in which combinations of drug(s) and clinical event(s) are disproportionately present in the database of reported suspected ADRs are used to reveal associations of interest. Although the rationale and the methodology of the various quantitative approaches differ, they all share the characteristic in that they express to what extent the number of observed cases differs from the number of expected cases. Recent years have shown that the use of quantitative measures in addition to qualitative analysis is a step forward in signal detection in pharmacovigilance. This paper uses historical, classic examples and studies to illustrate the principles, pros and cons of especially quantitative methods in signal detection and adds a flavour of future perspective. PMID:17604412

  7. Biological aerosol background characterization

    NASA Astrophysics Data System (ADS)

    Blatny, Janet; Fountain, Augustus W., III

    2011-05-01

    To provide useful information during military operations, or as part of other security situations, a biological aerosol detector has to respond within seconds or minutes to an attack by virulent biological agents, and with low false alarms. Within this time frame, measuring virulence of a known microorganism is extremely difficult, especially if the microorganism is of unknown antigenic or nucleic acid properties. Measuring "live" characteristics of an organism directly is not generally an option, yet only viable organisms are potentially infectious. Fluorescence based instruments have been designed to optically determine if aerosol particles have viability characteristics. Still, such commercially available biological aerosol detection equipment needs to be improved for their use in military and civil applications. Air has an endogenous population of microorganisms that may interfere with alarm software technologies. To design robust algorithms, a comprehensive knowledge of the airborne biological background content is essential. For this reason, there is a need to study ambient live bacterial populations in as many locations as possible. Doing so will permit collection of data to define diverse biological characteristics that in turn can be used to fine tune alarm algorithms. To avoid false alarms, improving software technologies for biological detectors is a crucial feature requiring considerations of various parameters that can be applied to suppress alarm triggers. This NATO Task Group will aim for developing reference methods for monitoring biological aerosol characteristics to improve alarm algorithms for biological detection. Additionally, they will focus on developing reference standard methodology for monitoring biological aerosol characteristics to reduce false alarm rates.

  8. Comparative mapping in the Poaceae family reveals translocations in the complex polyploid genome of sugarcane

    PubMed Central

    2014-01-01

    Background The understanding of sugarcane genetics has lagged behind that of other members of the Poaceae family such as wheat, rice, barley and sorghum mainly due to the complexity, size and polyploidization of the genome. We have used the genetic map of a sugarcane cultivar to generate a consensus genetic map to increase genome coverage for comparison to the sorghum genome. We have utilized the recently developed sugarcane DArT array to increase the marker density within the genetic map. The sequence of these DArT markers plus SNP and EST-SSR markers was then used to form a bridge to the sorghum genomic sequence by BLAST alignment to start to unravel the complex genomic architecture of sugarcane. Results Comparative mapping revealed that certain sugarcane chromosomes show greater levels of synteny to sorghum than others. On a macrosyntenic level a good collinearity was observed between sugarcane and sorghum for 4 of the 8 homology groups (HGs). These 4 HGs were syntenic to four sorghum chromosomes with from 98% to 100% of these chromosomes covered by these linked markers. Four major chromosome rearrangements were identified between the other four sugarcane HGs and sorghum, two of which were condensations of chromosomes reducing the basic chromosome number of sugarcane from x?=?10 to x?=?8. This macro level of synteny was transferred to other members within the Poaceae family such as maize to uncover the important evolutionary relationships that exist between sugarcane and these species. Conclusions Comparative mapping of sugarcane to the sorghum genome has revealed new information on the genome structure of sugarcane which will help guide identification of important genes for use in sugarcane breeding. Furthermore of the four major chromosome rearrangements identified in this study, three were common to maize providing some evidence that chromosome reduction from a common paleo-ancestor of both maize and sugarcane was driven by the same translocation events seen in both species. PMID:25059596

  9. 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

  10. Translocator protein mediates the anxiolytic and antidepressant effects of midazolam.

    PubMed

    Qiu, Zhi-Kun; Li, Ming-Sheng; He, Jia-Li; Liu, Xu; Zhang, Guan-Hua; Lai, Sha; Ma, Jian-Chun; Zeng, Jia; Li, Yan; Wu, Hong-Wei; Chen, Yong; Shen, Yong-Gang; Chen, Ji-Sheng

    2015-12-01

    The translocator protein (18kDa) (TSPO) plays an important role in stress-related disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD), caused by neurosteroids (e.g. allopregnanolone). The present study sought to evaluate the significance of TSPO in anxiolytic and antidepressant effects induced by midazolam. The animals were administrated midazolam (0.25, 0.5 and 1mg/kg, i.p.) and subjected to behavioral tests, including Vogel-type conflict test, elevated plus-maze test, forced swimming test. Midazolam produced anxiolytic- and antidepressant-like effects Vogel-type conflict test (1mg/kg, i.p.), elevated plus-maze test (0.5 and 1mg/kg, i.p.), and forced swimming test (0.5 and 1mg/kg, i.p.). These effects of Midazolam were totally blocked by the TSPO antagonist PK11195 (3mg/kg, i.p.). To evaluate the role of allopregnanolone in the anxiolytic- and antidepressant-like effects of midazolam, the animals were decapitated at the end of the behavioral tests. The allopregnanolone levels of the prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The allopregnanolone level of the prefrontal cortex and hippocampus was increased by midazolam (0.5, 1mg/kg, i.p.) and the increase was reversed by PK11195 (3mg/kg, i.p.). Overall, the results indicated that the anxiolytic- and antidepressant-like effects of midazolam were mediated by TSPO, via stimulation of allopregnanolone biosynthesis. PMID:26455280

  11. Two decades of demography reveals that seed and seedling transitions limit population persistence in a translocated shrub

    PubMed Central

    Gross, C. L.; Mackay, D.

    2014-01-01

    Background and Aims Olearia flocktoniae is an endangered shrub that was passively translocated from its natural ecosystem, where it has since gone extinct. This study aimed to determine sensitivities vital to populations persisting in human-created areas. Methods Population colonization, longevity and extinction were investigated over 20 years using 133 populations. Seed-bank longevity was determined from germination trials of seeds exhumed from extinct and extant sites via a 10-year glasshouse trial and by in situ sowing experiments. From 27 populations, 98 cohorts were followed and matrix models of transitions from seeds to adults were used to evaluate the intrinsic rate of population growth against disturbance histories. Ten populations (38 cohorts) with different disturbance histories were used to evaluate sensitivities in vital rates. Key Results Most populations had few individuals (?30) and were transient (<5 years above ground). The intrinsic population growth rate was rarely >1 and all but two populations were extinct at year 20. Seeds were short-lived in situ. Although >1000 seeds per plant were produced annually in most populations, sensitivity analysis showed that the transition to the seed bank and the transition from the seed bank to seedlings are key vulnerabilities in the life-cycle. Conclusions Seedling establishment is promoted by recent disturbance. Increasing the number of disturbance events in populations, even severe disturbances that almost extirpate populations, significantly increases longer-term population persistence. Only populations that were disturbed annually survived the full 20 years of the study. The results show that translocated populations of O. flocktoniae will fail to persist without active management. PMID:24844983

  12. 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

  13. 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 of a time when the entire universe was a black body with a temperature T 3000 K. Very uniform microwave

  14. Signal Peptide-Binding Drug as a Selective Inhibitor of Co-Translational Protein Translocation

    PubMed Central

    Vermeire, Kurt; Bell, Thomas W.; Van Puyenbroeck, Victor; Giraut, Anne; Noppen, Sam; Liekens, Sandra; Schols, Dominique; Hartmann, Enno

    2014-01-01

    In eukaryotic cells, surface expression of most type I transmembrane proteins requires translation and simultaneous insertion of the precursor protein into the endoplasmic reticulum (ER) membrane for subsequent routing to the cell surface. This co-translational translocation pathway is initiated when a hydrophobic N-terminal signal peptide (SP) on the nascent protein emerges from the ribosome, binds the cytosolic signal recognition particle (SRP), and targets the ribosome-nascent chain complex to the Sec61 translocon, a universally conserved protein-conducting channel in the ER-membrane. Despite their common function in Sec61 targeting and ER translocation, SPs have diverse but unique primary sequences. Thus, drugs that recognise SPs could be exploited to inhibit translocation of specific proteins into the ER. Here, through flow cytometric analysis the small-molecule macrocycle cyclotriazadisulfonamide (CADA) is identified as a highly selective human CD4 (hCD4) down-modulator. We show that CADA inhibits CD4 biogenesis and that this is due to its ability to inhibit co-translational translocation of CD4 into the lumen of the ER, both in cells as in a cell-free in vitro translation/translocation system. The activity of CADA maps to the cleavable N-terminal SP of hCD4. Moreover, through surface plasmon resonance analysis we were able to show direct binding of CADA to the SP of hCD4 and identify this SP as the target of our drug. Furthermore, CADA locks the SP in the translocon during a post-targeting step, possibly in a folded state, and prevents the translocation of the associated protein into the ER lumen. Instead, the precursor protein is routed to the cytosol for degradation. These findings demonstrate that a synthetic, cell-permeable small-molecule can be developed as a SP-binding drug to selectively inhibit protein translocation and to reversibly regulate the expression of specific target proteins. PMID:25460167

  15. Evaluating the thermal effects of translocation in a large-bodied pitviper.

    PubMed

    Holding, Matthew L; Owen, Dustin A S; Taylor, Emily N

    2014-10-01

    Acute stressors can be costly, often requiring alteration of normal physiological processes to mitigate their effects. Animal translocation may be a very stressful event and result in a reduced ability to maintain homeostasis. The impacts of translocation on the thermal ecology of ectothermic vertebrates, which may rely on preferred habitats for thermoregulation, are currently unknown. In this study, 22 adult male Northern Pacific rattlesnakes (Crotalus oreganus oreganus) were implanted with automated temperature loggers and radio-tracked. Snakes were assigned to one of three treatments: translocation, handling control, and undisturbed control. Short-distance translocation (SDT) and handling treatments were applied weekly for 6 weeks. Hourly body temperature (Tb ) was recorded during the course of the study. Mean Tb was impacted in a time-dependent fashion, where translocated snakes had lower mean Tb than handled controls during the first week of the study only, especially the first 24 hr after translocation. Separating the dataset into day and night revealed that this effect was localized to Tb variation during the day only. Variance in temperature was not impacted by translocation or handling. Snake body mass and time of year were the major factors influencing the thermal profiles of these rattlesnakes. Thermal ecology in male rattlesnakes is resilient to SDT, suggesting that they quickly resume normal behaviors following repeated bouts of acute capture stress and disturbance of their spatial ecology. This study provides support for SDT as a safe measure for mitigating human-snake interactions and facilitating conservation practices regarding male snakes, which are the most frequently encountered sex. PMID:24962181

  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. Intracellular translocation of calmodulin and Ca{sup 2+}/calmodulin-dependent protein kinase II during the development of hypertrophy in neonatal cardiomyocytes

    SciTech Connect

    Gangopadhyay, Jaya Pal; Ikemoto, Noriaki; Department of Neurology, Harvard Medical School, Boston, MA 02115

    2010-05-28

    We have recently shown that stimulation of cultured neonatal cardiomyocytes with endothelin-1 (ET-1) first produces conformational disorder within the ryanodine receptor (RyR2) and diastolic Ca{sup 2+} leak from the sarcoplasmic reticulum (SR), then develops hypertrophy (HT) in the cardiomyocytes (Hamada et al., 2009 ). The present paper addresses the following question. By what mechanism does crosstalk between defective operation of RyR2 and activation of the HT gene program occur? Here we show that the immuno-stain of calmodulin (CaM) is localized chiefly in the cytoplasmic area in the control cells; whereas, in the ET-1-treated/hypertrophied cells, major immuno-staining is localized in the nuclear region. In addition, fluorescently labeled CaM that has been introduced into the cardiomyocytes using the BioPORTER system moves from the cytoplasm to the nucleus with the development of HT. The immuno-confocal imaging of Ca{sup 2+}/CaM-dependent protein kinase II (CaMKII) also shows cytoplasm-to-nucleus shift of the immuno-staining pattern in the hypertrophied cells. In an early phase of hypertrophic growth, the frequency of spontaneous Ca{sup 2+} transients increases, which accompanies with cytoplasm-to-nucleus translocation of CaM. In a later phase of hypertrophic growth, further increase in the frequency of spontaneous Ca{sup 2+} transients results in the appearance of trains of Ca{sup 2+} spikes, which accompanies with nuclear translocation of CaMKII. The cardio-protective reagent dantrolene (the reagent that corrects the de-stabilized inter-domain interaction within the RyR2 to a normal mode) ameliorates aberrant intracellular Ca{sup 2+} events and prevents nuclear translocation of both CaM and CaMKII, then prevents the development of HT. These results suggest that translocation of CaM and CaMKII from the cytoplasm to the nucleus serves as messengers to transmit the pathogenic signal elicited in the surface membrane and in the RyR2 to the nuclear transcriptional sites to activate HT program.

  18. Integrable Background Geometries

    NASA Astrophysics Data System (ADS)

    Calderbank, David M. J.

    2014-03-01

    This work has its origins in an attempt to describe systematically the integrable geometries and gauge theories in dimensions one to four related to twistor theory. In each such dimension, there is a nondegenerate integrable geometric structure, governed by a nonlinear integrable differential equation, and each solution of this equation determines a background geometry on which, for any Lie group G, an integrable gauge theory is defined. In four dimensions, the geometry is selfdual conformal geometry and the gauge theory is selfdual Yang-Mills theory, while the lower-dimensional structures are nondegenerate (i.e., non-null) reductions of this. Any solution of the gauge theory on a k-dimensional geometry, such that the gauge group H acts transitively on an ?-manifold, determines a (k+?)-dimensional geometry (k+??4) fibering over the k-dimensional geometry with H as a structure group. In the case of an ?-dimensional group H acting on itself by the regular representation, all (k+?)-dimensional geometries with symmetry group H are locally obtained in this way. This framework unifies and extends known results about dimensional reductions of selfdual conformal geometry and the selfdual Yang-Mills equation, and provides a rich supply of constructive methods. In one dimension, generalized Nahm equations provide a uniform description of four pole isomonodromic deformation problems, and may be related to the {SU}(?) Toda and dKP equations via a hodograph transformation. In two dimensions, the {Diff}(S^1) Hitchin equation is shown to be equivalent to the hyperCR Einstein-Weyl equation, while the {SDiff}(?^2) Hitchin equation leads to a Euclidean analogue of Plebanski's heavenly equations. In three and four dimensions, the constructions of this paper help to organize the huge range of examples of Einstein-Weyl and selfdual spaces in the literature, as well as providing some new ! ones. The nondegenerate reductions have a long ancestry. More ! recently , degenerate or null reductions have attracted increased interest. Two of these reductions and their gauge theories (arguably, the two most significant) are also described.

  19. 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.

  20. Loss of the TEL/ETV6 gene by a second translocation in ALL patients with t(12;21).

    PubMed

    Coniat, M B; Poirel, H; Leblanc, T; Bernard, O A; Berger, R

    1999-10-01

    Inactivation of the non translocated TEL/ETV6 gene is commonly associated with translocation (12;21) of acute lymphoblastic leukemia (ALL). Translocations involving the short arm of chromosome 12 were analysed in two children with t(12;21) ALL. Fluorescence in situ hybridation studies showed that these associated translocations resulted in loss of TEL/ETV6. While hybridization with a YAC probe covering TEL/ETV6 was positive in one patient, analysis with cosmid probes covering the gene demonstrated that the gene was in fact deleted. It is concluded that deletions involving TEL/ETV6 can remain undetected by FISH using only YAC probes. PMID:10573134

  1. Spectrum of the microwave background radiation

    SciTech Connect

    Richards, P.L.

    1982-04-01

    A review is given of the present status of measurements of the spectrum of the microwave background. Factors which limit experimental accuracy are discussed with particular reference to high frequency measurements. A selection of the available measurements yields a data set which is reasonably consistent with the blackbody spectrum for a temperature of 2.9 K. A simple statistical analysis suggests either that there are errors in the data set, or that deviations from a blackbody spectrum exist. The difficulties inherent in property averaging the results from different observers are described. Prospects for improved measurements will be summarized.

  2. 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/.

  3. 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.

  4. Spontaneous membrane-translocating peptides: influence of peptide self-aggregation and cargo polarity

    PubMed Central

    Macchi, Sara; Signore, Giovanni; Boccardi, Claudia; Di Rienzo, Carmine; Beltram, Fabio; Cardarelli, Francesco

    2015-01-01

    Peptides that translocate spontaneously across cell membranes could transform the field of drug delivery by enabling the transport of otherwise membrane-impermeant molecules into cells. In this regard, a 9-aminoacid-long motif (representative sequence: PLIYLRLLR, hereafter Translocating Motif 9, TM9) that spontaneously translocates across membranes while carrying a polar dye was recently identified by high-throughput screening. Here we investigate its transport properties by a combination of in cuvette physico-chemical assays, rational mutagenesis, live-cell confocal imaging and fluorescence correlation spectroscopy measurements. We unveil TM9 ability to self-aggregate in a concentration-dependent manner and demonstrate that peptide self-aggregation is a necessary –yet not sufficient– step for effective membrane translocation. Furthermore we show that membrane crossing can occur with apolar payloads while it is completely inhibited by polar ones. These findings are discussed and compared to previous reports. The present results impose a careful rethinking of this class of sequences as direct-translocation vectors suitable for delivery purposes. PMID:26567719

  5. 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

  6. Translocation of dynorphin neuropeptides across the plasma membrane. A putative mechanism of signal transmission.

    PubMed

    Marinova, Zoya; Vukojevic, Vladana; Surcheva, Slavina; Yakovleva, Tatiana; Cebers, Gvido; Pasikova, Natalia; Usynin, Ivan; Hugonin, Loïc; Fang, Weijie; Hallberg, Mathias; Hirschberg, Daniel; Bergman, Tomas; Langel, Ulo; Hauser, Kurt F; Pramanik, Aladdin; Aldrich, Jane V; Gräslund, Astrid; Terenius, Lars; Bakalkin, Georgy

    2005-07-15

    Several peptides, including penetratin and Tat, are known to translocate across the plasma membrane. Dynorphin opioid peptides are similar to cell-penetrating peptides in a high content of basic and hydrophobic amino acid residues. We demonstrate that dynorphin A and big dynorphin, consisting of dynorphins A and B, can penetrate into neurons and non-neuronal cells using confocal fluorescence microscopy/immunolabeling. The peptide distribution was characterized by cytoplasmic labeling with minimal signal in the cell nucleus and on the plasma membrane. Translocated peptides were associated with the endoplasmic reticulum but not with the Golgi apparatus or clathrin-coated endocytotic vesicles. Rapid entry of dynorphin A into the cytoplasm of live cells was revealed by fluorescence correlation spectroscopy. The translocation potential of dynorphin A was comparable with that of transportan-10, a prototypical cell-penetrating peptide. A central big dynorphin fragment, which retains all basic amino acids, and dynorphin B did not enter the cells. The latter two peptides interacted with negatively charged phospholipid vesicles similarly to big dynorphin and dynorphin A, suggesting that interactions of these peptides with phospholipids in the plasma membrane are not impaired. Translocation was not mediated via opioid receptors. The potential of dynorphins to penetrate into cells correlates with their ability to induce non-opioid effects in animals. Translocation across the plasma membrane may represent a previously unknown mechanism by which dynorphins can signal information to the cell interior. PMID:15894804

  7. Membrane-active peptides: binding, translocation, and flux in lipid vesicles

    PubMed Central

    Almeida, Paulo F.

    2014-01-01

    Recently, new and improved methods have been developed to measure translocation of membrane-active peptides (antimicrobial, cytolytic, and amphipathic cell-penetrating peptides) across lipid bilayer membranes. The hypothesis that translocation of membrane-active peptides across a lipid bilayer is determined by the Gibbs energy of insertion of the peptide into the bilayer is re-examined in the light of new experimental tests. The original hypothesis and its motivation are first revisited, examining some specific predictions it generated and the results of initial tests. Translocation is understood as requiring two previous steps: binding and insertion in the membrane. The problem of peptide binding to membranes, its prediction, measurement, and calculation are addressed. Particular attention is given to understanding the reason for the need for amphipathic structures in the function of membrane-active peptides. Insertion into the membrane is then examined. Hydrophobicity scales are compared, and their influence on calculations is discussed. The relation between translocation and graded or all-or-none peptide-induced flux from or into lipid vesicles is also considered. Finally, the most recent work on translocation is examined, both experimental and from molecular dynamics simulations. PMID:24769436

  8. Foliar transfer into the biosphere: review of translocation factors to cereal grains.

    PubMed

    Colle, C; Madoz-Escande, C; Leclerc, E

    2009-09-01

    A review of the published literature about foliar transfer radionuclides to cereal grains was carried out with a special interest for translocation factors. Translocation describes the distribution of radionuclides within the plant after foliar deposition and radionuclide absorption onto the surface of leaves. It mainly depends on elements and the plant growth stage. The collected data were derived from both in-field and greenhouse experiments. They were analysed in order to select those coming from a contamination simulating a sprinkling irrigation or a rain. The data set contains 307 values. For each radionuclide the translocation factor values were sorted according to 5 characteristic stages of the cereal vegetative cycle: leaf development-tillering, stem elongation, earing-flowering, grain growth and ripening. Wheat, barley and rye have been treated together, independently of rice. For mobile elements such as cesium, the translocation factor is maximum when the contamination occurred at the earing-flowering stage. For less mobile elements such as strontium this maximum occurred for a foliar contamination at the grain growth stage. This review enabled us to propose the most probable value as well as the range of variation of translocation factors for some radionuclides according to the cereal vegetative cycle. Moreover, from these results, a radionuclide classification is proposed according to three mobility groups. PMID:19019504

  9. Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis

    PubMed Central

    Halter, David; Neumann, Sylvia; van Dijk, Suzanne M.; Wolthoorn, Jasja; de Mazière, Ann M.; Vieira, Otilia V.; Mattjus, Peter; Klumperman, Judith; van Meer, Gerrit; Sprong, Hein

    2007-01-01

    Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate across to the Golgi lumen for LacCer synthesis. However, only very little natural GlcCer translocates across the Golgi in vitro. As GlcCer reaches the cell surface when Golgi vesicular trafficking is inhibited, it must translocate across a post-Golgi membrane. Concanamycin, a vacuolar proton pump inhibitor, blocks translocation independently of multidrug transporters that are known to translocate short-chain GlcCer. Concanamycin did not reduce LacCer and GM3 synthesis. Thus, GlcCer destined for glycolipid synthesis follows a different pathway and transports back into the endoplasmic reticulum (ER) via the late Golgi protein FAPP2. FAPP2 knockdown strongly reduces GM3 synthesis. Overall, we show that newly synthesized GlcCer enters two pathways: one toward the noncytosolic surface of a post-Golgi membrane and one via the ER toward the Golgi lumen LacCer synthase. PMID:17923531

  10. Decatransin, a new natural product inhibiting protein translocation at the Sec61/SecYEG translocon

    PubMed Central

    Junne, Tina; Wong, Joanne; Studer, Christian; Aust, Thomas; Bauer, Benedikt W.; Beibel, Martin; Bhullar, Bhupinder; Bruccoleri, Robert; Eichenberger, Jürg; Estoppey, David; Hartmann, Nicole; Knapp, Britta; Krastel, Philipp; Melin, Nicolas; Oakeley, Edward J.; Oberer, Lukas; Riedl, Ralph; Roma, Guglielmo; Schuierer, Sven; Petersen, Frank; Tallarico, John A.; Rapoport, Tom A.; Spiess, Martin; Hoepfner, Dominic

    2015-01-01

    ABSTRACT A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon complex, the machinery for protein translocation and membrane insertion at the endoplasmic reticulum, is the target. The profiles were similar to those of cyclic heptadepsipeptides of a distinct chemotype (including HUN-7293 and cotransin) that had previously been shown to inhibit cotranslational translocation at the mammalian Sec61 translocon. Unbiased, genome-wide mutagenesis followed by full-genome sequencing in both fungal and mammalian cells identified dominant mutations in Sec61p (yeast) or Sec61?1 (mammals) that conferred resistance. Most, but not all, of these mutations affected inhibition by both chemotypes, despite an absence of structural similarity. Biochemical analysis confirmed inhibition of protein translocation into the endoplasmic reticulum of both co- and post-translationally translocated substrates by both chemotypes, demonstrating a mechanism independent of a translating ribosome. Most interestingly, both chemotypes were found to also inhibit SecYEG, the bacterial Sec61 translocon homolog. We suggest ‘decatransin’ as the name for this new decadepsipeptide translocation inhibitor. PMID:25616894

  11. Arsenic uptake, translocation and speciation in pho1 and pho2 mutants of Arabidopsis thaliana.

    PubMed

    Quaghebeur, Mieke; Rengel, Zed

    2004-02-01

    Arsenate [As (V)] is taken up by phosphate [P (V)] transporters in the plasma membrane of roots cells, but the translocation of As from roots to shoots is not well understood. Two mutants of Arabidopsis thaliana (L.) [(pho1, P deficient) and (pho2, P accumulator)], with defects in the regulation and translocation of P (V) from roots to shoots, were therefore used in this study to investigate uptake, translocation and speciation of As in roots and shoots of plants grown in soil or nutrient solution. The shoots of the pho2 mutant contained higher P concentrations, but similar or slightly higher As concentrations, in comparison with the wild type. In the pho1 mutant, the P concentration in the shoots was lower, and the As concentration was higher, in comparison with the wild type. Both pho2 and the wild type contained mainly As (III) in roots and shoot (67-90% of total As). Arsenic was likely to be translocated by a different pathway to P (V) in the pho2 and pho1 mutants. Therefore, it is suggested that As (III) is the main As species translocated from roots to shoots in Arabidopsis thaliana. PMID:15032863

  12. Presence of a fragile site and interstitial telomere repeat sequences in a(Y;13) translocation

    SciTech Connect

    Lemieux, N.; Fetni, R.; Boutouil, M.

    1994-09-01

    It has been proposed that the telomere repeat sequences (TTAGGG)n, when present at interstitial chromosomal locations, might promote site-specific fragility and recombinational activity. Nevertheless, in mammalians, only a few indications of such involvement of telomeric sequences have been observed. In this study, we show direct cytological evidence that a de novo interstitial telomere can cause the formation of a novel fragile site. Molecular cytogenetic studies of a de novo (Y;13) translocation, using centromeric and telomeric probes, have revealed the presence of two centromeres and interstitial telomere sequences. A fragile site was also found near the interstitial telomere loci. In this case, high-resolution cytogenetics was complemented by two-color FISH to give accurate information. Furthermore, an analysis with short arm Y chromosome DNA probes was carried out to detect possible deletion in this region, including the ZFY gene which is involved in human spermatogenesis. The Y chromosome appeared to be intact upon cytogenetic and in situ hybridization studies even for the telomeric region. Also, we observed two cells showing a normal karyotype without the Y;13 translocation suggesting the instability of this translocation. This finding shows the importance of telomere repeat sequences in translocations and other chromosome rearrangements. We are currently analyzing additional cases with similar analogies to obtain further insight on the role of telomeres and the dynamics of translocations.

  13. Optoelectronic control of surface charge and translocation dynamics in solid-state nanopores.

    PubMed

    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. PMID:24185943

  14. Spontaneous membrane-translocating peptides: influence of peptide self-aggregation and cargo polarity.

    PubMed

    Macchi, Sara; Signore, Giovanni; Boccardi, Claudia; Di Rienzo, Carmine; Beltram, Fabio; Cardarelli, Francesco

    2015-01-01

    Peptides that translocate spontaneously across cell membranes could transform the field of drug delivery by enabling the transport of otherwise membrane-impermeant molecules into cells. In this regard, a 9-aminoacid-long motif (representative sequence: PLIYLRLLR, hereafter Translocating Motif 9, TM9) that spontaneously translocates across membranes while carrying a polar dye was recently identified by high-throughput screening. Here we investigate its transport properties by a combination of in cuvette physico-chemical assays, rational mutagenesis, live-cell confocal imaging and fluorescence correlation spectroscopy measurements. We unveil TM9 ability to self-aggregate in a concentration-dependent manner and demonstrate that peptide self-aggregation is a necessary -yet not sufficient- step for effective membrane translocation. Furthermore we show that membrane crossing can occur with apolar payloads while it is completely inhibited by polar ones. These findings are discussed and compared to previous reports. The present results impose a careful rethinking of this class of sequences as direct-translocation vectors suitable for delivery purposes. PMID:26567719

  15. Detection of a complex translocation using fluorescent in situ hybridization (FISH)

    SciTech Connect

    Rosen, B.A.; Abuelo, D.N.; Mark, H.F.

    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.

  16. Pitch perception: dissociating frequency from fundamental-frequency discrimination.

    PubMed

    Oxenham, Andrew J; Micheyl, Christophe

    2013-01-01

    High-frequency pure tones (>6 kHz), which alone do not produce salient melodic pitch information, provide melodic pitch information when they form part of a harmonic complex tone with a lower fundamental frequency (F0). We explored this phenomenon in normal-hearing listeners by measuring F0 difference limens (F0DLs) for harmonic complex tones and pure-tone frequency difference limens (FDLs) for each of the tones within the harmonic complexes. Two spectral regions were tested. The low- and high-frequency band-pass regions comprised harmonics 6-11 of a 280- or 1,400-Hz F0, respectively; thus, for the high-frequency region, audible frequencies present were all above 7 kHz. Frequency discrimination of inharmonic log-spaced tone complexes was also tested in control conditions. All tones were presented in a background of noise to limit the detection of distortion products. As found in previous studies, F0DLs in the low region were typically no better than the FDL for each of the constituent pure tones. In contrast, F0DLs for the high-region complex were considerably better than the FDLs found for most of the constituent (high-frequency) pure tones. The data were compared with models of optimal spectral integration of information, to assess the relative influence of peripheral and more central noise in limiting performance. The results demonstrate a dissociation in the way pitch information is integrated at low and high frequencies and provide new challenges and constraints in the search for the underlying neural mechanisms of pitch. PMID:23716218

  17. Identification of genome-specific transcripts in wheat–rye translocation lines

    PubMed Central

    Lee, Tong Geon; Seo, Yong Weon

    2015-01-01

    Studying gene expression in wheat–rye translocation lines is complicated due to the presence of homeologs in hexaploid wheat and high levels of synteny between wheat and rye genomes (Naranjo and Fernandez-Rueda, 1991 [1]; Devos et al., 1995 [2]; Lee et al., 2010 [3]; Lee et al., 2013 [4]). To overcome limitations of current gene expression studies on wheat–rye translocation lines and identify genome-specific transcripts, we developed a custom Roche NimbleGen Gene Expression microarray that contains probes derived from the sequence of hexaploid wheat, diploid rye and diploid progenitors of hexaploid wheat genome (Lee et al., 2014). Using the array developed, we identified genome-specific transcripts in a wheat–rye translocation line (Lee et al., 2014). Expression data are deposited in the NCBI Gene Expression Omnibus (GEO) under accession number GSE58678. Here we report the details of the methods used in the array workflow and data analysis. PMID:26484243

  18. Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects.

    PubMed

    Rupprecht, Rainer; Rammes, Gerhard; Eser, Daniela; Baghai, Thomas C; Schüle, Cornelius; Nothdurfter, Caroline; Troxler, Thomas; Gentsch, Conrad; Kalkman, Hans O; Chaperon, Frederique; Uzunov, Veska; McAllister, Kevin H; Bertaina-Anglade, Valerie; La Rochelle, Christophe Drieu; Tuerck, Dietrich; Floesser, Annette; Kiese, Beate; Schumacher, Michael; Landgraf, Rainer; Holsboer, Florian; Kucher, Klaus

    2009-07-24

    Most antianxiety drugs (anxiolytics) work by modulating neurotransmitters in the brain. Benzodiazepines are fast and effective anxiolytic drugs; however, their long-term use is limited by the development of tolerance and withdrawal symptoms. Ligands of the translocator protein [18 kilodaltons (kD)] may promote the synthesis of endogenous neurosteroids, which also exert anxiolytic effects in animal models. Here, we found that the translocator protein (18 kD) ligand XBD173 enhanced gamma-aminobutyric acid-mediated neurotransmission and counteracted induced panic attacks in rodents in the absence of sedation and tolerance development. XBD173 also exerted antipanic activity in humans and, in contrast to benzodiazepines, did not cause sedation or withdrawal symptoms. Thus, translocator protein (18 kD) ligands are promising candidates for fast-acting anxiolytic drugs with less severe side effects than benzodiazepines. PMID:19541954

  19. 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

  20. Translocation of Carbon-14 in Sugarcane Plants Supplied with or Deprived of Phosphorus 1

    PubMed Central

    Hartt, Constance E.

    1972-01-01

    Translocation of radioactive carbon from the fed part of a blade to the rest of the plant was impaired by a deficiency in phosphorus only when the level of phosphorus was low enough to decrease growth. Phosphorus deficiency decreased the percentage of inorganic phosphorus more than that of organic phosphorus, indicating little effect of phosphorus deficiency upon phosphorylation. Thus phosphorus deficiency did not reduce phosphorylation enough to affect translocation. Evidence for the involvement of phosphorylation in translocation obtained from studies with potassium deficiency, light intensity and quality, 3-(p-chlorophenyl)-1, 1-dimethylurea and 3-(3,4-dichlorophenyl)-1, 1-dimethylurea, and carbon dioxide suggests that noncyclic photosynthetic phosphorylation provides the energy for phototranslocation. PMID:16658003

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Ion selectivity of the anthrax toxin channel and its effect on protein translocation.

    PubMed

    Schiffmiller, Aviva; Anderson, Damon; Finkelstein, Alan

    2015-08-01

    Anthrax toxin consists of three ? 85-kD proteins: lethal factor (LF), edema factor (EF), and protective antigen (PA). PA63 (the 63-kD, C-terminal portion of PA) forms heptameric channels ((PA63)7) in planar phospholipid bilayer membranes that enable the translocation of LF and EF across the membrane. These mushroom-shaped channels consist of a globular cap domain and a 14-stranded ?-barrel stem domain, with six anionic residues lining the interior of the stem to form rings of negative charges. (PA63)7 channels are highly cation selective, and, here, we investigate the effects on both cation selectivity and protein translocation of mutating each of these anionic residues to a serine. We find that although some of these mutations reduce cation selectivity, selectivity alone does not directly predict the rate of protein translocation; local changes in electrostatic forces must be considered as well. PMID:26170174

  7. Prenatal diagnosis of two different unbalanced forms of an inherited (Y;12) translocation.

    PubMed

    Mademont-Soler, Irene; Morales, Carme; Madrigal, Irene; Margarit, Ester; Bruguera, Jordi; Clusellas, Núria; Martínez, José M; Borrell, Antoni; Sánchez, Aurora; Soler, Anna

    2009-12-01

    The identification of an unexpected structural chromosome rearrangement at prenatal diagnosis can be problematic and raises unique genetic counseling issues. We describe two consecutive prenatal cases within a family with an inherited unbalanced (Y;12) translocation and discuss the genotype-phenotype correlation. The first fetus presented with 12qter monosomy and pseudoautosomal region 2 trisomy, while the second fetus had the alternative unbalanced state. Although the first fetus had a structural heart defect, such small imbalances might not give sonographic findings, making their prenatal diagnosis difficult. However, congenital abnormalities are expected in both unbalanced forms of the translocation, including mental retardation, which could be explained by the gene dosage variation of P2RX2. To our knowledge, these are the first published cases reporting this subtype of (Y;12) translocation, in both balanced and unbalanced states. PMID:19921651

  8. Estimating Stochastic Gravitational Wave Backgrounds with Sagnac Calibration

    E-print Network

    Craig J. Hogan; Peter L. Bender

    2001-08-03

    Armstrong et al. have recently presented new ways of combining signals to precisely cancel laser frequency noise in spaceborne interferometric gravitational wave detectors such as LISA. One of these combinations, the symmetrized Sagnac observable, is much less sensitive to external signals at low frequencies than other combinations, and thus can be used to determine the instrumental noise level. We note here that this calibration of the instrumental noise permits smoothed versions of the power spectral density of stochastic gravitational wave backgrounds to be determined with considerably higher accuracy than earlier estimates, at frequencies where one type of noise strongly dominates and is not substantially correlated between the six main signals generated by the antenna. We illustrate this technique by analyzing simple estimators of gravitational wave background power, and show that the instrumental sensitivity to broad-band backgrounds at some frequencies can be improved by more than an order of magnitude over the standard method, comparable to that which would be achieved by cross-correlating two separate antennas. The applications of this approach to studies of astrophysical gravitational wave backgrounds generated after recombination and to searches for a possible primordial background are discussed.

  9. Rewilding the tropics, and other conservation translocations strategies in the tropical Asia-Pacific region

    PubMed Central

    Louys, Julien; Corlett, Richard T; Price, Gilbert J; Hawkins, Stuart; Piper, Philip J

    2014-01-01

    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

  10. 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

  11. 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

  12. Polylysine-mediated translocation of the diphtheria toxin catalytic domain through the anthrax protective antigen pore.

    PubMed

    Sharma, Onkar; Collier, R John

    2014-11-11

    The protective antigen (PA) moiety of anthrax toxin forms oligomeric pores in the endosomal membrane, which translocate the effector proteins of the toxin to the cytosol. Effector proteins bind to oligomeric PA via their respective N-terminal domains and undergo N- to C-terminal translocation through the pore. Earlier we reported that a tract of basic amino acids fused to the N-terminus of an unrelated effector protein (the catalytic domain diphtheria toxin, DTA) potentiated that protein to undergo weak PA-dependent translocation. In this study, we varied the location of the tract (N-terminal or C-terminal) and the length of a poly-Lys tract fused to DTA and examined the effects of these variations on PA-dependent translocation into cells and across planar bilayers in vitro. Entry into cells was most efficient with ?12 Lys residues (K12) fused to the N-terminus but also occurred, albeit 10-100-fold less efficiently, with a C-terminal tract of the same length. Similarly, K12 tracts at either terminus occluded PA pores in planar bilayers, and occlusion was more efficient with the N-terminal tag. We used biotin-labeled K12 constructs in conjunction with streptavidin to show that a biotinyl-K12 tag at either terminus is transiently exposed to the trans compartment of planar bilayers at 20 mV; this partial translocation in vitro was more efficient with an N-terminal tag than a C-terminal tag. Significantly, our studies with polycationic tracts fused to the N- and C-termini of DTA suggest that PA-mediated translocation can occur not only in the N to C direction but also in the C to N direction. PMID:25317832

  13. 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

  14. Mitochondrial Uncoupling Inhibits p53 Mitochondrial Translocation in TPA-Challenged Skin Epidermal JB6 Cells

    PubMed Central

    Wang, Fei; Fu, Xueqi; Chen, Xia; Chen, Xinbin; Zhao, Yunfeng

    2010-01-01

    The tumor suppressor p53 is known to be able to trigger apoptosis in response to DNA damage, oncogene activation, and certain chemotherapeutic drugs. In addition to its transcriptional activation, a fraction of p53 translocates to mitochondria at the very early stage of apoptosis, which eventually contributes to the loss of mitochondrial membrane potential, generation of reactive oxygen species (ROS), cytochrome c release, and caspase activation. However, the mitochondrial events that affect p53 translocation are still unclear. Since mitochondrial uncoupling has been suggested to contribute to cancer development, herein, we studied whether p53 mitochondrial translocation and subsequent apoptosis were affected by mitochondrial uncoupling using chemical protonophores, and further verified the results using a siRNA approach in murine skin epidermal JB6 cells. Our results showed that mitochondrial uncoupling blocked p53 mitochondrial translocation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA), a known tumor promoter to induce p53-mediated apoptosis in skin carcinogenesis. This blocking effect, in turn, led to preservation of mitochondrial functions, and eventually suppression of caspase activity and apoptosis. Moreover, uncoupling protein 2 (UCP2), a potential suppressor of ROS in mitochondria, is important for TPA-induced cell transformation in JB6 cells. UCP2 knock down cells showed enhanced p53 mitochondrial translocation, and were less prone to form colonies in soft agar after TPA treatment. Altogether, our data suggest that mitochondrial uncoupling may serve as an important regulator of p53 mitochondrial translocation and p53-mediated apoptosis during early tumor promotion. Therefore, targeting mitochondrial uncoupling may be considered as a novel treatment strategy for cancer. PMID:20976134

  15. Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections.

    PubMed

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Tzavara, Eleni; Giros, Bruno; Exley, Christopher; Curmi, Patrick A; Shaw, Christopher A; Gherardi, Romain K; Cadusseau, Josette

    2015-11-01

    Concerns regarding vaccine safety have emerged following reports of potential adverse events in both humans and animals. In the present study, alum, alum-containing vaccine and alum adjuvant tagged with fluorescent nanodiamonds were used to evaluate i) the persistence time at the injection site, ii) the translocation of alum from the injection site to lymphoid organs, and iii) the behavior of adult CD1 mice following intramuscular injection of alum (400?gAl/kg). Results showed for the first time a strikingly delayed systemic translocation of adjuvant particles. Alum-induced granuloma remained for a very long time in the injected muscle despite progressive shrinkage from day 45 to day 270. Concomitantly, a markedly delayed translocation of alum to the draining lymph nodes, major at day 270 endpoint, was observed. Translocation to the spleen was similarly delayed (highest number of particles at day 270). In contrast to C57BL/6J mice, no brain translocation of alum was observed by day 270 in CD1 mice. Consistently neither increase of Al cerebral content, nor behavioral changes were observed. On the basis of previous reports showing alum neurotoxic effects in CD1 mice, an additional experiment was done, and showed early brain translocation at day 45 of alum injected subcutaneously at 200?gAl/kg. This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffusion of the adjuvant in lymph nodes and spleen of CD1 mice, and suggests the importance of mouse strain, route of administration, and doses, for future studies focusing on the potential toxic effects of aluminum-based adjuvants. PMID:26384437

  16. 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.

  17. 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.

  18. A genetic prion disease Background information:Background information

    E-print Network

    Brutlag, Doug

    on homo- or heterozygosity · Genetic counseling ­ Prenatal and pre-implantation diagnosis for familyA genetic prion disease #12;Background information:Background information: About PrionsAbout Prions· Structure ­ Misfolded proteins ­ Not alive; no genetic material · Pathogenesis ­ Convert normal proteins

  19. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    NASA Astrophysics Data System (ADS)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  20. Ionic Current Inversion in Pressure-Driven Polymer Translocation through Nanopores

    NASA Astrophysics Data System (ADS)

    Buyukdagli, Sahin; Blossey, Ralf; Ala-Nissila, T.

    2015-02-01

    We predict streaming current inversion with multivalent counterions in hydrodynamically driven polymer translocation events from a correlation-corrected charge transport theory including charge fluctuations around mean-field electrostatics. In the presence of multivalent counterions, electrostatic many-body effects result in the reversal of the DNA charge. The attraction of anions to the charge-inverted DNA molecule reverses the sign of the ionic current through the pore. Our theory allows for a comprehensive understanding of the complex features of the resulting streaming currents. The underlying mechanism is an efficient way to detect DNA charge reversal in pressure-driven translocation experiments with multivalent cations.

  1. Polychlorinated biphenyls in plant foliage: translocation or volatilization from contaminated soils

    SciTech Connect

    Bacci, E.; Gaggi, C.

    1985-11-01

    Physical properties such as water solubility, vapor pressure, and Henry's law constant suggest that polychlorinated biphenyls (PCB's) can easily reach the troposphere as vapor. The potential of plant foliar tissues to take up PCB's as vapor has probably been underrated in some of the previous works. Nevertheless recently it was reported that the level of PCB's found in the foliage is mainly due to vapor transport from the soil, rather than to translocation through the plant. This research has been planned to assess the influence of translocation on the concentration of PCB's in the foliage of different plant species.

  2. Ionic current inversion in pressure-driven polymer translocation through nanopores

    E-print Network

    Sahin Buyukdagli; Ralf Blossey; T. Ala-Nissila

    2015-02-01

    We predict streaming current inversion with multivalent counterions in hydrodynamically driven polymer translocation events from a correlation-corrected charge transport theory including charge fluctuations around mean-field electrostatics. In the presence of multivalent counterions, electrostatic many-body effects result in the reversal of the DNA charge. The attraction of anions to the charge-inverted DNA molecule reverses the sign of the ionic current through the pore. Our theory allows for a comprehensive understanding of the complex features of the resulting streaming currents. The underlying mechanism is an efficient way to detect DNA charge reversal in pressure-driven translocation experiments with multivalent cations.

  3. Translocation of Single-Stranded DNA Through Single-Walled Carbon Nanotubes

    SciTech Connect

    Liu, Haitao; He, Jin; Tang, Jinyao; Liu, Hao; Pang, Pei; Cao, Di; Krstic, Predrag S; Joseph, Sony nmn; Lindsay, Stuart; Nuckolls, Colin

    2009-01-01

    We report the fabrication of devices in which one single-walled carbon nanotube spans a barrier between two fluid reservoirs, enabling direct electrical measurement of ion transport through the tube. A fraction of the tubes pass anomalously high ionic currents. Electrophoretic transport of small single-stranded DNA oligomers through these tubes is marked by large transient increases in ion current and was confirmed by polymerase chain reaction analysis. Each current pulse contains about 10{sup 7} charges, an enormous amplification of the translocated charge. Carbon nanotubes simplify the construction of nanopores, permit new types of electrical measurements, and may open avenues for control of DNA translocation.

  4. Hexahydro-1,3,5-trinitro-1,3,5-triazine translocation in poplar trees

    SciTech Connect

    Thompson, P.L.; Ramer, L.A.; Schnoor, J.L.

    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.

  5. Through the Eye of the Needle: Recent Advances in Understanding Biopolymer Translocation

    E-print Network

    Debabrata Panja; Gerard T. Barkema; Anatoly B. Kolomeisky

    2013-08-21

    In recent years polymer translocation, i.e., transport of polymeric molecules through nanometer-sized pores and channels embedded in membranes, has witnessed strong advances. It is now possible to observe single-molecule polymer dynamics during the motion through channels with unprecedented spatial and temporal resolution. These striking experimental studies have stimulated many theoretical developments. In this short theory-experiment review, we discuss recent progress in this field with a strong focus on non-equilibrium aspects of polymer dynamics during the translocation process.

  6. 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.

  7. Stochastic gravitational-wave background from cosmological supernovae

    SciTech Connect

    Buonanno, Alessandra; Sigl, Guenter; Raffelt, Georg G.; Janka, Hans-Thomas; Mueller, Ewald

    2005-10-15

    Based on new developments in the understanding of supernovae (SNe) as gravitational-wave (GW) sources we estimate the GW background from all cosmic SNe. For a broad range of frequencies around 1 Hz, this background is crudely comparable to the GW background expected from standard inflationary models. While our estimate remains uncertain within several orders of magnitude, the SN GW background may become detectable by second-generation space-based interferometers such as the proposed Big Bang Observatory (BBO). By the same token, the SN GWs may become a foreground for searches of the inflationary GWs, in particular, for sub-Hz frequencies where the SN background is Gaussian and where the BBO will be most sensitive. SN simulations lasting far beyond the usual cutoff of about 1 s are needed for more robust predictions in the sub-Hz frequency band. An even larger GW background can arise from a hypothetical early population of massive stars, although their GW source strength as well as their abundance are currently poorly understood.

  8. SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7.

    PubMed

    Guo, Hao; Zhang, Jialong; Zhang, Xuyuan; Wang, Yanbing; Yu, Haisheng; Yin, Xiangyun; Li, Jingyun; Du, Peishuang; Plumas, Joel; Chaperot, Laurence; Chen, Jianzhu; Su, Lishan; Liu, Yongjun; Zhang, Liguo

    2015-05-15

    Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both ?-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7. PMID:25862818

  9. SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7

    PubMed Central

    Guo, Hao; Zhang, Jialong; Zhang, Xuyuan; Wang, Yanbing; Yu, Haisheng; Yin, Xiangyun; Li, Jingyun; Du, Peishuang; Plumas, Joel; Chaperot, Laurence; Chen, Jianzhu; Su, Lishan; Liu, Yongjun; Zhang, Liguo

    2015-01-01

    Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both ?-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7. PMID:25862818

  10. SEGREGATION PATTERNS IN OAT POPULATIONS DERIVED FROM PARENTS HETEROZYGOUS FOR TRANSLOCATIONS 7C-17 AND 6C-21.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mounting evidence points to the importance of chromosomal rearrangements like reciprocal translocations in the evolutionary history of the genus Avena. These translocations may have profound effects on genetic and breeding behavior of oats, particularly when parents of diverse origins are used in c...

  11. Effects of arsenate, chromate, and sulfate on arsenic and chromium uptake and translocation by arsenic hyperaccumulator Pteris vittata L.

    E-print Network

    Ma, Lena

    Effects of arsenate, chromate, and sulfate on arsenic and chromium uptake and translocation 18 July 2013 Accepted 16 August 2013 Keywords: Phytoremediation Hyperaccumulator Arsenic Chromium and translocation by PV. Published by Elsevier Ltd. 1. Introduction Arsenic (As) and chromium (Cr) are both

  12. EFFECT OF COYOTES AND RELEASE SITE SELECTION ON SURVIVAL AND MOVEMENT OF TRANSLOCATED SWIFT FOXES IN THE BADLANDS

    E-print Network

    EFFECT OF COYOTES AND RELEASE SITE SELECTION ON SURVIVAL AND MOVEMENT OF TRANSLOCATED SWIFT FOXES State University 2007 #12;ii EFFECT OF COYOTES AND RELEASE SITE SELECTION ON SURVIVAL AND MOVEMENT ABSTRACT EFFECT OF COYOTES AND RELEASE SITE SELECTION ON SURVIVAL AND MOVEMENT OF TRANSLOCATED SWIFT FOXES

  13. Nuclear translocation of active AKT is required for erythroid differentiation in erythropoietin treated K562 erythroleukemia cells.

    PubMed

    Missiroli, Silvia; Etro, Daniela; Buontempo, Francesca; Ye, Keqiang; Capitani, Silvano; Neri, Luca Maria

    2009-03-01

    Erythroid differentiation of human erythroleukemia cell line K562 induced by erythropoietin is a complex process that involves modifications at nuclear level, including nuclear translocation of phosphatidyl-inositol 3-kinase. In this work we show that erythropoietin stimulation of K562 cells can induce nuclear translocation of active Akt, a downstream molecule of the phosphatidyl-inositol 3-kinase signaling pathway. Akt shows a peak of activity in whole cell homogenates at earlier stage when compared to the nucleus, which shows a peak delayed of 10 min. Akt increases its intranuclear amount and activity rapidly and transiently in response to EPO. Almost all Akt kinase that translocates to the nucleus shows a marked phosphorylation on serine 473. Nuclear enzyme translocation is blocked by the phosphatidyl-inositol 3-kinase inhibitor Ly294002 or Wortmannin. The specific Akt pharmacological inhibitor VI, VII and VIII that act as blocking enzyme activation inhibited translocation as well, whereas Akt inhibitor IX, that inhibits Akt activity, did not block Akt nuclear translocation. When cells were treated by means of siRNA sequences or with the Akt inhibitors the differentiation process was arrested, thus showing the requirement of the nuclear translocation of the active enzyme to differentiate. These findings strongly suggest that the intranuclear translocation of active Akt kinase represents an important step in the signaling pathway that mediates erythropoietin-induced erythroid differentiation. PMID:18694847

  14. Sec and drugs and rock'n'roll: antibiotic targeting of bacterial protein translocation Anti-infectives

    E-print Network

    Economou, Tassos

    Economou Sec and drugs and rock'n'roll: antibiotic targeting of bacterial protein translocation Anti-infectives Sec, drugs and rock'n'roll: antibiotic targeting of bacterial protein translocation of these secretory and membrane polypeptides is mediated by the Sec pathway. Protein secretion requires the co

  15. Translocations of Chromosome End-Segments and Facultative Heterochromatin Promote Meiotic Ring Formation in Evening Primroses[W][OPEN

    PubMed Central

    Golczyk, Hieronim; Massouh, Amid; Greiner, Stephan

    2014-01-01

    Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories. PMID:24681616

  16. Incorporation of inactive x chromosomes in micronuclei of X;9 translocation individuals

    SciTech Connect

    Hando, J.; Nath, J.; Tucker, J.D.

    1995-11-01

    Several studies on aneuploidy have shown that the X is the most frequently lost chromosome in females. Recent studies have shown a significant increase in the number of X chromosome-positive micronuclei with age in females. This study was to determine if the X chromosome observed in micronuclei was active or inactive. Blood samples were obtained from two females, each with balanced X;9 translocations. The first subject was 36 years of age with a karyotype of 46,XX,t(X;9) (q13;q32). The second subject was 33 years of age with a karyotype of 46,XX,t(X;9) (p11.2;q13). Ten thousand binucleated cells were scored for the 36 year old donor, while 9500 were scored for the 33 year old donor. The kinetochore status K{sup +} or K{sup {minus}} of each micronucleau (MN) was recorded. Slides were then hybridized with the X centromere specific probe pBamX7 and a whole chromosome painting probe specific for chromosome 9. The X centromere probe was labeled with biotinylated UTP and visualized with fluorescein conjugated avidin. The chromosome 9 painting probe was directly conjugated with SpectrumOrange. All micronucleated cells were relocated and scored as X+9+, X+9-, X-9+; or X-9- depending on their probe status. The results were pooled since there was no significant difference between micronucleus frequencies, K-MN, X+MN or X+9-Mn. A total 217 mocronuclei were scored. Kinetochore labeling showed that 28.6% (62/217) were kinetochore positive, while 71.4% (155/217) were kinetochore negative. Of the 217 micronuclei, 44.2%(96/217) contained the X chromosome. Among the 96 X chromosome-positive micronuclei, 83.3% (80/96) contained the inactive X chromosome (9-), while only 16.7% (16/96) contained an active X chromosome. These data clearly show that inclusion of the inactive X chromosome in micronuclei is preferential (p <0.005; {chi}2 analysis 1 df).

  17. Complex pathogenesis of Hirschsprung's disease in a patient with hydrocephalus, vesico-ureteral reflux and a balanced translocation t(3;17)(p12;q11)

    PubMed Central

    Griseri, Paola; Vos, Yvonne; Giorda, Roberto; Gimelli, Stefania; Beri, Silvana; Santamaria, Giuseppe; Mognato, Guendalina; Hofstra, Robert M W; Gimelli, Giorgio; Ceccherini, Isabella

    2009-01-01

    Hirschsprung's disease (HSCR), a congenital complex disorder of intestinal innervation, is often associated with other inherited syndromes. Identifying genes involved in syndromic HSCR cases will not only help understanding the specific underlying diseases, but it will also give an insight into the development of the most frequent isolated HSCR. The association between hydrocephalus and HSCR is not surprising as a large number of patients have been reported to show the same clinical association, most of them showing mutations in the L1CAM gene, encoding a neural adhesion molecule often involved in isolated X-linked hydrocephalus. L1 defects are believed to be necessary but not sufficient for the occurrence of the intestinal phenotype in syndromic cases. In this paper, we have carried out the molecular characterization of a patient affected with Hirschsprung's disease and X-linked hydrocephalus, with a de novo reciprocal balanced translocation t(3;17)(p12;q21). In particular, we have taken advantage of this chromosomal defect to gain access to the predisposing background possibly leading to Hirschsprung's disease. Detailed analysis of the RET and L1CAM genes, and molecular characterization of MYO18A and TIAF1, the genes involved in the balanced translocation, allowed us to identify, besides the L1 mutation c.2265delC, different additional factors related to RET-dependent and -independent pathways which may have contributed to the genesis of enteric phenotype in the present patient. PMID:19300444

  18. Neutron Background at Boulby Mine

    NASA Astrophysics Data System (ADS)

    Kudryavtsev, V. A.; Lightfoot, P. K.; McMillan, J. E.; Robinson, M.; Spooner, N. J. C.; Smith, P. F.; Smith, N. J. T.; Lewin, J. D.; Lüscher, R.; Liubarsky, I.

    2003-03-01

    The neutron background at the underground laboratory at Boulby - a site for several dark matter experiments - is discussed. Special emphasis is put on the neutron background produced by cosmic-ray muons. The most recent versions of the muon propagation code MUSIC, and particle transport code FLUKA are used to evaluate muon and neutron fluxes. The results of simulations are compared with experimental data.

  19. Cosmic Superstring Scattering in Backgrounds

    E-print Network

    Mark G. Jackson

    2006-09-27

    We generalize the calculation of cosmic superstring reconnection probability to non-trivial backgrounds. This is done by modeling cosmic strings as wound tachyon modes in the 0B theory, and the spacetime effective action is then used to couple this to background fields. Simple examples are given including trivial and warped compactifications. Generalization to $(p,q)$ strings is discussed.

  20. Background: Extratropical Cyclones and NWP

    E-print Network

    Froude, Lizzie

    Chapter 2 Background: Extratropical Cyclones and NWP 2.1 Introduction This chapter provides background information about extratropical cyclones, numerical weather prediction (NWP) and ensemble prediction. It is organised as follows. Section 2.2 discusses extratropical cyclones and begins with a brief

  1. 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.

  2. Lattice QCD in Background Fields

    SciTech Connect

    William Detmold, Brian Tiburzi, Andre Walker-Loud

    2009-06-01

    Electromagnetic properties of hadrons can be computed by lattice simulations of QCD in background fields. We demonstrate new techniques for the investigation of charged hadron properties in electric fields. Our current calculations employ large electric fields, motivating us to analyze chiral dynamics in strong QED backgrounds, and subsequently uncover surprising non-perturbative effects present at finite volume.

  3. Lattice QCD in Background Fields

    E-print Network

    William Detmold; Brian C. Tiburzi; Andre Walker-Loud

    2009-08-25

    Electromagnetic properties of hadrons can be computed by lattice simulations of QCD in background fields. We demonstrate new techniques for the investigation of charged hadron properties in electric fields. Our current calculations employ large electric fields, motivating us to analyze chiral dynamics in strong QED backgrounds, and subsequently uncover surprising non-perturbative effects present at finite volume.

  4. Computerized Placement Tests: Background Readings.

    ERIC Educational Resources Information Center

    College Entrance Examination Board, Princeton, NJ.

    This document is a compilation of background readings for the user of Computerized Placement Tests (CPTs) developed by the College Board for student placement purposes. CPTs are computerized adaptive tests that test the individual abilities and backgrounds of examinees. CPTs are part of the ACCUPLACER student information management system. The…

  5. Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation

    PubMed Central

    Sugiura-Ogasawara, Mayumi; Nagayoshi, Motoi; Tanaka, Atsushi; Takeda, Satoru

    2015-01-01

    Background Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations, and abnormal embryonic karyotypes. The number of centers performing preimplantation genetic diagnosis (PGD) for patients with translocations has steadily increased worldwide. The live birth rate with PGD was reported to be 27-54%. The live birth rate with natural conception was reported to be 37-63% on the first trial and 65-83% cumulatively. To date, however, there has been no cohort study comparing age and the number of previous miscarriages in matched patients undergoing or not undergoing PGD. Thus, we compared the live birth rate of patients with RPL associated with a translocation undergoing PGD with that of patients who chose natural conception. Methods and Findings After genetic counseling, 52 patients who desired natural conception and 37 patients who chose PGD were matched for age and number of previous miscarriages and these comprised the subjects of our study. PGD was performed by means of fluorescence in situ hybridization analysis. The live birth rates on the first PGD trial and the first natural pregnancy after ascertainment of the carrier status were 37.8% and 53.8%, respectively (odds ratio 0.52, 95% confidence interval 0.22-1.23). Cumulative live birth rates were 67.6% and 65.4%, respectively, in the groups undergoing and not undergoing PGD. The time required to become pregnancy was similar in both groups. PGD was found to reduce the miscarriage rate significantly. The prevalence of twin pregnancies was significantly higher in the PGD group. The cost of PGD was $7,956 U.S. per patient. Conclusions While PGD significantly prevented further miscarriages, there was no difference in the live birth rate. Couples should be fully informed of the similarity in the live birth rate, the similarity in time to become pregnancy, the advantages of PGD, such as the reduction in the miscarriage rate, as well as its disadvantages, such as the higher cost, and the advantages of a natural pregnancy, such as the avoidance of IVF failure. The findings presented here should be incorporated into the genetic counseling of patients with RPL and carrying a translocation. PMID:26083495

  6. Cosmic backgrounds of relic gravitons and their absolute normalization

    NASA Astrophysics Data System (ADS)

    Giovannini, Massimo

    2014-11-01

    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 or 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-frequency 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.

  7. Through the eye of the needle: recent advances in understanding biopolymer translocation This article has been downloaded from IOPscience. Please scroll down to see the full text article.

    E-print Network

    Through the eye of the needle: recent advances in understanding biopolymer translocation.1088/0953-8984/25/41/413101 TOPICAL REVIEW Through the eye of the needle: recent advances in understanding biopolymer translocation

  8. In this paper, a fast pixel-level adapting background detection algorithm is presented. The proposed

    E-print Network

    Dudek, Piotr

    4321 Abstract In this paper, a fast pixel-level adapting background detection algorithm is presented. The proposed background model records not only each pixel's historical background values process adjusts the individual decision threshold for each pixel, and reduces high frequency temporal

  9. 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.

  10. Backgrounder

    Cancer.gov

    There may be more than 200 different types of cancer and many more subtypes, each caused by glitches in DNA that trigger the uncontrolled growth of cells. Identifying the changes in each cancer’s complete set of DNA - its genome - and understanding how such changes interact to drive the disease process will lay the foundation for an era of precision medicine in cancer care that treats each patient as a unique case.

  11. Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature

    PubMed Central

    Armah, Henry B; Parwani, Anil V; Surti, Urvashi; Bastacky, Sheldon I

    2009-01-01

    The recently recognized renal cell carcinomas (RCCs) associated with Xp11.2 translocations (TFE3 transcription factor gene fusions) are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present. Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19)(p11.2;q13.1). Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course, this adult case occurring during pregnancy with a novel translocation involving chromosome 19 followed an indolent clinical course. PMID:19450277

  12. Temperature jump study of charge translocation during the bacteriorhodopsin photocycle.

    PubMed

    Butt, H J; Fendler, K; Dér, A; Bamberg, E

    1989-11-01

    Temperature jump experiments were carried out on purple membranes oriented and fixed in polyacrylamide gel. With green background illumination a relaxation of the photocurrent after an infrared laser pulse could be observed. To simulate the temperature jump signals different models of the bacteriorhodopsin photocycle were tested. The parameters of these models were obtained by measuring absorbance changes and photocurrent after excitation with a 575-nm laser flash.A model with a temperature-dependent branching before the M state turned out to be satisfying. Other models, especially those with a late branching or without branching, could not reproduce the temperature jump measurements. PMID:19431749

  13. Low background counting at the LBNL low background facility

    SciTech Connect

    Thomas, K. J.; Norman, E. B.; Smith, A. R.; Chan, Y. D.; Hurley, D. L.; Wang, B. S.

    2013-08-08

    The Low Background Facility (LBF) at the Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to end-users in two unique facilities: locally within a carefully-constructed, low background laboratory space; and a satellite underground station (600 m.w.e) in Oroville, CA. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic and anthropogenic products, as well as active screening via neutron activation analysis for specific applications. A general overview of the facilities, services, and capabilities will be discussed. Recent activities will also be presented, including the recent installation of a 3? muon veto at the surface facility, cosmogenic activation studies of TeO{sub 2} for CUORE, and environmental monitoring of Fukushima fallout.

  14. Aluminum as a source of background in low background experiments

    E-print Network

    B. Majorovits; I. Abt; M. Laubenstein; O. Volynets

    2011-05-18

    Neutrinoless double beta decay would be a key to understanding the nature of neutrino masses. The next generation of High Purity Germanium experiments will have to be operated with a background rate of better than 10^-5 counts/(kg y keV) in the region of interest around the Q value of the decay. Therefore, so far irrelevant sources of background have to be considered. The metalization of the surface of germanium detectors is in general done with aluminum. The background from the decays of 22Na, 26Al, 226Ra and 228Th introduced by this metalization is discussed. It is shown that only a special selection of aluminum can keep these background contributions acceptable.

  15. 34 High Frequency Electronics High Frequency Design

    E-print Network

    Popovic, Zoya

    consists of a baseband or IF modulator, an up-converter, and a power- amplifier chain (Figure 20 Electronics Copyright © 2003 Summit Technical Media, LLC #12;36 High Frequency Electronics High Frequency

  16. Jumping translocation of 15q24-qter resulting in partial trisomy: a case report.

    PubMed

    Czakó, Márta; Hadzsiev, Kinga; Melegh, Béla; Kosztolányi, György

    2012-07-15

    We report on a jumping translocation with five different cell lines detected in four tissues in a 2-year-old patient. This rare type of chromosomal abnormality (not more than 30 cases published so far) proved to be a series of non-reciprocal translocations of the 15q24-qter donor chromosome segment to the telomeric region of chromosomes 5q, 10q, 16q and 19p, respectively. The process, in addition to a few cells without translocation, resulted in partial trisomy of 15q24-qter which was associated with somatic overdevelopment in the patient, with hemihypertrophy and minor anomalies. The phenotype of our patient was different from that of the other two patients found in the literature having the same donor chromosome segment involved in a similar rearrangement. Possibly, the difference in the phenotype lies in the various ratios of somatic mosaicism with five cell lines, in particular the presence of normal one which is extremely rare in patients with jumping translocation. Here we discuss the various ways on how the rearrangement could arise. PMID:22546223

  17. Characterization of a 3;6 Translocation Associated with Renal Cell Carcinoma

    PubMed Central

    Foster, Rebecca E.; Abdulrahman, Mahera; Morris, Mark R.; Prigmore, Elena; Gribble, Susan; Ng, Beeling; Gentle, Dean; Ready, Steven; Weston, Phil M. T.; Wiesener, Michael S.; Kishida, Takeshi; Yao, Masahiro; Davison, Val; Barbero, Jose Luis; Chu, Carol; Carter, Nigel P.; Latif, Farida; Maher, Eamonn R.

    2009-01-01

    The most frequent cause of familial clear cell renal cell carcinoma (RCC) is von Hippel–Lindau disease and the VHL tumor suppressor gene (TSG) is inactivated in most sporadic clear cell RCC. Although there is relatively little information on the mechanisms of tumorigenesis of clear cell RCC without VHL inactivation, a subset of familial cases harbors a balanced constitutional chromosome 3 translocation. To date nine different chromosome 3 translocations have been associated with familial or multicentric clear cell RCC; and in three cases chromosome 6 was also involved. To identify candidate genes for renal tumorigenesis we characterized a constitutional translocation, t(3;6)(q22;q16.1) associated with multicentric RCC without evidence of VHL target gene dysregulation. Analysis of breakpoint sequences revealed a 1.3-kb deletion on chromosome 6 within the intron of a 2 exon predicted gene (NT_007299.434). However, RT-PCR analysis failed to detect the expression of this gene in lymphoblast, fibroblast, or kidney tumor cell lines. No known genes were disrupted by the translocation breakpoints but several candidate TSGs (e.g., EPHB1, EPHA7, PPP2R3A RNF184, and STAG1) map within close proximity to the breakpoints. PMID:17205537

  18. Translocation, Homing Behavior and Habitat Use of Groundfishes Associated with Oil Platforms in

    E-print Network

    Sorin, Eric J.

    Translocation, Homing Behavior and Habitat Use of Groundfishes Associated with Oil Platforms between natural and platform habitats were monitored over a two-year period. Twenty-five percent of all of an obsolete platform will result in a complete loss of complex habitat and its associated marine community

  19. Ribosomal crystallography: a flexible nucleotide anchoring tRNA translocation, facilitates peptide-bond formation,

    E-print Network

    Yonath, Ada E.

    Minireview Ribosomal crystallography: a flexible nucleotide anchoring tRNA translocation Rehovot, Israel b Max-Planck-Research Unit for Ribosomal Structure, 22603 Hamburg, Germany Received 11 The linkage between internal ribosomal symmetry and transfer RNA (tRNA) positioning confirmed positional

  20. Structural studies on decoding, termination and translocation in the bacterial ribosome

    E-print Network

    Ramakrishnan, Venki

    Structural studies on decoding, termination and translocation in the bacterial ribosome Venki Ramakrishnan 2 1. Introduction With the determination of the atomic structures of the ribosomal subunits of these studies could be carried out using crystals of the ribosomal subunits, recognition of codon

  1. Free Radicals Generated by Ionizing Radiation Signal Nuclear Translocation of p53

    NASA Technical Reports Server (NTRS)

    Martinez, J. D.; Pennington, M. E.; Craven, M. T.; Warters, R. L.

    1997-01-01

    The p53 tumor suppressor is a transcription factor that regulates several pathways, which function collectively to maintain the integrity of the genome. Nuclear localization is critical for wild-type function. However, the signals that regulate subcellular localization of p53 have not been identified. Here, we examine the effect of ionizing radiation on the subcellular localization of p53 in two cell lines in which p63 is normally sequestered in the cytoplasm and found that ionizing radiation caused a biphasic translocation response. p53 entered the nucleus 1-2 hours postirradiation (early response), subsequently emerged from the nucleus, and then again entered the nucleus 12-24 hours after the cells had been irradiated (delayed response). These changes in subcellular localization could be completely blocked by the free radical scavenger, WR1065. By comparison, two DNA-damaging agents that do not generate free radicals, mitomycin C and doxorubicin, caused translocation only after 12-24 h of exposure to the drugs, and this effect could not be inhibited by WR1065. Hence, although all three DNA-damaging agents induced relocalization of p53 to the nucleus, only the translocation caused by radiation was sensitive to free radical scavenging. We suggest that the free radicals generated by ionizing radiation can signal p53 translocation to the nucleus.

  2. A SIMPLE MODEL FOR THE UPTAKE, TRANSLOCATION, AND ACCUMULATION OF PERCHLORATE IN TOBACCO PLANTS

    EPA Science Inventory

    A simple mathematical model is being developed to describe the uptake, translocation, and accumulation of perchlorate in tobacco plants. The model defines a plant as a set of compartments, consisting of mass balance differential equations and plant-specific physiological paramet...

  3. A Membrane-Translocating Peptide Penetrates into Bilayers without Significant Bilayer Perturbations

    PubMed Central

    Cruz, Juan; Mihailescu, Mihaela; Wiedman, Greg; Herman, Katherine; Searson, Peter C.; Wimley, William C.; Hristova, Kalina

    2013-01-01

    Using a high throughput screen, we have identified a family of 12-residue long peptides that spontaneously translocate across membranes. These peptides function by a poorly understood mechanism that is very different from that of the well-known, highly cationic cell penetrating peptides such as the tat peptide from HIV. The newly discovered translocating peptides can carry polar cargoes across synthetic bilayers and across cellular membranes quickly and spontaneously without disrupting the membrane. Here we report on the biophysical characterization of a representative translocating peptide from the selected family, TP2, as well as a negative control peptide, ONEG, from the same library. We measured the binding of the two peptides to lipid bilayers, their secondary structure propensities, their dispositions in bilayers by neutron diffraction, and the response of the bilayer to the peptides. Compared to the negative control, TP2 has a greater propensity for membrane partitioning, although it still binds only weakly, and a higher propensity for secondary structure. Perhaps most revealing, TP2 has the ability to penetrate deep into the bilayer without causing significant bilayer perturbations, a property that may help explain its ability to translocate without bilayer permeabilization. PMID:23746514

  4. Translocation of polymers with folded configurations across nanopores Stanislav Kotsev and Anatoly B. Kolomeiskya

    E-print Network

    Translocation of polymers with folded configurations across nanopores Stanislav Kotsev and Anatoly August 2007; accepted 26 September 2007; published online 9 November 2007 The transport of polymers segment through the channel followed by the linear part of the polymer. The transition rates vary

  5. Allosteric signalling in the outer membrane translocation domain of PapC usher.

    PubMed

    Farabella, Irene; Pham, Thieng; Henderson, Nadine S; Geibel, Sebastian; Phan, Gilles; Thanassi, David G; Delcour, Anne H; Waksman, Gabriel; Topf, Maya

    2014-01-01

    PapC ushers are outer-membrane proteins enabling assembly and secretion of P pili in uropathogenic E. coli. Their translocation domain is a large ?-barrel occluded by a plug domain, which is displaced to allow the translocation of pilus subunits across the membrane. Previous studies suggested that this gating mechanism is controlled by a ?-hairpin and an ?-helix. To investigate the role of these elements in allosteric signal communication, we developed a method combining evolutionary and molecular dynamics studies of the native translocation domain and mutants lacking the ?-hairpin and/or the ?-helix. Analysis of a hybrid residue interaction network suggests distinct regions (residue 'communities') within the translocation domain (especially around ?12-?14) linking these elements, thereby modulating PapC gating. Antibiotic sensitivity and electrophysiology experiments on a set of alanine-substitution mutants confirmed functional roles for four of these communities. This study illuminates the gating mechanism of PapC ushers and its importance in maintaining outer-membrane permeability. PMID:25271373

  6. Translocation and thermal inactivation of Shiga-toxin producing Escherichia coli in non-intact beef

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We compared translocation of genetically-marked strains of serotype O157:H7 Escherichia coli (ECOH) to non-O157:H7 Shiga-Toxin producing Escherichia coli (STEC) following blade tenderization of beef subprimals and the subsequent lethality of these pathogens following cooking of steaks prepared from ...

  7. Molecular cytogenetic characterization of Thinopyrum and wheat Thinopyrum translocated chromosomes in a wheatThinopyrum

    E-print Network

    Pappu, Hanu R.

    Molecular cytogenetic characterization of Thinopyrum and wheat± Thinopyrum translocated chromosomes in a wheat±Thinopyrum amphiploid Xiwen Cai, Stephen S. Jones & Timothy D. Murray Received 24 September 1997-Harrison 7 January 1998 The wheat±Thinopyrum amphiploid `Agrotriticum # 3425' (AT 3425), which is highly

  8. Increased egg infertility associated with translocating inbred takahe (Porphyrio hochstetteri) to island refuges in New Zealand

    E-print Network

    Jamieson, Ian

    Increased egg infertility associated with translocating inbred takahe (Porphyrio hochstetteri infertility than birds that have remained within their natural habitat range. For takahe, whether breeders had success. The coecient of inbreeding was high for island takahe but high infertility and low juvenile

  9. Endocytosis Regulates Cell Soma Translocation and the Distribution of Adhesion Proteins in Migrating Neurons

    E-print Network

    McConnell, Susan

    Endocytosis Regulates Cell Soma Translocation and the Distribution of Adhesion Proteins their attachments. We show that the machinery for clathrin- mediated endocytosis is positioned to regulate. These results suggest that endocytosis may play a critical role in regulating substrate detachment to enable

  10. CARBON EXPORT FROM ARBUSCULAR MYCORRHIZAL ROOTS INVOLVES THE TRANSLOCATION OF CARBOYHDRATE AS WELL AS LIPID

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arbuscular mycorrhizal (AM) fungi take up photosynthetically fixed carbon from plant roots and translocate it to their external mycelium. Previous experiments have shown that fungal lipid synthesized from carbohydrate in the root is one form of exported carbon. In this study an analysis of the labe...

  11. Supporting Information Direct Observation of Enhanced Translocation of a Homeodomain between DNA Cognate Sites

    E-print Network

    Clore, G. Marius

    /reassociation mechanism: If Scheme 1 is the only mechanism of translocation, the time-dependence of the auto- and cross The phenomenological mixing time-dependence of the auto- and exchange cross peaks for a simple two-site exchange system ab app az z z 1 complex = - +( ) [4] M aa z : z-magnetization of complex a that arises auto peak (F1

  12. Efficient Twin Arginine Translocation (Tat) Pathway Transport of a Precursor Protein Covalently Anchored

    E-print Network

    Efficient Twin Arginine Translocation (Tat) Pathway Transport of a Precursor Protein Covalently and Cellular Biology Program, University of Florida, Gainesville, Florida 32611 The thylakoid twin arginine vicinity of the twin arginine motif. Hcf106 cross-linked less strongly to residues in the hydrophobic core

  13. A Hands-On Approach to Teaching Protein Translation & Translocation into the ER

    ERIC Educational Resources Information Center

    LaBonte, Michelle L.

    2013-01-01

    The process of protein translation and translocation into the endoplasmic reticulum (ER) can often be challenging for introductory college biology students to visualize. To help them understand how proteins become oriented in the ER membrane, I developed a hands-on activity in which students use Play-Doh to simulate the process of protein…

  14. Velocity of DNA during translocation through a solid-state nanopore.

    PubMed

    Plesa, Calin; van Loo, Nick; Ketterer, Philip; Dietz, Hendrik; Dekker, Cees

    2015-01-14

    While understanding translocation of DNA through a solid-state nanopore is vital for exploiting its potential for sensing and sequencing at the single-molecule level, surprisingly little is known about the dynamics of the propagation of DNA through the nanopore. Here we use linear double-stranded DNA molecules, assembled by the DNA origami technique, with markers at known positions in order to determine for the first time the local velocity of different segments along the length of the molecule. We observe large intramolecular velocity fluctuations, likely related to changes in the drag force as the DNA blob unfolds. Furthermore, we observe an increase in the local translocation velocity toward the end of the translocation process, consistent with a speeding up due to unfolding of the last part of the DNA blob. We use the velocity profile to estimate the uncertainty in determining the position of a feature along the DNA given its temporal location and demonstrate the error introduced by assuming a constant translocation velocity. PMID:25496458

  15. Atypical X-Chromosome Inactivation in an X;1 Translocation Patient Demonstrating Xq28 Functional Disomy

    PubMed Central

    Cottrell, Catherine E; Sommer, Annemarie; Wenger, Gail D; Bullard, Steven; Busch, Tamara; Krahn, Katherine Nash; Lidral, Andrew C; Gastier-Foster, Julie M

    2009-01-01

    X-chromosome inactivation is an epigenetic process used to regulate gene dosage in mammalian females by silencing genes on one X-chromosome. While the pattern of X-chromosome inactivation is typically random in normal females, abnormalities of the X-chromosome may result in skewing due to disadvantaged cell growth. We describe a female patient with an X;1 translocation [46,X,t(X;1)(q28;q21)] and unusual pattern of X-chromosome inactivation who demonstrates functional disomy of the Xq28 region distal to the translocation breakpoint. There was complete skewing of X-chromosome inactivation in the patient, along with the atypical findings of an active normal X chromosome and an inactive derivative X. Characterization of the translocation revealed that the patient’s Xq28 breakpoint interrupts the DKC1 gene. Molecular analysis of the breakpoint region revealed functional disomy of Xq28 genes distal to DKC1. We propose that atypical X-chromosome inactivation occurred in the patient due to a post-inactivation cell selection mechanism likely initiated by disruption of DKC1. As a result, the pattern of X-chromosome inactivation is opposite that of the expected for an X;autosome translocation. Therefore, we suggest the phenotypic abnormalities found in the patient are a result of functional disomy in the Xq28 region. PMID:19215059

  16. Trisomy 16q arising from a maternal 15p;16q translocation.

    PubMed Central

    Ridler, M A; McKeown, J A

    1979-01-01

    Trisomy 16q is reported in a malformed infant who died at 12 days of age. The karyotype was 46,XX,der(15)t(15;16) (p11;q11)mat. A balanced translocation was found in the mother. The consequences of various types of aneuploidy of chromosome 16 are discussed. Images PMID:490587

  17. Absorption and Translocation of Aminocyclopyrachlor and Aminocyclopyrachlor Methyl Ester in Canada Thistle (Cirsium arvense)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laboratory studies were conducted using radiolabeled aminocyclopyrachlor (DPX-MAT28) and its methyl ester (DPX-KJM44) to determine the 1) importance of surfactants for herbicide absorption 2) translocation patterns of the two formulations and 3) rate that aminocyclopyrachlor methyl ester was metabol...

  18. StructureFunction Analysis of the DNA Translocating Portal of the Bacteriophage

    E-print Network

    Kihara, Daisuke

    Structure­Function Analysis of the DNA Translocating Portal of the Bacteriophage T4 Packaging.jmb.2013.10.011 Edited by J. Johnson Abstract Tailed bacteriophages and herpesviruses consist bacteriophages and herpesviruses use powerful molecular machines to package their gen- omes into a head

  19. Facilitated phospholipid translocation in vesicles and nucleated cells using synthetic small molecule scramblases

    E-print Network

    Smith, Bradley D.

    membranes and endogenous phosphatidylserine across the plasma membrane of nucleated cells. More than half: Phosphatidylserine Translocation Molecular recognition Flip-flop Membrane transport Membrane scramblase a b s t r a c that the synthetic scramblases are rapidly trafficked out of the cell plasma membrane and into the membranes

  20. Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix

    E-print Network

    molecules attached to its C terminus across the plasma membranes of living cells. Translocation is selective control, or cell regulation. drug delivery peptide nucleic acid delivery tumors membrane transport helix, the formation of indepen- dently stable helices across the membrane lipid bilayer occurs first

  1. PUMA promotes Bax translocation by competitive binding to Bcl-Xl during UV-induced apoptosis

    NASA Astrophysics Data System (ADS)

    Zhang, Yingjie; Xing, Da; Wu, Yinyuan; Liu, Lei

    2008-02-01

    Ultraviolet (UV) irradiation can induce apoptosis through both the membrane death receptor and the intrinsic apoptotic signaling pathways as DNA-damaging agents. PUMA, a BH3-only Bcl-2 family protein, plays an essential role in DNA damage-induced apoptosis. Bax, also a Bcl-2 family member, translocates from the cytosol to the mitochondrial membrane during UV-induced apoptosis. However, the regulation of Bax activation induced by UV irradiation remains poorly understood. In this study, the FRET (fluorescence resonance energy transfer) technique was used to study the interactions of Bax, Bcl-Xl, and PUMA in ASTC-a-1 cells. The results show that Bax translocated from the cytosol to the mitochondrial membrane at about 7 h after UV irradiation, and the translocation can not be blocked completely when overexpressed Bcl-xl. Moreover, The interaction of Bax and Bcl-Xl weakened markedly. In addition, Co-immunoprecipitation shows that PUMA released Bax by directly binding to Bcl-XL after UV irradiation in ASTC-a-1 cells. Taken together, these results indicated that PUMA can promote Bax translocation by binding to Bcl-Xl during UV-induced apoptosis.

  2. Functional adaptation of the switch-2 nucleotide sensor enables rapid processive translocation by myosin-5.

    PubMed Central

    Nagy, Nikolett T.; Sakamoto, Takeshi; Takács, Balázs; Gyimesi, Máté; Hazai, Eszter; Bikádi, Zsolt; Sellers, James R.; Kovács, Mihály

    2010-01-01

    Active site loops that are conserved across superfamilies of myosins, kinesins, and G proteins play key roles in allosteric coupling of NTP hydrolysis to interaction with track filaments or effector proteins. In this study, we investigated how the class-specific natural variation in the switch-2 active site loop contributes to the motor function of the intracellular transporter myosin-5. We used single-molecule, rapid kinetic and spectroscopic experiments and semiempirical quantum chemical simulations to show that the class-specific switch-2 structure including a tyrosine (Y439) in myosin-5 enables rapid processive translocation along actin filaments by facilitating Mg2+-dependent ADP release. Using wild-type control and Y439 point mutant myosin-5 proteins, we demonstrate that the translocation speed precisely correlates with the kinetics of nucleotide exchange. Switch-2 variants can thus be used to fine-tune translocation speed while maintaining high processivity. The class-specific variation of switch-2 in various NTPase superfamilies indicates its general role in the kinetic tuning of Mg2+-dependent nucleotide exchange.—Nagy, N.T., Sakamoto, T., Takács, B., Gyimesi, M., Hazai, E., Bikádi, Z., Sellers, J.R., Kovács, M. Functional adaptation of the switch-2 nucleotide sensor enables rapid processive translocation by myosin-5. PMID:20631329

  3. Differential uptake and translocation of ?-HCH and dieldrin by several plant species from hydroponic medium.

    PubMed

    Namiki, Sayuri; Otani, Takashi; Seike, Nobuyasu; Satoh, Shinobu

    2015-03-01

    To compare the uptake and translocation of hydrophobic organic chemicals by plant species, the authors performed uptake experiments with ?-1,2,3,4,5,6-hexachlorocyclohexane (?-HCH) and 1,2,3,4,10,10-Hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-1,4-exo-5,8-dimethanonaphthalene (dieldrin) using 5 species: Hordeum vulgare, Glycine max, Solanum lycopersicum, Brassica oleracea, and Cucurbita pepo. The present study evaluated uptake ability using root concentration factor (RCF) and translocation ability by transpiration stream concentration factor (TSCF). The RCFs of ?-HCH and dieldrin did not differ remarkably among species, except that the RCF of ?-HCH in B. oleracea was high. The TSCFs of ?-HCH and dieldrin were high in C. pepo, which was not superior in uptake as estimated by RCF. The TSCF of dieldrin in C. pepo was decreased in darkness and was markedly decreased by heating of roots. These results support the hypothesis that transport proteins produced in the root contribute to dieldrin translocation. In contrast, TSCF of ?-HCH was not decreased by these treatments. Therefore, translocation of ?-HCH might not need the contribution of transport proteins. It is possible that C. pepo has a certain function to transport hydrophobic organic chemicals smoothly in root tissues. PMID:25470472

  4. Computer analysis of organelle translocation in primary neuronal cultures and continuous cell lines

    PubMed Central

    1975-01-01

    Organelle translocation in a number of cell types in tissue culture as seen by high-resolution Zeiss-Nomarski differential interference contrast optics was filmed and analyzed by computer. Principal cell types studied included primary chick spinal cord, chick dorsal root ganglion, ratbrain, and various clones of continuous cell lines. Organelle translocations in all cell types studied exhibited frequent, large changes in velocity during any one translocation. The appearance of particles as seen with Nomarski optics was correlated with their fine structures in one dorsal root ganglion neurite by fixing the cell as it was being filmed and obtaining electron micrographs of the region filmed. This revealed the identity of several organelles as well as the presence of abundant neurotubules but no neurofilaments. Primary cell cultures exhibited more high-velocity organelle movements than continuous cell lines. The net progress of an organelle in a given direction was greater in primary neuronal cells than in fibroblasts or continuous cell lines. These findings are correlated with the literature on organelle translocation and axoplasmic transport. PMID:48515

  5. Viscosity and solute dependence of F-actin translocation by rabbit skeletal heavy meromyosin

    E-print Network

    Daniel, Tom

    Viscosity and solute dependence of F-actin translocation by rabbit skeletal heavy meromyosin P, Ying Chen, Kristi L. Kulin, and Thomas L. Daniel. Viscosity and solute dependence of F the hypothesis that solvent viscosity affects transloca- tion of rhodamine phalloidin-labeled F-actin by rabbit

  6. Author's personal copy Uptake and translocation of arsenite by Pteris vittata L.: Effects of glycerol,

    E-print Network

    Ma, Lena

    Author's personal copy Uptake and translocation of arsenite by Pteris vittata L.: Effects the effects of AsIII analogs glycerol and antimonite (SbIII) at 0e100 mM and aquaporin inhibitor AgNO3 at 0e0 been observed in Escherichia coli (Willsky and Malamy, 1980), yeast (Yompakdee et al., 1996

  7. LMO2 at 25 years: a paradigm of chromosomal translocation proteins

    PubMed Central

    Chambers, Jennifer; Rabbitts, Terence H.

    2015-01-01

    LMO2 was first discovered through proximity to frequently occurring chromosomal translocations in T cell acute lymphoblastic leukaemia (T-ALL). Subsequent studies on its role in tumours and in normal settings have highlighted LMO2 as an archetypical chromosomal translocation oncogene, activated by association with antigen receptor gene loci and a paradigm for translocation gene activation in T-ALL. The normal function of LMO2 in haematopoietic cell fate and angiogenesis suggests it is a master gene regulator exerting a dysfunctional control on differentiation following chromosomal translocations. Its importance in T cell neoplasia has been further emphasized by the recurrent findings of interstitial deletions of chromosome 11 near LMO2 and of LMO2 as a target of retroviral insertion gene activation during gene therapy trials for X chromosome-linked severe combined immuno-deficiency syndrome, both types of event leading to similar T cell leukaemia. The discovery of LMO2 in some B cell neoplasias and in some epithelial cancers suggests a more ubiquitous function as an oncogenic protein, and that the current development of novel inhibitors will be of great value in future cancer treatment. Further, the role of LMO2 in angiogenesis and in haematopoietic stem cells (HSCs) bodes well for targeting LMO2 in angiogenic disorders and in generating autologous induced HSCs for application in various clinical indications. PMID:26108219

  8. Single-Molecule Protein Unfolding and Translocation by an ATP-Fueled

    E-print Network

    Lang, Matthew

    Single-Molecule Protein Unfolding and Translocation by an ATP-Fueled Proteolytic Machine Marie ATP-powered proteases for protein- quality control and regulation. In the ClpXP protease, Clp with ClpXP. INTRODUCTION In all organisms, AAA+ family molecular machines harness the energy of ATP binding

  9. Fecal glucocorticoid metabolite analysis as an indicator of stress during translocation and acclimation in an

    E-print Network

    Rubenstein, Daniel I.

    -1795.2008.00175.x Abstract Fecal glucocorticoid metabolite (FGM) analysis provides a non-invasive method-translocated controls (16.2 Æ 1.2 ng gÀ1 ). This suggests that the stress of captivity elevated FGMs. FGM concentrations. The return of FGM concentrations to baseline suggests successful acclimation to the new environment

  10. Mobilizing Learning Resources in a Transnational Classroom: Translocal and Digital Resources in a Community Technology Center

    ERIC Educational Resources Information Center

    Noguerón-Liu, Silvia

    2014-01-01

    Drawing from transnational and activity theory frameworks, this study analyzes the ways translocal flows shape learning in a community technology center serving adult immigrants in the US Southwest. It also explores students' constructions of the transnational nature of the courses they took, where they had access to both online and…

  11. Wogonin inhibits osteoclast differentiation by inhibiting NFATc1 translocation into the nucleus

    PubMed Central

    GENG, XIAOLIN; YANG, LIBIN; ZHANG, CHAO; QIN, HUA; LIANG, QIUDONG

    2015-01-01

    The aim of the present study was to identify a natural product with the ability to inhibit nuclear factor of activated T cells c1 (NFATc1) translocation from the cytoplasm to the nucleus by high-throughput screening, and to investigate the effect of the natural product upon osteoclast differentiation and its underlying mechanism. An NFATc1 antagonist redistribution assay was performed in U2OS-NFATc1 cells against a natural product library, and Wogonin was found to have the ability to inhibit the NFATc1 translocation from the cytoplasm to the nucleus. The effect of Wogonin on NFATc1 transcription activation was further determined by luciferase assay. An osteoclast differentiation assay was executed to evaluate the effect of Wogonin on osteoclast differentiation. The effect of Wogonin upon the vital genes in osteoclast differentiation was investigated using fluorescent quantitative polymerase chain reaction analysis. The natural product Wogonin significantly inhibited the translocation of NFATc1 from the cytoplasm to the nucleus and its transcriptional activation activity. Wogonin also significantly inhibited osteoclast differentiation and decreased the transcription of osteoclast-associated immunoglobulin-like receptor, tartrate-resistant acid phosphatase and calcitonin receptor. In conclusion, the natural product Wogonin inhibited osteoclast differentiation through the inhibition of NFATc1 translocation from the cytoplasm to the nucleus, and thus the downregulation of genes associated with osteoclast differentiation, which marked Wogonin as a potential treatment for osteoporosis.

  12. Research methods in weed science: herbicide absorption and translocation in plants using radioisotopes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Herbicide absorption and translocation in plants is a key component in the study of herbicide physiology, mode of action, selectivity, resistance mechanisms, and in the registration process. Radioactive herbicides have been in use for over half-a-century in the research and study of herbicide absorp...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accounting for the acclimation of respiration of plants to temperature remains a major problem in analysis of carbon balances of ecosystems. It is possible that the thermal acclimation of leaf respiration simply reflects changes in substrate supply caused by temperature effects on translocation. T...

  14. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the reporting recommendations as specified under 40 CFR part 792, subpart J, the following specific... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable...

  15. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the reporting recommendations as specified under 40 CFR part 792, subpart J, the following specific... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable...

  16. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the reporting recommendations as specified under 40 CFR part 792, subpart J, the following specific... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable...

  17. Aminopyralid and Clopyralid Absorption and Translocation Differences in Canada Thistle (Cirsium arvense)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopyralid (4-amino-3,6-dichloro-2-pyridinecarboxylic acid) is a new auxinic herbicide that provides Canada thistle control at lower use rates than clopyralid (3,6-dichloro-2-pyridinecarboxylic acid). Studies were conducted to determine if differences in absorption, translocation, or metabolism ac...

  18. Bipolar DNA Translocation Contributes to Highly Processive DNA Unwinding by RecBCD Enzyme*S

    E-print Network

    Kowalczykowski, Stephen C.

    Bipolar DNA Translocation Contributes to Highly Processive DNA Unwinding by RecBCD Enzyme*SBCD enzyme is a bipolar DNA helicase that employs two single-stranded DNA motors of opposite polarity the exceptionally high rate and processivity of DNA unwinding cata- lyzed by the RecBCD enzyme. Using a stopped

  19. Experimental and theoretical investigations on temperature modulated translocation of IgG molecules through nanopore arrays.

    PubMed

    Liu, Lei; Zhu, Lizhong

    2015-07-21

    In the past few decades, nanopore based biosensing has attracted more and more attention. In this work, a novel fluidic sensor was fabricated using two separated liquid cells, which were linked by polycarbonate (PC) ultrafiltration membranes containing nanopore arrays. The trans-membrane ionic current generated by the applied voltage and the current changes modulated by a goat antibody to human immunoglobulin G (IgG) translocation were recorded simultaneously. The experimental results show that the ionic current is modulated by the physical place-holding effect generated by IgG translocation through nanopore arrays. For different temperatures (4 °C, 22 °C, and 45 °C) and different concentrations of the electrolyte (0.01 mol L(-1), 0.10 mol L(-1) and 1.0 mol L(-1)), the relative variance of the ionic current ((I0-I)/I0) modulated by IgG translocation increases at first and then decreases and stabilizes. With the increase of the IgG concentration, there is an obvious "inflection point" corresponding to the maximum value of the relative variance of the ionic current. The concentration of the electrolyte does not affect the position of the "inflection point", while temperature increment makes the "inflection point" shift to the high IgG concentration direction. Finally, a simplified model is suggested and the calculated results contribute to the understanding of the temperature induced IgG translocation behavior, which matches the ionic current changing tendency obtained in our experiments. PMID:26090531

  20. PELARGONIC ACID AND RAINFALL EFFECTS ON TOXICITY, ABSORPTION, AND TRANSLOCATION OF GLYPHOSATE IN TRUMPETCREEPER (CAMPSIS RADICANS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of pelargonic acid and rainfall on glyphosate activity, absorption, and translocation in trumpetcreeper were investigated. Four- to six-leaf stage (18 to 24 cm tall) trumpetcreeper plants raised from rootstocks were treated with glyphosate at 0, 0.56, 1.12, 2.24, and 4.48 kg ai/ha. Gly...

  1. Recurrent spontaneous abortions due to a homologous Robertsonian translocation (14q14q)

    PubMed Central

    Gracias-Espinal, R; Roberts, S H; Duckett, D P; Laurence, K M

    1982-01-01

    A female with a history of recurrent spontaneous abortions was shown to carry a balanced Robertsonian translocation involving the No 14 homologues. One abortus had trisomy 14 with a 46,XX,-14,+t(14q14q)mat karyotype. Images PMID:7154046

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

    E-print Network

    Dekker, Nynke

    and 3 Department of Biochemistry, School of Medical Sciences, Bristol, UK Type I restriction enzymes use translocation; molecular motor; restriction enzymes; SF2 helicase; single molecules Introduction For the linear of a complete superfamily 2 (SF2) helicase­loader complex, the Type I restriction­modification (RM) enzyme Eco

  3. Detecting intracellular translocation of native proteins quantitatively at the single cell level

    E-print Network

    Lu, Chang

    and selectively transit between functionally distinct subcellular compartments including plasma membrane, cytosol Zhenning Cao,a Shuo Geng,b Liwu Lib and Chang Lu*ac The intracellular localization and movement (i.e. translocation) of proteins are critically correlated with the functions and activation states of these proteins

  4. Running Title: Chloroplast Sec and Tat protein transport THE SEC AND TAT PROTEIN TRANSLOCATION PATHWAYS IN

    E-print Network

    the targeting pathways of the nuclear encoded thylakoid proteins. Chloroplasts are readily isolated from1 Running Title: Chloroplast Sec and Tat protein transport THE SEC AND TAT PROTEIN TRANSLOCATION proteins are encoded by nuclear genes, translated in the cytosol as precursor proteins, and post

  5. Edinburgh Research Explorer Effects of a balanced translocation between chromosomes 1 and

    E-print Network

    Millar, Andrew J.

    disrupting the DISC1 locus on white matter integrity Citation for published version: Whalley, H, Dimitrova, RIntosh, A & Lawrie, S 2015, 'Effects of a balanced translocation between chromosomes 1 and 11 disrupting the DISC1 and 11 Disrupting the DISC1 Locus on White Matter Integrity Heather C. Whalley1 * , Rali Dimitrova1

  6. Hungarian case with Costello syndrome and translocation t(1,22)

    SciTech Connect

    1995-07-03

    The purpose of this short case report is to document the presence of the Costello syndrome in a Hungarian girl. Clinical manifestations include characteristic facial changes, skeletal involvements, mild mental retardation. Chromosome analysis showed a balanced translocation: 46,XX,t(1,22)(q25,q11). 7 refs., 1 fig.

  7. Molecular signals required for type III secretion and translocation of the Xanthomonas campestris

    E-print Network

    Molecular signals required for type III secretion and translocation of the Xanthomonas campestris Halle, Germany Contributed by Brian J. Staskawicz, September 20, 2000 Strains of Xanthomonas campestris of a potential mRNA secretion signal. Bacterial spot disease of tomato and pepper is caused by Xanthomonas

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

    E-print Network

    ) The bacterial pathogen Xanthomonas campestris pv. vesicatoria (Xcv) uses a type III secretion system (TTSS outside plant cells (3). We are interested in elucidating how Xanthomonas campestris pv. vesicatoria (XcvA genetic screen to isolate type III effectors translocated into pepper cells during Xanthomonas

  9. Long-term apparent survival of translocated gopher tortoises: A comparison of newly released

    E-print Network

    Todd, Brian

    Long-term apparent survival of translocated gopher tortoises: A comparison of newly released disturbance as a result of increased mortality or dispersal of released animals. The gopher tortoise (Gopherus that dispersal by released tortoises is common, but few long-term data are available to determine if losses

  10. Disease dynamics during wildlife translocations: disruptions to the host population and potential

    E-print Network

    Bansal, Shweta

    consequences for transmission in desert tortoise contact networks C. M. Aiello1,2 , K. E. Nussear1 , A. D transmission dynamics; contact networks; desert tortoise; Mycoplasma. Correspondence Christina M. Aiello, U of conservation concern often translocated in the presence of infectious disease, the Mojave Desert tortoise

  11. A molecular switch in SecA protein couples ATP hydrolysis to protein translocation

    E-print Network

    Economou, Tassos

    A molecular switch in SecA protein couples ATP hydrolysis to protein translocation SpyridoulaA dimers. NBD1 is suffi- cient for single rounds of SecA ATP hydrolysis. Multi- ple ATP turnovers at NBD1. This intramolecular regulator of ATP hydrolysis (IRA) mediates N-/C-domain binding and acts as a molecular switch

  12. The effect of iron plaque on lead translocation in soil-Carex cinerascens kukenth. system.

    PubMed

    Liu, Chunying; Gong, Xiaofeng; Chen, Chunli; Yang, Juyun; Xu, Sheng

    2016-01-01

    A pot experiment was conducted to investigate the effect of iron plaque on Pb uptake by and translocation in Carex cinerascens Kukenth. grown under open-air conditions. Using Scanning Electron Microscopy and Energy Dispersive X-Ray Spectrometry, iron plaque was present as an amorphous coating on root surfaces with uneven distribution. The amount of iron plaque increased significantly with increasing Fe additions regardless of Pb additions. The presence of iron plaque on the root surface of Carex cinerascens Kukenth. increased the concentrations of Pb adsorbed by iron plaque. The Pb percentage in whole roots increased by 14.52% at 500 mg kg(-1) Fe treatment than at 0 mg kg(-1) Fe, and the distribution coefficient (DC) of Pb and translocation factor (TF) root increased with Fe additions, but translocation factor (TF) shoot decreased with Fe additions. The results suggested that iron plaque could promote the translocation of Pb from soil to roots to some extent, and it played a role to reduce heavy metals pollution of Poyang Lake wetland. PMID:26364868

  13. Visualization of two transfer RNAs trapped in transit during elongation factor G-mediated translocation.

    PubMed

    Ramrath, David J F; Lancaster, Laura; Sprink, Thiemo; Mielke, Thorsten; Loerke, Justus; Noller, Harry F; Spahn, Christian M T

    2013-12-24

    During protein synthesis, coupled translocation of messenger RNAs (mRNA) and transfer RNAs (tRNA) through the ribosome takes place following formation of each peptide bond. The reaction is facilitated by large-scale conformational changes within the ribosomal complex and catalyzed by elongtion factor G (EF-G). Previous structural analysis of the interaction of EF-G with the ribosome used either model complexes containing no tRNA or only a single tRNA, or complexes where EF-G was directly bound to ribosomes in the posttranslocational state. Here, we present a multiparticle cryo-EM reconstruction of a translocation intermediate containing two tRNAs trapped in transit, bound in chimeric intrasubunit ap/P and pe/E hybrid states. The downstream ap/P-tRNA is contacted by domain IV of EF-G and P-site elements within the 30S subunit body, whereas the upstream pe/E-tRNA maintains tight interactions with P-site elements of the swiveled 30S head. Remarkably, a tight compaction of the tRNA pair can be seen in this state. The translocational intermediate presented here represents a previously missing link in understanding the mechanism of translocation, revealing that the ribosome uses two distinct molecular ratchets, involving both intra- and intersubunit rotational movements, to drive the synchronous movement of tRNAs and mRNA. PMID:24324168

  14. Slowing down single-molecule trafficking through a protein nanopore reveals intermediates for peptide translocation

    PubMed Central

    Mereuta, Loredana; Roy, Mahua; Asandei, Alina; Lee, Jong Kook; Park, Yoonkyung; Andricioaei, Ioan; Luchian, Tudor

    2014-01-01

    The microscopic details of how peptides translocate one at a time through nanopores are crucial determinants for transport through membrane pores and important in developing nano-technologies. To date, the translocation process has been too fast relative to the resolution of the single molecule techniques that sought to detect its milestones. Using pH-tuned single-molecule electrophysiology and molecular dynamics simulations, we demonstrate how peptide passage through the ?-hemolysin protein can be sufficiently slowed down to observe intermediate single-peptide sub-states associated to distinct structural milestones along the pore, and how to control residence time, direction and the sequence of spatio-temporal state-to-state dynamics of a single peptide. Molecular dynamics simulations of peptide translocation reveal the time- dependent ordering of intermediate structures of the translocating peptide inside the pore at atomic resolution. Calculations of the expected current ratios of the different pore-blocking microstates and their time sequencing are in accord with the recorded current traces. PMID:24463372

  15. Literacy as a Translocal Practice: Digital Multimodal Literacy Practices among Girls Resettled as Refugees

    ERIC Educational Resources Information Center

    Omerbašic, Delila

    2015-01-01

    Situated in critical sociocultural theory of literacy with a particular focus on literacy in relation to space and displacement, this qualitative study considers how nine teenage girls who were resettled as refugees from Thailand engage in productions of translocality through multimodal literacy practices in digital spaces. The girls are…

  16. Biphasic character of ribosomal translocation and non-Michaelis-Menten kinetics of translation

    NASA Astrophysics Data System (ADS)

    Xie, Ping

    2014-12-01

    We study theoretically the kinetics of mRNA translocation in the wild-type (WT) Escherichia coli ribosome, which is composed of a small 30 S and large 50 S subunit, and the ribosomes with mutations to some intersubunit bridges such as B1a, B4, B7a, and B8. The theoretical results reproduce well the available in vitro experimental data on the biphasic kinetics of the forward mRNA translocation catalyzed by elongation factor G (EF-G) hydrolyzing GTP, which can be best fit by the sum of two exponentials, and the monophasic kinetics of the spontaneous reverse mRNA translocation in the absence of the elongation factor, which can be best fit by a single-exponential function, in both the WT and mutant ribosomes. We show that both the mutation-induced increase in the maximal rate of the slow phase for the forward mRNA translocation and that in the rate of the spontaneous reverse mRNA translocation result from a reduction in the intrinsic energy barrier to resist the rotational movements between the two subunits, giving the same degree of increase in the two rates. The mutation-induced increase in the maximal rate of the fast phase for the forward mRNA translocation results mainly from the increase in the rate of the ribosomal unlocking, a conformational change in the ribosome that widens the mRNA channel for the mRNA translocation to take place, which could be partly due to the effect of the mutation on the intrasubunit 30S head rotation. Moreover, we study the translation rate of the WT and mutant ribosomes. It is shown that the translation rate versus the concentration of EF-G-GTP does not follow the Michaelis-Menten (MM) kinetics, which is in sharp contrast to the general property of other enzymes that the rate of the enzymatic reaction versus the concentration of a substrate follows the MM kinetics. The physical origin of this non-MM kinetics for the ribosome is revealed.

  17. The study of the mechanisms of the different phenotypical manifestations in patients with reciprocal translocations

    NASA Astrophysics Data System (ADS)

    Lozynskyi, Rostyslav; Lozynska, Maria

    2006-04-01

    Cytogenetical study of lymphocytes using the light microscopy could reveal a large amount of chromosomal abnormalities, which determine corresponding hereditary disorders. However, geneticists sometimes observe the cases where the same chromosomal rearrangements seen in light microscope cause quite different phenotype (from normal to abnormal) in relatives. The aim of the study was to explain the mechanisms of the different phenotype appearance in family members carrying the same reciprocal translocations. It was carried out the standard chromosome analysis in 12 families, where some relatives had reciprocal translocations. Chromosomes were differentially stained using G-method. The samples were analysed in optical microscope (x1000). Using OMIM gene map, UCSC Genome Browser, eGenome Release v2.3 and Unigene databases it was revealed transposons and transposon derivates in chromosome regions involved in translocations. We suppose that the variability of clinical manifestations in translocation-bearing patient is caused by the influence of the transposons, such as Hsmar2, Alu-elements or some others. We propose the following mechanisms of transposone action in these patients. The first may lie on recombination between the 2 specific DNA-transposon containing sites on different chromosomes resulting in balanced reciprocal translocation with no significant influence on the most genes' activity in corresponding regions. The weakening of transposase repression, which may follow in gametes, increases the transposase activity, and hereby, the probability of transposon dislocation. Dislocation can change the activity of groups of genes, because transposons often carry the regulatory sequences. This can induce multiply innate disorders in the progeny of the phenotypically healthy parents, carrying the translocation. According to the second mechanism, the reciprocal translocation is caused by recombination between 2 Alu repeats. These repeats can undergo reverse transcription, and a DNA-product, formed during this process, can paste in a new chromosome region in gametes. As the Alu repeats contain the CpG-islands, they can change the gene activity resulting in a disorder. The understanding of the cases of such genetical disorders might help to predict the appearance of the progeny with pathological karyotype, making the light microscopy more informative in diagnostic of the diseases.

  18. Tumor suppressor, AT motif binding factor 1 (ATBF1), translocates to the nucleus with runt domain transcription factor 3 (RUNX3) in response to TGF-{beta} signal transduction

    SciTech Connect

    Mabuchi, Motoshi; Koseiin Medical Welfare Center, Nagoya ; Kataoka, Hiromi; Miura, Yutaka; Kim, Tae-Sun; Kawaguchi, Makoto; Ebi, Masahide; Tanaka, Mamoru; Mori, Yoshinori; Kubota, Eiji; Mizushima, Takashi; Shimura, Takaya; Mizoshita, Tsutomu; Tanida, Satoshi; Kamiya, Takeshi; Asai, Kiyofumi; Joh, Takashi

    2010-07-23

    Research highlights: {yields} Significant correlation between ATBF1 and RUNX3 nuclear localization in gastric cancer. {yields} Co-IP reveals a physical association between ATBF1 and RUNX3. {yields} ATBF1 and RUNX3 up-regulates p21 promoter activity synergistically. {yields} TGF-{beta}1 induces endogenous ATBF1 and RUNX3 nuclear translocation. -- Abstract: Background and aims: AT motif binding factor 1 (ATBF1), a homeotic transcription factor, was identified as a tumor suppressor, and loss of heterozygosity at ATBF1 locus occurs frequently in gastric cancers. We previously showed that ATBF1 expression inversely correlated with the malignant character of gastric cancer and that ATBF1 enhanced the promoter activity of p21{sup Waf1/Cip1}. We also found that ATBF1 moves between cytoplasm and nucleus, but the precise mechanism of translocation is unknown. In this study, we investigated the mechanism of ATBF1 translocation to the nucleus with the runt domain transcription factor 3 (RUNX3) in cooperation with TGF-{beta} signal transduction. Materials and methods: To analyze the expression of ATBF1 and RUNX3 in gastric cancer cells, we performed immunohistochemistry on 98 resected gastric cancer tissue samples and scored the nuclear staining intensity as grade 0 to grade 5. Co-immunoprecipitation (co-IP) of ATBF1 and RUNX3 was performed. Dual luciferase assays were performed by transfecting ATBF1 and RUNX3 with a p21{sup Waf1/Cip1} reporter vector. To investigate the nuclear translocation of endogenous ATBF1 and RUNX3 in response to TGF-{beta} signal, we examined the subcellular localization of ATBF1 and RUNX3 in gastric cancer cells treated with recombinant TGF-{beta}1 using confocal laser scanning microscopy. Results: Strong immunohistochemical nuclear staining of ATBF1 was observed in 37 (37.8%) of the gastric cancer tissue samples, and RUNX3 nuclear staining was observed in 15 (15.3%). There was a statistically significant correlation between ATBF1 and RUNX3 nuclear localization (rs = 0.433, p < 0.001). Co-IP revealed a physical association between ATBF1 and RUNX3. ATBF1 and RUNX3 up-regulated p21{sup Waf1/Cip1} promoter activity synergistically. In SNU16 gastric cancer cells, ATBF1 and RUNX3 were cytoplasmic before TGF-{beta}1 stimulation, but after 24 h of TGF-{beta}1 stimulation, endogenous ATBF1 and RUNX3 translocated to the nucleus. Conclusion: ATBF1 associates with RUNX3 and translocates to the nucleus in response to TGF-{beta} signal transduction and might function in the nucleus as tumor suppressor and transcriptional regulator.

  19. Impact of tamoxifen on adipocyte lineage tracing: Inducer of adipogenesis and prolonged nuclear translocation of Cre recombinase

    PubMed Central

    Ye, Risheng; Wang, Qiong A.; Tao, Caroline; Vishvanath, Lavanya; Shao, Mengle; McDonald, Jeffery G.; Gupta, Rana K.; Scherer, Philipp E.

    2015-01-01

    Background The selective estrogen receptor modulator tamoxifen, in combination with the Cre-ERT2 fusion protein, has been one of the mainstream methods to induce genetic recombination and has found widespread application in lineage tracing studies. Methods & results Here, we report that tamoxifen exposure at widely used concentrations remains detectable by mass-spectrometric analysis in adipose tissue after a washout period of 10 days. Surprisingly, its ability to maintain nuclear translocation of the Cre-ERT2 protein is preserved beyond 2 months of washout. Tamoxifen treatment acutely leads to transient lipoatrophy, followed by de novo adipogenesis that reconstitutes the original fat mass. In addition, we find a “synthetically lethal” phenotype for adipocytes when tamoxifen treatment is combined with adipocyte-specific loss-of-function mutants, such as an adipocyte-specific PPAR? knockout. This is observed to a lesser extent when alternative inducible approaches are employed. Conclusions These findings highlight the potential for tamoxifen-induced adipogenesis, and the associated drawbacks of the use of tamoxifen in lineage tracing studies, explaining the discrepancy in lineage tracing results from different systems with temporal control of gene targeting. PMID:26629402

  20. SepD/SepL-Dependent Secretion Signals of the Type III Secretion System Translocator Proteins in Enteropathogenic Escherichia coli

    PubMed Central

    Deng, Wanyin; Yu, Hong B.; Li, Yuling

    2015-01-01

    ABSTRACT The type III protein secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE) is essential for the pathogenesis of attaching/effacing bacterial pathogens, including enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. These pathogens use the T3SS to sequentially secrete three categories of proteins: the T3SS needle and inner rod protein components; the EspA, EspB, and EspD translocators; and many LEE- and non-LEE-encoded effectors. SepD and SepL are essential for translocator secretion, and mutations in either lead to hypersecretion of effectors. However, how SepD and SepL control translocator secretion and secretion hierarchy between translocators and effectors is poorly understood. In this report, we show that the secreted T3SS components, the translocators, and both LEE- and non-LEE-encoded effectors all carry N-terminal type III secretion and translocation signals. These signals all behave like those of the effectors and are sufficient for mediating type III secretion and translocation by wild-type EPEC and hypersecretion by the sepD and sepL mutants. Our results extended previous observations and suggest that the secretion hierarchy of the different substrates is determined by a signal other than the N-terminal secretion signal. We identified a domain located immediately downstream of the N-terminal secretion signal in the translocator EspB that is required for SepD/SepL-dependent secretion. We further demonstrated that this EspB domain confers SepD/SepL- and CesAB-dependent secretion on the secretion signal of effector EspZ. Our results thus suggest that SepD and SepL control and regulate secretion hierarchy between translocators and effectors by recognizing translocator-specific export signals. IMPORTANCE Many bacterial pathogens use a syringe-like protein secretion apparatus, termed the type III protein secretion system (T3SS), to secrete and inject numerous proteins directly into the host cells to cause disease. The secreted proteins perform different functions at various stages during infection and are classified into three substrate categories (T3SS components, translocators, and effectors). They all contain secretion signals at their N termini, but how their secretion hierarchy is determined is poorly understood. Here, we show that the N-terminal secretion signals from different substrate categories all behave the same and do not confer substrate specificity. We further characterize the secretion signals of the translocators and identify a translocator-specific signal, demonstrating that substrate-specific secretion signals are required in regulating T3SS substrate hierarchy. PMID:25645555