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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. BCL2 translocation frequency rises with age in humans

    SciTech Connect

    Liu, Y.; Hernandez, A.M.; Shibata, D.; Cortopassi, G.A.

    1994-09-13

    The background frequency of t(14;18) (q32;q21) chromosomal translocations at the locus associated with B-cell leukemia/lymphoma-2 (BCL2) was determined from a survey of the peripheral blood lymphocytes (PBLs) of 53 living individuals and from tissues of 31 autopsies by using a nested PCR assay. The translocation was detected in 55% of PBLs and 35% of autopsied spleens with a frequency of between less than 1 to 853 translocations per million cells. Translocations copurified with B lymphocytes. The frequency of translocations significantly increased with age in PBLs and spleens, as does human risk for lymphoma. Average translocation frequency was more than 40 times greater in the spleen and 13 times greater in the peripheral blood in the oldest individuals (61 yr and older) compared with the youngest individuals (20 yr or younger). Particular t(14;18)-bearing clones persisted over a period of 5 months in two individuals. These findings demonstrate that clones harboring the oncogenic t(14;18) chromosomal translocation are commonly present in normal humans, that such clones are long-lived, and that they rise in frequency with age. A multihit model of lymphomagenesis involving t(14;18) translocation followed by antigen stimulation is proposed. 49 refs., 8 figs., 1 tab.

  3. The Effects of Translocations on Recombination Frequency in Caenorhabditis Elegans

    PubMed Central

    McKim, K. S.; Howell, A. M.; Rose, A. M.

    1988-01-01

    In the nematode Caenorhabditis elegans, recombination suppression in translocation heterozygotes is severe and extensive. We have examined the meiotic properties of two translocations involving chromosome I, szT1(I;X) and hT1(I;V). No recombination was observed in either of these translocation heterozygotes along the left (let-362-unc-13) 17 map units of chromosome I. Using half-translocations as free duplications, we mapped the breakpoints of szT1 and hT1. The boundaries of crossover suppression coincided with the physical breakpoints. We propose that DNA sequences at the right end of chromosome I facilitate pairing and recombination. We use the data from translocations of other chromosomes to map the location of pairing sites on four other chromosomes. hT1 and szT1 differed markedly in their effect on recombination adjacent to the crossover suppressed region. hT1 had no effect on recombination in the adjacent interval. In contrast, the 0.8 map unit interval immediately adjacent to the szT1(I;X) breakpoint on chromosome I increased to 2.5 map units in translocation heterozygotes. This increase occurs in a chromosomal interval which can be expanded by treatment with radiation. These results are consistent with the suggestion that the szT1(I) breakpoint is in a region of DNA in which meiotic recombination is suppressed relative to the genomic average. We propose that DNA sequences disrupted by the szT1 translocation are responsible for determining the frequency of meiotic recombination in the vicinity of the breakpoint. PMID:3224815

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

    PubMed Central

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

    2009-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  6. 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.

  7. 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.

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

    PubMed

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

    2015-07-01

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

  9. 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

  10. 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.

  11. 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

  12. Background-Free Fourth-Order Sum Frequency Generation Spectroscopy.

    PubMed

    Schleeger, Michael; Grechko, Maksim; Bonn, Mischa

    2015-06-01

    The recently developed 2D sum frequency generation spectroscopy offers new possibilities to analyze the structure and structural dynamics of interfaces in a surface-specific manner. Its implementation, however, has so far remained limited to the pump-probe geometry, with its inherent restrictions. Here we present 2D SFG experiments utilizing a novel noncollinear geometry of four incident laser pulses generating a 2D SFG response, analogous to the triangle geometry applied in bulk-sensitive 2D infrared spectroscopy. This approach allows for background-free measurements of fourth-order nonlinear signals, which is demonstrated by measuring the fourth-order material response from a GaAs (110) surface. The implementation of phase-sensitive detection and broadband excitation pulses allows for both highest possible time resolution and high spectral resolution of the pump axis of a measured 2D SFG spectrum. To reduce the noise in our spectra, we employ a referencing procedure, for which we use noncollinear pathways and individual focusing for the signal and local oscillator beams. The 2D spectra recorded from the GaAs (110) surface show nonzero responses for the real and imaginary component, pointing to contributions from resonant electronic pathways to the ?((4)) response. PMID:26266512

  13. ROUTINE DIAGNOSTIC X-RAY EXAMINATIONS AND INCREASED FREQUENCY OF CHROMOSOME TRANSLOCATIONS AMONG U. S. RADIOLOGIC TECHNOLOGISTS

    PubMed Central

    Sigurdson, Alice J.; Bhatti, Parveen; Preston, Dale L.; Doody, Michele Morin; Kampa, Diane; Alexander, Bruce H.; Petibone, Dayton; Yong, Lee C.; Edwards, Alan A.; Ron, Elaine; Tucker, James D.

    2008-01-01

    The U.S. population has nearly one radiographic examination per person per year and concern about cancer risks associated with medical radiation has increased. Radiologic technologists were surveyed to determine whether their personal cumulative exposure to diagnostic x-rays was associated with increased frequencies of chromosome translocations, an established radiation biomarker and possible intermediary suggesting increased cancer risk. Within a large cohort of U. S. radiologic technologists, 150 provided a blood sample for whole chromosome painting and were interviewed about past x-ray examinations. The number and types of examinations reported were converted to a red bone marrow (RBM) dose score with units that approximated 1 mGy. The relationship between dose score and chromosome translocation frequency was assessed using Poisson regression. The estimated mean cumulative RBM radiation dose score was 49 (range 0 303). After adjustment for age, translocation frequencies significantly increased with increasing RBM dose score with an estimate of 0.004 translocations per 100 cell equivalents per score unit (95% confidence interval 0.002 to 0.007; P < 0.001). Removing extreme values or adjustment for gender, cigarette smoking, occupational radiation dose, allowing practice x-rays while training, work with radioisotopes, and radiotherapy for benign conditions did not affect the estimate. Cumulative radiation exposure from routine x-ray examinations was associated independently with increased chromosome damage, suggesting the possibility of elevated long-term health risks, including cancer. The slope estimate was consistent with expectation based on cytogenetic experience and atomic bomb survivor data. PMID:18974125

  14. Genetic counseling in Robertsonian translocations der(13;14): frequencies of reproductive outcomes and infertility in 101 pedigrees.

    PubMed

    Engels, Hartmut; Eggermann, Thomas; Caliebe, Almut; Jelska, Anna; Schubert, Regine; Schüler, Herdit M; Panasiuk, Barbara; Zaremba, Jacek; Latos-Bieleńska, Anna; Jakubowski, Lucjusz; Zerres, Klaus P; Schwanitz, Gesa; Midro, Alina T

    2008-10-15

    Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 +/- 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 +/- 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 +/- 1.6% for female carriers and 1.4 +/- 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample. PMID:18798317

  15. 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

  16. 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

  17. 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.

  18. Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host

    PubMed Central

    Alaish, Samuel M.; Smith, Alexis D.; Timmons, Jennifer; Greenspon, Jose; Eyvazzadeh, Daniel; Murphy, Ebony; Shea-Donahue, Terez; Cirimotich, Shana; Mongodin, Emmanuel; Zhao, Aiping; Fasano, Alessio; Nataro, James P.; Cross, Alan S

    2013-01-01

    Failure of the intestinal barrier is a characteristic feature of cholestasis. We have previously observed higher mortality in C57BL/6J compared with A/J mice following common bile duct ligation (CBDL). We hypothesized the alteration in gut barrier function following cholestasis would vary by genetic background. Following one week of CBDL, jejunal TEER was significantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TEER was significantly lower in both sham and ligated C57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was significantly increased in C57BL/6J mice vs. A/J mice. Four of 15 C57BL/6J mice were bacteremic; whereas, none of the 17 A/J mice were. Jejunal IFN-γ mRNA expression was significantly elevated in C57BL/6J compared with A/J mice. Western blot analysis demonstrated a significant decrease in occludin protein expression in C57BL/6J compared with A/J mice following both sham operation and CBDL. Only C57BL/6J mice demonstrated a marked decrease in ZO-1 protein expression following CBDL compared with shams. Pyrosequencing of the 16S rRNA gene in fecal samples showed a dysbiosis only in C57BL/6J mice following CBDL when compared with shams. This study provides evidence of strain differences in gut microbiota, tight junction protein expression, intestinal resistance and bacterial translocation which supports the notion of a genetic predisposition to exaggerated injury following cholestasis. PMID:23652772

  19. Enhancing unsupervised canonical correlation analysis-based frequency detection of SSVEPs by incorporating background EEG.

    PubMed

    Nakanishi, Masaki; Wang, Yijun; Wang, Yu-Te; Mitsukura, Yasue; Jung, Tzyy-Ping

    2014-01-01

    Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) have potential to provide a fast communication channel between human brain and external devices. In SSVEP-based BCIs, Canonical Correlation Analysis (CCA) has been widely used to detect frequency-coded SSVEPs due to its high efficiency and robustness. However, the detectability of SSVEPs differs among frequencies due to a power-law distribution of the power spectra of spontaneous electroencephalogram (EEG) signals. This study proposed a new method based on the fact that changes of canonical correlation coefficients for SSVEPs and background EEG signals follow the same trend along frequency. The proposed method defined a normalized canonical correlation coefficient, the ratio of the canonical correlation coefficient for SSVEPs to the mean of the canonical correlation coefficients for background EEG signals, to enhance the frequency detection of SSVEPs. An SSVEP dataset from 13 subjects was used for comparing classification performance between the proposed method and the standard CCA method. Classification accuracy and simulated information transfer rates (ITR) suggest that, in an unsupervised way, the proposed method could considerably improve the frequency detection accuracy of SSVEPs with little computational effort. PMID:25570635

  20. 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.

  1. Combined effects of frequency and layer removal on background track characteristics of ECE polycarbonate detectors

    NASA Astrophysics Data System (ADS)

    Sohrabi, Mehdi; Soltani, Zahra; Hakimi, Amir

    2016-02-01

    Polycarbonate track detectors (PCTD) when electrochemically etched (ECE) provide excellent characteristics for registering relatively lower-LET charged particles (e.g. alphas, fast-neutron-induced recoils) for many health physics and ion detection applications.The layer removal method of PCTDs by ethylenediamine (EDA) developed in our laboratory reduces the background track (BGT) density significantly. The frequency of the applied electric field strongly affects the BGT density and diameter and thus affects the minimum detection limit (MDL). In order to study the combined effects of the frequency and layer removal on the BGT density and thus on the MDL, this research was conducted. The BGT density versus the layer thickness removed at frequencies up to 12 kHz decrease rapidly to about 10-20 μm above which they reach a minimum constant level, while the mean BGT diameter verses layer removed at all frequencies are constant with flat responses. On the other hand the BGT density and diameter versus frequency at different layers removed up to ~50 μm increase till 4 kHz above which they reach plateaus. The PCTDs with ~20 μm layer removal at frequencies up 1 to 2 kHz showed the lowest MDL. The results are presented and discussed.

  2. State transition induced by higher-order effects and background frequency

    NASA Astrophysics Data System (ADS)

    Liu, Chong; Yang, Zhan-Ying; Zhao, Li-Chen; Yang, Wen-Li

    2015-02-01

    The state transition between the Peregrine rogue wave and W-shaped traveling wave induced by higher-order effects and background frequency is studied. We find that this intriguing transition, described by an exact explicit rational solution, is consistent with the modulation instability (MI) analysis that involves a MI region and a stability region in a low perturbation frequency region. In particular, the link between the MI growth rate and the transition characteristic analytically demonstrates that the localization characteristic of transition is positively associated with the reciprocal of the zero-frequency growth rate. Furthermore, we investigate the case for nonlinear interplay of multilocalized waves. It is interesting that the interaction of second-order waves in the stability region features a line structure rather than an elastic interaction between two W-shaped traveling waves.

  3. 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

  4. 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

  5. Short Segment Frequency Equalization: A Simple and Effective Alternative Treatment of Background Models in Motif Discovery

    NASA Astrophysics Data System (ADS)

    Shida, Kazuhito

    One of the most important pattern recognition problems in bioinformatics is the de novo motif discovery. In particular, there is a large room of improvement in motif discovery from eukaryotic genome, where the sequences have complicated background noise. The short segment frequency equalization (SSFE) is a novel treatment method to incorporate Markov background models into de novo motif discovery algorithms, namely Gibbs sampling. Despite its apparent simplicity, SSFE shows a large performance improvement over the current method ( Q/P scheme) when tested on artificial DNA datasets with Markov background of human and mouse. Furthermore, SSFE shows a better performance than other methods including much more complicated and sophisticated method, Weeder 1.3, when tested with several biological datasets from human promoters.

  6. 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

  7. 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

  8. 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. .

  9. 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.

  10. Prepulse Inhibition of Acoustic Startle Reflex as a Function of the Frequency Difference between Prepulse and Background Sounds in Mice

    PubMed Central

    Basavaraj, Sidhesh; Yan, Jun

    2012-01-01

    Background Prepulse inhibition (PPI) depicts the effects of a weak sound preceding strong acoustic stimulus on acoustic startle response (ASR). Previous studies suggest that PPI is influenced by physical parameters of prepulse sound such as intensity and preceding time. The present study characterizes the impact of prepulse tone frequency on PPI. Methods Seven female C57BL mice were used in the present study. ASR was induced by a 100 dB SPL white noise burst. After assessing the effect of background sounds (white noise and pure tones) on ASR, PPI was tested by using prepulse pure tones with the background tone of either 10 or 18 kHz. The inhibitory effect was assessed by measuring and analyzing the changes in the first peak-to-peak magnitude, root mean square value, duration and latency of the ASR as the function of frequency difference between prepulse and background tones. Results Our data showed that ASR magnitude with pure tone background varied with tone frequency and was smaller than that with white noise background. Prepulse tone systematically reduced ASR as the function of the difference in frequency between prepulse and background tone. The 0.5 kHz difference appeared to be a prerequisite for inducing substantial ASR inhibition. The frequency dependence of PPI was similar under either a 10 or 18 kHz background tone. Conclusion PPI is sensitive to frequency information of the prepulse sound. However, the critical factor is not tone frequency itself, but the frequency difference between the prepulse and background tones. PMID:22984620

  11. Haplotypic Background of a Private Allele at High Frequency in the Americas

    PubMed Central

    Schroeder, Kari B.; Jakobsson, Mattias; Crawford, Michael H.; Schurr, Theodore G.; Boca, Simina M.; Conrad, Donald F.; Tito, Raul Y.; Osipova, Ludmilla P.; Tarskaia, Larissa A.; Zhadanov, Sergey I.; Wall, Jeffrey D.; Pritchard, Jonathan K.; Malhi, Ripan S.; Smith, David G.; Rosenberg, Noah A.

    2009-01-01

    Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the “American Modal Haplotype” (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all modern Native Americans and Western Beringians trace a large portion of their ancestry to a single founding population that may have been isolated from other Asian populations prior to expanding into the Americas. PMID:19221006

  12. Observations of the radio noise background in the frequency range 150-180 kHz

    NASA Astrophysics Data System (ADS)

    Knowles, S. H.; Kelly, F. J.; Waltman, W. B.; Odenwald, S.

    1985-05-01

    Observations were made of the radio noise background in the frequency range 150-180 kHz to provide reference data for the design of the ground wave emergency network system. These observations were undertaken at Nanjemoy, Maryland, during early summer 1983 and included 41 days of data recording. The noise environment was found to be dominated by impulsive thunderstorm noise. A typical nighttime mean noise power spectral density was 110-15 W m-2 Hz-1 (noise factor of 107 dB above kT0), while a typical daytime level was at least 14 dB quieter. However, the daytime level was at times significantly higher, especially during the presence of a local thunderstorm front. During local thunderstorm activity, impulses with peak power spectral density of 110-14 W m-2 Hz-1 were observed frequently, while the most energetic pulse detected during our monitoring period had a peak power spectral density of 6.810-14 W m-2 Hz-1 (Fa = 125 dB). Sample amplitude probability distributions and time probability distributions are presented for day/quiet, night, and thunderstorm conditions. Agreement with the mean noise level predictions of CCIR report 322 is satisfactory within the accuracy limits of the CCIR data.

  13. 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

  14. 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.

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

    PubMed

    Szymaniec, Krzysztof; Lea, Stephen; Liu, Kun

    2014-01-01

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

  16. DNA Repair and Chromosomal Translocations.

    PubMed

    Bohlander, Stefan K; Kakadia, Purvi M

    2015-01-01

    The balance between DNA damage, especially double strand breaks, and DNA damage repair is a critical determinant of chromosomal translocation frequency. The non-homologous end-joining repair (NHEJ) pathways seem to play the major role in the generation of chromosomal translocations. The "landscape" of chromosomal translocation identified in malignancies is largely due to selection processes which operate on the growth advantages conveyed to the cells by the functional consequences of chromosomal translocations (i.e., oncogenic fusion proteins and overexpression of oncogenes, both compromising tumor suppressor gene functions). Newer studies have shown that there is an abundance of local rearrangements in many tumors, like small deletions and inversions. A better understanding of the interplay between DNA repair mechanisms and the generation of tumorigenic translocations will, among many other things, depend on an improved understanding of DNA repair mechanisms and their interplay with chromatin and the 3D organization of the interphase nucleus. PMID:26376870

  17. 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.

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

    SciTech Connect

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

    1983-06-01

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

  19. Low Frequency Measurement of the Spectrum of the Cosmic Background Radiation

    DOE R&D Accomplishments Database

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

    1983-06-01

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

  20. Wave number refraction and frequency modulation of medium scale gravity waves in 3-dimensional time-dependent background flows

    NASA Astrophysics Data System (ADS)

    Senf, Fabian; Achatz, Ulrich

    2010-05-01

    Going beyond the frame of classical vertical column thinking the inclusion of horizontal gradients of a background flow in the description of gravity waves (GWs) can have important impacts on GW propagation and its action back on that type of flows. The horizontal wave number and the wave-related horizontal pseudo-momentum can be refracted to different scales and azimuth directions which may lead to substantial changes in regions of dissipative pseudo-momentum deposition and therefore mean flow forcing. In this sense wave number refraction can have a remote effect in a distant dissipation region. Additionally, the time dependence of a background flow may lead to changes in the absolute, or sometimes called ground-based, frequency of the GWs moving through it. For periodic background flows a periodic frequency modulation is excited. Beside the conservative transient forcing the periodicity of frequency also changes the background flow forcing in dissipation regions. This effect does not appear in the commonly used approximation of an instantaneously adjusting GW train. In our contribution we use a sophisticated ray tracing method to infer the effects of the time dependence and horizontal gradients of diurnal solar-thermal tides plus a realistic 3-dimensional steady mean flow on the propagation of medium scale gravity waves in the middle atmosphere. Strongest wave number refraction and frequency modulation effects occur for slowly propagating GWs. Due to large tidal wind variations in the upper mesosphere most parts of the assumed GW spectrum are slowed down in critical layer type regions. Then, the combined action of horizontal wave number refraction and frequency modulation induce changes in the horizontal phase speed which may exceed orders of magnitude compared to the initial phase speed. The phase speed variations have the tendency to follow the shape of the tidal background wind. This effect leads to less critical layer filtering of GWs and therefore decreased periodic background flow forcing due to momentum flux divergences as compared to a classical vertical column parametrization of instantaneously adjusting GW trains.

  1. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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.

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

    PubMed

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

    2012-07-01

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

  4. 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.

  5. 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

  6. A Model of the Mixture of Background Noise and Lumped Interference During Reception of a High-Frequency Chirp Signal

    NASA Astrophysics Data System (ADS)

    Nedopekin, A. E.

    2015-11-01

    We present a statistical model of the mixture of background noise and spectrally lumped interference. Such a mixture is realized in the case of wideband reception of a high-frequency signal with chirp modulation over the entire decameter-wave range. The types of the probability distributions statistically describing the random noise and interference, as well as their sum in the time and frequency domains, are established. The level of lumped interference with respect to noise is estimated using the signal-envelope parameters and a method of the useful-signal isolation in the power spectrum on the basis of describing the noise and interference sum by the Weibull distribution is proposed.

  7. 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.

  8. Adaptation of frequency-domain readout for Transition Edge Sensor bolometers for the POLARBEAR-2 Cosmic Microwave Background experiment

    NASA Astrophysics Data System (ADS)

    Hattori, Kaori; Arnold, Kam; Barron, Darcy; Dobbs, Matt; de Haan, Tijmen; Harrington, Nicholas; Hasegawa, Masaya; Hazumi, Masashi; Holzapfel, William L.; Keating, Brian; Lee, Adrian T.; Morii, Hideki; Myers, Michael J.; Smecher, Graeme; Suzuki, Aritoki; Tomaru, Takayuki

    2013-12-01

    The POLARBEAR-2 Cosmic Microwave Background (CMB) experiment aims to observe B-mode polarization with high sensitivity to explore gravitational lensing of CMB and inflationary gravitational waves. POLARBEAR-2 is an upgraded experiment based on POLARBEAR-1, which had first light in January 2012. For POLARBEAR-2, we will build a receiver that has 7588 Transition Edge Sensor (TES) bolometers coupled to two-band (95 and 150 GHz) polarization-sensitive antennas. For the large array's readout, we employ digital frequency-domain multiplexing and multiplex 32 bolometers through a single superconducting quantum interference device (SQUID). An 8-bolometer frequency-domain multiplexing readout has been deployed with the POLARBEAR-1 experiment. Extending that architecture to 32 bolometers requires an increase in the bandwidth of the SQUID electronics to 3 MHz. To achieve this increase in bandwidth, we use Digital Active Nulling (DAN) on the digital frequency multiplexing platform. In this paper, we present requirements and improvements on parasitic inductance and resistance of cryogenic wiring and capacitors used for modulating bolometers. These components are problematic above 1 MHz. We also show that our system is able to bias a bolometer in its superconducting transition at 3 MHz.

  9. Spectroscopic Measurement of High-Frequency Electric Fields in the Interaction of Explosive Debris Plasma with Ambient, Magnetized Background Plasma

    NASA Astrophysics Data System (ADS)

    Bondarenko, Anton; Schaeffer, Derek; Everson, Erik; Clark, Eric; Vincena, Stephen; van Compernolle, Bart; Tripathi, Shreekrishna; Constantin, Carmen; Niemann, Chris

    2014-10-01

    The explosive expansion of dense, high-beta debris plasma into relatively tenuous, magnetized background plasma is relevant to a wide variety of astrophysical and space environments. Electric fields play a fundamental role in the coupling of momentum and energy from debris to background, and emission spectroscopy provides a powerful diagnostic for assessing electric fields via the Stark effect. A recent experiment utilizing a unique experimental platform at UCLA that combines the Large Plasma Device and the Raptor laser facility has investigated the super-Alfvénic, quasi-perpendicular expansion of a laser-produced carbon (C) debris plasma through a preformed, ambient, magnetized helium (He) background plasma via emission spectroscopy. Spectral profiles of the He II 468.6 nm line have been analyzed via single-mode and multi-mode time-dependent Stark broadening models for hydrogen-like ions, yielding large magnitude (~100 kV/cm), high-frequency (~100 GHz) electric fields. The measurements suggest the development of an electron beam-plasma instability, and a simple instability saturation model demonstrates that the measured electric field magnitudes are feasible under the experimental conditions.

  10. 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).

  11. IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques.

    PubMed

    Ortiz, A M; Klase, Z A; DiNapoli, S R; Vujkovic-Cvijin, I; Carmack, K; Perkins, M R; Calantone, N; Vinton, C L; Riddick, N E; Gallagher, J; Klatt, N R; McCune, J M; Estes, J D; Paiardini, M; Brenchley, J M

    2016-03-01

    Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4(+) T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals. PMID:26286233

  12. Signal photon flux and background noise in a coupling electromagnetic detecting system for high-frequency gravitational waves

    SciTech Connect

    Li Fangyu; Yang Nan; Fang Zhenyun; Wen Hao; Baker, Robert M. L. Jr.; Stephenson, Gary V.

    2009-09-15

    A coupling system among Gaussian-type microwave photon flux, a static magnetic field, and fractal membranes (or other equivalent microwave lenses) can be used to detect high-frequency gravitational waves (HFGWs) in the microwave band. We study the signal photon flux, background photon flux, and the requisite minimal accumulation time of the signal in the coupling system. Unlike the pure inverse Gertsenshtein effect (G effect) caused by the HFGWs in the gigahertz band, the electromagnetic (EM) detecting scheme proposed by China and the U.S. HFGW groups is based on the composite effect of the synchroresonance effect and the inverse G effect. The key parameter in the scheme is the first-order perturbative photon flux (PPF) and not the second-order PPF; the distinguishable signal is the transverse first-order PPF and not the longitudinal PPF; the photon flux focused by the fractal membranes or other equivalent microwave lenses is not only the transverse first-order PPF but the total transverse photon flux, and these photon fluxes have different signal-to-noise ratios at the different receiving surfaces. Theoretical analysis and numerical estimation show that the requisite minimal accumulation time of the signal at the special receiving surfaces and in the background noise fluctuation would be {approx}10{sup 3}-10{sup 5} seconds for the typical laboratory condition and parameters of h{sub rms}{approx}10{sup -26}-10{sup -30}/{radical}(Hz) at 5 GHz with bandwidth {approx}1 Hz. In addition, we review the inverse G effect in the EM detection of the HFGWs, and it is shown that the EM detecting scheme based only on the pure inverse G effect in the laboratory condition would not be useful to detect HFGWs in the microwave band.

  13. Investigating binding particles distribution effects on polymer translocation through nanopore

    NASA Astrophysics Data System (ADS)

    Haji Abdolvahab, Rouhollah

    2016-03-01

    Chaperone driven polymer translocation is an important model for biopolymer's translocation in vivo. Binding proteins spatial distribution is a significant factor in calculating the translocation time of the polymer in this type of translocation. Here using a dynamical Monte Carlo simulation we compare the results of the usual uniform distribution with the exponential distribution of different rates for a stiff polymer. Our simulation results show that just by changing the chaperones spatial distribution the translocation time of the biopolymer will change by as large as an order. It can change the translocation regime of the polymer completely from a diffusive to a ballistic one. Although generally increasing the exponential rate and the background concentration will increase the translocation velocity, it is not always true and one should consider both the sequence and the background concentration. We show that the results depend on the sequence and changing the distribution rates for increasing the translocation velocity will change the whole Probability Density Function (PDF) of the polymer translocation time accordance to its sequence. The translocation time sequence dependency will change in the extreme cases e.g. in the high exponential rate. Investigating the binding protein size, λ, also shows the importance of the so called parking lot effect in distribution dependency of the translocation velocity. Although there is not any important dependency for λ = 1, translocation time depends clearly on the chaperone spatial distribution for the case of λ ≥ 2.

  14. 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.

  15. Increase in frequencies of circulating Th-17 cells correlates with microbial translocation, immune activation and exhaustion in HIV-1 infected patients with poor CD4 T-cell reconstitution.

    PubMed

    Valiathan, Ranjini; Asthana, Deshratn

    2016-05-01

    We analyzed the association of circulating Th-17 cells (cTh-17) with immune activation (IA), immune exhaustion (IE) and regulatory T-cells (T-regs) in 20 human immunodeficiency virus-1 (HIV-1) infected patients with impaired restoration of CD4 T-cell counts despite prolonged suppression of plasma viremia (discordant) and compared it with 20 HIV-1 infected patients showing good immunologic and virologic responses (concordant) following highly active antiretroviral therapy (HAART). Discordant HIV-1 infected patients showed significantly higher frequencies of cTh-17 cells compared to concordant patients and healthy controls after PMA+Ionomicin stimulation. Discordant patients also showed higher CD4 T-cell immune activation (HLA-DR+CD38+) than concordant patients which directly correlated with microbial translocation. Additionally, CD4 T-cells of discordant patients showed higher frequencies of CD4 T-cells expressing multiple immune exhaustion markers (Tim3+PD-1+) which correlated with immune activation indicating that combined analysis of inhibitory molecules along with PD-1 might be a better predictor for immune exhaustion of CD4 T-cells. Increased cTh-17 cell frequency correlated inversely with CD4 T-cell percentages and absolute counts and directly with CD4 T-cell immune activation and T-reg frequencies. Persistent CD4 T-cell immune activation might favor differentiation of activated CD4 T-cells toward cTh-17 phenotype in discordant patients. Discordant patients had significantly lower baseline CD4 T-cell counts and higher viral load at the initiation of HAART and higher immune activation and immune exhaustion after being on HAART for long time indicating that these factors might be associated with an increase in cTh-17 cell frequency, thus, increasing the risk of disease progression despite virologic control. PMID:26817581

  16. 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. ...

  17. The cytokinesis-blocked micronucleus assay: dose-response calibration curve, background frequency in the population and dose estimation.

    PubMed

    Rastkhah, E; Zakeri, F; Ghoranneviss, M; Rajabpour, M R; Farshidpour, M R; Mianji, F; Bayat, M

    2016-03-01

    An in vitro study of the dose responses of human peripheral blood lymphocytes was conducted with the aim of creating calibrated dose-response curves for biodosimetry measuring up to 4 Gy (0.25-4 Gy) of gamma radiation. The cytokinesis-blocked micronucleus (CBMN) assay was employed to obtain the frequencies of micronuclei (MN) per binucleated cell in blood samples from 16 healthy donors (eight males and eight females) in two age ranges of 20-34 and 35-50 years. The data were used to construct the calibration curves for men and women in two age groups, separately. An increase in micronuclei yield with the dose in a linear-quadratic way was observed in all groups. To verify the applicability of the constructed calibration curve, MN yields were measured in peripheral blood lymphocytes of two real overexposed subjects and three irradiated samples with unknown dose, and the results were compared with dose values obtained from measuring dicentric chromosomes. The comparison of the results obtained by the two techniques indicated a good agreement between dose estimates. The average baseline frequency of MN for the 130 healthy non-exposed donors (77 men and 55 women, 20-60 years old divided into four age groups) ranged from 6 to 21 micronuclei per 1000 binucleated cells. Baseline MN frequencies were higher for women and for the older age group. The results presented in this study point out that the CBMN assay is a reliable, easier and valuable alternative method for biological dosimetry. PMID:26507139

  18. 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

  19. 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

  20. 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

  1. 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

  2. Clinical significance of translocation.

    PubMed Central

    Van Leeuwen, P A; Boermeester, M A; Houdijk, A P; Ferwerda, C C; Cuesta, M A; Meyer, S; Wesdorp, R I

    1994-01-01

    The gastrointestinal tract, besides being the organ responsible for nutrient absorption, is also a metabolic and immunological system, functioning as an effective barrier against endotoxin and bacteria in the intestinal lumen. The passage of viable bacteria from the gastrointestinal tract through the epithelial mucosa is called bacterial translocation. Equally important may be the passage of bacterial endotoxin through the mucosal barrier. This article reviews the evidence that translocation of both endotoxin and bacteria is of clinical significance. It summarises recent published works indicating that translocation of endotoxin in minute amounts is a physiological important phenomenon to boost the reticuloendothelial system (RES), especially the Kupffer cells, in the liver. Breakdown of both the mucosal barrier and the RES capacity results in systemic endotoxaemia. Systemic endotoxaemia results in organ dysfunction, impairs the mucosal barrier, the clotting system, the immune system, and depresses Kupffer cell function. If natural defence mechanisms such as lipopolysaccharide binding protein, high density lipoprotein, in combination with the RES, do not respond properly, dysfunction of the gut barrier results in bacterial translocation. Extensive work on bacterial translocation has been performed in animal models and occurs notably in haemorrhagic shock, thermal injury, protein malnutrition, endotoxaemia, trauma, and intestinal obstruction. It is difficult to extrapolate these results to humans and its clinical significance is not clear. The available data show that the resultant infection remains important in the development of sepsis, especially in the critically ill patient. Uncontrolled infection is, however, neither necessary nor sufficient to account for the development of multiple organ failure. A more plausible sequelae is that bacterial translocation is a later phenomenon of multiple organ failure, and not its initiator. It is hypothesized that multiple organ failure is more probably triggered by the combination of tissue damage and systemic endotoxaemia. Endotoxaemia, as seen in trauma patients especially during the first 24 hours, in combination with tissue elicits a systemic inflammation, called Schwartzmann reaction. Interferon gamma, a T cell produced cytokine, is thought to play a pivotal part in the pathogenesis of this reaction. This reaction might occur only if the endotoxin induced cytokines like tumour necrosis factor and interleukin 1, act on target cells prepared by interferon gamma. After exposure to interferon gamma target cells become more sensitive to stimuli like endotoxin, thus boosting the inflammatory cycle. Clearly, following this line of reasoning, minor tissue damage or retroperitoneal haematoma combined with systemic endotoxaemia could elicit this reaction. The clinically observed failure of multiple organ systems might thus be explained by the interaction of tissue necrosis and high concentrations of endotoxin because of translocation. Future therapeutic strategies could therefore focus more on binding endotoxin in the gut before the triggering event, for example before major surgery. Such a strategy could be combined with the start of early enteral feeding, which has been shown in animal studies to have a beneficial effect on intestinal mucosal barrier function and in traumatized patients to reduce the incidence of septic complications. PMID:8125386

  3. Protein translocation across biological membranes.

    PubMed

    Wickner, William; Schekman, Randy

    2005-12-01

    Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work. Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work. PMID:16322447

  4. Translocations induced by fast neutrons and X-rays in Delia antiqua.

    PubMed

    Robinson, A S; van Heemert, K

    1981-09-01

    A comparison was made using X-rays and fast neutrons for the induction of translocations in Delia antiqua. Using the same radiation dose, no difference in efficiency between the two radiation types could be observed. However, with fast neutrons many multiple translocations were induced, including a quadruple translocation involving 4 out of 5 autosomes. One male linked translocation was also induced.The reciprocal translocations were assigned into two classes: symmetrical and asymmetrical, and ten of the latter were chosen for inbreeding to produce homozygotes. Asymmetrical exchanges were chosen so that translocation homozygotes could be differentiated cytologically from the normal karyotype. In seven different translocations, homozygous larvae were observed, but often at a low frequency. In four of these lines, viable adult homozygotes were observed. Subsequent random sib-crossing failed to produce a homozygous line. PMID:24276515

  5. 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.

  6. 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

  7. 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

  8. Translocation of a heterogeneous polymer

    PubMed Central

    Mirigian, Stephen; Wang, Yanbo; Muthukumar, Murugappan

    2012-01-01

    We present results on the sequence dependence of translocation kinetics for a partially charged heteropolymer moving through a very thin pore using theoretical tools and Langevin dynamics simulational techniques. The chain is composed of two types of monomers of differing frictional interaction with the pore and charge. We present exact analytical expressions for passage probability, mean first passage time, and mean successful passage times for both reflecting/absorbing and absorbing/absorbing boundary conditions, showing rich and unexpected dependence of translocation behavior on charge fraction, distribution along the chain, and electric field configuration. We find excellent qualitative and good quantitative agreement between theoretical and simulation results. Surprisingly, there emerges a threshold charge fraction of a diblock copolymer beyond which the success rate of translocation is independent of charge fraction. Also, the mean successful translocation time of a diblock copolymer displays non-monotonic behavior with increasing length of the charged block; there is an optimum length of the charged block where the mean translocation rate is the slowest; and there can be a substantial range of higher charge fractions which make the translocation slower than even a minimally charged chain. Additionally, we find for a fixed total charge on the chain, finer distribution along the backbone significantly decreases mean translocation time. PMID:22897308

  9. HIGH-FREQUENCY-PEAKED BL LACERTAE OBJECTS AS SPECTRAL CANDLES TO MEASURE THE EXTRAGALACTIC BACKGROUND LIGHT IN THE FERMI AND AIR CHERENKOV TELESCOPES ERA

    SciTech Connect

    Mankuzhiyil, Nijil; Persic, Massimo; Tavecchio, Fabrizio

    2010-05-20

    The extragalactic background light (EBL) is the integrated light from all the stars that have ever formed, and spans the IR-UV range. The interaction of very high-energy (VHE: E > 100 GeV) {gamma}-rays, emitted by sources located at cosmological distances, with the intervening EBL results in e {sup -} e {sup +} pair production that leads to energy-dependent attenuation of the observed VHE flux. This introduces a fundamental ambiguity into the interpretation of measured VHE {gamma}-ray spectra: neither the intrinsic spectrum nor the EBL are separately known-only their combination is. In this Letter, we propose a method to measure the EBL photon number density. It relies on using simultaneous observations of BL Lac objects in the optical, X-ray, high-energy (HE: E > 100 MeV) {gamma}-ray (from the Fermi telescope), and VHE {gamma}-ray (from Cherenkov telescopes) bands. For each source, the method involves best-fitting the spectral energy distribution from optical through HE {gamma}-rays (the latter being largely unaffected by EBL attenuation as long as z {approx_lt} 1) with a synchrotron self-Compton model. We extrapolate such best-fitting models into the VHE regime and assume they represent the BL Lacs' intrinsic emission. Contrasting measured versus intrinsic emission leads to a determination of the {gamma}{gamma} opacity to VHE photons. Using, for each given source, different states of emission will only improve the accuracy of the proposed method. We demonstrate this method using recent simultaneous multifrequency observations of the high-frequency-peaked BL Lac object PKS 2155-304 and discuss how similar observations can more accurately probe the EBL.

  10. 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

  11. 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.

  12. [The influence of combinations of alien translocations on in vitro androgenesis in near-isogenic lines of spring bread wheat].

    PubMed

    Sibikeeva, Yu E; Sibikeev, S N

    2014-07-01

    The features of in vitro androgenesis were studied in Cultured anthers of spring bread wheats L503 and Dobrynya, having 7DS-7DL-7Ae#1 L translocation with genes Lrl9/Sr25 (Lrl9 translocation) from Agropyron elongatum (Host.) P.B. and their near-isogenic lines carrying combinations of Lrl9 translocation with translocations: 1BL-IR#1S with genes Pm8/Sr31/Lr26/Yr9 (Lr26translocation) from Secale cereal L., 4BS-4BL-2R#1L with genes Lr25/Pm7 (Lr25 translocation) from Secale cereal, 3DS-3DL-3Ae#1L with genes Lr24/Sr24 (Lr24 translocation) from Agropyron elongatum and 6BS-6BL-6U#1L with gene Lr9 (Lr9 translocation) from Aegilops umbellulata Zhuk. In comparison with those varieties having received the Lrl9 translocation, the following was established: (1) the combination of translocations Lr19+26 increased embryo frequency and green plant regeneration; (2) the combination of translocations Lr19+9 decreased embryo frequency but increased green plant regeneration; (3) the combination of translocations Lr19+24 decreased embryo frequency but increased green and albino plant regeneration; (4) the combination of translocations Lr19+25 increased embryo frequency and green plant regeneration but decreased albino plant regeneration. Thus, on near-isogenic lines of spring bread wheat, the influences of genotypes of four alien translocation combinations on in vitro androgenesis were determined. PMID:25720141

  13. Downside risk of wildlife translocation.

    PubMed

    Chipman, R; Slate, D; Rupprecht, C; Mendoza, M

    2008-01-01

    Translocation has been used successfully by wildlife professionals to enhance or reintroduce populations of rare or extirpated wildlife, provide hunting or wildlife viewing opportunities, farm wild game, and reduce local human-wildlife conflicts. However, accidental and intentional translocations may have multiple unintended negative consequences, including increased stress and mortality of relocated animals, negative impacts on resident animals at release sites, increased conflicts with human interests, and the spread of diseases. Many wildlife professionals now question the practice of translocation, particularly in light of the need to contain or eliminate high profile, economically important wildlife diseases and because using this technique may jeopardize international wildlife disease management initiatives to control rabies in raccoons, coyotes, and foxes in North America. Incidents have been documented where specific rabies variants (Texas gray fox, canine variant in coyotes, and raccoon) have been moved well beyond their current range as a result of translocation, including the emergence of raccoon rabies in the eastern United States. Here, we review and discuss the substantial challenges of curtailing translocation in the USA, focusing on movement of animals by the public, nuisance wildlife control operators, and wildlife rehabilitators. PMID:18634483

  14. 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 . 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 tRNA2mRNA complex inside the ribosome during translocation. This review inspects and surveys these achievements. PMID:25514765

  15. Local time variation of high-frequency gravity wave momentum flux and its relationship with background wind derived from LIDAR measurements

    NASA Astrophysics Data System (ADS)

    Agner, R. M.; Liu, A. Z.

    2013-12-01

    Gravity waves and atmospheric tides have strong interactions in the mesopause region and is a major contributor to the large variabilities in this region. How these two large perturbations interact with each other is not well understood. Observational studies of their relationships are needed to help clarify some contradictory results from modeling studies. Due to large differences in temporal and spatial scales between gravity waves and tides, they are not easily observed simultaneously and consistently with extended periods of time. In this work, we use four-hundred hours of Na LIDAR observation at Starfire Optical Range (SOR, 35.0 N, 106.5 W), New Mexico to derive the local time variation of gravity wave momentum flux and corresponding background wind. Their relationship is then examined in detail. The effects of gravity waves on the background wind at the tidal time scale are deduced. These results are explained through gravity wave propagation in a varying background atmosphere.

  16. Male carriers of balanced reciprocal translocations in Northeast China: sperm count, reproductive performance, and genetic counseling.

    PubMed

    Zhang, H G; Wang, R X; Li, L L; Sun, W T; Zhang, H Y; Liu, R Z

    2015-01-01

    Balanced chromosomal translocations in men can cause failure of spermatogenesis owing to meiotic impairment. Male carriers may exhibit normozoospermia, although clinical manifestations can include oligozoospermia or azoospermia, oligozoospermia or normozoospermia. Here, we reported the characteristics of balanced reciprocal translocations in men from northeastern China, and explored the relationship between sperm count and reproductive performance, to enable informed genetic counseling. The frequency of balanced reciprocal translocations was found to be 1.62%. Semen analysis showed that 5.9% of male carriers had azoospermia, 43.1% had oligozoospermia, and 51.0% had normozoospermia. Of the 25 men with a balanced reciprocal translocation and azoospermia or oligozoospermia, chromosome 1 was the most commonly often involved in the translocation. However, in the 26 normozoospermic men with a balanced reciprocal translocation and normozoospermia, chromosome 3 was most commonly implicated. Fifty percent of men with a balanced reciprocal translocation conceived a pregnancy that went to term. Our data suggest that of all chromosomes, chromosomes 1 and 3 are the most commonly involved chromosomes in balanced reciprocal such translocations in northeastern Chinese men. Karyotype analysis should be performed for men with azoospermia, oligozoospermia, and those in couples having suffered recurrent miscarriages. Natural conception should be discussed during genetic counseling for male carriers of balanced chromosomal translocations with normozoospermia. PMID:26782529

  17. 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

  18. The ABC of Phytohormone Translocation.

    PubMed

    Hellsberg, Eva; Montanari, Floriane; Ecker, Gerhard F

    2015-04-01

    ATP-driven transport across biological membranes is a key process to translocate solutes from the interior of the cell to the extracellular environment. In humans, ATP-binding cassette transporters are involved in absorption, distribution, metabolism, excretion, and toxicity, and also play a major role in anticancer drug resistance. Analogous transporters are also known to be involved in phytohormone translocation. These include, e.g., the transport of auxin by ABCB1/19 in Arabidopsis thaliana, the transport of abscisic acid by AtABCG25, and the transport of strigolactone by the Petunia hybrida ABC transporter PDR1. Within this article, we outline the current knowledge about plant ABC transporters with respect to their structure and function, and provide, for the first time, a protein homology model of the strigolactone transporter PDR1 from P. hybrida. PMID:25905596

  19. Dynamics of polymer translocation through kinked nanopores.

    PubMed

    Wang, Junfang; Wang, Yilin; Luo, Kaifu

    2015-02-28

    Polymer translocation through nanopore has potential technological applications for DNA sequencing, where one challenge problem is to slow down translocation speed. Inspired by experimental findings that kinked nanopores exhibit a large reduction in translocation velocity compared with their straight counterparts, we investigate the dynamics of polymer translocation through kinked nanopores in two dimensions under an applied external field. With increasing the tortuosity of an array of nanopores, our analytical results show that the translocation probability decreases. Langevin dynamics simulation results support this prediction and further indicate that with increasing the tortuosity, translocation time shows a slow increase followed by a rapid increase after a critical tortuosity. This behavior demonstrates that kinked nanopores can effectively reduce translocation speed. These results are interpreted by the roles of the tortuosity for decreasing the effective nanopore diameter, increasing effective nanopore length, and greatly increasing the DNA-pore friction. PMID:25725751

  20. Frequencies of background cytoplasmic Ig-containing cells in various lymphoid organs of athymic and euthymic mice as a function of age and immune status.

    PubMed Central

    Van Oudenaren, A; Haaijman, J J; Benner, R

    1984-01-01

    The distribution of background Ig-secreting cells, measured as cells containing cytoplasmic immunoglobulin (C-Ig cells), over spleen, bone marrow, lymph nodes and Peyer's patches was studied in congenitally athymic (nude) mice and heterozygous euthymic mice as a function of age and immune status (germ-free (GF) vs specific pathogen-free (SPF]. In young athymic as well as in young euthymic mice, the spleen was found to contain the great part of all C-Ig cells, irrespective of whether the mice were GF or SPF. The number of C-Ig cells in the spleen was found to be rather constant over the life span, while the number of C-Ig cells in the bone marrow of all groups of mice greatly increased with age. This indicates that the relative shift of C-Ig cells to the bone marrow is neither dependent on the presence of the thymus, nor on the microbiological status of the mice. However, at young and intermediate age the microbiological status of the mice did affect the total number of C-Ig cells per mouse. This was mainly due to the effect upon the bone marrow, mesenteric lymph nodes and Peyer's patches. At these ages the background Ig synthesis in these organs appeared to be mainly dependent on external antigenic stimulation, in contrast to the spleen, where the Ig synthesis appeared to be mainly due to endogenous stimulation. The Ig (sub)class distribution of the C-Ig cells was different for all different organs tested. Hardly or no difference in percentage distribution was found between the GF nude and GF heterozygous mice. Most C-Ig cells in spleen, bone marrow and lymph nodes of the GF mice were of the IgM isotype. C-IgG and C-IgA cells occurred in substantial percentages only in bone marrow and lymph nodes. In the lymph nodes of GF nude mice a remarkably high percentage of C-IgA cells was found. PMID:6231241

  1. 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.

  2. Toponomics method for the automated quantification of membrane protein translocation

    PubMed Central

    2011-01-01

    Background Intra-cellular and inter-cellular protein translocation can be observed by microscopic imaging of tissue sections prepared immunohistochemically. A manual densitometric analysis is time-consuming, subjective and error-prone. An automated quantification is faster, more reproducible, and should yield results comparable to manual evaluation. The automated method presented here was developed on rat liver tissue sections to study the translocation of bile salt transport proteins in hepatocytes. For validation, the cholestatic liver state was compared to the normal biological state. Results An automated quantification method was developed to analyze the translocation of membrane proteins and evaluated in comparison to an established manual method. Firstly, regions of interest (membrane fragments) are identified in confocal microscopy images. Further, densitometric intensity profiles are extracted orthogonally to membrane fragments, following the direction from the plasma membrane to cytoplasm. Finally, several different quantitative descriptors were derived from the densitometric profiles and were compared regarding their statistical significance with respect to the transport protein distribution. Stable performance, robustness and reproducibility were tested using several independent experimental datasets. A fully automated workflow for the information extraction and statistical evaluation has been developed and produces robust results. Conclusions New descriptors for the intensity distribution profiles were found to be more discriminative, i.e. more significant, than those used in previous research publications for the translocation quantification. The slow manual calculation can be substituted by the fast and unbiased automated method. PMID:21929784

  3. 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

  4. Adaptive background model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaochun; Xiao, Yijun; Chai, Zhi; Wang, Bangping

    2007-11-01

    An adaptive background model aiming at outdoor vehicle detection is presented in this paper. This model is an improved model of PICA (pixel intensity classification algorithm), it classifies pixels into K-distributions by color similarity, and then a hypothesis that the background pixel color appears in image sequence with a high frequency is used to evaluate all the distributions to determine which presents the current background color. As experiments show, the model presented in this paper is a robust, adaptive and flexible model, which can deal with situations like camera motions, lighting changes and so on.

  5. DNA translocation through grapheme nanopores

    NASA Astrophysics Data System (ADS)

    Merchant, Christopher A.; Healy, Ken; Wanunu, Meni; Ray, Vishva; Peterman, Neil; Bartel, John; Fischbein, Michael D.; Venta, Kim; Luo, Zhengtang; Johnson, A. T. Charlie; Drndic, Marija

    2011-03-01

    We report on DNA translocations through nanopores created in graphene membranes. Devices consist of nanometer-thick graphene membranes with electron-beam sculpted nanopores. Due to the thin nature of the graphene membranes, we observe larger blocked currents than for traditional solid-state nanopores. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore.

  6. The cellular etiology of chromosome translocations

    PubMed Central

    Roukos, Vassilis; Burman, Bharat; Misteli, Tom

    2013-01-01

    Chromosome translocations are the most severe form of genome defect. Translocations represent the end product of a series of cellular mistakes and they form after cells suffer multiple DNA double strand breaks (DSBs), which evade the surveillance mechanisms that usually eliminate them. Rather than being accurately repaired, translocating DSBs are misjoined to form aberrant fusion chromosomes. Although translocations have been extensively characterized using cytological methods and their pathological relevance in cancer and numerous other diseases is well established, how translocations form in the context of the intact cell nucleus is poorly understood. A combination of imaging approaches and biochemical methods to probe genome architecture and chromatin structure suggest that the spatial organization of the genome and features of chromatin, including sequence properties, higher order chromatin structure and histone modifications, are key determinants of translocation formation. PMID:23498663

  7. 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.

  8. 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.

  9. Thoracic duct in patients with multiple organ failure: no major route of bacterial translocation.

    PubMed Central

    Lemaire, L C; van Lanschot, J B; Stoutenbeek, C P; van Deventer, S J; Dankert, J; Oosting, H; Gouma, D J

    1999-01-01

    OBJECTIVE: To determine whether translocation of bacteria or endotoxin occurred into the thoracic duct in patients with multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Translocation of bacteria or endotoxin has been proposed as a causative factor for MOF in patients without an infectious focus, although it has rarely been demonstrated in patients at risk for MOF. Most studies have investigated the hematogenic route of translocation, but it has been argued that lymphatic translocation of bacteria or endotoxin by the thoracic duct is the major route of translocation. METHODS: The thoracic duct was drained for 5 days in patients with MOF caused either by generalized fecal peritonitis (n = 4) or by an event without clinical and microbiologic evidence of infection (n = 4). Patients without MOF who were undergoing a transthoracic esophageal resection served as controls. In lymph and blood, concentrations of endotoxin, proinflammatory cytokines, and antiinflammatory cytokines were measured. RESULTS: Endotoxin concentrations in lymph and blood of patients with MOF ranged from 39 to 63 units per liter and were not significantly different from concentrations in patients without MOF. The quantity of endotoxin transported by the thoracic duct in the study group was small. In patients with MOF, low levels of proinflammatory cytokines and high levels of antagonists of these cytokines were found. CONCLUSION: This study provides evidence that translocation (especially of endotoxin) occurs into the thoracic duct. However, these data do not support the concept that the thoracic duct is a major route of bacterial translocation in patients with MOF. PMID:9923810

  10. Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation and IL-17 production in the absence of SIV infection

    PubMed Central

    Klatt, Nichole R.; Harris, Levelle D.; Vinton, Carol L.; Sung, Hannah; Briant, Judith A.; Tabb, Brian; Morcock, David; McGinty, John W.; Lifson, Jeffrey D.; Lafont, Bernard A.; Martin, Malcolm A.; Levine, Alan D.; Estes, Jacob D.; Brenchley, Jason M.

    2010-01-01

    Pigtail macaques (PTM) rapidly progress to AIDS after SIV infection. Given the strong association between HIV/SIV disease progression and microbial translocation and immune activation, we assessed whether high basal levels of immune activation and microbial translocation exist in PTM. We found that prior to SIV infection, PTM had high levels of microbial translocation that correlated with significant damage to the structural barrier of the GI tract. Moreover, this increased microbial translocation correlated with high levels of immune activation and was associated with high frequencies of IL-17-producing T cells. These data highlight the relationship between mucosal damage, microbial translocation and systemic immune activation in the absence of HIV/SIV replication and underscore the importance of microbial translocation in the rapid course of disease progression in SIV-infected PTM. Furthermore, these data suggest that PTM may be an ideal model to study therapeutic interventions aimed at decreasing microbial translocation-induced immune activation. PMID:20357762

  11. Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection.

    PubMed

    Klatt, N R; Harris, L D; Vinton, C L; Sung, H; Briant, J A; Tabb, B; Morcock, D; McGinty, J W; Lifson, J D; Lafont, B A; Martin, M A; Levine, A D; Estes, J D; Brenchley, J M

    2010-07-01

    Pigtail macaques (PTMs) rapidly progress to AIDS after simian immunodeficiency virus (SIV) infection. Given the strong association between human immunodeficiency virus (HIV) and SIV disease progression and microbial translocation and immune activation, we assessed whether high basal levels of immune activation and microbial translocation exist in PTMs. We found that before SIV infection, PTMs had high levels of microbial translocation that correlated with significant damage to the structural barrier of the gastrointestinal tract. Moreover, this increased microbial translocation correlated with high levels of immune activation and was associated with high frequencies of interleukin-17-producing T cells. These data highlight the relationship among mucosal damage, microbial translocation and systemic immune activation in the absence of SIV replication, and underscore the importance of microbial translocation in the rapid course of disease progression in SIV-infected PTMs. Furthermore, these data suggest that PTM may be an ideal model to study therapeutic interventions aimed at decreasing microbial translocation-induced immune activation. PMID:20357762

  12. 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.

  13. Periarrest intestinal bacterial translocation and resuscitation outcome.

    PubMed

    Chalkias, Athanasios; Scheetz, Marc H; Gulati, Anil; Xanthos, Theodoros

    2016-02-01

    During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims. PMID:26481507

  14. DNA translocation through graphene nanopores.

    PubMed

    Merchant, Christopher A; Healy, Ken; Wanunu, Meni; Ray, Vishva; Peterman, Neil; Bartel, John; Fischbein, Michael D; Venta, Kimberly; Luo, Zhengtang; Johnson, A T Charlie; Drndi?, Marija

    2010-08-11

    We report on DNA translocations through nanopores created in graphene membranes. Devices consist of 1-5 nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, we observe larger blocked currents than for traditional solid-state nanopores. However, ionic current noise levels are several orders of magnitude larger than those for silicon nitride nanopores. These fluctuations are reduced with the atomic-layer deposition of 5 nm of titanium dioxide over the device. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore. PMID:20698604

  15. Cosmic Tachyon Background Radiation

    NASA Astrophysics Data System (ADS)

    Tomaschitz, Roman

    The equilibrium statistical mechanics of a background radiation of superluminal particles is investigated, based on a vectorial wave equation for tachyons of the Proca type. The partition function, the spectral energy density, and the various thermodynamic variables of an ideal Bose gas of tachyons in an open Robertson-Walker cosmology are derived. The negative mass square in the wave equation changes the frequency scaling in the Rayleigh-Jeans law, and there are also significant changes in the low temperature regime as compared to the microwave background, in particular in the caloric and thermal equations of state.

  16. RNA polymerase stalls in a post-translocated register and can hyper-translocate.

    PubMed

    Nedialkov, Yuri A; Nudler, Evgeny; Burton, Zachary F

    2012-01-01

    Exonuclease (Exo) III was used to probe translocation states of RNA polymerase (RNAP) ternary elongation complexes (TECs). Escherichia coli RNAP stalls primarily in a post-translocation register that makes relatively slow excursions to a hyper-translocated state or to a pre-translocated state. Tagetitoxin (TGT) strongly inhibits hyper-translocation and inhibits backtracking, so, as indicated by Exo III mapping, TGT appears to stabilize both the pre- and probably a partially post-translocation state of RNAP. Because the pre-translocated to post-translocated transition is slow at many template positions, these studies appear inconsistent with a model in which RNAP makes frequent and rapid (i.e., millisecond phase) oscillations between pre- and post-translocation states. Nine nucleotides (9-nt) and 10-nt TECs, and TECs with longer nascent RNAs, have distinct translocation properties consistent with a 9-10 nt RNA/DNA hybrid. RNAP mutant proteins in the bridge helix and trigger loop are identified that inhibit or stimulate forward and backward translocation. PMID:23132506

  17. Direct segregation analysis of reciprocal translocations: a study of 283 sperm karyotypes from four carriers.

    PubMed Central

    Pellestor, F; Sle, B; Jalbert, H; Jalbert, P

    1989-01-01

    Using the technique of in vitro human-hamster fertilization, sperm of four men heterozygous for 4 reciprocal translocations--t(4;17),t(5;13),t(6;7), and t(9;18)--was studied. Frequencies of numerical abnormalities unrelated to the translocations range from 8.3% to 13.3%, and the incidence of imbalances ranges from 23.0% to 66.0%. Results are pooled with data from the nine other reciprocal translocations reported elsewhere, and the combined data demonstrate that male meiotic segregation is not random: whatever the type of translocation may be, the distribution of imbalances in sperm is constant, with approximately 72.0% adjacent 1, 18.5% adjacent 2, and 9.5% 3:1 segregations. The same prevalence of adjacent 1 segregations as that reported at term for translocations of paternal origin is observed. There is a strong postzygotic elimination process; for a given translocation it affects selectively the maximum-imbalance zygotes so that imbalanced segregations observed at term are always predetermined. Images Figure 4 Figure 2 Figure 3 Figure 5 PMID:2818710

  18. 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

  19. What Drives the Translocation of Proteins?

    NASA Astrophysics Data System (ADS)

    Simon, Sanford M.; Peskin, Charles S.; Oster, George F.

    1992-05-01

    We propose that protein translocation across membranes is driven by biased random thermal motion. This "Brownian ratchet" mechanism depends on chemical asymmetries between the cis and trans sides of the membrane. Several mechanisms could contribute to rectifying the thermal motion of the protein, such as binding and dissociation of chaperonins to the translocating chain, chain coiling induced by pH and/or ionic gradients, glycosylation, and disulfide bond formation. This helps explain the robustness and promiscuity of these transport systems.

  20. Driven Polymer Translocation into a Crosslinked Gel

    NASA Astrophysics Data System (ADS)

    Sean, David; Slater, Gary

    2015-03-01

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

  1. Ratcheting up protein translocation with anthrax toxin.

    PubMed

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

    2012-05-01

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

  2. 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

  3. 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

  4. Disease risks associated with wildlife translocation projects.

    PubMed

    Woodford, M H; Rossiter, P B

    1993-03-01

    Translocation is defined as the movement of living organisms from one area for free release in another. Throughout the world, increasing numbers of native and exotic species are translocated every year. Most of these movements involve native mammals, birds and fish, and are made by private and national wildlife agencies to augment existing populations, usually for sporting purposes. The translocation of endangered species, often to reintroduce them into a part of the historical range from which they have been extirpated, has also become an important conservation technique. The success of potentially expensive, high-profile wildlife translocation projects depends to a large extent on the care with which wildlife biologists and their veterinary advisers evaluate the suitability of the chosen release site, and on the ability of the translocated animals to colonise the area. The veterinary aspects of reintroduction projects are proving to be of extreme importance. There are already instances of inadequate disease risk assessment resulting in expensive failures and, worse still, the introduction of destructive pathogens into naive resident wildlife populations. In this paper, some of the disease risks attending wildlife translocation projects are described and suggestions are made for the development of systematic procedures to reduce these risks both at the source of the founder animals and at the proposed release site. PMID:8518439

  5. 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

  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. Earth's background free oscillations

    PubMed

    Suda; Nawa; Fukao

    1998-03-27

    Earth's free oscillations were considered to be transient phenomena occurring after large earthquakes. An analysis of records of the IDA (International Deployment of Accelerometers) gravimeter network shows that Earth is freely oscillating at an observable level even in seismically inactive periods. The observed oscillations are the fundamental spheroidal modes at frequencies between 2 and 7 millihertz. Numerical modeling indicates that these incessant excitations cannot be explained by stacked effects of a large number of small earthquakes. The observed "background" free oscillations represent some unknown dynamic process of Earth. PMID:9516105

  8. Cosmic Background Radiation

    NASA Astrophysics Data System (ADS)

    Sidharth, B. G.; Valluri, S. R.

    2015-08-01

    It is shown that a collection of photons with nearly the same frequency exhibits a "condensation" type of phenomenon corresponding to a peak intensity. The observed cosmic background radiation can be explained from this standpoint. We have obtained analogous results by extremization of the occupation number for photons with the use of the Lambert W function. Some of the interesting applications of this function are briefly discussed in the context of graphene which exhibits an interesting two dimensional structure with several characteristic properties and diverse practical applications.

  9. Molecular studies of free and translocation trisomy

    SciTech Connect

    Robinson, W.P.; Bernasconi, F.; Lefort, G.

    1994-09-01

    Twenty cases of trisomy 13 were examined with molecular markers to determine the origin of the extra chromosome. Six cases had translocation trisomy: two de novo rob(13q;14q), one paternally derived rob(13q;14q), two de novo t(13q;13q), and one mosaic de novo t(13q;14q), one paternally derived rob(13q;14q), two de novo t(13q;13q), and one mosaic de novo t(13q;13q)r(13). Eighteen of nineteen informative patients were consistant with a maternal origin of the extra chromosome. Lack of a third allele at any locus in any of the three t(13q;13q) cases indicate that all were most likely isochromosomes of post-meiotic origin. In addition, two free trisomy cases were compatible with a somatic origin. Two mosaic free trisomy-13 cases, however, were both consistent with a maternal meiotic origin. The patient with a paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13;14) carrier and most trisomies are maternal in origin, this result should not be surprising; however it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. One balanced (non-trisomic) case with a non-mosaic 45,-13,-13,+t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologs, as has been found for all homologous Robertsonian translocations so far investigated. It is therefore also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. We cannot therefore infer anything about the origin of the chromosomes 13 and 14 involved in the two cases with de novo t(13q;14q) plus a maternally derived trisomy 13.

  10. 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

  11. 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.

  12. [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

  13. Protein translocation across the rough endoplasmic reticulum.

    PubMed

    Mandon, Elisabet C; Trueman, Steven F; Gilmore, Reid

    2013-02-01

    The rough endoplasmic reticulum is a major site of protein biosynthesis in all eukaryotic cells, serving as the entry point for the secretory pathway and as the initial integration site for the majority of cellular integral membrane proteins. The core components of the protein translocation machinery have been identified, and high-resolution structures of the targeting components and the transport channel have been obtained. Research in this area is now focused on obtaining a better understanding of the molecular mechanism of protein translocation and membrane protein integration. PMID:23251026

  14. Founder event and its effect on genetic variation in translocated populations of noble crayfish (Astacus astacus).

    PubMed

    Blha, Martin; urovcov, Martina; Kouba, Antonn; Policar, Tom; Kozk, Pavel

    2016-02-01

    Establishing translocated populations is a common process to preserve and maintain genetic diversity of threatened species. In 2001, three translocated populations of noble crayfish (Astacus astacus) were established in the Czech Republic, founded by either adult or juvenile individuals from three particular source populations. We assessed genetic diversity at seven microsatellite loci after one decade (assumed three generations) from establishment. Although the translocated populations exhibited a slight but non-significant reduction in genetic diversity (A R?=?2.2-5.0; H O?=?0.11-0.31), the most striking result was generally very low genetic diversity in source populations (A R?=?3.0-5.3; H O?=?0.15-0.38). Similarly, a high degree of inbreeding (F IS?=?0.36-0.60) demonstrates the nature of source populations, already affected by isolation and small size. In spite of that, based on the results of this study, the establishment of new translocated noble crayfish populations was successful, since there is no significant decline in genetic variability and all populations are still viable. Although source populations did not exhibit high genetic diversity, their distinctiveness makes them possible to use for conservation purposes. Continued monitoring is necessary to track the long-term progress of the translocation program, including other parameters describing the state of the population, such as the occurrence and frequency of diseases or morphological changes. PMID:26077200

  15. Telomerase Deficiency Affects the Formation of Chromosomal Translocations by Homologous Recombination in Saccharomyces cerevisiae

    PubMed Central

    Meyer, Damon H.; Bailis, Adam M.

    2008-01-01

    Telomerase is a ribonucleoprotein complex required for the replication and protection of telomeric DNA in eukaryotes. Cells lacking telomerase undergo a progressive loss of telomeric DNA that results in loss of viability and a concomitant increase in genome instability. We have used budding yeast to investigate the relationship between telomerase deficiency and the generation of chromosomal translocations, a common characteristic of cancer cells. Telomerase deficiency increased the rate of formation of spontaneous translocations by homologous recombination involving telomere proximal sequences during crisis. However, telomerase deficiency also decreased the frequency of translocation formation following multiple HO-endonuclease catalyzed DNA double-strand breaks at telomere proximal or distal sequences before, during and after crisis. This decrease correlated with a sequestration of the central homologous recombination factor, Rad52, to telomeres determined by chromatin immuno-precipitation. This suggests that telomerase deficiency results in the sequestration of Rad52 to telomeres, limiting the capacity of the cell to repair double-strand breaks throughout the genome. Increased spontaneous translocation formation in telomerase-deficient yeast cells undergoing crisis is consistent with the increased incidence of cancer in elderly humans, as the majority of our cells lack telomerase. Decreased translocation formation by recombinational repair of double-strand breaks in telomerase-deficient yeast suggests that the reemergence of telomerase expression observed in many human tumors may further stimulate genome rearrangement. Thus, telomerase may exert a substantial effect on global genome stability, which may bear significantly on the appearance and progression of cancer in humans. PMID:18830407

  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. Molecular cytogenetic characterization of novel wheat-Thinopyrum bessarabicum recombinant lines carrying intercalary translocations.

    PubMed

    Patokar, Chetan; Sepsi, Adel; Schwarzacher, Trude; Kishii, Masahiro; Heslop-Harrison, J S

    2016-03-01

    Thinopyrum bessarabicum (2n = 2x = 14, JJ or E(b)E(b)) is a valuable source of genes for bread wheat (2n = 6x = 42) improvement because of its salinity tolerance and disease resistance. Development of wheat-Th. bessarabicum translocation lines by backcrossing the amphiploid in the absence of the Ph1 gene (allowing intergenomic recombination) can assist its utilization in wheat improvement. In this study, six novel wheat-Th. bessarabicum translocation lines involving different chromosome segments (T4BS.4BL-4JL, T6BS.6BL-6JL, T5AS.5AL-5JL, T5DL.5DS-5JS, T2BS.2BL-2JL, and the whole arm translocation T1JS.1AL) were identified and characterized using genomic in situ hybridization (GISH) and fluorescent in situ hybridization (FISH). No background translocations between wheat genomes were observed. The involvement of five of the seven chromosomes and small terminal segments of Th. bessarabicum chromosome arm were important, contributing to both reduced linkage drag of the derived lines by minimizing agronomically deleterious genes from the alien species and high stability including transmission of the alien segment. All three wheat genomes were involved in the translocations with the alien chromosome, and GISH showed the Th. bessarabicum genome was more closely related to the D genome in wheat. All the introgression lines were disomic, stable, and with good morphological characters. PMID:26238987

  18. Signatures of Selection in Fusion Transcripts Resulting From Chromosomal Translocations in Human Cancer

    PubMed Central

    Ortiz de Mendbil, Iigo; Vizmanos, Jos L.; Novo, Francisco J.

    2009-01-01

    Background The recurrence and non-random distribution of translocation breakpoints in human tumors are usually attributed to local sequence features present in the vicinity of the breakpoints. However, it has also been suggested that functional constraints might contribute to delimit the position of translocation breakpoints within the genes involved, but a quantitative analysis of such contribution has been lacking. Methodology We have analyzed two well-known signatures of functional selection, such as reading-frame compatibility and non-random combinations of protein domains, on an extensive dataset of fusion proteins resulting from chromosomal translocations in cancer. Conclusions Our data provide strong experimental support for the concept that the position of translocation breakpoints in the genome of cancer cells is determined, to a large extent, by the need to combine certain protein domains and to keep an intact reading frame in fusion transcripts. Additionally, the information that we have assembled affords a global view of the oncogenic mechanisms and domain architectures that are used by fusion proteins. This can be used to assess the functional impact of novel chromosomal translocations and to predict the position of breakpoints in the genes involved. PMID:19279687

  19. A Rare De Novo Balanced X; 1 Translocation in an Indian Female with Primary Amenorrhea

    PubMed Central

    Venkateshwari, Ananthapur; Srilekha, Avvari; Veena, Koka; Sujatha, Madireddy; Jyothy, Akka

    2015-01-01

    Background: Translocations involving X chromosome and an autosome are rather rare due to associated infertility in men and subfertility in women. X chromosome translocations are frequently associated with primary or secondary amenorrhea. In this report, a case of primary amenorrhea with a de novo balanced reciprocal translocation was presented between chromosomes X and 1. Case Presentation: A 24 year-old proposita with the complaint of primary amenorrhea was found to have hypoplastic uterus and streak gonads with a normal hormonal profile. Chromosomal analysis of the proband revealed a de novo translocation of 46, X, t(X; 1) (q21; p32) chromosomal constitution. Parental karyotypes of the proband showed normal karyotype. Conclusion: The observed translocation between chromosome X and 1 in the patient suggest either the disruption of a critical gene expression due to position effect or deletion of one or more essential genes in the disrupted long arm of the affected X chromosome. To the best of our knowledge, this is the first report from our ethnic group.

  20. Dysbiotic bacteria translocate in progressive SIV infection.

    PubMed

    Klase, Z; Ortiz, A; Deleage, C; Mudd, J C; Quiones, M; Schwartzman, E; Klatt, N R; Canary, L; Estes, J D; Brenchley, J M

    2015-09-01

    Infection of gut-resident CD4(+) memory T cells during acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is associated with rapid loss of these cells and damage to the epithelial barrier. Damage to the epithelial barrier allows translocation of microbial products from the intestinal lumen into the body. Immune activation caused by these microbial products has been associated with disease progression. Although microbial translocation has been demonstrated in SIV-infected nonhuman primates, the identity of translocating bacteria has not been determined. In this study we examined the communities of bacteria both within the gastrointestinal (GI) tract and systemic tissues of both healthy and experimentally SIV-infected Asian macaques. Although there were only modest changes in the GI tract-associated microbiome resulting from infection, there is substantial dysbiosis after administration of antiretrovirals. Analysis of bacterial DNA isolated from tissues of infected animals revealed a preference for the phylum Proteobacteria, suggesting that they preferentially translocate. Consistent with this finding, we observed increased metabolic activity of Proteobacterial species within the colonic lumen of SIV-infected animals. Overall, these data provide insights into disease progression and suggest that therapies aimed at altering the composition and metabolic activity of the GI tract microbiome could benefit chronically HIV-infected individuals, particularly those on antiretroviral therapies. PMID:25586559

  1. Dysbiotic Bacteria Translocate in Progressive SIV Infection

    PubMed Central

    Klase, Zachary; Ortiz, Alexandra; Deleage, Claire; Mudd, Joseph C.; Quiñones, Mariam; Schwartzman, Elias; Klatt, Nichole R.; Canary, Lauren; Estes, Jacob D.; Brenchley, Jason M.

    2014-01-01

    Infection of gut-resident CD4+ memory T-cells during acute HIV and SIV infection is associated with rapid loss of these cells and damage to the epithelial barrier. Damage to the epithelial barrier allows translocation of microbial products from the intestinal lumen into the body. Immune activation caused by these microbial products has been associated with disease progression. Although microbial translocation has been demonstrated in SIV-infected nonhuman primates, the identity of translocating bacteria has not been determined. In this study we examined the communities of bacteria both within the GI tract and systemic tissues of both healthy and experimentally SIV-infected Asian macaques. While there were only modest changes in the GI tract-associated microbiome resulting from infection, there is substantial dysbiosis after administration of antiretrovirals. Analysis of bacterial DNA isolated from tissues of infected animals revealed a preference for the phylum Proteobacteria, suggesting that they preferentially translocate. Consistent with this finding, we observed increased metabolic activity of Proteobacterial species within the colonic lumen of SIV-infected animals. Overall these data provide insights into disease progression and suggest that therapies aimed at altering the composition and metabolic activity of the GI tract microbiome could benefit chronically-HIV infected individuals particularly those on antiretroviral therapies. PMID:25586559

  2. Familial cryptic translocation in Angelman syndrome

    SciTech Connect

    Weyerts, L.K.; Wiley, J.E.; Loud, K.M.

    1994-09-01

    The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

  3. Rapid Directional Translocations in Virus Replication

    PubMed Central

    Willard, Mark

    2002-01-01

    By viewing virus development in real time, the experiments reported here reveal novel processesrapid directional translocationsthat are likely to be important elements of virus replication. Herpes simplex virus type 1 (HSV-1) was labeled by the fusion of the green fluorescent protein to a structural protein of its tegument (VP11/12), the product of gene UL46. Infection of cultured cells with this recombinant virus (GHSV-UL46) produced fluorescent particles that were distributed throughout the cytoplasm with concentrations in the perinuclear region; they were absent from the nucleus. Viewing infected cells in real time by means of video microscopy produced a novel dynamic picture of virus development. Most strikingly, some of the fluorescent particles exhibited extremely rapid directional translocations at velocities as great as 5 ?m/s. The trajectories and destinations of these particles suggest that the rapid directional translocations serve at least three functions: the rapid transport of viral components to and between cytoplasmic processing stations, the delivery of materials for functions specific to the perinuclear region, and the conveyance of maturing virus particles to the plasma membrane. These rapid directional translocations are novel elements of virus assembly that are likely to be critical for efficient replication. PMID:11967336

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

    PubMed

    Zhang, Miao; Schmidt, Torsten; Jemt, Anders; Sahln, 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

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

    PubMed Central

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

    2011-01-01

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

  6. Histone modifications predispose genome regions to breakage and translocation

    PubMed Central

    Burman, Bharat; Zhang, Zhuzhu Z.; Pegoraro, Gianluca; Lieb, Jason D.; Misteli, Tom

    2015-01-01

    Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations. PMID:26104467

  7. 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.

  8. A new approach to polymer translocation

    NASA Astrophysics Data System (ADS)

    Dubbeldam, Johan; Rostiashvili, Vakhtang; Milchev, Andrey; Vilgis, Thomas

    2011-03-01

    Polymer translocation is ubiquitous in nature. It plays a role in phenomena like virus infections and in trafficking of proteins through pores in a cell membrane. Many theoretical models have been developed to explain scaling properties of simple polymer chains through tiny nanopores. This has not resolved the controversies in this field, however. In this paper we employ novel methods to shed light on the results that were obtained using the different models that are in use today. We use, for example fractional Brownian motion to explain the scaling of the variance in the translocation length with time and find good agreement between simulation results and theoretical predictions. An extension of the theory to nanopores with more complex geometries are discussed.

  9. Protein targeting and translocation; a comparative survey.

    PubMed

    Baker, A; Kaplan, C P; Pool, M R

    1996-11-01

    The last few years has seen enormous progress in understanding of protein targeting and translocation across biological membranes. Many of the key molecules involved have been identified, isolated, and the corresponding genes cloned, opening up the way for detailed analysis of the structure and function of these molecular machines. It has become clear that the protein translocation machinery of the endoplasmic reticulum is very closely related to that of bacteria, and probably represents an ancient solution to the problem of how to get a protein across a membrane. One of the thylakoid translocation systems looks as if it will also be very similar, and probably represents a pathway inherited from the ancestral endosymbiont. It is interesting that, so far, there is a perfect correlation between thylakoid proteins which are present in photosynthetic prokaryotes and those which use the sec pathway in chloroplasts; conversely, OE16 and 23 which use the delta pH pathway are not found in cyanobacteria. To date, no Sec-related proteins have been found in mitochondria, although these organelles also arose as a result of endosymbiotic events. However, virtually nothing is known about the insertion of mitochondrially encoded proteins into the inner membrane. Is the inner membrane machinery which translocates cytoplasmically synthesized proteins capable of operating in reverse to export proteins from the matrix, or is there a separate system? Alternatively, do membrane proteins encoded by mitochondrial DNA insert independently of accessory proteins? Unlike nuclear-encoded proteins, proteins encoded by mtDNA are not faced with a choice of membrane and, in principle, could simply partition into the inner membrane. The ancestors of mitochondria almost certainly had a Sec system; has this been lost along with many of the proteins once encoded in the endosymbiont genome, or is there still such a system waiting to be discovered? The answer to this question may also shed light on the controversy concerning the sorting of the inter-membrane space proteins cytochrome c1 and cytochrome b2, as the conservative-sorting hypothesis would predict re-export of matrix intermediates via an ancestral (possibly Sec-type) pathway. Whereas the ER and bacterial systems clearly share homologous proteins, the protein import machineries of mitochondria and chloroplasts appear to be analogous rather than homologous. In both cases, import occurs through contact sites and there are separate translocation complexes in each membrane, however, with the exception of some of the chaperone molecules, the individual protein components do not appear to be related. Their similarities may be a case of convergent rather than divergent evolution, and may reflect what appear to be common requirements for translocation, namely unfolding, a receptor, a pore complex and refolding. There are also important differences. Translocation across the mitochondrial inner membrane is absolutely dependent upon delta psi, but no GTP requirement has been identified. In chloroplasts the reverse is the case. The roles of delta psi and GTP, respectively, remain uncertain, but it is tempting to speculate that they may play a role in regulating the import process, perhaps by controlling the assembly of a functional translocation complex. In the case of peroxisomes, much still remains to be learned. Many genes involved in peroxisome biogenesis have been identified but, in most cases, the biochemical function remains to be elucidated. In this respect, understanding of peroxisome biogenesis is at a similar stage to that of the ER 10 years ago. The coming together of genetic and biochemical approaches, as with the other organelles, should provide many of the answers. PMID:8923800

  10. A novel selection system for chromosome translocations in Saccharomyces cerevisiae.

    PubMed Central

    Tennyson, Rachel B; Ebran, Nathalie; Herrera, Anissa E; Lindsley, Janet E

    2002-01-01

    Chromosomal translocations are common genetic abnormalities found in both leukemias and solid tumors. While much has been learned about the effects of specific translocations on cell proliferation, much less is known about what causes these chromosome rearrangements. This article describes the development and use of a system that genetically selects for rare translocation events using the yeast Saccharomyces cerevisiae. A translocation YAC was created that contains the breakpoint cluster region from the human MLL gene, a gene frequently involved in translocations in leukemia patients, flanked by positive and negative selection markers. A translocation between the YAC and a yeast chromosome, whose breakpoint falls within the MLL DNA, physically separates the markers and forms the basis for the selection. When RAD52 is deleted, essentially all of the selected and screened cells contain simple translocations. The detectable translocation rates are the same in haploids and diploids, although the mechanisms involved and true translocation rates may be distinct. A unique double-strand break induced within the MLL sequences increases the number of detectable translocation events 100- to 1000-fold. This novel system provides a tractable assay for answering basic mechanistic questions about the development of chromosomal translocations. PMID:11973293

  11. Unforced polymer translocation compared to the forced case

    NASA Astrophysics Data System (ADS)

    Lehtola, V. V.; Linna, R. P.; Kaski, K.

    2010-03-01

    We present results for unforced polymer translocation from simulations using Langevin dynamics in two dimensions (2D) to four dimensions and stochastic rotation dynamics supporting hydrodynamic modes in three dimensions (3D). We compare our results to forced translocation and a simplified model where the polymer escapes from an infinite pore. The simple model shows that the scaling behavior of unforced translocation is independent of the dimension of the side to which the polymer is translocating. We find that, unlike its forced counterpart, unforced translocation dynamics is insensitive to pore design. Hydrodynamics is seen to markedly speed up the unforced translocation process but not to affect the scaling relations. Average mean-squared displacement shows scaling with average transition time in unforced but not in forced translocation. The waiting-time distribution in unforced translocation follows closely Poissonian distribution. Our measured transfer probabilities align well with those obtained from an equilibrium theory in 3D, but somewhat worse in 2D, where a polymers relaxation toward equilibrium with respect to its translocation time is slower. Consequently, in stark contrast to forced translocation, unforced translocation is seen to remain close to equilibrium and shows clear universality.

  12. Stiff filamentous virus translocations through solid-state nanopores.

    PubMed

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

    2014-01-01

    The ionic conductance through a nanometer-sized pore in a membrane changes when a biopolymer slides through it, making nanopores sensitive to single molecules in solution. Their possible use for sequencing has motivated numerous studies on how DNA, a semi-flexible polymer, translocates nanopores. Here we study voltage-driven dynamics of the stiff filamentous virus fd with experiments and simulations to investigate the basic physics of polymer translocations. We find that the electric field distribution aligns an approaching fd with the nanopore, promoting its capture, but it also pulls fd sideways against the membrane after failed translocation attempts until thermal fluctuations reorient the virus for translocation. fd is too stiff to translocate in folded configurations. It therefore translocates linearly, exhibiting a voltage-independent mobility and obeying first-passage-time statistics. Surprisingly, lengthwise Brownian motion only partially accounts for the translocation velocity fluctuations. We also observe a voltage-dependent contribution whose origin is only partially determined. PMID:24932700

  13. D/D Translocations in Males Examined for Military Service

    PubMed Central

    Zeuthen, Eva; Nielsen, Johannes

    1973-01-01

    Three males with Robertsonian translocations were found in a sample of 1115 males examined for military service. One was a 14/15 translocation, and two were 13/14 translocations. One was spontaneous and two familial. The segregation rate of the translocations did not deviate significantly from unity in the sibships where the mother was the carrier, whereas all five children had the translocation in the two sibships where the father was the carrier. There were no abortions and no aneuploid chromosome abnormalities in the progeny of carriers with D/D translocation. There were no indications of any association between the D/D translocations and physical or mental development. Images PMID:4129971

  14. Stepwise nucleosome translocation by RSC remodeling complexes

    PubMed Central

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-01-01

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 12 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome. DOI: http://dx.doi.org/10.7554/eLife.10051.001 PMID:26895087

  15. Stepwise nucleosome translocation by RSC remodeling complexes.

    PubMed

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-01-01

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome. PMID:26895087

  16. Stepwise translocation of nucleic acid motors.

    PubMed

    Myong, Sua; Ha, Taekjip

    2010-02-01

    Recent single molecule studies have made a significant contribution to the understanding of the molecular mechanism involved in the movement of motor proteins which process DNA and RNA. Measurement of stepsize in two disparate motors, NS3 helicase and ribosome both revealed 3-bp steps, which consist of three hidden substeps. Combined with previous structural studies, NS3 is likely taking a single nucleotide step of translocation coupled to one ATP binding event and this mode may be conserved in multitude of helicases. Such a stepwise translocation movement appears to occur through main contacts with the phosphate backbone. Double stranded RNA and DNA motor, RIG-I and phi29, respectively, showed translocation on a duplex while tracking exclusively a single strand of RNA or DNA in a directional manner, 5'-3' in both cases. Spontaneous dynamics displayed by ribosome ratcheting and SSB (single stranded DNA binding protein) diffusing on DNA were rectified by interacting cofactors and proteins, EF-G and RecA, respectively. PMID:20061135

  17. Stepwise translocation of nucleic acid motors

    PubMed Central

    Myong, Sua; Ha, Taekjip

    2010-01-01

    Summary Recent single molecule studies have made a significant contribution to the understanding of the molecular mechanism involved in the movement of motor proteins which process DNA and RNA. Measurement of stepsize in two disparate motors, NS3 helicase and ribosome both revealed three basepair steps which consist of three hidden substeps. Combined with previous structural studies, NS3 is likely taking a single nucleotide step of translocation coupled to one ATP binding event and this mode may be conserved in multitude of helicases. Such a stepwise translocation movement appears to occur through main contacts with the phosphate backbone. Double stranded RNA and DNA motor, RIG-I and Φ29 respectively showed translocation on a duplex while tracking exclusively a single stranded RNA/DNA in a directional manner, 5′ to 3′ in both cases. Spontaneous dynamics displayed by ribosome ratcheting and SSB (single stranded DNA binding protein) diffusing on DNA were rectified by interacting cofactors and proteins, EF-G and RecA respectively. PMID:20061135

  18. 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

  19. 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

  20. [Genetic background of preeclampsia].

    PubMed

    Seremak-Mrozikiewicz, Agnieszka; Drews, Krzysztof

    2007-10-01

    Population studies have been suggesting genetic predisposition to the appearance of preeclampsia (PE) for a considerable period of time now. In familial occurrence of the disease higher frequency of preeclampsia has been observed in mothers, daughters and sisters of women burned of this poor medical history and higher risk to severe PE development. Although a single gene may contribute to the development of the patomechanizm of PE, most authors focus on the analysis of the common influence of candidate genes which are involved in a series of pathophysiological processes of PE. Thus, PE is often believed to be the final phenotype (increase of blood pressure and multiorgan complications development), being the result of intermediate phenotypes acting at the same time and being modulated by environmental factors. PE belongs to the complex human disease. The results of the findings connected with the contribution of maternal, paternal and fetal genotypes in PE development remain unclear, though a stronger influence of maternal genes, with a weaker influence of those transferred from the father, may be observed. Despite the existing divergences (the findings on the genetic background of PE are in conflict, no doubt due to the population differences and small number of investigated groups), the results obtained so far stress the necessity to discover the genetic risk factors as it may do both: facilitate the identification of groups of women predisposed to preeclampsia and allow for an early prophylactic administration. PMID:18200973

  1. 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

  2. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress

    PubMed Central

    Zareie, M; Johnson‐Henry, K; Jury, J; Yang, P‐C; Ngan, B‐Y; McKay, D M; Soderholm, J D; Perdue, M H; Sherman, P M

    2006-01-01

    Background and aim Chronic psychological stress, including water avoidance stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal defences against luminal bacteria. The aim of this study was to determine the ability of a defined probiotic regimen to prevent WAS induced intestinal pathophysiology. Methods Male rats were subjected to either WAS or sham stress for one hour per day for 10 consecutive days. Additional animals received seven days of Lactobacillus helveticus and L rhamnosus in the drinking water prior to stress and remained on these probiotics for the duration of the study. Rats were then sacrificed, intestinal segments assessed in Ussing chambers, and mesenteric lymph nodes cultured to determine bacterial translocation. Results All animals remained healthy for the duration of the study. Chronic WAS induced excess ion secretion (elevated baseline short circuit current) and barrier dysfunction (increased conductance) in both the ileum and colon, associated with increased bacterial adhesion and penetration into surface epithelial cells. Approximately 70% of rats subjected to WAS had bacterial translocation to mesenteric lymph nodes while there was no bacterial translocation in controls. Probiotic pretreatment alone had no effect on intestinal barrier function. However, WAS induced increased ileal short circuit current was reduced with probiotics whereas there was no impact on altered conductance. Pretreatment of animals with probiotics also completely abrogated WAS induced bacterial adhesion and prevented translocation of bacteria to mesenteric lymph nodes. Conclusion These findings indicate that probiotics can prevent chronic stress induced intestinal abnormalities and, thereby, exert beneficial effects in the intestinal tract. PMID:16638791

  3. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress.

    TOXLINE Toxicology Bibliographic Information

    Zareie M; Johnson-Henry K; Jury J; Yang PC; Ngan BY; McKay DM; Soderholm JD; Perdue MH; Sherman PM

    2006-11-01

    BACKGROUND AND AIMS: Chronic psychological stress, including water avoidance stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal defences against luminal bacteria. The aim of this study was to determine the ability of a defined probiotic regimen to prevent WAS induced intestinal pathophysiology.METHODS: Male rats were subjected to either WAS or sham stress for one hour per day for 10 consecutive days. Additional animals received seven days of Lactobacillus helveticus and L rhamnosus in the drinking water prior to stress and remained on these probiotics for the duration of the study. Rats were then sacrificed, intestinal segments assessed in Ussing chambers, and mesenteric lymph nodes cultured to determine bacterial translocation.RESULTS: All animals remained healthy for the duration of the study. Chronic WAS induced excess ion secretion (elevated baseline short circuit current) and barrier dysfunction (increased conductance) in both the ileum and colon, associated with increased bacterial adhesion and penetration into surface epithelial cells. Approximately 70% of rats subjected to WAS had bacterial translocation to mesenteric lymph nodes while there was no bacterial translocation in controls. Probiotic pretreatment alone had no effect on intestinal barrier function. However, WAS induced increased ileal short circuit current was reduced with probiotics whereas there was no impact on altered conductance. Pretreatment of animals with probiotics also completely abrogated WAS induced bacterial adhesion and prevented translocation of bacteria to mesenteric lymph nodes.CONCLUSION: These findings indicate that probiotics can prevent chronic stress induced intestinal abnormalities and, thereby, exert beneficial effects in the intestinal tract.

  4. 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

  5. Genomic Heterogeneity of Translocation Renal Cell Carcinoma

    PubMed Central

    Couturier, Jrme; Molini, Vincent; Escudier, Bernard; Camparo, Philippe; Su, Xiaoping; Yao, Hui; Tamboli, Pheroze; Lopez-Terrada, Dolores; Picken, Maria; Garcia, Marileila; Multani, Asha S.; Pathak, Sen; Wood, Christopher G.; Tannir, Nizar M.

    2013-01-01

    Purpose Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer involving the TFEB/TFE3 genes. We aimed to investigate the genomic and epigenetic features of this entity. Experimental design Cytogenomic analysis was performed with 250K single-nucleotide polymorphism microarrays on 16 tumor specimens and 4 cell lines. LINE-1 methylation, a surrogate marker of DNA methylation, was performed on 27 cases using pyrosequencing. Results tRCC showed cytogenomic heterogeneity, with 31.2% and 18.7% of cases presenting similarities with clear-cell and papillary RCC profiles, respectively. The most common alteration was a 17q gain in 7 tumors (44%), followed by a 9p loss in 6 cases (37%). Less frequent were losses of 3p and 17p in 5 cases (31%) each. Patients with 17q gain were older (P = 0.0006), displayed more genetic alterations (P < 0.003) and had a worse outcome (P = 0.002) than patients without it. Analysis comparing gene-expression profiling of a subset of tumors bearing 17q gain and those without suggest large scale dosage effects and TP53 haploinsufficiency without any somatic TP53 mutation identified. Cell-line based cytogenetic studies revealed that 17q gain can be related to isochromosome 17 and/or to multiple translocations occurring around 17q breakpoints. Finally, LINE-1 methylation was lower in tRCC tumors from adults compared to tumors from young patients (71.1% vs. 76.7%, P = 0.02). Conclusions Our results reveal genomic heterogeneity of tRCC with similarities to other renal tumor subtypes and raise important questions about the role of TFEB/TFE3 translocations and other chromosomal imbalances in tRCC biology. PMID:23817689

  6. Common principles of protein translocation across membranes.

    PubMed

    Schatz, G; Dobberstein, B

    1996-03-15

    Most major systems that transport proteins across a membrane share the following features: an amino-terminal transient signal sequence on the transported protein, a targeting system on the cis side of the membrane, a hetero-oligomeric transmembrane channel that is gated both across and within the plane of the membrane, a peripherally attached protein translocation motor that is powered by the hydrolysis of nucleoside triphosphate, and a protein folding system on the trans side of the membrane. These transport systems are divided into two families: export systems that export proteins out of the cytosol, and import systems that transport proteins into cytosol-like compartments. PMID:8599107

  7. 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

  8. 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

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

    NASA Astrophysics Data System (ADS)

    Suhonen, P. M.; Linna, R. P.

    2016-01-01

    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 site 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 β ≈1.26 for the exponent for the scaling of the translocation time with polymer length. This fairly low value can be explained by the additional friction due to binding particles. The multiple-site binding leads to translocation the dynamics of which is mainly determined by the trans side. For this process we obtain β ≈1.36 . This value can be explained by our derivation of β =4 /3 for constant-bias translocation, where translocated polymer segments form a globule on the trans side. Our results pave the way for understanding and utilizing chaperone-assisted translocation where variations in microscopic details lead to rich variations in the emerging dynamics.

  10. Translocation as a species conservation tool: Status and strategy

    USGS Publications Warehouse

    Griffith, B.; Scott, J.M.; Carpenter, J.W.; Reed, C.

    1989-01-01

    Surveys of recent (1973 to 1986) intentional releases of native birds and mammals to the wild in Australia, Canada, Hawaii, New Zealand, and the United States, were conducted to document current activities, identify factors associated with success, and suggest guidelines for enhancing future work. Nearly 700 translocations were conducted each year. Native game species constituted percent of translocations and were more successful (86 percent) than were translocations of threatened, endangered, or sensitive species (46 percent). Knowledge of habitat quality, location of release area within the species range, number of animals released, program length, and reproductive traits, allowed currect classification of 81 percent of observed translocations as successful or not.

  11. The major pathways of protein translocation across membranes.

    PubMed

    Ito, K

    1996-04-01

    The initial events in the localization of cell surface proteins include targeting of precursor molecules to the membrane and subsequent translocation across the membrane. The translocation reaction is mediated through a series of molecular interactions involving a number of protein factors. The trimeric SecY/Sec61 core complex, which is conserved throughout evolution, provides a proteinaceous pathway for translocation. The driving force for translocation is provided by the dynamic motion of the SecA ATPase in prokaryotes and by polypeptide elongation through the ribosome-Sec61 junction in eukaryotes. PMID:9135078

  12. 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

  13. DNA Translocation in Nanometer Thick Silicon Nanopores.

    PubMed

    Rodrguez-Manzo, Julio A; Puster, Matthew; Nicola, Adrien; Meunier, Vincent; Drndi?, Marija

    2015-06-23

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

  14. A Translocation Motif in Relaxase TrwC Specifically Affects Recruitment by Its Conjugative Type IV Secretion System

    PubMed Central

    Alperi, Anabel; Larrea, Delfina; Fernndez-Gonzlez, Esther; Dehio, Christoph; Zechner, Ellen L.

    2013-01-01

    Type IV secretion system (T4SS) substrates are recruited through a translocation signal that is poorly defined for conjugative relaxases. The relaxase TrwC of plasmid R388 is translocated by its cognate conjugative T4SS, and it can also be translocated by the VirB/D4 T4SS of Bartonella henselae, causing DNA transfer to human cells. In this work, we constructed a series of TrwC variants and assayed them for DNA transfer to bacteria and human cells to compare recruitment requirements by both T4SSs. Comparison with other reported relaxase translocation signals allowed us to determine two putative translocation sequence (TS) motifs, TS1 and TS2. Mutations affecting TS1 drastically affected conjugation frequencies, while mutations affecting either motif had only a mild effect on DNA transfer rates through the VirB/D4 T4SS of B. henselae. These results indicate that a single substrate can be recruited by two different T4SSs through different signals. The C terminus affected DNA transfer rates through both T4SSs tested, but no specific sequence requirement was detected. The addition of a Bartonella intracellular delivery (BID) domain, the translocation signal for the Bartonella VirB/D4 T4SS, increased DNA transfer up to 4% of infected human cells, providing an excellent tool for DNA delivery to specific cell types. We show that the R388 coupling protein TrwB is also required for this high-efficiency TrwC-BID translocation. Other elements apart from the coupling protein may also be involved in substrate recognition by T4SSs. PMID:23995644

  15. 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.

  16. 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.

  17. Role of bacterial adherence and the mucus barrier on bacterial translocation: effects of protein malnutrition and endotoxin in rats.

    PubMed Central

    Katayama, M; Xu, D; Specian, R D; Deitch, E A

    1997-01-01

    OBJECTIVE: The purpose of the study was to investigate the potential relations between mucosal bacterial adherence, intestinal mucus and mucin content, and bacterial translocation. SUMMARY BACKGROUND DATA: The attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most bacterial infections that originate at mucosal surfaces, such as the gut. The intestinal mucus layer appears to function as a defensive barrier limiting micro-organisms present in the intestinal lumen from colonizing enterocytes. Consequently, studies focusing on the biology of bacterial adherence to the intestinal mucosa likely are to be important in clarifying the pathogenesis of gut origin sepsis. METHODS: To explore the relations between intestinal bacterial adherence, mucus bacterial binding, and bacterial translocation, two models were used. One (protein malnutrition) in which profound alterations in intestinal morphology occurs in the absence of significant translocation and one (endotoxin challenge) in which bacterial translocation occurs and intestinal morphology is relatively normal. RESULTS: Protein malnutrition was not associated with bacterial translocation and measurement of enteroadherent, mucosally associated bacterial population levels documented that the total number of gram-negative enteric bacilli adherent to the ileum and cecum was less in the protein-malnourished rats than in the normally nourished animals (p < 0.01). Furthermore, there was an inverse relation between the duration of protein malnutrition and bacterial adherence to the intestinal mucosa (r = 0.62, p < 0.002). In contrast, after endotoxin challenge, the level of enteroadherent bacteria was increased and bacterial translocation was observed. The binding of Escherichia coli to immobilized ileal mucus in vitro was decreased significantly in protein-malnourished rats, whereas E. coli binding to insoluble ileal mucus was increased in the rats receiving endotoxin. CONCLUSIONS: This study indicates that the adherence of bacteria to the intestinal mucosal surface is an important factor in bacterial translocation, that intestinal mucus modulates bacterial adherence, and that increased levels of mucosally associated bacteria are associated with a loss intestinal barrier function to bacteria. PMID:9060589

  18. Melanotic Xp11 translocation renal cancer: report of a case with a unique intratumoral sarcoid-like reaction

    PubMed Central

    2014-01-01

    Background Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature. Case Report Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year-old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy. Conclusion This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping features between Xp11 translocation renal cell carcinoma, melanoma, and perivascular epithelioid cell neoplasms. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7225796341180634 PMID:24735727

  19. 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; DallIgna, 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

  20. Adsorption-driven translocation of polymer chain into nanopores

    NASA Astrophysics Data System (ADS)

    Yang, Shuang; Neimark, Alexander V.

    2012-06-01

    The polymer translocation into nanopores is generally facilitated by external driving forces, such as electric or hydrodynamic fields, to compensate for entropic restrictions imposed by the confinement. We investigate the dynamics of translocation driven by polymer adsorption to the confining walls that is relevant to chromatographic separation of macromolecules. By using the self-consistent field theory, we study the passage of a chain trough a small opening from cis to trans compartments of spherical shape with adsorption potential applied in the trans compartment. The chain transfer is modeled as the Fokker-Plank diffusion along the free energy landscape of the translocation pass represented as a sum of the free energies of cis and trans parts of the chain tethered to the pore opening. We investigate how the chain length, the size of trans compartment, the magnitude of adsorption potential, and the extent of excluded volume interactions affect the translocation time and its distribution. Interplay of these factors brings about a variety of different translocation regimes. We show that excluded volume interactions within a certain range of adsorption potentials can cause a local minimum on the free energy landscape, which is absent for ideal chains. The adsorption potential always leads to the decrease of the free energy barrier, increasing the probability of successful translocation. However, the translocation time depends non-monotonically of the magnitude of adsorption potential. Our calculations predict the existence of the critical magnitude of adsorption potential, which separates favorable and unfavorable regimes of translocation.

  1. Polymer translocation through a nanopore: The effect of solvent conditions

    NASA Astrophysics Data System (ADS)

    Kapahnke, Felix; Schmidt, Ulrich; Heermann, Dieter W.; Weiss, Matthias

    2010-04-01

    We study the translocation of a polymer through a nanopore by means of dissipative particle dynamics (DPD). Unlike Langevin approaches, DPD explicitly takes into account the interactions of solvent and polymer. We find that the translocation time for unforced translocation follows a scaling τ ˜Nβ with β ≈2.24 in good agreement with the prediction β =1+2ν that has been derived by considering hydrodynamics and memory effects within the chain. For bad-solvent conditions β →2, i.e., a diffusive scaling arises as a consequence of the reduced polymer relaxation time. Biased translocation between a good and a bad-solvent reservoir (tuned via the repulsion between solvent and polymer) yields a preferential translocation toward the good solvent with β ≈1.2. This observation is consistent with the recent theoretical prediction β =3ν/(1+ν) for driven translocation. When varying the solvent quality by imposing attractive monomer-monomer interactions (such as in Langevin approaches), an artificial translocation toward the bad-solvent side emerges. Using attractive monomer-monomer interactions to mimic a bad solvent hence does not capture the essential physics of the translocation process.

  2. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Rodent heritable translocation assays. 798.5460 Section 798.5460 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798.5460 Rodent heritable translocation assays. (a)...

  3. Dermatofibrosarcoma protuberans: from translocation to targeted therapy.

    PubMed

    Noujaim, Jonathan; Thway, Khin; Fisher, Cyril; Jones, Robin L

    2015-12-01

    Dermatofibrosarcoma protuberans (DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery (MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13) (COL1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGF?R, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management. PMID:26779374

  4. Dermatofibrosarcoma protuberans: from translocation to targeted therapy

    PubMed Central

    Noujaim, Jonathan; Thway, Khin; Fisher, Cyril; Jones, Robin L.

    2015-01-01

    Dermatofibrosarcoma protuberans (DFSP), the most common dermal sarcoma, is a low-grade, slow growing fibroblastic malignant neoplasm that most frequently affects middle aged adults and is characterized by a high local recurrence rate and a low propensity for metastasis. Wide surgical resection or Mohs micrographic surgery (MMS) are the preferred approaches for localized disease, while radiation therapy is warranted for inoperable disease or for cases with positive margins where re-excision is not possible. DFSP is generally regarded as refractory to conventional chemotherapy. Treatment options for systemic disease were limited until the discovery of a unique translocation, t(17;22)(q22;q13) (COL1A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGF?R, ABL and KIT inhibitor, has revolutionized systemic therapy in DFSP. In this review, we summarize the epidemiological, clinical, histological and genetic characteristics of DFSP and update the readers on its current management. PMID:26779374

  5. Membrane translocation assayed by fluorescence spectroscopy.

    PubMed

    Broecker, Jana; Keller, Sandro

    2010-01-01

    Assessing the ability of biomolecules or drugs to overcome lipid membranes in a receptor-independent way is of great importance in both basic research and applications involving the use of liposomes. A combination of uptake, release, and dilution experiments performed by steady-state fluorescence spectroscopy provides a powerful, straightforward, and inexpensive way of monitoring membrane translocation of fluorescent compounds. This is particularly true for peptides and proteins carrying intrinsic tryptophan residues, which eliminates the need for attaching extrinsic labeling moieties to the compound of interest. The approach encompasses three different kinds of fluorescence titrations and some simple calculations that can be carried out in a spreadsheet program. A complete set of experiments and data analyses can typically be completed within two days. PMID:20013403

  6. Strandwise translocation of a DNA glycosylase on undamaged DNA

    SciTech Connect

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

    2012-05-14

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

  7. 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.

  8. Scaling Theory of Polymer Translocation into Confined Regions

    PubMed Central

    Wong, Chiu Tai Andrew; Muthukumar, Murugappan

    2008-01-01

    We examine the voltage-driven polymer translocation from a spacious region into a confined region imposed by two parallel planes, so that the entry is impeded by the entropic confinement but aided by the electric field inside the confined region. Two modes of entry are examined: linear translocation where a chain enters the confined region with chain ends, and hairpin translocation where a chain enters the confined region by forming a hairpin. Our calculation shows that translocation time increases with polymer length for linear entries but decreases with polymer length for hairpin entries. Applying to electrophoresis of DNA molecules through periodic spacious and confined regions, our theory shows that the dominance of hairpin translocations leads to the experimentally observed faster migration of longer DNA molecules. Our theory predicts experimental conditions for the validity of this law in terms of polymer length, size of the confined region, and solution conditions. PMID:18621833

  9. 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)

  10. Interaction prolonged DNA translocation through solid-state nanopores

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  11. Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis

    PubMed Central

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

    2015-01-01

    Unbalanced translocations are a relatively common type of copy number variation and a major contributor to neurodevelopmental disorders. We analyzed the breakpoints of 57 unique unbalanced translocations to investigate the mechanisms of how they form. Fifty-one are simple unbalanced translocations between two different chromosome ends, and six rearrangements have more than three breakpoints involving two to five chromosomes. Sequencing 37 breakpoint junctions revealed that simple translocations have between 0 and 4 base pairs (bp) of microhomology (n = 26), short inserted sequences (n = 8), or paralogous repeats (n = 3) at the junctions, indicating that translocations do not arise primarily from nonallelic homologous recombination but instead form most often via nonhomologous end joining or microhomology-mediated break-induced replication. Three simple translocations fuse genes that are predicted to produce in-frame transcripts of SIRPG-WWOX, SMOC2-PROX1, and PIEZO2-MTA1, which may lead to gain of function. Three complex translocations have inversions, insertions, and multiple breakpoint junctions between only two chromosomes. Whole-genome sequencing and fluorescence in situ hybridization analysis of two de novo translocations revealed at least 18 and 33 breakpoints involving five different chromosomes. Breakpoint sequencing of one maternally inherited translocation involving four chromosomes uncovered multiple breakpoints with inversions and insertions. All of these breakpoint junctions had 04 bp of microhomology consistent with chromothripsis, and both de novo events occurred on paternal alleles. Together with other studies, these data suggest that germline chromothripsis arises in the paternal genome and may be transmitted maternally. Breakpoint sequencing of our large collection of chromosome rearrangements provides a comprehensive analysis of the molecular mechanisms behind translocation formation. PMID:26070663

  12. MODY-like diabetes associated with an apparently balanced translocation: possible involvement of MPP7 gene and cell polarity in the pathogenesis of diabetes

    PubMed Central

    Bhoj, Elizabeth J; Romeo, Stefano; Baroni, Marco G; Bartov, Guy; Schultz, Roger A; Zinn, Andrew R

    2009-01-01

    Background Characterization of disease-associated balanced translocations has led to the discovery of genes responsible for many disorders, including syndromes that include various forms of diabetes mellitus. We studied a man with unexplained maturity onset diabetes of the young (MODY)-like diabetes and an apparently balanced translocation [46,XY,t(7;10)(q22;p12)] and sought to identify a novel diabetes locus by characterizing the translocation breakpoints. Results Mutations in coding exons and splice sites of known MODY genes were first ruled out by PCR amplification and DNA sequencing. Fluorescent in situ hybridization (FISH) studies demonstrated that the translocation did not disrupt two known diabetes-related genes on 10p12. The translocation breakpoints were further mapped to high resolution using FISH and somatic cell hybrids and the junctions PCR-amplified and sequenced. The translocation did not disrupt any annotated transcription unit. However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 (MPP7) gene, which encodes a protein required for proper cell polarity. This biological function is shared by HNF4A, a known MODY gene. Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. The translocation did not appear to alter lymphoblastoid expression of MPP7 or other genes near the breakpoints. Conclusion The balanced translocation and MODY-like diabetes in the proband could be coincidental. Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study. PMID:19216786

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

    PubMed

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

    2015-08-01

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

  14. 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.

  15. The Athena Background

    NASA Astrophysics Data System (ADS)

    Piro, Luigi; Lotti, Simone; Macculi, Claudio; Molendi, Silvano; Eraerds, Tanja; Laurent, Philippe

    2015-09-01

    Estimating, reducing and controlling the residual particle background is fundamental for achieving the objectives of several science topics of Athena, in particular those connected with background dominated observations of faint and/or diffuse sources. This requires assessing the particle environment in L2, propagating the various particle components throughout the mirror, spacecraft, and instruments via proper modelling and simulations of various physical processes, implementing design and h/w measures at instrument and mission level to reduce the un-rejected background and identifying proper calibration methods to control the background variations. Likewise, an adequate knowledge of the XRB, made of components that may vary spatially or temporally, is required as well. Here we will review the present status of the background knowledge, and summarize the activities on-going within Athena at various levels.

  16. Evidence for separate translocation pathways in determining cadmium accumulation in grain and aerial plant parts in rice

    PubMed Central

    Kashiwagi, Takayuki; Shindoh, Kumiko; Hirotsu, Naoki; Ishimaru, Ken

    2009-01-01

    Background Cadmium (Cd) translocation and accumulation in the grain and aerial plant parts of rice (Oryza sativa L.) is an important aspect of food safety and phytoextraction in areas with contaminated soil. Because control of Cd translocation and accumulation is likely to be determined by the plants genetics, the Cd contents of grain and the aerial parts of rice may be manipulated to improve food safety and for phytoextraction ability. This study studied Cd translocation and accumulation and their genetic control in aerial parts of rice to provide a starting point for improving food safety and phytoextraction in Cd-contaminated soils. Results In the japonica rice cultivar "Nipponbare", Cd accumulated in leaves and culms until heading, and in culms and ears after heading. Two quantitative trait loci (QTLs) from indica cv. "Kasalath", qcd4-1 and qcd4-2, affect Cd concentrations in upper plant parts just before heading. Three near-isogenic lines (NILs) with qcd4-1 and qcd4-2 were selected from the "Nipponbare" background, and were analyzed for the effects of each QTL, and for interactions between the two QTLs. From the results compared between "Nipponbare" and each NIL, neither QTL influenced total Cd accumulation in aerial parts at 5 days after heading, but the interaction between two QTLs increased Cd accumulation. At 35 days after heading, qcd4-2 had increased Cd accumulation in the aerial plant parts and decreased translocation from leaves other than flag leaf, but interaction between the two QTLs increased translocation from leaves. NILqcd4-1,2 accumulated higher concentrations of Cd in brown rice than "Nipponbare". Conclusion Three types of Cd translocation and accumulation patterns demonstrated by NILs suggested that the accumulation of Cd in leaves and culms before heading, and translocation from them after heading are responsible for Cd accumulation in grain. Cd translocation from roots to culms and ears after heading may direct Cd to the aerial organs without influencing brown rice accumulation. PMID:19154618

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

    PubMed Central

    2013-01-01

    Background Listeria adhesion protein (Lap), an alcohol acetaldehyde dehydrogenase (lmo1634) promotes bacterial paracellular translocation through epithelial cell junctions during gastrointestinal phase of infection. Secreted Lap is critical for pathogenesis and is mediated by SecA2 system; however, if strain dependent variation in Lap secretion would affect L. monocytogenes paracellular translocation through epithelial barrier is unknown. Methods Amounts of Lap secretion were examined in clinical isolates of L. monocytogenes by cell fractionation analysis using Western blot. Quantitative reverse transcriptase PCR (qRT-PCR) was used to verify protein expression profiles. Adhesion and invasion of isolates were analyzed by in vitro Caco-2 cell culture model and paracellular translocation was determined using a trans-well model pre-seeded with Caco-2 cells. Results Western blot revealed that expression of Lap in whole cell preparation of isolates was very similar; however, cell fractionation analysis indicated variable Lap secretion among isolates. The strains showing high Lap secretion in supernatant exhibited significantly higher adhesion (3.4 - 4.8% vs 1.5 - 2.3%, P < 0.05), invasion and paracellular translocation in Caco-2 cells than the low secreting isolates. In cell wall fraction, Lap level was mostly uniform for both groups, while Lap accumulated in cytosol in low secreting strains indicating that Lap distribution in cellular compartments is a strain-dependent phenomenon, which may be controlled by the protein transport system, SecA2. ΔsecA2 mutants showed significantly reduced paracellular translocation through epithelial barrier (0.48 ± 0.01 vs 0.24 ± 0.02, P < 0.05). qRT-PCR did not show any discernible variation in lap transcript levels in either high or low secreting isolates. Conclusion This study revealed that secreted Lap is an important determinant in Lap-mediated L. monocytogenes translocation through paracellular route and may serve as an indicator for pathogenic potential of an isolate. PMID:23799938

  18. Analyzing kinesin motor domain translocation in cultured hippocampal neurons.

    PubMed

    Yang, Rui; Bentley, Marvin; Huang, Chung-Fang; Banker, Gary

    2016-01-01

    Neuronal microtubules are subject to extensive posttranslational modifications and are bound by MAPs, tip-binding proteins, and other accessory proteins. All of these features, which are difficult to replicate in vitro, are likely to influence the translocation of kinesin motors. Here we describe assays for evaluating the translocation of a population of fluorescently labeled kinesin motor domains, based on their accumulation in regions of the cell enriched in microtubule plus ends. Neurons lend themselves to these experiments because of their microtubule organization. In axons, microtubules are oriented with their plus ends out; dendrites contain a mixed population of microtubules, but those near the tips are also plus end out. The assays involve the expression of constitutively active kinesins that can walk processively, but that lack the autoinhibitory domain in the tail that normally prevents their binding to microtubules until they attach to vesicles. The degree to which such motor domains accumulate at neurite tips serves as a measure of the efficiency of their translocation. Although these assays cannot provide the kind of quantitative kinetic information obtained from in vitro assays, they offer a simple way to examine kinesin translocation in living neurons. They can be used to compare the translocation efficiency of different kinesin motors and to evaluate how mutations or posttranslational modifications within the motor domain influence kinesin translocation. Changes to motor domain accumulation in these assays can also serve as readout for changes in the microtubule cytoskeleton that affect kinesin translocation. PMID:26794516

  19. 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.

  20. [The translocation carcinoma : A pediatric renal tumor also in adults].

    PubMed

    Bruder, E; Moch, H

    2016-03-01

    The MiT family of translocation-associated renal cell carcinomas comprise approximately 40 % of renal cell carcinomas in young patients but only up to 4 % of renal cell carcinomas in adult patients. The Xp11.2 translocation-associated tumors are the most frequent and were included in the 2004 World Health Organization (WHO) classification. They contain a fusion of the TFE3 gene with ASPSCR1, PRCC, NONO, SPFQ or CLTC resulting in an immunohistochemically detectable nuclear overexpression of TFE3. The Xp11.2 translocation-associated renal cell carcinomas are characterized by ample clear cytoplasm, papillary architecture and abundant psammoma bodies. The TFEB translocation-associated renal cell carcinomas are much rarer and show a biphasic architecture. Fluorescence in situ hybridization permits the detection of a translocation by means of a break apart probe for the TFE3 and TFEB genes and is recommended for the diagnosis of renal cell carcinomas in patients under 30 years of age. The TFE3 and TFEB translocation-associated tumors are classified as MiT family translocation carcinomas in the new WHO classification.The rare renal cell carcinomas harboring an ALK rearrangement with fusion to VCL in young patients with sickle cell trait show a characteristic morphology and are listed in the new WHO classification as a provisional entity. PMID:26972595

  1. Protein translocation across the membrane of the endoplasmic reticulum.

    PubMed

    Wilkinson, B M; Regnacq, M; Stirling, C J

    1997-02-01

    Eukaryotic cells are characterized by the existence of membrane-bound subcellular compartments which perform a variety of specialized functions. Proteins destined for these compartments begin their synthesis in the cytosol and must be subsequently targeted to their functional compartment by specific signal sequences present in the newly synthesized polypeptide chain. The translocation of preproteins across biological membranes is a fundamental process of intracellular trafficking and organelle biogenesis. Entry into the secretory pathway occurs by translocation of proteins into or across the membrane of the endoplasmic reticulum (ER). This process involves two distinct steps which are dependent on the orchestrated action of several proteins. The initial step of targeting involves recognition of the signal sequence and delivery of the protein precursor to the ER in a translocation competent conformation. The subsequent translocation event is characterized by interaction of the preprotein with the translocation channel followed by unidirectional movement across the lipid bilayer of the ER membrane into the lumenal space. The study of the mechanism of the translocation process is one of the most intriguing and rapidly advancing areas in cell biology. Here we review recent findings in both the yeast Saccharomyces cerevisiae and mammals concerning the mechanisms of the translocation step and discuss the roles of the proteins implicated in this process. PMID:9050442

  2. The archaeal Sec-dependent protein translocation pathway.

    PubMed

    Bolhuis, Albert

    2004-06-29

    Over the past three decades, transport of proteins across cellular membranes has been studied extensively in various model systems. One of the major transport routes, the so-called Sec pathway, is conserved in all domains of life. Very little is known about this pathway in the third domain of life, archaea. The core components of the archaeal, bacterial and eucaryal Sec machinery are similar, although the archaeal components appear more closely related to their eucaryal counterparts. Interestingly, the accessory factors of the translocation machinery are similar to bacterial components, which indicates a unique hybrid nature of the archaeal translocase complex. The mechanism of protein translocation in archaea is completely unknown. Based on genomic sequencing data, the most likely system for archaeal protein translocation is similar to the eucaryal co-translational translocation pathway for protein import into the endoplasmic reticulum, in which a protein is pushed across the translocation channel by the ribosome. However, other models can also be envisaged, such as a bacterial-like system in which a protein is translocated post-translationally with the aid of a motor protein analogous to the bacterial ATPase SecA. This review discusses the different models. Furthermore, an overview is given of some of the other components that may be involved in the protein translocation process, such as those required for protein targeting, folding and post-translational modification. PMID:15306407

  3. Translocation of Carbon in Powdery Mildewed Barley 1

    PubMed Central

    Edwards, H. H.

    1971-01-01

    This paper compares translocation in healthy and powdery mildew (Erysiphe graminis f. sp. hordei, race CR3) infected barley (Hordeum vulgare, variety Manchuria). The sink-like properties of the powdery mildew infection were used to determine what effect imposing a sink in the midst of normal source tissue (mature primary leaf) had on the translocation process. The pattern of translocation was determined by monitoring the movement of 14C which was photosynthetically incorporated from 14C either by the primary or second leaf. In the healthy primary leaf of barley, 14C fixed in the tip section of the blade was preferentially translocated to the root, whereas 14C fixed in the basal section was primarily translocated to the shoot. When a sporulating powdery mildew infection was present in the mid-section of the primary leaf, 14C fixed in that section or in the acropetal healthy tip section readily accumulated in the infection area. Labeled carbon fixed in the healthy basal section was translocated into the other parts of the plant with only a small fraction moving acropetally into the infected mid-section. The 14C fixed by the second leaf was translocated to the root and younger shoot with very little entering the primary leaf. The presence of the mildew infection did not alter this pattern. PMID:16657616

  4. 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.

  5. 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 δt of translocation times of m-th monomer δtm^1.5 is stronger than the thermal broadening δtm^1.25 The predictions of our deterministic model were verified by extensive molecular dynamics simulations

  6. EML4-ALK translocation is associated with early onset of disease and other clinicopathological features in Chinese female never-smokers with non-small-cell lung cancer

    PubMed Central

    REN, WEIHONG; ZHANG, BO; MA, JIE; LI, WENCAI; LAN, JIANYUN; MEN, HUI; ZHANG, QINXIAN

    2015-01-01

    Non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation is resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib, but responds to the ALK-TKI crizotinib. Characterization of EML4-ALK translocation may provide invaluable information to facilitate disease diagnosis and improve the outcome of customized treatment. Although the occurrence of EML4-ALK translocation is likely to be affected by the smoking habits and gender of patients, the translocation has not been characterized extensively in female never-smokers with NSCLC. Therefore, 280 female never-smokers that were diagnosed with NSCLC were enrolled in the present study, and characteristics of EML4-ALK translocation, including the frequency, were determined in these NSCLC patients. EML4-ALK fusion variants were detected using Multiplex one-step reverse transcription-polymerase chain reaction and subsequently confirmed by DNA sequencing and Vysis ALK Break Apart fluorescence in situ hybridization analysis. The EML4-ALK fusion variants were detected in 21 carcinoma tissue specimens, accounting for 7.5% of the enrolled patients. Out of these patients with EML4-ALK fusion variants, EML4-ALK fusion variant 1 was identified in 12 patients, indicating that variant 1 is the most common type of EML4-ALK fusion gene in the present cohort of patients. ALK mRNA was aberrantly expressed in all the tissues with EML4-ALK translocation, but not in the carcinoma tissues without EML4-ALK translocation. In addition, the EML4-ALK translocation was more frequently found in younger patients. The median age of patients with EML4-ALK translocation was 50.952.29 years, which was significantly younger (P<0.01) than the median age of the patients without EML4-ALK translocation (57.150.56). The EML4-ALK translocation was detected exclusively in undifferentiated tumors that were graded as poorly- or moderately-differentiated carcinomas and suspected to be more malignant compared with well-differentiated tumors. In summary, the present study found that 7.5% of patients with NSCLC that are female never-smokers harbor EML4-ALK translocations, which are associated with the aberrant expression of ALK mRNA, early onset of disease and undifferentiated carcinomas.

  7. The cosmic neutrino background

    NASA Technical Reports Server (NTRS)

    Dar, Arnon

    1991-01-01

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

  8. Background Underground at WIPP

    NASA Astrophysics Data System (ADS)

    Esch, Ernst-Ingo; Hime, A.; Bowles, T. J.

    2001-04-01

    Recent interest to establish a dedicated underground laboratory in the United States prompted an experimental program at to quantify the enviromental backgrounds underground at the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. An outline of this program is provided along with recent experimental data on the cosmic ray muon flux at the 650 meter level of WIPP. The implications of the cosmic ray muon and fast neutron background at WIPP will be discussed in the context of new generation, low background experiments envisioned in the future.

  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. Translocator Receptor Blockade Reduces Prostate Tumor Growth

    PubMed Central

    Fafalios, Arlee; Akhavan, Ardavan; Parwani, Anil V.; Bies, Robert R.; McHugh, Kevin J.; Pflug, Beth R.

    2009-01-01

    Statement of Translational Relevance Although benzodiazepines have been used clinically for over 50 years, their application as a form of cancer therapy is largely unexplored. Here we show that lorazepam, a benzodiazepine commonly prescribed to treat anxiety disorders and acts on both central and peripheral receptors, inhibits prostate cancer cell growth and survival. Our studies further elucidate the mechanism by which Translocator Protein (TSPO) antagonists alter cancer cell function. Antagonists for TSPO are already used in the clinic for other indications and demonstrate very minor side effects. Because lorazepam is a commonly prescribed FDA-approved drug, the translation of our preclinical results to the prostate cancer patient population could be readily achieved. Our studies could lead to a significant change in the management of prostate cancer by providing a treatment option with minimal toxicity for use after failure of androgen-deprivation therapy and could ultimately prevent prostate cancer deaths. Purpose The transmembrane molecule, Translocator Protein (TSPO) has been implicated in the progression of epithelial tumors. TSPO gene expression is high in tissues involved in steroid biosynthesis, neurodegenerative disease and in cancer and overexpression has been shown to contribute to pathologic conditions including cancer progression in several different models. The goal of our study was to examine the expression and biological relevance of TSPO in prostate cancer and demonstrate that the commonly prescribed benzodiazepine lorazepam, a ligand for TSPO, exhibits anti-cancer properties. Experimental Design Immunohistochemical analysis using tissue microarrays was used to determine the expression profile of TSPO in human prostate cancer tissues. To demonstrate the effect of benzodiazepines (lorazepam and PK11195) in prostate cancer, we utilized cell proliferation assays, apoptosis ELISA, prostate cancer xenograft study, and immunohistochemistry. Results TSPO expression is increased in prostatic intraepithelial neoplasia, primary prostate cancer, and metastases compared to normal prostate tissue and benign prostatic hyperplasia. Furthermore, TSPO expression correlates with disease progression, as TSPO levels increased with increasing Gleason sum and stage with prostate cancer metastases demonstrating the highest level of expression among all tissues examined. Functionally, we have demonstrated that lorazepam has anti-proliferative and pro-apoptotic properties in vitro and in vivo. Additionally, we have shown that TSPO overexpression in nontumorigenic cells conferred susceptibility to lorazepam-induced growth inhibition. Conclusion These data suggest that blocking TSPO function in tumor cells induces cell death and denotes a survival role for TSPO in prostate cancer and provide the first evidence for the use of benzodiazepines in prostate cancer therapeutics. PMID:19789311

  11. Translocation of threatened plants as a conservation measure in China.

    PubMed

    Liu, Hong; Ren, Hai; Liu, Qiang; Wen, XiangYing; Maunder, Michael; Gao, JiangYun

    2015-12-01

    We assessed the current status of plant conservation translocation efforts in China, a topic poorly reported in recent scientific literature. We identified 222 conservation translocation cases involving 154 species, of these 87 were Chinese endemic species and 101 (78%) were listed as threatened on the Chinese Species Red List. We categorized the life form of each species and, when possible, determined for each case the translocation type, propagule source, propagule type, and survival and reproductive parameters. A surprisingly large proportion (26%) of the conservation translocations in China were conservation introductions, largely implemented in response to large-scale habitat destruction caused by the Three-Gorge Dam and another hydropower project. Documentation and management of the translocations varied greatly. Less than half the cases had plant survival records. Statistical analyses showed that survival percentages were significantly correlated with plant life form and the type of planting materials. Thirty percent of the cases had records on whether or not individuals flowered or fruited. Results of information theoretic model selection indicated that plant life form, translocation type, propagule type, propagule source, and time since planting significantly influenced the likelihood of flowering and fruiting on the project level. We suggest that the scientific-based application of species conservation translocations should be promoted as part of a commitment to species recovery management. In addition, we recommend that the common practice of within and out of range introductions in nature reserves to be regulated more carefully due to its potential ecological risks. We recommend the establishment of a national office and database to coordinate conservation translocations in China. Our review effort is timely considering the need for a comprehensive national guideline for the newly announced nation-wide conservation program on species with extremely small populations, which is expected to stimulate conservation translocations for many species in the near future. PMID:26372611

  12. 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.

  13. Sizing the protein translocation pathway of colicin Ia channels.

    PubMed

    Kienker, Paul K; Jakes, Karen S; Blaustein, Robert O; Miller, Christopher; Finkelstein, Alan

    2003-08-01

    The bacterial toxin colicin Ia forms voltage-gated channels in planar lipid bilayers. The toxin consists of three domains, with the carboxy-terminal domain (C-domain) responsible for channel formation. The C-domain contributes four membrane-spanning segments and a 68-residue translocated segment to the open channel, whereas the upstream domains and the amino-terminal end of the C-domain stay on the cis side of the membrane. The isolated C-domain, lacking the two upstream domains, also forms channels; however, the amino terminus and one of the normally membrane-spanning segments can move across the membrane. (This can be observed as a drop in single-channel conductance.) In longer carboxy-terminal fragments of colicin Ia that include translocated. Presumably, a portion of the C-domain creates a pathway for the polar upstream region to move through the membrane. To determine the size of this translocation pathway, we have attached "molecular stoppers," small disulfide-bonded polypeptides, to the amino terminus of the C-domain, and determined whether they could be translocated. We have found that the translocation rate is strongly voltage dependent, and that at voltages >/=90 mV, even a 26-A stopper is translocated. Upon reduction of their disulfide bonds, all of the stoppers are easily translocated, indicating that it is the folded structure, rather than some aspect of the primary sequence, that slows translocation of the stoppers. Thus, the pathway for translocation is >/=26 A in diameter, or can stretch to this value. This is large enough for an alpha-helical hairpin to fit through. PMID:12860927

  14. The GLAST Background Model

    SciTech Connect

    Ormes, J.F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Mizuno, T.; Ritz, S.; /NASA, Goddard

    2007-10-17

    In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

  15. The GLAST Background Model

    SciTech Connect

    Ormes, J. F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Ritz, S.; Mizuno, T.

    2007-07-12

    In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

  16. Protein translocation through the Sec61/SecY channel.

    PubMed

    Cheng, Zhiliang

    2010-06-01

    Special codes are embedded in the primary sequence of newly synthesized proteins to determine their final destination. Protein translocation across biological membranes requires co-operation between the targeting and translocation machineries. A conserved membrane channel, the Sec61/SecY complex, mediates protein translocation across or integration into the endoplasmic reticulum membrane in eukaryotes and the plasma membrane in prokaryotes. A combination of recent biochemical and structural data provides novel insights into the mechanism of how the channel allows polypeptide movement into the exoplasmic space and the lipid bilayer. PMID:20156192

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

    PubMed Central

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

    2013-01-01

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

  18. Gut Microbiota Dysbiosis Is Associated with Inflammation and Bacterial Translocation in Mice with CCl4-Induced Fibrosis

    PubMed Central

    Gmez-Hurtado, Isabel; Santacruz, Arlette; Peir, Gloria; Zapater, Pedro; Gutirrez, Ana; Prez-Mateo, Miguel; Sanz, Yolanda; Francs, Rubn

    2011-01-01

    Background Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. Hypothesis and Aims We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. Animals and Methods Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n?=?6/week) and control animals (n?=?4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. Results Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. Conclusions Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice. PMID:21829583

  19. 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

  20. Translocation of signalling proteins to the plasma membrane revealed by a new bioluminescent procedure

    PubMed Central

    2011-01-01

    Background Activation by extracellular ligands of G protein-coupled (GPCRs) and tyrosine kinase receptors (RTKs), results in the generation of second messengers that in turn control specific cell functions. Further, modulation/amplification or inhibition of the initial signalling events, depend on the recruitment onto the plasma membrane of soluble protein effectors. High throughput methodologies to monitor quantitatively second messenger production, have been developed over the last years and are largely used to screen chemical libraries for drug development. On the contrary, no such high throughput methods are yet available for the other aspect of GPCRs regulation, i.e. protein translocation to the plasma membrane, despite the enormous interest of this phenomenon for the modulation of receptor downstream functions. Indeed, to date, the experimental procedures available are either inadequate or complex and expensive. Results Here we describe the development of a novel conceptual approach to the study of cytosolic proteins translocation to the inner surface of the plasma membrane. The basis of the technique consists in: i) generating chimeras between the protein of interests and the calcium (Ca2+)-sensitive, luminescent photo-protein, aequorin and ii) taking advantage of the large Ca2+ concentration [Ca2+] difference between bulk cytosolic and the sub-plasma membrane rim. Conclusion This approach, that keeps unaffected the translocation properties of the signalling protein, can in principle be applied to any protein that, upon activation, moves from the cytosol to the plasma membrane. Thus, not only the modulation of GPCRs and RTKs can be investigated in this way, but that of all other proteins that can be recruited to the plasma membrane also independently of receptor activation. Moreover, its automated version, which can provide information about the kinetics and concentration-dependence of the process, is also applicable to high throughput screening of drugs affecting the translocation process. PMID:21658234

  1. Meiotic chromosome asynapsis in a boar with a reciprocal translocation and acquired testicular degeneration.

    PubMed

    Villagmez, D A; Gustavsson, I; Alabay, B; Plen, L

    1993-01-01

    During a period of performance testing, a boar used for artificial insemination purposes was found responsible for reduced litter size and slightly increased incidence of repeat breeding. The qualitative and quantitative semen characteristics, however, were within normal limits. Later, evaluation of the semen during a period of 3 months revealed a decreased sperm concentration, but sperm cell morphology and mobility were normal. At castration, the boar, which had suffered from scrotal inflammation, was found to have hypoplastic gonads, the right testis being smaller than the left one. Histologically there was spermatogenic arrest at the primary spermatocyte level in almost all tubules of the right testis. In the left testis, histology was more heterogeneous, with some tubules containing all developmental stages, while others had an almost complete spermatogenic arrest. Cytogenetically the boar was carrying a translocation, rcp(2;14)(p14;q23). Synaptonemal complex analysis revealed complete quadrivalent pairing in 21 out of 43 cells analysed. The remaining cells demonstrated quadrivalents with axes moderately or extensively unpaired. There was a distinct difference between cells from the right vs. the left testis. The latter cells showed more completely paired translocation configurations. Moreover, in 14 and 7 cells analysed from the right and left testis, respectively, the translocation configuration could not be identified. This was due to chromosome asynapsis and frequent occurrence of gaps in the chromosomes, including others than those of the translocation, plus an abundant cellular deposit which formed a dense cell background. Association or pairing of the quadrivalent with the sex bivalent was seen in one cell only. At diakinesis-MI, most cells had a ring-shaped quadrivalent. It is believed that the asynapsis of chromosomes during the prophase of meiosis was to a large extent due to the degeneration caused by the inflammation processes. PMID:8335471

  2. Pseudomonas fluorescens alters epithelial permeability and translocates across Caco-2/TC7 intestinal cells

    PubMed Central

    2010-01-01

    Background Pseudomonas fluorescens has long been considered as a psychrotrophic microorganism. Recently, we have shown that clinical strains of P. fluorescens (biovar 1) are able to adapt at a growth temperature of 37°C or above and induce a specific inflammatory response. Interestingly, a highly specific antigen of P. fluorescens, I2, is detected in the serum of patients with Crohn's disease but the possible role of this bacterium in the disease has not yet been explored. In the present study, we examined the ability of a psychrotrophic and a clinical strain of P. fluorescens to modulate the permeability of a Caco-2/TC7 intestinal epithelial model, reorganize the actin cytoskeleton, invade the target cells and translocate across the epithelium. The behaviour of these two strains was compared to that of the well known opportunistic pathogen P. aeruginosa PAO1. Results Both strains of P. fluorescens were found to decrease the transepithelial resistance (TER) of Caco-2/TC7 differentiated monolayers. This was associated with an increase in paracellular permeability and F-actin microfilaments rearrangements. Moreover, the invasion and translocation tests demonstrated that the two strains used in this study can invade and translocate across the differentiated Caco-2/TC7 cell monolayers. Conclusions The present work shows for the first time, that P. fluorescens is able to alter the intestinal epithelial barrier function by disorganizing the F-actin microfilament network. Moreover, we reveal that independently of their origins, the two P. fluorescens strains can translocate across differentiated Caco-2/TC7 cell monolayers by using the transcellular pathway. These findings could, at least in part, explain the presence of the P. fluorescens specific I2 antigen in the serum of patients with Crohn's disease. PMID:21110894

  3. 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

  4. 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.

  5. 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

  6. Energy-dependent intracellular translocation of proparathormone.

    PubMed

    Chu, L L; MacGregor, R R; Cohn, D V

    1977-01-01

    We previously suggested that after synthesis, proparathormone is transferred from rough endoplasmic reticulum to the Golgi region where its conversion to parathormone occurs. We have attempted to define more closely this transfer process. In the first type of study, bovine parathyroid slices were incubated with [3H]leucine for 10 min and then radioisotope labeling was restricted by addition of a large excess of nonradioactive leucine. Under these conditions, more than 90% of the initially labeled proparathormone was converted to parathormone in 40 min. Lowered temperature in the chase period markedly inhibited the conversion. Several chemical agents were employed individually in the chase period to examine their effect on the conversion process. Antimycin A, dinitrophenol, oligomycin, and anaerobiosis (N2) inhibited the conversion, whereas sodium flouride and cycloheximide had no effect. In the second type of study, parathyroid slices were incubated with [3H]leucine for the entire incubation period. Lowered temperature and inhibitors of energy metabolism and microtubular function all lengthened the interval (lag) between the initial synthesis of [3H]parathormone. Cycloheximide, Tris, and chloroquine decreased the rates of protein synthesis and conversion, respectively, but none had any effect on the lag. We interpret the lag to represent the time of transit for proparathormone from rough endoplasmic reticulum to the Golgi region. We conclude that this transfer process is independent of the synthesis of the prohormone and its conversion to the hormone. Moreover, this translocation requires metabolic energy and appears to be mediated by microtubules. PMID:556615

  7. Control of Protein Function through Optochemical Translocation

    PubMed Central

    2015-01-01

    Controlled manipulation of proteins and their function is important in almost all biological disciplines. Here, we demonstrate control of protein activity with light. We present two different applicationslight-triggered transcription and light-triggered protease cleavageboth based on the same concept of protein mislocation, followed by optochemically triggered translocation to an active cellular compartment. In our approach, we genetically encode a photocaged lysine into the nuclear localization signal (NLS) of the transcription factor SATB1. This blocks nuclear import of the protein until illumination induces caging group removal and release of the protein into the nucleus. In the first application, prepending this NLS to the transcription factor FOXO3 allows us to optochemically switch on its transcription activity. The second application uses the developed light-activated NLS to control nuclear import of TEV protease and subsequent cleavage of nuclear proteins containing TEV cleavage sites. The small size of the light-controlled NLS (only 20 amino acids) minimizes impact of its insertion on protein function and promises a general approach to a wide range of optochemical applications. Since the light-activated NLS is genetically encoded and optically triggered, it will prove useful to address a variety of problems requiring spatial and temporal control of protein function, for example, in stem-cell, developmental, and cancer biology. PMID:24933258

  8. Multiscale model of platelet translocation and collision

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  9. Ion-translocating properties of calcifiable proteolipids

    SciTech Connect

    Swain, L.D.; Boyan, B.D.

    1988-03-01

    De novo formation of calcium hydroxyapatite in biological systems occurs on membrane surfaces through specific interactions of Ca, Pi, phospholipids, calcifiable proteolipids, and ion flux to and from the nucleating site. This paper reports an in vitro model demonstrating an ion transport function for calcifiable proteolipid. Bacterionema matruchotii proteolipid was incubated with a radiolabeled H+-channel inhibitor, 14C-dicyclohexyl-carbodiimide, and binding characterized by displacement studies with DCCD or ethyldimethylaminopropylcarbodiimide. A carboxyl binding site was suggested by displacement of DCCD by the nucleophile, glycine ethyl ester. The displacement studies indicated that proteolipid bound DCCD via carboxyl group interaction in a hydrophobic region of the protein. SDS-polyacrylamide gel electrophoresis showed that all label was associated with a single band of 8500 Mr. No non-specific binding of 14C-DCCD to phospholipids occurred, since all bound label was associated with protein following Sephadex LH-20 chromatography of crude proteolipid. Phospholipid liposomes were prepared containing bacteriorhodopsin and proteolipid or proteolipid-14C-DCCD, via cholate dialysis. Transmembrane pH changes established by the bacteriorhodopsin H+ pump were measured in the presence and absence of added proteolipid. Proteolipid had an effect similar to those of uncouplers such as tetraphenylboron. Both the rate and extent of proton translocation increased following addition of proteolipid to BR-liposomes. 14C-DCCD abolished the proteolipid-augmented ion transport. When tetraphenylboron was used to abolish the transmembrane electrical potential, calcifiable proteolipid did not augment proton transport.

  10. Polymer Translocation Dynamics in the Quasi-Static Limit

    NASA Astrophysics Data System (ADS)

    Polson, James

    2013-03-01

    Monte Carlo and Langevin dynamics simulations are used to study the dynamics of polymer translocation through a nanopore using a coarse-grained model. We examine the relationship between the translocation free energy barrier and the translocation times through a comparison of the simulation results to predictions using the Fokker-Planck formalism. We illustrate the importance of using free energy profiles obtained from precise numerical calculations rather than those obtained from simple theoretical models. In addition, we determine the parameter regime within which the Focker-Planck approach is valid and beyond which non-equilibrium effects become appreciable. The relevance of these results to recent theoretical and simulation studies of polymer translocation dynamics is discussed. Funding provided by the Natural Sciences and Engineering Research Council of Canada

  11. Influence of Methylobacterium on iron translocation in plants.

    PubMed

    Bishop, Yvonne M; Barton, Larry L; Johnson, Gordon V

    2011-06-01

    Iron metabolism in plants is essential to maintain optimal growth and iron nutrition is dependent on uptake of iron from the environment and movement of iron in the plant tissues. We have examined the translocation of iron in plant leaves following foliar application of FeEDTA to Vicia faba and Zea mays. Using radiolabeled iron, we observed that iron translocation is stimulated by products of Methylobacterium mesophylicum and by the cytokinin, kinetin. When cytokinins were applied to leaves along with (55)FeEDTA, the rate of iron translocation was greater than in controls without cytokinin addition. Since recent studies indicate that M. mesophylicum is widely distributed in the environment as a pyllospheric bacterium, this organism may have an important role in enhancing translocation of nutrients in plant leaves. PMID:21240540

  12. 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

  13. Concentration Polarization in Translocation of DNA through Nanopores and Nanochannels

    NASA Astrophysics Data System (ADS)

    Das, Siddhartha; Dubsky, Pavel; van den Berg, Albert; Eijkel, J. C. T.

    2012-03-01

    In this Letter we provide a theory to show that high-field electrokinetic translocation of DNA through nanopores or nanochannels causes large transient variations of the ionic concentrations in front and at the back of the DNA due to concentration polarization (CP). The CP causes strong local conductivity variations, which can successfully explain the nontrivial current transients and ionic distributions observed in molecular dynamics simulations of nanopore DNA translocations as well as the transient current dips and spikes measured for translocating hairpin DNA. Most importantly, as the future of sequencing of DNA by nanopore translocation will be based on time-varying electrical conductance, CP, must be considered in experimental design and interpretationcurrently these studies are mostly based on the incomplete pore conductance models that ignore CP and transients in the electrical conductance.

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

    PubMed

    Trksi, Edina; Farkas, Andrs; Aranyi, Nikolett Rka; Hoffmann, Borbla; Tth, Viola; Molnr-Lng, Mrta

    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 Martonvsr 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 Martonvsr and Keszthely, Hungary. PMID:25806585

  15. Translocation of bacterial DNA from Gram-positive microorganisms is associated with a species-specific inflammatory response in serum and ascitic fluid of patients with cirrhosis.

    PubMed

    Francs, R; Gonzlez-Navajas, J M; Zapater, P; Muoz, C; Cao, R; Pascual, S; Santana, F; Mrquez, D; Prez-Mateo, M; Such, J

    2007-11-01

    Translocation of bacterial-DNA in patients with cirrhosis and ascites triggers an innate immune response. Identification of characteristics to which this response is sensitive is relevant from a clinical standpoint. The aim of this study has been to determine if the proinflammatory immune response established in vivo in cirrhotic patients with ascites as a consequence of bacterial-DNA translocation is related to the identified bacterial species and their frequency of cytosine-guanosine content in serum and ascitic fluid. Patients with advanced cirrhosis and ascites were included in the study and distributed into groups I and II according to the absence or presence of bacterial-DNA translocation, respectively. Serum and ascitic fluid levels of proinflammatory cytokines after normalization of bacterial-DNA concentration and the activated form of nuclear factor-kappa B in ascitic fluid pellets were measured by enzyme-linked immunosorbent assay techniques. Translocation of bacterial-DNA with higher cytosine-guanosine content induced the highest cytokine response, which was higher than that in patients without bacterial-DNA translocation. The activated form of nuclear factor-kappa B in ascitic fluid pellets of patients with bacterial-DNA translocation was greater in patients with higher bacterial-DNA cytosine-guanosine content, whereas the amount of total nuclear factor-kappa B remained unaltered. Bacterial-DNA translocation induces a marked immune reaction in vivo in patients with advanced cirrhosis and ascites which is related, among other factors, to the bacterial-DNA cytosine-guanosine content. Therefore, the host's immune response to bacterial-DNA translocation constitutes a species-specific phenomenon. PMID:17822441

  16. Survival of mountain quail translocated from two distinct source populations

    USGS Publications Warehouse

    Troy, Ronald J.; Coates, Peter S.; Connelly, John W.; Gillette, Gifford; Delehanty, David J.

    2013-01-01

    Translocation of mountain quail (Oreortyx pictus) to restore viable populations to their former range has become a common practice. Because differences in post-release vital rates between animals from multiple source populations has not been well studied, wildlife and land managers may arbitrarily choose the source population or base the source population on immediate availability when planning translocation projects. Similarly, an understanding of the optimal proportion of individuals from different age and sex classes for translocation would benefit translocation planning. During 2006 and 2007, we captured and translocated 125 mountain quail from 2 ecologically distinct areas: 38 from southern California and 87 from southwestern Oregon. We released mountain quail in the Bennett Hills of south-central Idaho. We radio-marked and monitored a subsample of 58 quail and used them for a 2-part survival analysis. Cumulative survival probability was 0.23??0.05 (SE) at 150 days post-release. We first examined an a priori hypothesis (model) that survival varied between the 2 distinct source populations. We found that source population did not explain variation in survival. This result suggests that wildlife managers have flexibility in selecting source populations for mountain quail translocation efforts. In a post hoc examination, we pooled the quail across source populations and evaluated differences in survival probabilities between sex and age classes. The most parsimonious model indicated that adult male survival was substantially less than survival rates of other mountain quail age and sex classes (i.e., interaction between sex and age). This result suggests that translocation success could benefit by translocating yearling males rather than adult males, perhaps because adult male breeding behavior results in vulnerability to predators

  17. Molecular studies of translocations and trisomy involving chromosome 13

    SciTech Connect

    Robinson, W.P.; Bernasconi, F.; Dutly, F.; Schinzel, A.A.

    1996-01-11

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

  18. 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.

  19. Surface modification of graphene nanopores for protein translocation

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-05-28

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

  1. The role of translocation in recovery of woodland caribou populations.

    PubMed

    Decesare, Nicholas J; Whittington, Jesse; Hebblewhite, Mark; Robinson, Hugh; Bradley, Mark; Neufeld, Lalenia; Musiani, Marco

    2011-04-01

    Maintenance of viable populations of many endangered species will require conservation action in perpetuity. Efforts to conserve these species are more likely to be successful if their reliance on conservation actions is assessed at the population level. Woodland caribou (Rangifer tarandus caribou) were extirpated recently from Banff National Park, Canada, and translocations of caribou to Banff and neighboring Jasper National Park are being considered. We used population viability analysis to assess the relative need for and benefits from translocation of individuals among caribou populations. We measured stochastic growth rates and the probability of quasi extinction of four populations of woodland caribou with and without translocation. We used two vital rates in our analysis: mean adult female survival and mean number of calves per breeding-age female as estimates of mean fecundity. We isolated process variance for each vital rate. Our results suggested the Tonquin caribou population in Jasper is likely to remain viable without translocation, but that translocation is probably insufficient to prevent eventual extirpation of the two other populations in Jasper. Simulated reintroductions of caribou into Banff resulted in a 53-98% probability of >8 females remaining after 20 years, which suggests translocation may be an effective recovery tool for some caribou populations. PMID:21091770

  2. Atomic structure of anthrax PA pore elucidates toxin translocation

    PubMed Central

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

    2015-01-01

    Summary Anthrax toxin, comprising protective antigen (PA), lethal factor (LF) and edema factor (EF), is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in human and animals. PA forms oligomeric prepores that undergo conversion to membrane-spanning pores by endosomal acidification, and these pores translocate the enzymes LF and EF into the cytosol of target cells1. PA 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. Based on biochemical and electrophysiological results, researchers have proposed that a ?-clamp composed of Phe427 residues of PA catalyzes protein translocation via a charge-state dependent Brownian ratchet29. Although atomic structures of PA prepores are available1014, how PA senses low pH, converts to active pore and translocates LF and EF are not well defined without an atomic model of the PA pore. Here, by cryo electron microscopy (cryoEM) with direct electron counting, we have determined the PA pore structure at 2.9- 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

  3. Dominant-lethal mutation and heritable translocation tests in mice

    SciTech Connect

    Generoso, W.M.

    1980-01-01

    The spontaneous occurrence of chromosome breakage-related genetic anomalies in humans is estimated to be 0.24%, not including spontaneous abortions. More balanced reciprocal translocations are being discovered among mentally handicapped individuals. Chromosome breakage can result in chromosome loss, which often leads to embryonic lethality and occassionally to viable aneuploids, or to viable reciprocal translocations and inversions. In mice, transmitted chromosome breakage effects may be measured by using dominant-lethal mutations, heritable translocations, heritable inversions, sex-chromosome loss, and chromosome breakage and rearrangement scored cytologically in early embryos. The dominant-lethal mutation and the heritable translocation tests are the most widely used tests. The heritable translocation procedure described here applies only to the induction of translocations in male germ cells. The use of treated females in the dominant-lethal test has its drawback too. When the fertility of treated female is reduced or when embryonic lethality is observed, it is difficult to ascertain whether these effects are attributable to true genetic damage or to physiological imbalances in the treated females. Therefore the dominant-lethal test as it is used in practical testing has almost exclusively employed the treatment of males. This is not to say that treatment of females has no advantages whatsoever. On the contrary, there is a good example of a case whereby dominant-lethal effects of the test compound was unequivocably demonstrated in treated females but not in treated males.

  4. 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.

  5. Mapping RFLP Loci in Maize Using B-a Translocations

    PubMed Central

    Weber, D.; Helentjaris, T.

    1989-01-01

    Plants hypoploid for specific segments of each of the maize (Zea mays L.) chromosomes were generated using 24 different B-A translocations. Plants carrying each of the B-A translocations were crossed as male parents to inbreds, and sibling progeny hypoploid or not hypoploid for specific chromosomal segments were recovered. Genomic DNAs from the parents, hypoploid progeny, and nonhypoploid (euploid or hyperploid) progeny for each of these B-A translocations were digested with restriction enzymes, electrophoresed in agarose gels, blotted onto reusable nylon membranes, and probed with nick-translated, cloned DNA fragments which had been mapped previously by restriction fragment length polymorphism (RFLP) analysis to the chromosome involved in the B-A translocation. The chromosomal segment on our RFLP map which was uncovered by each of the - B-A translocations was determined. This work unequivocally identified the short and long arms of each chromosome on this map, and it also identified the region on each chromosome which contains the centromere. Because the breakpoints of the B-A translocations were previously known on the cytological and the conventional genetic maps, this study also allowed this RFLP map to be more highly correlated with these maps. PMID:2565856

  6. 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.

  7. Uptake, translocation, and debromination of polybrominated diphenyl ethers in maize.

    PubMed

    Zhao, Moming; Zhang, Shuzhen; Wang, Sen; Huang, Honglin

    2012-01-01

    Uptake, translocation and debromination of three polybrominated diphenyl ethers (PBDEs), BDE-28, -47 and -99, in maize were studied in a hydroponic experiment. Roots took up most of the PBDEs in the culture solutions and more highly brominated PBDEs had a stronger uptake capability. PBDEs were detected in the stems and leaves of maize after exposure but rarely detected in the blank control plants. Furthermore, PBDE concentrations decreased from roots to stems and then to leaves, and a very clear decreasing gradient was found in segments upwards along the stem. These altogether provide substantiating evidence for the acropetal translocation of PBDEs in maize. More highly brominated PBDEs were translocated with more difficulty. Radial translocation of PBDEs from nodes to sheath inside maize was also observed. Both acropetal and radial translocations were enhanced at higher transpiration rates, suggesting that PBDE transport was probably driven by the transpiration stream. Debromination of PBDEs occurred in all parts of the maize, and debromination patterns of different parent PBDEs and in different parts of a plant were similar but with some differences. This study for the first time provides direct evidence for the acropetal translocation of PBDEs within plants, elucidates the process of PBDE transport and clarifies the debromination products of PBDEs in maize. PMID:22655352

  8. Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers

    PubMed Central

    Roberts, Carol L; Keita, Åsa V; Duncan, Sylvia H; O'Kennedy, Niamh; Söderholm, Johan D; Rhodes, Jonathan M

    2010-01-01

    Background Crohn's disease is common in developed nations where the typical diet is low in fibre and high in processed food. Primary lesions overlie Peyer's patches and colonic lymphoid follicles where bacterial invasion through M-cells occurs. We have assessed the effect of soluble non-starch polysaccharide (NSP) and food emulsifiers on translocation of Escherichia coli across M-cells. Methods To assess effects of soluble plant fibres and food emulsifiers on translocation of mucosa-associated E coli isolates from Crohn's disease patients and from non-Crohn's controls, we used M-cell monolayers, generated by co-culture of Caco2-cl1 and Raji B cells, and human Peyer's patches mounted in Ussing chambers. Results E coli translocation increased across M-cells compared to parent Caco2-cl1 monocultures; 15.8-fold (IQR 6.2–32.0) for Crohn's disease E coli (N=8) and 6.7-fold (IQR 3.7–21.0) for control isolates (N=5). Electron microscopy confirmed E coli within M-cells. Plantain and broccoli NSP markedly reduced E coli translocation across M-cells at 5 mg/ml (range 45.3–82.6% inhibition, p<0.01); apple and leek NSP had no significant effect. Polysorbate-80, 0.01% vol/vol, increased E coli translocation through Caco2-cl1 monolayers 59-fold (p<0.05) and, at higher concentrations, increased translocation across M-cells. Similarly, E coli translocation across human Peyer's patches was reduced 45±7% by soluble plantain NSP (5 mg/ml) and increased 2-fold by polysorbate-80 (0.1% vol/vol). Conclusions Translocation of E coli across M-cells is reduced by soluble plant fibres, particularly plantain and broccoli, but increased by the emulsifier Polysorbate-80. These effects occur at relevant concentrations and may contribute to the impact of dietary factors on Crohn's disease pathogenesis. PMID:20813719

  9. 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.

  10. 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.

  11. Taiwan: Background Notes Series.

    ERIC Educational Resources Information Center

    Reams, Joanne Reppert

    Concise background information on Taiwan is provided. The publication begins with a profile of Taiwan, discussing the people, geography, political establishment, and economy. A map of the country is provided. The bulk of the publication then provides more detailed information on Taiwan's people, geography, history, administration, political

  12. 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

  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. Nonthermal cosmic neutrino background

    NASA Astrophysics Data System (ADS)

    Chen, Mu-Chun; Ratz, Michael; Trautner, Andreas

    2015-12-01

    We point out that, for Dirac neutrinos, in addition to the standard thermal cosmic neutrino background (C ν B ), there could also exist a nonthermal neutrino background with comparable number density. As the right-handed components are essentially decoupled from the thermal bath of standard model particles, relic neutrinos with a nonthermal distribution may exist until today. The relic density of the nonthermal (nt) background can be constrained by the usual observational bounds on the effective number of massless degrees of freedom Neff and can be as large as nν nt≲0.5 nγ. In particular, Neff can be larger than 3.046 in the absence of any exotic states. Nonthermal relic neutrinos constitute an irreducible contribution to the detection of the C ν B and, hence, may be discovered by future experiments such as PTOLEMY. We also present a scenario of chaotic inflation in which a nonthermal background can naturally be generated by inflationary preheating. The nonthermal relic neutrinos, thus, may constitute a novel window into the very early Universe.

  15. 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

  16. 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

  17. Computer simulation of viral-assembly and translocation

    NASA Astrophysics Data System (ADS)

    Mahalik, Jyoti Prakash

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

  18. The other backgrounds

    NASA Astrophysics Data System (ADS)

    Trimble, Virginia

    2006-06-01

    The significance of the cosmic microwave background or CMB (3K, ther- mal, relict, black body, isotropic, etc) radiation in confirming a hot big bang model of the early Universe and in setting precise values of many of the parameters of that model is widely known and has recently been enhanced by the results of three years of operation of the Wilkinson Microwave Anisotropy Probe (WMAP). There are, however, also backgrounds of astrophysical and cosmological significance consisting of photons of other wavelengths, other forms of radiation, particles, and fields. Several predate the discovery of the CMB, while others are relatively recent discoveries. This article explores the history of their predictions and discoveries and their cosmological and astrophysical implications as currently understood.

  19. Lost in translocation: the functions of the 18-kD translocator protein.

    PubMed

    Gut, Philipp; Zweckstetter, Markus; Banati, Richard B

    2015-07-01

    Research spanning nearly four decades has assigned to the translocator protein (18 kDa) (TSPO) a critical role, among others, in the mitochondrial import of cholesterol, the subsequent steps of (neuro)steroid production, and systemic endocrine regulation, with implications for the pathophysiology of immune, inflammatory, neurodegenerative, and psychiatric as well as neoplastic diseases. Recent knockout studies in mice unexpectedly report normal or latent phenotypes, raising doubts about the protein's role in steroidogenesis and other previously postulated functions and challenging the validity of earlier data on the selectivity of TSPO-binding drugs. Here we provide a synthesis of the current debate from a structural and molecular biology perspective, discuss the limits of inference in loss-of-function (gene knockout) studies, and suggest new functions of TSPO. PMID:26026242

  20. 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

  1. Type 3 Secretion Translocators Spontaneously Assemble a Hexadecameric Transmembrane Complex.

    PubMed

    Romano, Fabian B; Tang, Yuzhou; Rossi, Kyle C; Monopoli, Kathryn R; Ross, Jennifer L; Heuck, Alejandro P

    2016-03-18

    A type 3 secretion system is used by many bacterial pathogens to inject proteins into eukaryotic cells. Pathogens insert a translocon complex into the target eukaryotic membrane by secreting two proteins known as translocators. How these translocators form a translocon in the lipid bilayer and why both proteins are required remains elusive. Pseudomonas aeruginosa translocators PopB and PopD insert pores into membranes forming homo- or hetero-complexes of undetermined stoichiometry. Single-molecule fluorescence photobleaching experiments revealed that PopD formed mostly hexameric structures in membranes, whereas PopB displayed a bi-modal distribution with 6 and 12 subunits peaks. However, individually the proteins are not functional for effector translocation. We have found that when added together, the translocators formed distinct hetero-complexes containing 8 PopB and 8 PopD molecules. Thus, the interaction between PopB and PopD guide the assembly of a unique hetero-oligomer in membranes. PMID:26786106

  2. Criteria for minimal model of driven polymer translocation

    NASA Astrophysics Data System (ADS)

    Suhonen, P. M.; Kaski, K.; Linna, R. P.

    2014-10-01

    While the characteristics of the driven translocation for asymptotically long polymers are well understood, this is not the case for finite-sized polymers, which are relevant for real-world experiments and simulation studies. Most notably, the behavior of the exponent α, which describes the scaling of the translocation time with polymer length, when the driving force fp in the pore is changed, is under debate. By Langevin dynamics simulations of regular and modified translocation models using the freely jointed-chain polymer model we find that a previously reported incomplete model, where the trans side and fluctuations were excluded, gives rise to characteristics that are in stark contradiction with those of the complete model, for which α increases with fp. Our results suggest that contribution due to fluctuations is important. We construct a minimal model where dynamics is completely excluded to show that close alignment with a full translocation model can be achieved. Our findings set very stringent requirements for a minimal model that is supposed to describe the driven polymer translocation correctly.

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

    PubMed

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

    2010-11-15

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

  4. Translocation and Endocytosis for Cell-penetrating Peptide Internalization

    PubMed Central

    Jiao, Chen-Yu; Delaroche, Diane; Burlina, Fabienne; Alves, Isabel D.; Chassaing, Grard; 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

  5. 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.

  6. A deubiquitinase negatively regulates retro-translocation of nonubiquitinated substrates

    PubMed Central

    Bernardi, Kaleena M.; Williams, Jeffrey M.; Inoue, Takamasa; Schultz, Aric; Tsai, Billy

    2013-01-01

    Endoplasmic reticulum (ER) membranebound E3 ubiquitin ligases promote ER-associated degradation (ERAD) by ubiquitinating a retro-translocated substrate that reaches the cytosol from the ER, targeting it to the proteasome for destruction. Recent findings implicate ERAD-associated deubiquitinases (DUBs) as positive and negative regulators during ERAD, reflecting the different consequences of deubiquitinating a substrate prior to proteasomal degradation. These observations raise the question of whether a DUB can control the fate of a nonubiquitinated ERAD substrate. In this study, we probed the role of the ERAD-associated DUB, YOD1, during retro-translocation of the nonubiquitinated cholera toxin A1 (CTA1) peptide, a critical intoxication step. Through combining knockdown, overexpression, and binding studies, we demonstrated that YOD1 negatively controls CTA1 retro-translocation, likely by deubiquitinating and inactivating ubiquitinated ERAD components that normally promote toxin retro-translocation. YOD1 also antagonizes the proteasomal degradation of nonglycosylated pro-? factor, a postulated nonubiquitinated yeast ERAD substrate, in mammalian cells. Our findings reveal that a cytosolic DUB exerts a negative function during retro-translocation of nonubiquitinated substrates, potentially by acting on elements of the ERAD machinery. PMID:24068323

  7. Sorting genomes by reciprocal translocations, insertions, and deletions.

    PubMed

    Qi, Xingqin; Li, Guojun; Li, Shuguang; Xu, Ying

    2010-01-01

    The problem of sorting by reciprocal translocations (abbreviated as SBT) arises from the field of comparative genomics, which is to find a shortest sequence of reciprocal translocations that transforms one genome Pi into another genome Gamma, with the restriction that Pi and Gamma contain the same genes. SBT has been proved to be polynomial-time solvable, and several polynomial algorithms have been developed. In this paper, we show how to extend Bergeron's SBT algorithm to include insertions and deletions, allowing to compare genomes containing different genes. In particular, if the gene set of Pi is a subset (or superset, respectively) of the gene set of Gamma, we present an approximation algorithm for transforming Pi into Gamma by reciprocal translocations and deletions (insertions, respectively), providing a sorting sequence with length at most OPT + 2, where OPT is the minimum number of translocations and deletions (insertions, respectively) needed to transform Pi into Gamma; if Pi and Gamma have different genes but not containing each other, we give a heuristic to transform Pi into Gamma by a shortest sequence of reciprocal translocations, insertions, and deletions, with bounds for the length of the sorting sequence it outputs. At a conceptual level, there is some similarity between our algorithm and the algorithm developed by El Mabrouk which is used to sort two chromosomes with different gene contents by reversals, insertions, and deletions. PMID:20431155

  8. 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.

  9. The Backgrounds Data Center

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  10. Flow-induced polymer translocation through narrow and patterned channels

    NASA Astrophysics Data System (ADS)

    Nikoubashman, Arash; Likos, Christos N.

    2010-08-01

    We consider linear and branched polymers driven through narrow and patterned channels by imposing a Poiseuille flow on the ambient solvent. We establish, by means of scaling arguments, that the translocation probability of dendrimers through the pore is independent of the number of monomers and that it takes place above a viscosity-dependent critical external current. When the channel walls are smooth, the translocation times of linear and branched polymers with the same monomer number are very similar. However, for walls that are decorated with attractive patches, dramatic differences show up: whereas a dendrimer successively docks at the patches and "walks" from one to the next, being carried away by the solvent flow, linear chains spread themselves along the channel wall without achieving translocation within simulation times. Our findings are relevant for, e.g., drug delivery through dendritic carrier molecules in capillary arterioles.

  11. 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.

  12. 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

  13. 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 .

  14. 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

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

    PubMed Central

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

    2014-01-01

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

  16. Difference in the ratio of dominant-lethal mutations to heritable translocations produced in mouse spermatids and fully mature sperm after treatment with triethylenemelamine (TEM)

    SciTech Connect

    Generoso, W.M.; Cain, K.T.; Cornett, C.V.; Russell, E.W.; Hellwig, C.S.; Horton, C.Y.

    1982-04-01

    The relative induction of dominant-lethal mutations and heritable translocations in triethylenemelamine-treated male postmeiotic germ cells of mice was determined depending on the stage treated. Males were mated either 11.5 to 14.5 days after treatment (middle spermatids) or less than 2.5 hours after treatment (fully mature sperm). Results clearly showed that, even though similar levels of dominant-lethal mutations were induced in fully mature sperm and in middle spermatids, the frequency of heritable translocations induced in mature sperm was markedly lower than that induced in middle spermatids. This observation was used, together with earlier ones, to suggest a mechanism by which dominant-lethal mutations and heritable translocations are produced following chemical treatment of male postmeiotic germ cels.

  17. Ultraviolet Background Radiation

    NASA Astrophysics Data System (ADS)

    Henry, R. C.; Murthy, J.

    1993-12-01

    The UVX experiment was carried on the Space Shuttle Columbia between 1986 January 12 and 19 (STS-61C). Several ultraviolet spectrometers were used to obtain measurements of the diffuse ultraviolet background at 8 locations in the sky. We have reanalysed the UVX measurements of the surface brightness of the diffuse ultraviolet background above b = 40 using the dust-scattering model of Onaka & Kodaira (1991), which explicitly takes into account the variation of the source function with galactic longitude. The range of allowed values of interstellar grain albedoJa, and scattering asymmetry parameter g, is considerably expanded over those of a previous analysis. The new chi square probability contours come close to, but do not include, the values of a and g found for the interstellar grains by Witt et al. (1992) using the Ultraviolet Imaging Telescope (UIT) on the Astro mission. If we hypothesize in additon to the dust-scattered light an extragalactic component, of 300 1 100 photons cm-2 s-1 sr-1 A-1, attenuated by a cosecant b law, the new reduction of the UVX data gives complete consistency with the Witt et al. determination of the optical parameters of the grains in the ultraviolet. This work was supported by United States Air Force Contract F19628-93-K-0004, and by National Aeronautics and Space Administration grant NASA NAG5-619. We are grateful for the encouragement of Dr. Stephan Price, and we thank Dr. L. Danly for information. Onaka, T., & Kodaira, K. 1991, ApJ, 379, 532 Witt, A. N., Petersohn, J. K., Bohlin, R. C., O'Connell, R. W., Roberts, M. S., Smith, A. M., & Stecher, T. P. 1992, ApJ, 395, L5

  18. "Understanding Adam" multiple reciprocal translocations: complex case presentation.

    PubMed

    Linder, Carie E; Lu, Xianglan; Kim, Young Mi; Li, Shibo; Pineda, Jose

    2009-01-01

    This article presents a case review of a newborn diagnosed with a complex chromosomal rearrangement, as demonstrated through a painted chromosomal analysis. This infant presented with multiple dysmorphology including cutis aplasia, multiple ocular malformations, bilateral cleft lip and palate, and postnatal hydrocephaly. A chromosomal analysis revealed multiple-ways, balanced translocation involving chromosomes 3, 4, 6, 8, and 9. This case study provides a unique opportunity to, in retrospect, trace each malformation exploring the pathophysiology, etiology, and correlating origin with chromosomal variation. Careful review of this case, enhanced by the visually augmented representation of each translocation, will increase understanding of chromosomal anomalies and their implications in embryological development and clinical presentation. PMID:19474586

  19. The role of phospholipase D in Glut-4 translocation.

    PubMed

    Huang, Ping; Frohman, Michael A

    2003-01-01

    Insulin-stimulated Glut-4 translocation is regulated through a complex pathway. Increasing attention is being paid to the role undertaken in this process by Phospholipase D, a signal transduction-activated enzyme that generates the lipid second-messenger phosphatidic acid. Phospholipase D facilitates Glut-4 translocation at potentially multiple steps in its outward movement. Current investigation is centered on Phospholipase D promotion of Glut-4-containing membrane vesicle trafficking and vesicle fusion into the plasma membrane, in part through activation of atypical protein kinase C isoforms. PMID:14648804

  20. Circadian clock gene aryl hydrocarbon receptor nuclear translocator-like polymorphisms are associated with seasonal affective disorder: An Indian family study

    PubMed Central

    Rajendran, Bhagya; Janakarajan, Veeramahali Natarajan

    2016-01-01

    Background and Aim: Polymorphisms in aryl hydrocarbon receptor nuclear translocator-like (ARNTL) gene, the key component of circadian clock manifests circadian rhythm abnormalities. As seasonal affective disorder (SAD) is associated with disrupted circadian rhythms, the main objective of this study was to screen an Indian family with SAD for ARNTL gene polymorphisms. Materials and Methods: In this study, 30 members of close-knit family with SAD, 30 age- and sex-matched controls of the same caste with no prior history of psychiatric illness and 30 age- and sex-matched controls belonging to 17 different castes with no prior history of psychiatric illness were genotyped for five different single nucleotide polymorphisms (SNPs) in ARNTL gene by TaqMan allele-specific genotyping assay. Statistical Analysis: Statistical significance was assessed by more powerful quasi-likelihood score test-XM. Results: Most of the family members carried the risk alleles and we observed a highly significant SNP rs2279287 (A/G) in ARNTL gene with an allelic frequency of 0.75. Conclusions: Polymorphisms in ARNTL gene disrupt circadian rhythms causing SAD and genetic predisposition becomes more deleterious in the presence of adverse environment. PMID:26985106

  1. Mitotic Crossing over and Nondisjunction in Translocation Heterozygotes of Aspergillus

    PubMed Central

    Kfer, Etta

    1976-01-01

    To analyze mitotic recombination in translocation heterozygotes of A. nidulans two sets of well-marked diploids were constructed, homo- or heterozygous for the reciprocal translocations T1(IL;VIIR) or T2(IL;VIIIR) and heterozygous for selective markers on IL. It was found that from all translocation heterozygotes some of the expected mitotic crossover types could be selected. Such crossovers are monosomic for one translocated segment and trisomic for the other and recovery depends on the relative viabilities of these unbalanced types. The obtained segregants show characteristically reduced growth rates and conidiation dependent on sizes and types of mono- and trisomic segments, and all spontaneously produce normal diploid sectors. Such secondary diploid types either arose in one step of compensating crossing over in the other involved arm, ormore conspicuouslyin two steps of nondisjunction via a trisomic intermediate.In both of the analyzed translocations the segments translocated to IL were extremely long, while those translocated from IL were relatively short. The break in I for T1(I;VII) was located distal to the main selective marker in IL, while that of T2(I;VIII) had been mapped proximal but closely linked to it. Therefore, as expected, the selected primary crossover from the two diploids with T2( I;VIII) in coupling or in repulsion to the selective marker, showed the same chromosomal imbalance and poor growth. These could however be distinguished visually because they spontaneously produced different trisomic intermediates in the next step, in accordance with the different arrangement of the aneuploid segments. On the other hand, from diploids heterozygous for T1( I;VII) mitotic crossovers could only be selected when the selective markers were in coupling with the translocation; these crossovers were relatively well-growing and produced frequent secondary segregants of the expected trisomic, 2n+VII, type. For both translocations it was impossible to recover the reciprocal crossover types (which would be trisomic for the distal segments of I and monosomic for most of groups VII or VIII) presumably because these were too inviable to form conidia.In addition to the selected segregants of expected types a variety of unexpected ones were isolated. The conditions of selection used favour visual detection of aneuploid types, even if these produce only a few conidial heads and are not at a selective advantage. For T2(I;VIII) these "non-selected" unbalanced segregants were mainly "reciprocal" crossovers of the same phenotype and imbalance as the selected ones. For T1(I;VII) two quite different types were obtained, both possibly originating with loss of the small VIII translocation chromosome. One was isolated when the selective marker in repulsion to T1(I;VII) was used and, without being homo- or hemizygous for the selective marker, it produced stable sectors homozygous for this marker. The other was obtained from both coupling and repulsion diploids and showed a near-diploid genotype; it produced practically only haploid stable sectors of the type expected from monosomics, 2n1 for the short translocation chromosome. PMID:773747

  2. 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.

  3. 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.

  4. The cosmic background explorer

    SciTech Connect

    Gulkis, G. ); Lubin, P.M. ); Meyer, S.S. ); Silverberg, R.F.

    1990-01-01

    Late last year the National Aeronautics and Space Administration launched its first satellite dedicated to the study of phenomena related to the origins of the universe. The satellite, called the Cosmic Background Explorer (COBE), carries three complementary detectors that will make fundamental measurements of the celestial radiation. Part of that radiation is believed to have originated in processes that occurred at the very dawn of the universe. By measuring the remnant radiation at wavelengths from one micrometer to one centimeter across the entire sky, scientists hope to be able to solve many mysteries regarding the origin and evolution of the early universe. Unfortunately, these radiative relics of the early universe are weak and veiled by local astrophysical and terrestrial sources of radiation. The wavelengths of the various cosmic components may also overlap, thereby making the understanding of the diffuse celestial radiation a challenge. Nevertheless, the COBE instruments, with their full-sky coverage, high sensitivity to a wide range of wavelengths and freedom from interference from the earth's atmosphere, will constitute for astrophysicists an observatory of unprecedented sensitivity and scope. The interesting cosmic signals will then be separated from one another and from noncosmic radiation sources by a comprehensive analysis of the data.

  5. 1,3-Butadiene, CML and the t(9:22) translocation: A reality check.

    PubMed

    Albertini, Richard J; Carter, Elizabeth W; Nicklas, Janice A; Vacek, Pamela M; Walker, Vernon E

    2015-11-01

    Epidemiological studies of 1,3-butadiene have suggest that exposures to humans are associated with chronic myeloid leukemia (CML). CML has a well-documented association with ionizing radiation, but reports of associations with chemical exposures have been questioned. Ionizing radiation is capable of inducing the requisite CML-associated t(9:22) translocation (Philadelphia chromosome) in appropriate cells in vitro but, thus far, chemicals have not shown this capacity. We have proposed that 1,3-butadiene metabolites be so tested as a reality check on the epidemiological reports. In order to conduct reliable testing in this regard, it is essential that a positive control for induction be available. We have used ionizing radiation to develop such a control. Results described here demonstrate that this agent does in fact induce pathogenic t(9:22) translocations in a human myeloid cell line in vitro, but does so at low frequencies. Conditions that will be required for studies of 1,3-butadiene are discussed. PMID:26002693

  6. Robertsonian Translocations: An Overview of 872 Robertsonian Translocations Identified in a Diagnostic Laboratory in China

    PubMed Central

    Chen, Fan; Jiang, Shuai; Su, Hui; Liang, Jianfen; Deng, Chunhua; Hu, Chaohui; Yu, Shihui

    2015-01-01

    Robertsonian translocations (ROBs) have an estimated incidence rate of 1/1000 births, making this type of rearrangement the most common structural chromosomal abnormalities seen in the general population. In this study, we reports 872 cases of ROBs from 205,001 specimens karyotyped postnatally in a single accredited laboratory in China, including 583 balanced ROBs, 264 unbalanced ROBs, 9 mosaic ROBs, and 18 complex ROBs. Ninety-three percent of the balanced ROBs observed were adults with infertility, miscarriage, or offspring(s) with known chromosomal abnormalities. Significant excess of females were found to be carriers of balanced ROBs with an adjusted male/female ratio of 0.77. Ninety-eight percent of the unbalanced ROBs observed were children with variable referral reasons. Almost all of the unbalanced ROBs involved chromosome 21 except a single ROB with [46,XX,der(13;14),+13] identified in a newborn girl with multiple congenital anomalies. Multiple novel ROB karyotypes were reported in this report. This study represents the largest collections of ROBs in Chinese population. PMID:25932913

  7. Noise correlations in cosmic microwave background experiments

    NASA Technical Reports Server (NTRS)

    Dodelson, Scott; Kosowsky, Arthur; Myers, Steven T.

    1995-01-01

    Many analysis of microwave background experiments neglect the correlation of noise in different frequency of polarization channels. We show that these correlations, should they be present, can lead to serve misinterpretation of an experiment. In particular, correlated noise arising from either electronics or atmosphere may mimic a cosmic signal. We quantify how the likelihood function for a given experiment varies with noise correlation, using both simple analytic models and actual data. For a typical microwave background anisotropy experiment, noise correlations at the level of 1% of the overall noise can seriously reduce the significance of a given detection.

  8. 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.

  9. Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Kim, Tae-Hee; Kim, Yesol; Jeong, Do-Won; Lee, Eun-Gyeong; Jeon, Dong-Su; Kim, Jun-Mo

    2015-08-01

    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

  11. 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...

  12. Observing cellulose biosynthesis and membrane translocation in crystallo.

    PubMed

    Morgan, Jacob L W; McNamara, Joshua T; Fischer, Michael; Rich, Jamie; Chen, Hong-Ming; Withers, Stephen G; Zimmer, Jochen

    2016-03-17

    Many biopolymers, including polysaccharides, must be translocated across at least one membrane to reach their site of biological function. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. Here, in crystallo enzymology with the catalytically active bacterial cellulose synthase BcsA-BcsB complex reveals structural snapshots of a complete cellulose biosynthesis cycle, from substrate binding to polymer translocation. Substrate- and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Furthermore, the structural snapshots show that BcsA translocates cellulose via a ratcheting mechanism involving a 'finger helix' that contacts the polymer's terminal glucose. Cooperating with BcsA's gating loop, the finger helix moves 'up' and 'down' in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA's transmembrane channel. This mechanism is validated experimentally by tethering BcsA's finger helix, which inhibits polymer translocation but not elongation. PMID:26958837

  13. Accumulation and translocation of 198Hg in four crop species.

    PubMed

    Cui, Liwei; Feng, Xinbin; Lin, Che-Jen; Wang, Xinming; Meng, Bo; Wang, Xun; Wang, Heng

    2014-02-01

    The uptake and transport of mercury (Hg) through vegetation play an important role in the biogeochemical cycling of Hg. However, quantitative information regarding Hg translocation in plants is poorly understood. In the present study, Hg uptake, accumulation, and translocation in 4 crops-rice (Oryza.sativa?L.), wheat (Triticum?L.), corn (Zea mays L.), and oilseed rape (Brassica campestris L.)-grown in Hoagland solution were investigated using a stable isotope ((198)Hg) tracing technique. The distribution of (198)Hg in root, stem, and leaf after uptake was quantified, and the release of (198)Hg into the air from crop leaf was investigated. It was found that the concentration of Hg accumulated in the root, stem, and leaf of rice increased linearly with the spiked (198)Hg concentration. The uptake equilibrium constant was estimated to be 2.35?mol Hg/g dry weight in rice root per mol/L Hg remaining in the Hoagland solution. More than 94% of (198)Hg uptake was accumulated in the roots for all 4 crops examined. The translocation to stem and leaf was not significant because of the absence of Hg(2+) complexes that facilitate Hg transport in plants. The accumulated (198)Hg in stem and leaf was not released from the plant at air Hg(0) concentration ranging from 0?ng/m(3) to 10?ng/m(3). Transfer factor data analysis showed that Hg translocation from stems to leaves was more efficient than that from roots to stems. PMID:24173818

  14. Nuclear translocation of urokinase-type plasminogen activator

    PubMed Central

    Lebedeva, Tatiana; Kuo, Alice; Yarovoi, Serge; Tkachuk, Sergei; Zaitsev, Sergei; Bdeir, Khalil; Dumler, Inna; Marks, Michael S.; Parfyonova, Yelena; Tkachuk, Vsevolod A.; Higazi, Abd Al-Roof; Cines, Douglas B.

    2008-01-01

    Urokinase-type plasminogen activator (uPA) participates in diverse (patho)physiological processes through intracellular signaling events that affect cell adhesion, migration, and proliferation, although the mechanisms by which these occur are only partially understood. Here we report that upon cell binding and internalization, single-chain uPA (scuPA) translocates to the nucleus within minutes. Nuclear translocation does not involve proteolytic activation or degradation of scuPA. Neither the urokinase receptor (uPAR) nor the low-density lipoprotein-related receptor (LRP) is required for nuclear targeting. Rather, translocation involves the binding of scuPA to the nucleocytoplasmic shuttle protein nucleolin through a region containing the kringle domain. RNA interference and mutational analysis demonstrate that nucleolin is required for the nuclear transport of scuPA. Furthermore, nucleolin is required for the induction smooth muscle α-actin (α-SMA) by scuPA. These data reveal a novel pathway by which uPA is rapidly translocated to the nucleus where it might participate in regulating gene expression. PMID:18337556

  15. Translocation pathway of protein substrates in ClpAP protease.

    PubMed

    Ishikawa, T; Beuron, F; Kessel, M; Wickner, S; Maurizi, M R; Steven, A C

    2001-04-10

    Intracellular protein degradation, which must be tightly controlled to protect normal proteins, is carried out by ATP-dependent proteases. These multicomponent enzymes have chaperone-like ATPases that recognize and unfold protein substrates and deliver them to the proteinase components for digestion. In ClpAP, hexameric rings of the ClpA ATPase stack axially on either face of the ClpP proteinase, which consists of two apposed heptameric rings. We have used cryoelectron microscopy to characterize interactions of ClpAP with the model substrate, bacteriophage P1 protein, RepA. In complexes stabilized by ATPgammaS, which bind but do not process substrate, RepA dimers are seen at near-axial sites on the distal surface of ClpA. On ATP addition, RepA is translocated through approximately 150 A into the digestion chamber inside ClpP. Little change is observed in ClpAP, implying that translocation proceeds without major reorganization of the ClpA hexamer. When translocation is observed in complexes containing a ClpP mutant whose digestion chamber is already occupied by unprocessed propeptides, a small increase in density is observed within ClpP, and RepA-associated density is also seen at other axial sites. These sites appear to represent intermediate points on the translocation pathway, at which segments of unfolded RepA subunits transiently accumulate en route to the digestion chamber. PMID:11287666

  16. Translocation pathway of protein substrates in ClpAP protease

    PubMed Central

    Ishikawa, Takashi; Beuron, Fabienne; Kessel, Martin; Wickner, Sue; Maurizi, Michael R.; Steven, Alasdair C.

    2001-01-01

    Intracellular protein degradation, which must be tightly controlled to protect normal proteins, is carried out by ATP-dependent proteases. These multicomponent enzymes have chaperone-like ATPases that recognize and unfold protein substrates and deliver them to the proteinase components for digestion. In ClpAP, hexameric rings of the ClpA ATPase stack axially on either face of the ClpP proteinase, which consists of two apposed heptameric rings. We have used cryoelectron microscopy to characterize interactions of ClpAP with the model substrate, bacteriophage P1 protein, RepA. In complexes stabilized by ATP?S, which bind but do not process substrate, RepA dimers are seen at near-axial sites on the distal surface of ClpA. On ATP addition, RepA is translocated through ?150 ? into the digestion chamber inside ClpP. Little change is observed in ClpAP, implying that translocation proceeds without major reorganization of the ClpA hexamer. When translocation is observed in complexes containing a ClpP mutant whose digestion chamber is already occupied by unprocessed propeptides, a small increase in density is observed within ClpP, and RepA-associated density is also seen at other axial sites. These sites appear to represent intermediate points on the translocation pathway, at which segments of unfolded RepA subunits transiently accumulate en route to the digestion chamber. PMID:11287666

  17. 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

  18. 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...

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

    PubMed Central

    Muzard, J.; Martinho, M.; Math, 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

  20. 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 ...

  1. 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...

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

    PubMed Central

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

    2013-01-01

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

  3. 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.

  4. 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.

  5. MiT family translocation renal cell carcinoma.

    PubMed

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. PMID:25758327

  6. A harbor background suppression approach

    NASA Astrophysics Data System (ADS)

    Gong, Xun; Shi, Wen-Jun

    2015-12-01

    In order to resolve false segmentation and false tracking problems caused by the influence of complex harbor background during IR moving target detection, a harbor background suppression approach is presented. Firstly, Sky-sea line region can be obtained by Otsu segmentation, which is applied to split images obtained through wavelet transform. Secondly, harbor background suppression point in sequential images can be located by multilevel filter. Finally, harbor background suppression can be realized according to those background suppression points. The proposed approach is validated by using actual IR in complex harbor background to realize background suppression. Experiment results indicate the feasibility and effectiveness of the proposed method.

  7. Complex Y-linked translocations in Delia antiqua produced by irradiation of a fertile Y-linked translocation.

    PubMed

    Robinson, A S; van Heemert, K

    1981-02-01

    In the onion fly, Delia antiqua, a fertile, Y-linked translocation involving chromosomes Y and 2 was irradiated with fast neutrons to induce new complexes involving the Y-chromosome. This chromosome is male determining in the onion fly. Such complexes can be used for the development of genetic sexing systems and also for the introduction of sterility into field populations following release. Irradiation reduced egg fertility by 54 per cent and significantly reduced larval survival but it had no effect on the F1 sex ratio. By measuring the fertility of 807 F1 males following outcrossing, 112 semi-sterile progenies were isolated of which 11 were lost, 29 showed no inheritance of the semi-sterility, 59 were new autosomal translocations and 13 were new complex Y-linked translocations. This classification was accomplished by checking the fertilities of outcrossed F2 males and females. Following cytological observation it was revealed that one of these new complexes involved four chromosome pairs, the remainder involved three. There appeared to be no correlation between the fertility of the translocation and the complexity of the rearrangement. The utilization of these rearrangements in the development of the genetic sexing technique for the onion fly is discussed, together with an assessment of their use for fertility reduction in natural populations. PMID:7263278

  8. Background Lamb waves in the Earth's atmosphere

    NASA Astrophysics Data System (ADS)

    Nishida, K.; Kobayashi, N.; Fukao, Y.

    2013-12-01

    Lamb waves of the Earth's atmosphere in the millihertz band have been considered as transient phenomena excited only by large events [e.g. the major volcanic eruption of Krakatoa in 1833, the impact of Siberian meteorite in 1908, the testing of large nuclear tests and the huge earthquakes, Garrett1969]. In a case of the solid Earth, observation of background free oscillations in the millihertz band-now known as Earth's background free oscillations or seismic hum, has been firmly established. Above 5 mHz, their dominant excitation sources are oceanic infragravity waves. At 3.7 and 4.4 mHz an elasto-acoustic resonance between the solid Earth and the atmosphere was observed [Nishida et al., 2000]. These seismic observations show that the contribution of atmospheric disturbances to the seismic hum is dominant below 5 mHz. Such contribution implies background excitations of acoustic-gravity waves in this frequency range. For direct detection of the background acoustic-gravity waves, our group conducted observations using an array of barometers [Nishida et al. 2005]. However, the spatial scale of the array of about 10 km was too small to detect acoustic modes below 10 mHz. Since then, no direct observations of these waves have been reported. In 2011, 337 high-resolution microbarometers were installed on a continental scale at USArray Transportable Array. The large and dense array enables us to detect the background atmospheric waves. Here, we show the first evidence of background Lamb waves in the Earth's atmosphere from 0.2 to 10 mHz, based on the array analysis of microbarometer data from the USArray in 2012. The observations suggest that the excitation sources are atmospheric disturbances in the troposphere. Theoretically, their energy in the troposphere tunnels into the thermosphere at a resonant frequency via thermospheric gravity wave, where the observed amplitudes indeed take a local minimum. The energy leak through the frequency window could partly contribute to thermospheric wave activity. Tropospheric disturbances exciting background Lamb waves may also be responsible for seismic hum at frequencies below 5 mHz.

  9. 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

  10. 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

  11. 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.

  12. 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 bright extragalactic radio and infrared sources; (5) observing the local interstellar medium, distributed synchrotron emission, and the galactic magnetic field; (6) studying the local Solar System (planets, asteroids, comets, and the zodiacal light). Planck is expected to yield data on a number of astronomical issues by 2012. It is thought that Planck measurements will mostly be limited by the efficiency of foreground removal, rather than the detector performance or duration of the mission - this is particularly important for the polarization measurements. Technological developments over the last two decades have accelerated the progress in observational cosmology. The interplay between the new theoretical ideas and new observational data has taken cosmology from a purely theoretical domain into a field of rigorous experimental science andwe are nowin what is called the precision cosmology era. The CMB measurements have made the inflationary Big Bang theory the standard model of the early Universe. This theory predicts a roughly Gaussian distribution for the initial conditions of the Universe. The power spectrum of these fluctuations agrees well with the observations, although certain observables, such as the overall amplitude of the fluctuations, remain as free parameters of the cosmic inflation model.

  13. 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).

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

    PubMed

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

    2015-01-01

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

  15. 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.

  16. 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.

  17. The cosmic far-infrared background at high galactic latitudes

    NASA Technical Reports Server (NTRS)

    Stecker, F. W.; Puget, J. L.; Fazio, G. G.

    1976-01-01

    Far-infrared background fluxes from various cosmic sources are predicted. These fluxes lie near the high frequency side of the blackbody radiation spectrum. These sources could account for a significant fraction of the background radiation at frequencies above 400 GHz which might be misinterpreted as a comptonization distortion of the blackbody radiation. Particular attention is paid to the possible contributions from external galaxies, rich clusters of galaxies and from galactic dust emission.

  18. 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.

  19. Balanced nonacrocentric whole-arm reciprocal translocations: A de novo case and literature review

    SciTech Connect

    Farrell, S.A.; Fan, Y.S.

    1995-02-13

    We report a new de novo case of a balanced whole-arm reciprocal translocation, detected at prenatal diagnosis for late maternal age. A review of previous cases indicates there is a risk of chromosomally abnormal liveborn offspring when a parent is a carrier of this type of translocation, particularly when the translocated region is a small chromosomal segment. Due to the limited number of cases, exact reproductive risks are not available. This is the second example of such a translocation of chromosomes 1 and 5, raising the possibility of nonrandom involvement of certain chromosomes in balanced nonacrocentric whole-arm reciprocal translocations. 18 refs., 1 fig., 1 tab.

  20. Phosphatidylserine-binding protein lactadherin inhibits protein translocation across the ER membrane.

    PubMed

    Yamamoto, Hitoshi; Kida, Yuichiro; Sakaguchi, Masao

    2013-05-10

    Secretory and membrane proteins are translocated across and inserted into the endoplasmic reticulum membrane via translocon channels. To investigate the effect of the negatively-charged phospholipid phosphatidylserine on the translocation of nascent polypeptide chains through the translocon, we used the phosphatidylserine-binding protein lactadherin C2-domain. Lactadherin inhibited targeting of nascent chain to the translocon by signal sequence and the initiation of translocation. Moreover, lactadherin inhibited the movement of the translocating polypeptide chain regardless of the presence or absence of positively-charged residues. Phosphatidylserine might be critically involved in translocon function, but it is not a major determinant for translocation arrest of positively-charged residues. PMID:23583395

  1. Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: Relevance to atopic dermatitis

    PubMed Central

    Zhang, Bodi; Alysandratos, Konstantinos-Dionysios; Angelidou, Asimenia; Asadi, Shahrzad; Sismanopoulos, Nikolaos; Delivanis, Danae-Anastasia; Weng, Zuyi; Miniati, Alexandra; Vasiadi, Magdalini; Katsarou-Katsari, Alexandra; Miao, Benchun; Leeman, Susan E.; Kalogeromitros, Dimitrios; Theoharides, Theoharis C.

    2012-01-01

    Background Mast cells derive from hematopoietic cell precursors and participate in tissue allergic, immune, and inflammatory processes. They secrete many mediators, including preformed TNF, in response to allergic, neuropeptide, and environmental triggers. However, regulation of mast cell degranulation is not well understood. Objective We investigated the role of mitochondrial dynamics in degranulation of human cultured mast cells. Methods Human umbilical cord blood–derived mast cells (hCBMCs) and Laboratory of Allergic Diseases 2 (LAD2) mast cells were examined by confocal and differential interference contrast microscopy during activation by IgE/antigen and substance P (SP). Mast cells in control and atopic dermatitis (AD) skin were evaluated by transmission electron microscopy. LAD2 cells were pretreated with mitochondrial division inhibitor, a dynamin-related protein 1 (Drp1) inhibitor, and small interfering RNA for Drp1, which is necessary for mitochondrial fission and translocation. Calcineurin and Drp1 gene expression was analyzed in stimulated LAD2 cells and AD skin biopsies. Results Stimulation of hCBMCs with IgE/antigen or LAD2 cells with SP leads to rapid (30 minutes) secretion of preformed TNF. Degranulation is accompanied by mitochondrial translocation from a perinuclear location to exocytosis sites. Extracellular calcium depletion prevents these effects, indicating calcium requirement. The calcium-dependent calcineurin and Drp1 are activated 30 minutes after SP stimulation. Reduction of Drp1 activity by mitochondrial division inhibitor and decrease of Drp1 expression using small interfering RNA inhibit mitochondrial translocation, degranulation, and TNF secretion. Mitochondrial translocation is also evident by transmission electron microscopy in skin mast cells from AD biopsies, in which gene expression of calcineurin, Drp1, and SP is higher than in normal skin. Conclusion Human mast cell degranulation requires mitochondrial dynamics, also implicated in AD. (J Allergy Clin Immunol 2011;127:1522-31.) PMID:21453958

  2. 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.

  3. A Novel Mode of Translocation for Cytolethal Distending Toxin

    PubMed Central

    Guerra, Lina; Nemec, Kathleen N.; Massey, Shane; Tatulian, Suren A.; Thelestam, Monica; Frisan, Teresa; Teter, Ken

    2008-01-01

    Summary Thermal instability in the toxin catalytic subunit may be a common property of toxins that exit the endoplasmic reticulum (ER) by exploiting the mechanism of ER-associated degradation (ERAD). The Haemophilus ducreyi cytolethal distending toxin (HdCDT) does not utilize ERAD to exit the ER, so we predicted the structural properties of its catalytic subunit (HdCdtB) would differ from other ER-translocating toxins. Here, we document the heat-stable properties of HdCdtB which distinguish it from other ER-translocating toxins. Cell-based assays further suggested that HdCdtB does not unfold before exiting the ER and that it may move directly from the ER lumen to the nucleoplasm. These observations suggest a novel mode of ER exit for HdCdtB. PMID:19118582

  4. Slowing down DNA translocation through a nanopore in lithium chloride

    PubMed Central

    Kowalczyk, Stefan W.; Wells, David B.; Aksimentiev, Aleksei; Dekker, Cees

    2012-01-01

    The charge of a DNA molecule is a crucial parameter in many DNA detection and manipulation schemes such as gel electrophoresis and lab-on-a-chip applications. Here, we study the partial reduction of the DNA charge due to counterion binding by means of nanopore translocation experiments and all-atom molecular dynamics (MD) simulations. Surprisingly, we find that the translocation time of a DNA molecule through a solid-state nanopore strongly increases as the counterions decrease in size from K+ to Na+ to Li+, both for double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA). MD simulations elucidate the microscopic origin of this effect: Li+ and Na+ bind DNA stronger than K+. These fundamental insights into the counterion binding to DNA also provide a practical method for achieving at least ten-fold enhanced resolution in nanopore applications. PMID:22229707

  5. Beam induced backgrounds: CDF experience

    SciTech Connect

    Tesarek, R.J.; /Fermilab

    2008-05-01

    We summarize the experiences of the Collider Detector at Fermilab (CDF) experiment in the presence of backgrounds originating from the counter circulating beams in the Fermilab Tevatron. These backgrounds are measured and their sources identified. Finally, we outline the strategies employed to reduce the effects of these backgrounds on the experiment.

  6. Gq-mediated Akt translocation to the membrane: a novel PIP3-independent mechanism in platelets

    PubMed Central

    Badolia, Rachit; Manne, Bhanu Kanth; Dangelmaier, Carol; Chernoff, Jonathan

    2015-01-01

    Akt is an important signaling molecule regulating platelet aggregation. Akt is phosphorylated after translocation to the membrane through Gi signaling pathways by a phosphatidylinositol-3,4,5-trisphosphate (PIP3)-dependent mechanism. However, Akt is more robustly phosphorylated by thrombin compared with adenosine 5?-diphosphate in platelets. This study investigated the mechanisms of Akt translocation as a possible explanation for this difference. Stimulation of washed human platelets with protease-activated receptor agonists caused translocation of Akt to the membrane rapidly, whereas phosphorylation occurred later. The translocation of Akt was abolished in the presence of a Gq-selective inhibitor or in Gq-deficient murine platelets, indicating that Akt translocation is regulated downstream of Gq pathways. Interestingly, phosphatidylinositol 3-kinase (PI3K) inhibitors or P2Y12 antagonist abolished Akt phosphorylation without affecting Akt translocation to the membrane, suggesting that Akt translocation occurs through a PI3K/PIP3/Gi-independent mechanism. An Akt scaffolding protein, p21-activated kinase (PAK), translocates to the membrane after stimulation with protease-activated receptor agonists in a Gq-dependent manner, with the kinetics of translocation similar to that of Akt. Coimmunoprecipitation studies showed constitutive association of PAK and Akt, suggesting a possible role of PAK in Akt translocation. These results show, for the first time, an important role of the Gq pathway in mediating Akt translocation to the membrane in a novel Gi/PI3K/PIP3-independent mechanism. PMID:25331114

  7. Gq-mediated Akt translocation to the membrane: a novel PIP3-independent mechanism in platelets.

    PubMed

    Badolia, Rachit; Manne, Bhanu Kanth; Dangelmaier, Carol; Chernoff, Jonathan; Kunapuli, Satya P

    2015-01-01

    Akt is an important signaling molecule regulating platelet aggregation. Akt is phosphorylated after translocation to the membrane through Gi signaling pathways by a phosphatidylinositol-3,4,5-trisphosphate (PIP3)-dependent mechanism. However, Akt is more robustly phosphorylated by thrombin compared with adenosine 5'-diphosphate in platelets. This study investigated the mechanisms of Akt translocation as a possible explanation for this difference. Stimulation of washed human platelets with protease-activated receptor agonists caused translocation of Akt to the membrane rapidly, whereas phosphorylation occurred later. The translocation of Akt was abolished in the presence of a Gq-selective inhibitor or in Gq-deficient murine platelets, indicating that Akt translocation is regulated downstream of Gq pathways. Interestingly, phosphatidylinositol 3-kinase (PI3K) inhibitors or P2Y12 antagonist abolished Akt phosphorylation without affecting Akt translocation to the membrane, suggesting that Akt translocation occurs through a PI3K/PIP3/Gi-independent mechanism. An Akt scaffolding protein, p21-activated kinase (PAK), translocates to the membrane after stimulation with protease-activated receptor agonists in a Gq-dependent manner, with the kinetics of translocation similar to that of Akt. Coimmunoprecipitation studies showed constitutive association of PAK and Akt, suggesting a possible role of PAK in Akt translocation. These results show, for the first time, an important role of the Gq pathway in mediating Akt translocation to the membrane in a novel Gi/PI3K/PIP3-independent mechanism. PMID:25331114

  8. 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.

  9. 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.

  10. 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.

  11. Translocation of alkane through graphene nanopore: A molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Li, Jun-Yin; Yang, Hua; Sheng, Yan-Zhen; Zhao, Xin-Ting; Sun, Miao

    2015-02-01

    The process of molecules translocation through nanopore is important to understand many interesting phenomena. Molecular dynamics simulations have been carried out to study the translocation of alkane through graphene nanopore. The results detail relative distance, average translation time, etc. The translocation process can be divided into three stages: finding-entering-moving through the nanopore. Alkane must climb an energy barrier in every stage. The dependence of translocation on chain length is also discussed. Shorter alkanes are easy to transport through the nanopore and the average translocation time is short when alkane translocates through nanopore one by one. Our simulations show a visualized translocation process, which can favor our understanding of this important process.

  12. Single Nanoparticle Translocation Through Chemically Modified Solid Nanopore

    NASA Astrophysics Data System (ADS)

    Tan, Shengwei; Wang, Lei; Liu, Hang; Wu, Hongwen; Liu, Quanjun

    2016-02-01

    The nanopore sensor as a high-throughput and low-cost technology can detect single nanoparticle in solution. In the present study, the silicon nitride nanopores were fabricated by focused Ga ion beam (FIB), and the surface was functionalized with 3-aminopropyltriethoxysilane to change its surface charge density. The positively charged nanopore surface attracted negatively charged nanoparticles when they were in the vicinity of the nanopore. And, nanoparticle translocation speed was slowed down to obtain a clear and deterministic signal. Compared with previous studied small nanoparticles, the electrophoretic translocation of negatively charged polystyrene (PS) nanoparticles (diameter ~100 nm) was investigated in solution using the Coulter counter principle in which the time-dependent nanopore current was recorded as the nanoparticles were driven across the nanopore. A linear dependence was found between current drop and biased voltage. An exponentially decaying function ( t d ~ e -v/v0 ) was found between the duration time and biased voltage. The interaction between the amine-functionalized nanopore wall and PS microspheres was discussed while translating PS microspheres. We explored also translocations of PS microspheres through amine-functionalized solid-state nanopores by varying the solution pH (5.4, 7.0, and 10.0) with 0.02 M potassium chloride (KCl). Surface functionalization showed to provide a useful step to fine-tune the surface property, which can selectively transport molecules or particles. This approach is likely to be applied to gene sequencing.

  13. Dieldrin uptake and translocation in plants growing in hydroponic medium.

    PubMed

    Murano, Hirotatsu; Otani, Takashi; Seike, Nobuyasu; Sakai, Mizuki

    2010-01-01

    It has been known that the Cucurbitaceae family takes up a large amount of persistent organic pollutants from soils and that the translocation of those compounds in cucurbits is higher than those in non-cucurbits. To understand the persistent organic pollutant uptake mechanisms of plant species, we compared the dieldrin absorption and transportation potentials of several plants in hydroponic medium. Sorghum (Sorghum vulgare Moench), sunflower (Helianthus annuus L.), soybean (Glycine max), komatsuna (Brassica rapa var. peruviridis), white-flowered gourd (Lagenaria siceraria var. hispida), cucumber (Cucumis sativus L.), and zucchini (Cucurbita pepo L.) were grown in a dieldrin-added hydroponic medium for 10 d, and then the amount of dieldrin in their shoots and roots was measured. All of the roots contained dieldrin, whereas only the cucurbits (white-flowered gourd, cucumber, and zucchini) contained considerable amounts of dieldrin in their shoots. The dieldrin uptake to the roots depended on the concentration of the n-hexane soluble components in the roots, regardless of whether the dieldrin in the roots was translocated to shoots or not. The dieldrin uptake from the solution to the roots was thought to be due to a passive response, such as adsorption on the roots. The translocation of dieldrin from the roots to the shoots was probably through the xylems. The amounts of dieldrin in the shoots per transpiration rates were higher for cucurbits than for non-cucurbits. It seems likely that cucurbits have uptake mechanisms for hydrophobic organic chemicals. PMID:20821429

  14. Single Nanoparticle Translocation Through Chemically Modified Solid Nanopore.

    PubMed

    Tan, Shengwei; Wang, Lei; Liu, Hang; Wu, Hongwen; Liu, Quanjun

    2016-12-01

    The nanopore sensor as a high-throughput and low-cost technology can detect single nanoparticle in solution. In the present study, the silicon nitride nanopores were fabricated by focused Ga ion beam (FIB), and the surface was functionalized with 3-aminopropyltriethoxysilane to change its surface charge density. The positively charged nanopore surface attracted negatively charged nanoparticles when they were in the vicinity of the nanopore. And, nanoparticle translocation speed was slowed down to obtain a clear and deterministic signal. Compared with previous studied small nanoparticles, the electrophoretic translocation of negatively charged polystyrene (PS) nanoparticles (diameter ~100 nm) was investigated in solution using the Coulter counter principle in which the time-dependent nanopore current was recorded as the nanoparticles were driven across the nanopore. A linear dependence was found between current drop and biased voltage. An exponentially decaying function (t d   ~ e (-v/v0) ) was found between the duration time and biased voltage. The interaction between the amine-functionalized nanopore wall and PS microspheres was discussed while translating PS microspheres. We explored also translocations of PS microspheres through amine-functionalized solid-state nanopores by varying the solution pH (5.4, 7.0, and 10.0) with 0.02 M potassium chloride (KCl). Surface functionalization showed to provide a useful step to fine-tune the surface property, which can selectively transport molecules or particles. This approach is likely to be applied to gene sequencing. PMID:26831688

  15. Growth hormone reduces mortality and bacterial translocation in irradiated rats.

    PubMed

    Gmez-de-Segura, I A; Prieto, I; Grande, A G; Garca, P; Guerra, A; Mendez, J; De Miguel, E

    1998-01-01

    Growth hormone stimulates the growth of intestinal mucosa and may reduce the severity of injury caused by radiation. Male Wistar rats underwent abdominal irradiation (12 Gy) and were treated with either human growth hormone (hGH) or saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation, and the ileal mucosal thickness, proliferation, and disaccharidase activity were assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement (29%, p < 0.05). Bacterial translocation was also reduced by hGH (p < 0.05). Treating irradiated rats with hGH prevented body weight loss (p < 0.05). Mucosal thickness increased faster in irradiated hGH-treated animals. The proliferative index showed an increment in hGH-treated animals (p < 0.05). Giving hGH to irradiated rats prevented decrease in sucrose activity, and increment in lactase activity. In conclusion, giving hGH to irradiated rats promotes the adaptative process of the intestine and acute radiation-related negative effects, including mortality, bacterial translocation, and weight loss. PMID:9636013

  16. Compositions and methods for detecting gene rearrangements and translocations

    DOEpatents

    Rowley, Janet D.; Diaz, Manuel O.

    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.

  17. Flow-induced translocation of star polymers through a nanopore.

    PubMed

    Ding, Mingming; Duan, Xiaozheng; Shi, Tongfei

    2016-03-01

    We study the flow-induced translocation of the star polymers through a nanopore using a hybrid simulation method that incorporates a lattice-Boltzmann approach for the fluid into a molecular dynamics model for the polymer. Our simulation demonstrates the existence of an optimal forward arm number of the star polymers captured by the nanopore, and illustrates its significance in determining the critical velocity flux of the star polymer translocation through the nanopore. Importantly, we find that the critical velocity flux of the star polymers is independent of the arm polymerization degree, but exhibits a linear dependence on the arm number. Based on previous scaling arguments and our simulation results, we conclude a linear dependence of the critical velocity flux on the arm number of the star polymers, which can successfully describe the dynamics of the star polymer translocation. Our simulation results rationalize the experimental results for the dependence of the critical velocity flux on the arm polymerization degree and the arm number of the star polymers, which provide new insights for the characterization and the purification of the star polymers. PMID:26879130

  18. 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.

  19. Aminoglycoside activity observed on single pre-translocation ribosome complexes

    PubMed Central

    Feldman, Michael B; Terry, Daniel S; Altman, Roger B; Blanchard, Scott C

    2010-01-01

    Aminoglycoside-class antibiotics bind directly to ribosomal RNA, imparting pleiotropic effects on ribosome function. Despite in-depth structural investigations of aminoglycosideRNA oligonucleotide and aminoglycoside-ribosome interactions, mechanisms explaining the unique ribosome inhibition profiles of chemically similar aminoglycosides remain elusive. Here, using single-molecule fluorescence resonance energy transfer (smFRET) methods, we show that high-affinity aminoglycoside binding to the conserved decoding site region of the functional pre-translocation ribosome complex specifically remodels the nature of intrinsic dynamic processes within the particle. The extents of these effects, which are distinct for each member of the aminoglycoside class, strongly correlate with their inhibition of EF-Gcatalyzed translocation. Neomycin, a 4,5-linked amino-glycoside, binds with lower affinity to one or more secondary binding sites, mediating distinct structural and dynamic perturbations that further enhance translocation inhibition. These new insights help explain why closely related aminoglycosides elicit pleiotropic translation activities and demonstrate the potential utility of smFRET as a tool for dissecting the mechanisms of antibiotic action. PMID:19946275

  20. Ancient class of translocated oomycete effectors targets the host nucleus

    PubMed Central

    Schornack, Sebastian; van Damme, Mireille; Bozkurt, Tolga O.; Cano, Liliana M.; Smoker, Matthew; Thines, Marco; Gaulin, Elodie; Kamoun, Sophien; Huitema, Edgar

    2010-01-01

    Pathogens use specialized secretion systems and targeting signals to translocate effector proteins inside host cells, a process that is essential for promoting disease and parasitism. However, the amino acid sequences that determine host delivery of eukaryotic pathogen effectors remain mostly unknown. The Crinkler (CRN) proteins of oomycete plant pathogens, such as the Irish potato famine organism Phytophthora infestans, are modular proteins with predicted secretion signals and conserved N-terminal sequence motifs. Here, we provide direct evidence that CRN N termini mediate protein transport into plant cells. CRN host translocation requires a conserved motif that is present in all examined plant pathogenic oomycetes, including the phylogenetically divergent species Aphanomyces euteiches that does not form haustoria, specialized infection structures that have been implicated previously in delivery of effectors. Several distinct CRN C termini localized to plant nuclei and, in the case of CRN8, required nuclear accumulation to induce plant cell death. These results reveal a large family of ubiquitous oomycete effector proteins that target the host nucleus. Oomycetes appear to have acquired the ability to translocate effector proteins inside plant cells relatively early in their evolution and before the emergence of haustoria. Finally, this work further implicates the host nucleus as an important cellular compartment where the fate of plant–microbe interactions is determined. PMID:20847293

  1. Requirements for translocation of periplasmic domains in polytopic membrane proteins.

    PubMed Central

    Uhland, K; Ehrle, R; Zander, T; Ehrmann, M

    1994-01-01

    Periplasmic domains of cytoplasmic membrane proteins require export signals for proper translocation. These signals were studied by using a MalF-alkaline phosphatase fusion in a genetic selection that allowed the isolation of mislocalization mutants. In the original construct, alkaline phosphatase is fused to the second periplasmic domain of the membrane protein, and its activity is thus confined exclusively to the periplasm. Mutants that no longer translocated alkaline phosphatase were selected by complementation of a serB mutation. A total of 11 deletions in the amino terminus were isolated, all of which spanned at least the third transmembrane segment. This domain immediately precedes the periplasmic domain to which alkaline phosphatase was fused. Our results obtained in vivo support the model that amino-terminal membrane-spanning segments are required for translocation of large periplasmic domains. In addition, we found that the inability to export the alkaline phosphatase domain could be suppressed by a mutation, prlA4, in the secretion apparatus. Images PMID:8045887

  2. 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.

  3. 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.

  4. 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.

  5. The influence of hydrogen peroxide and histamine on lung permeability and translocation of iridium nanoparticles in the isolated perfused rat lung

    PubMed Central

    Meiring, James J; Borm, Paul JA; Bagate, Karim; Semmler, Manuela; Seitz, Jürgen; Takenaka, Shinji; Kreyling, Wolfgang G

    2005-01-01

    Background Translocation of ultrafine particles (UFP) into the blood that returns from the lungs to the heart has been forwarded as a mechanism for particle-induced cardiovascular effects. The objective of this study was to evaluate the role of the endothelial barrier in the translocation of inhaled UFP from the lung into circulation. Methods The isolated perfused rat lung (IPRL) was used under negative pressure ventilation, and radioactive iridium particles (18 nm, CMD, 192Ir-UFP) were inhaled during 60 minutes to achieve a lung burden of 100 – 200 μg. Particle inhalation was done under following treatments: i) control perfusion, ii) histamine (1 μM in perfusate, iii) luminal histamine instillation (1 mM), and iv) luminal instillation of H2O2. Particle translocation to the perfusate was assessed by the radioactivity of 192Ir isotope. Lung permeability by the use of Tc99m-labeled diethylene triamine pentaacetic acid (DTPA). In addition to light microscopic morphological evaluation of fixed lungs, alkaline phosphatase (AKP) and angiotensin converting enzyme (ACE) in perfusate were measured to assess epithelial and endothelial integrity. Results Particle distribution in the lung was homogenous and similar to in vivo conditions. No translocation of Ir particles at negative pressure inhalation was detected in control IPL, but lungs pretreated with histamine (1 μM) in the perfusate or with luminal H2O2 (0.5 mM) showed small amounts of radioactivity (2–3 % dose) in the single pass perfusate starting at 60 min of perfusion. Although the kinetics of particle translocation were different from permeability for 99mTc-DTPA, the pretreatments (H2O2, vascular histamine) caused similar changes in the translocation of particles and soluble mediator. Increased translocation through epithelium and endothelium with a lag time of one hour occurred in the absence of epithelial and endothelial damage. Conclusion Permeability of the lung barrier to UFP or nanoparticles is controlled both at the epithelial and endothelial level. Conditions that affect this barrier function such as inflammation may affect translocation of NP. PMID:15982423

  6. Isolation and analysis of the 21q+ chromosome in the acute myelogenous leukemia 8; 21 translocation: evidence that c-mos is not translocated

    SciTech Connect

    Drabkin, H.A.; Diaz, M.; Bradley, C.M.; Le Beau, M.M.; Rowley, J.D.; Patterson, D.

    1985-01-01

    Acute myelogenous leukemia (AML), subgroup M2, is associated with a nonrandom chromosomal translocation, t(8;21)(q22,q22). The oncogene c-mos also has been localized to the q22 band on chromosome 8. There is also evidence that genes on chromosome 21 may be important in the development of leukemia. To determine whether the c-mos oncogene has been translocated in AML-M2 with this translocation and to isolate DNA sequences and genes from these two chromosomes that may be important in malignancy, the authors constructed somatic cell hybrids between a Chinese hamster ovary cell (CHO) mutant defective in glycine metabolism and myeloblasts with an 8;21 translocation from a patient with AML. The authors isolated the 21q+ chromosome of this translocation in a somatic cell hybrid and showed that the c-mos oncogene had not been translocated to chromosome 21, ruling out the possibility that translocation of c-mos to chromosome 21 is necessary for development of AML-M2. In addition, there was no detectable rearrangement of the c-mos locus within a 12.4-kilobase region surrounding the gene, indicating that rearrangement of the coding region of the gene itself or alteration of proximal 5' or 3' flanking sequences is not involved. The authors used this hybrid to determine whether specific DNA sequences and biochemical markers from chromosomes 8 and 21 had been translocated in this case.

  7. 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, Iaki; 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

  8. 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.

  9. 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.

  10. Silhouette and background information analysis

    NASA Astrophysics Data System (ADS)

    Moore, Michelle N.; O'Connor, John D.

    2007-04-01

    Thermal target identification testing was conducted to explore some of the potential differences in the perception of ID cues in conventional gray shade images, and those same target images when rendered as various types of silhouette, including one with no background. Such experiments may give insight into the human target identification and discrimination tasks relevant to emerging laser-based imaging technology. For example, laser range gating is known to produce silhouetted grey shade targets with a single grey shade background like the ones included here. Well-understood thermal imagery of a well-understood target set was chosen as a convenient and relevant baseline image set for initial exploration. Experiments were formed to compare human vehicle ID performance when viewing full gray-shade imagery versus viewing various combinations of silhouette images. Experiments were performed using 1) Original gray-shade imagery, 2) Silhouette (uniform target) with no background (i.e. background consisting of uniform grey shade, 3) silhouette (target) with (original grey shade) background, and 4) Original target with no background. An eight target set was presented at three different aspects. Notional viewing ranges were simulated by applying two levels of Gaussian blur and two down sampling rates to the complete experimental target set. Observer results indicate higher target identification scores for the "target with no background" and "silhouette with no background" imagery than for the original gray shade imagery. However, ID results were lower for "silhouette with background" imagery than for the original imagery.

  11. 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

  12. T-DNA-associated duplication/translocations in Arabidopsis. Implications for mutant analysis and functional genomics.

    PubMed

    Tax, F E; Vernon, D M

    2001-08-01

    T-DNA insertion mutants have become a valuable resource for studies of gene function in Arabidopsis. In the course of both forward and reverse genetic projects, we have identified novel interchromosomal rearrangements in two Arabidopsis T-DNA insertion lines. Both rearrangements were unilateral translocations associated with the left borders of T-DNA inserts that exhibited normal Mendelian segregation. In one study, we characterized the embryo-defective88 mutation. Although emb88 had been mapped to chromosome I, molecular analysis of DNA adjacent to the T-DNA left border revealed sequence from chromosome V. Simple sequence length polymorphism mapping of the T-DNA insertion demonstrated that a >40-kbp region of chromosome V had inserted with the T-DNA into the emb88 locus on chromosome I. A similar scenario was observed with a prospective T-DNA knockout allele of the LIGHT-REGULATED RECEPTOR PROTEIN KINASE (LRRPK) gene. Whereas wild-type LRRPK is on lower chromosome IV, mapping of the T-DNA localized the disrupted LRRPK allele to chromosome V. In both these cases, the sequence of a single T-DNA-flanking region did not provide an accurate picture of DNA disruption because flanking sequences had duplicated and inserted, with the T-DNA, into other chromosomal locations. Our results indicate that T-DNA insertion lines--even those that exhibit straightforward genetic behavior--may contain an unexpectedly high frequency of rearrangements. Such duplication/translocations can interfere with reverse genetic analyses and provide misleading information about the molecular basis of mutant phenotypes. Simple mapping and polymerase chain reaction methods for detecting such rearrangements should be included as a standard step in T-DNA mutant analysis. PMID:11500551

  13. Voltage-driven translocation of DNA through a high throughput conical solid-state nanopore.

    PubMed

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

    2012-01-01

    Nanopores have become an important tool for molecule detection at single molecular level. With the development of fabrication technology, synthesized solid-state membranes are promising candidate substrates in respect of their exceptional robustness and controllable size and shape. Here, a 30-60 (tip-base) nm conical nanopore fabricated in 100 nm thick silicon nitride (Si(3)N(4)) membrane by focused ion beam (FIB) has been employed for the analysis of λ-DNA translocations at different voltage biases from 200 to 450 mV. The distributions of translocation time and current blockage, as well as the events frequencies as a function of voltage are investigated. Similar to previously published work, the presence and configurations of λ-DNA molecules are characterized, also, we find that greater applied voltages markedly increase the events rate, and stretch the coiled λ-DNA molecules into linear form. However, compared to 6-30 nm ultrathin solid-state nanopores, a threshold voltage of 181 mV is found to be necessary to drive DNA molecules through the nanopore due to conical shape and length of the pore. The speed is slowed down ∼5 times, while the capture radius is ∼2 fold larger. The results show that the large nanopore in thick membrane with an improved stability and throughput also has the ability to detect the molecules at a single molecular level, as well as slows down the velocity of molecules passing through the pore. This work will provide more motivations for the development of nanopores as a Multi-functional sensor for a wide range of biopolymers and nano materials. PMID:23029365

  14. 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.

  15. Electromagnetic PIC modeling with a background gas

    NASA Astrophysics Data System (ADS)

    Verboncoeur, J. P.; Cooperberg, D.

    1997-02-01

    Modeling the interaction of relativistic electromagnetic plasmas with a background gas is described. The timescales range over many orders of magnitude, from the electromagnetic Courant condition (˜10-12 sec) to electron-neutral collision times (˜10-7 sec) to ion transit times (˜10-5 sec). For this work, the traditional Monte Carlo algorithm [1] is described for relativistic electrons. Subcycling is employed to improve efficiency, and smoothing is employed to reduce particle noise. Applications include plasma-focused electron guns, gas-filled microwave tubes, surface wave discharges driven at microwave frequencies, and electron-cyclotron resonance discharges. The method is implemented in the OOPIC code [2].

  16. Electromagnetic PIC modeling with a background gas

    SciTech Connect

    Verboncoeur, J. P.; Cooperberg, D.

    1997-02-01

    Modeling the interaction of relativistic electromagnetic plasmas with a background gas is described. The timescales range over many orders of magnitude, from the electromagnetic Courant condition ({approx}10{sup -12} sec) to electron-neutral collision times ({approx}10{sup -7} sec) to ion transit times ({approx}10{sup -5} sec). For this work, the traditional Monte Carlo algorithm [1] is described for relativistic electrons. Subcycling is employed to improve efficiency, and smoothing is employed to reduce particle noise. Applications include plasma-focused electron guns, gas-filled microwave tubes, surface wave discharges driven at microwave frequencies, and electron-cyclotron resonance discharges. The method is implemented in the OOPIC code [2].

  17. 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 μg/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-α 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

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

    PubMed

    Rey, Mara-Dolores; Caldern, Mara-Carmen; Rodrigo, Mara Jess; Zacaras, Lorenzo; Als, 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

  20. 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 7Hchα and 7Hchβ 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 7Hchα∙7AL and 7AS∙7Hchβ disomic translocation lines. The carotenoid content in 7Hchα∙7AL and 7AS∙7Hchβ 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 7Hchα 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

  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. FAMILY BACKGROUND OF RURAL YOUTH.

    ERIC Educational Resources Information Center

    COPP, JAMES H.

    FAMILY BACKGROUNDS OF RURAL YOUTH ARE DISCUSSED. THE BACKGROUND PROVIDED BY THE FAMILY HAS IMPLICATIONS FOR THE ADJUSTMENT OF RURAL YOUTH IN AN URBANIZED, HIGHLY TECHNICAL SOCIETY. THE BASIC ECOLOGICAL CONDITIONS OF RURAL AREAS INFLUENCE THE RATE OF SOCIAL CHANGE, THE IMPORTANCE OF THE FAMILY AS A SOCIAL UNIT, AND THE ORIENTATION TOWARD LEGAL

  3. 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.

  4. Background estimation in experimental spectra

    SciTech Connect

    Fischer, R.; Hanson, K. M.; Los Alamos National Laboratory, MS P940, Los Alamos, New Mexico 87545 ; Dose, V.; Linden, W. von der

    2000-02-01

    A general probabilistic technique for estimating background contributions to measured spectra is presented. A Bayesian model is used to capture the defining characteristics of the problem, namely, that the background is smoother than the signal. The signal is allowed to have positive and/or negative components. The background is represented in terms of a cubic spline basis. A variable degree of smoothness of the background is attained by allowing the number of knots and the knot positions to be adaptively chosen on the basis of the data. The fully Bayesian approach taken provides a natural way to handle knot adaptivity and allows uncertainties in the background to be estimated. Our technique is demonstrated on a particle induced x-ray emission spectrum from a geological sample and an Auger spectrum from iron, which contains signals with both positive and negative components. (c) 2000 The American Physical Society.

  5. Geochemical background - an environmental perspective

    NASA Astrophysics Data System (ADS)

    Gałuszka, Agnieszka; Migaszewski, Zdzisław M.

    2011-01-01

    This article presents the concept of geochemical background from an environmental perspective. The idea of establishing the typical concentrations of elements in various environmental compartments, proposed by exploratory geochemists almost 50 years ago was important for the detection of anomalous element concentrations, thus providing a basic tool in the search for new mineral deposits. At present, the knowledge of the geochemical background of hazardous elements is essential for: defining pollution, identifying the source of contamination, and for establishing reliable environmental quality criteria for soils, sediments and surface waters. The article presents geochemical methods of evaluation of anthropogenic influence on the environment and discusses the problem of defining and understanding the term "geochemical background" and related terms in environmental sciences. It also briefly presents methods of geochemical background evaluation based on the results of environmental sample analyses. It stresses the role of geochemical background in our understanding of environmental pollution and pollution prevention.

  6. Cytogenetic and molecular characteristics of 25 Chilean patients with a variant Ph translocation.

    PubMed

    Legues, Maria E; Encina, Andrea; Valenzuela, Mercedes; Palma, Tamara; Undurraga, Maria S

    2011-07-01

    Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome (Ph), which results from a balanced translocation between chromosomes 9 and 22, the t(9;22)(q34;q11.2). In 5-10% of the cases, variants of the Ph (vPh) are detected, involving various breakpoints in addition to 9q34 and 22q11.2. Deletions on the der(9) and der(22) can be detected in approximately 10-15% of CML patients. The frequency of a deletion of the der(9) in vPh CML is variable. Most studies have shown high frequencies (30-45%) in this subgroup. We report the cytogenetic evaluation of 25 vPh cases, which represents 6.8% of the CML cases diagnosed at one institution in 20 years. The breakpoints of the partners of the vPh in our patients agree with those reported previously, except for a novel 18q23. We found a low incidence of deletions of the der(9) (10%) and der(22) (5%) in these patients, contrasting with several reports in the literature. This finding may reflect the extensive spectrum of aberrations in vPh, and the possibility that a considerable group of these aberrations may not affect the genetic stability of 5'ABL1 and 3'BCR. Epidemiologic differences may also exist and could explain our results. These differences would require further investigation. PMID:21872829

  7. 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; Prtner, 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 (015C), capacities of mitochondrial respiration and enzymatic function in the liver could only be increased until 9C. 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

  8. Biopersistence and brain translocation of aluminum adjuvants of vaccines.

    PubMed

    Gherardi, Romain Kroum; Eidi, Housam; Crpeaux, Guillemette; Authier, Franois Jerome; Cadusseau, Josette

    2015-01-01

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

  9. Biopersistence and Brain Translocation of Aluminum Adjuvants of Vaccines

    PubMed Central

    Gherardi, Romain Kroum; Eidi, Housam; Crpeaux, Guillemette; Authier, Franois Jerome; Cadusseau, Josette

    2015-01-01

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

  10. Complex translocation in a boy with trichorhinophalangeal syndrome.

    PubMed Central

    Snchez, L M; Labarta, J D; De Negrotti, T C; Migliorini, A M

    1985-01-01

    We report a boy with a trichorhinophalangeal syndrome (TRP syndrome), severe mental retardation, and transient megacephaly, whose karyotype showed complex, apparently balanced, translocations with breakpoints in bands 3q13, 8p22, 8q13, 11p12, and 11q21. The fact that cases presenting with phenotypes corresponding to the TRP II syndrome and deletions of the long arm of chromosome 8 have been recently reported prompted us to report this case to help in the clarification of the possible relation between 8q chromosomal mutation and the aetiology of TRP syndromes. Images PMID:4045963

  11. 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.

  12. Inhibitors of Protein Translocation Across the ER Membrane.

    PubMed

    Kalies, Kai-Uwe; Rmisch, Karin

    2015-10-01

    Protein translocation into the endoplasmic reticulum (ER) constitutes the first step of protein secretion. ER protein import is essential in all eukaryotic cells and is particularly critical in fast-growing tumour cells. Thus, the process can serve as target both for potential cancer drugs and for bacterial virulence factors. Inhibitors of protein transport across the ER membrane range from broad-spectrum to highly substrate-specific and can interfere with virtually any stage of this multistep process, and even with transport of endocytosed antigens into the cytosol for cross-presentation. PMID:26122014

  13. Reciprocal translocation identified in Vigna angularis dominates the wild population in East Japan.

    PubMed

    Wang, Lixia; Kikuchi, Shinji; Muto, Chiaki; Naito, Ken; Isemura, Takehisa; Ishimoto, Masao; Cheng, Xuzhen; Kaga, Akito; Tomooka, Norihiko

    2015-07-01

    Using an F2 population derived from cultivated and wild azuki bean, we previously detected a reciprocal translocation and a seed size QTL near the translocation site. To test the hypothesis that the translocation in the cultivated variety contributed to the larger seed size, we performed further linkage analyses with several cross combinations between cultivated and wild azuki beans. In addition, we visually confirmed the translocation by cytogenetic approach using 25 wild and cultivated accessions. As a result, we found the translocation-type chromosomes in none of the cultivated accessions, but in a number of the wild accessions. Interestingly, all the wild accessions with the translocation were originally collected from East Japan, while all the accessions with normal chromosomes were from West Japan or the Sea of Japan-side region. Such biased geographical distribution could be explained by the glacial refugium hypothesis, and supported narrowing down the domestication origin of cultivated azuki bean. PMID:25796202

  14. Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling.

    PubMed

    Shindo, Yuki; Iwamoto, Kazunari; Mouri, Kazunari; Hibino, Kayo; Tomita, Masaru; Kosako, Hidetaka; Sako, Yasushi; Takahashi, Koichi

    2016-01-01

    The phosphorylation cascade in the extracellular signal-regulated kinase (ERK) pathway is a versatile reaction network motif that can potentially act as a switch, oscillator or memory. Nevertheless, there is accumulating evidence that the phosphorylation response is mostly linear to extracellular signals in mammalian cells. Here we find that subsequent nuclear translocation gives rise to a switch-like increase in nuclear ERK concentration in response to signal input. The switch-like response disappears in the presence of ERK inhibitor, suggesting the existence of autoregulatory mechanisms for ERK nuclear translocation involved in conversion from a graded to a switch-like response. In vitro reconstruction of ERK nuclear translocation indicates that ERK-mediated phosphorylation of nucleoporins regulates ERK translocation. A mathematical model and knockdown experiments suggest a contribution of nucleoporins to regulation of the ERK nuclear translocation response. Taken together, this study provides evidence that nuclear translocation with autoregulatory mechanisms acts as a switch in ERK signalling. PMID:26786866

  15. Trisomy 15 rescue with jumping translocation of distal 15q in Prader-Willi syndrome.

    PubMed Central

    Devriendt, K; Petit, P; Matthijs, G; Vermeesch, J R; Holvoet, M; De Muelenaere, A; Marynen, P; Cassiman, J J; Fryns, J P

    1997-01-01

    We report a patient with Prader-Willi syndrome (PWS) and mosaicism for a de novo jumping translocation of distal chromosome 15q, resulting in partial trisomy for 15q24-qter. A maternal uniparental heterodisomy for chromosome 15 was present in all cells, defining the molecular basis for the PWS in this patient. The translocated distal 15q fragment was of paternal origin and was present as a jumping translocation, involving three different translocation partners, chromosomes 14q, 4q, and 16p. The recipient chromosomes appeared cytogenetically intact and interstitial telomere DNA sequences were present at the breakpoint junctions. This strongly suggests that the initial event leading to the translocation of distal 15q was a non-reciprocal translocation, with fusion between the 15q24 break-point and the telomeres of the recipient chromosomes. These observations are best explained by a partial zygotic trisomy rescue and comprise a previously undescribed mechanism leading to partial trisomy. Images PMID:9152837

  16. Mechanisms of Sec61/SecY-mediated protein translocation across membranes.

    PubMed

    Park, Eunyong; Rapoport, Tom A

    2012-01-01

    The Sec61 or SecY channel, a universally conserved protein-conducting channel, translocates proteins across and integrates proteins into the eukaryotic endoplasmic reticulum (ER) membrane and the prokaryotic plasma membrane. Depending on channel-binding partners, polypeptides are moved by different mechanisms. In cotranslational translocation, the ribosome feeds the polypeptide chain directly into the channel. In posttranslational translocation, a ratcheting mechanism is used by the ER-lumenal chaperone BiP in eukaryotes, and a pushing mechanism is utilized by the SecA ATPase in bacteria. In prokaryotes, posttranslational translocation is facilitated through the function of the SecD/F protein. Recent structural and biochemical data show how the channel opens during translocation, translocates soluble proteins, releases hydrophobic segments of membrane proteins into the lipid phase, and maintains the barrier for small molecules. PMID:22224601

  17. Arrestin translocation is stoichiometric to rhodopsin isomerization and accelerated by phototransduction in Drosophila photoreceptors

    PubMed Central

    Satoh, Akiko K.; Xia, Hongai; Yan, Limin; Liu, Che-Hsiung; Hardie, Roger C.; Ready, Donald F.

    2010-01-01

    Upon illumination visual arrestin translocates from photoreceptor cell bodies to rhodopsin and membrane-rich photosensory compartments - vertebrate outer segments or invertebrate rhabdomeres - where it quenches activated rhodopsin. Both the mechanism and function of arrestin translocation are unresolved and controversial. In dark-adapted photoreceptors of the fruitfly Drosophila, confocal immunocytochemistry shows arrestin (Arr2) associated with distributed photoreceptor endomembranes. Immunocytochemistry and live imaging of GFP-tagged Arr2 demonstrate rapid reversible translocation to stimulated rhabdomeres in stoichiometric proportion to rhodopsin photoisomerization. Translocation is very rapid in normal photoreceptors (time constant <10 s), and can also be resolved in the time course of electroretinogram recordings. Genetic elimination of key phototransduction proteins, including phospholipase C (PLC), Gq and the light-sensitive Ca2+ permeable TRP channels, slows translocation by 10-100 fold. Our results indicate that Arr2 translocation in Drosophila photoreceptors is driven by diffusion, but profoundly accelerated by phototransduction and Ca2+ influx. PMID:20869596

  18. Induction of site-specific chromosomal translocations in embryonic stem cells by CRISPR/Cas9.

    PubMed

    Jiang, Junfeng; Zhang, Li; Zhou, Xingliang; Chen, Xi; Huang, Guanyi; Li, Fengsheng; Wang, Ruizhe; Wu, Nancy; Yan, Youzhen; Tong, Chang; Srivastava, Sankalp; Wang, Yue; Liu, Houqi; Ying, Qi-Long

    2016-01-01

    Chromosomal translocation is the most common form of chromosomal abnormality and is often associated with congenital genetic disorders, infertility, and cancers. The lack of cellular and animal models for chromosomal translocations, however, has hampered our ability to understand the underlying disease mechanisms and to develop new therapies. Here, we show that site-specific chromosomal translocations can be generated in mouse embryonic stem cells (mESCs) via CRISPR/Cas9. Mouse ESCs carrying translocated chromosomes can be isolated and expanded to establish stable cell lines. Furthermore, chimeric mice can be generated by injecting these mESCs into host blastocysts. The establishment of ESC-based cellular and animal models of chromosomal translocation by CRISPR/Cas9 provides a powerful platform for understanding the effect of chromosomal translocation and for the development of new therapeutic strategies. PMID:26898344

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    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.

  20. 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.

  1. Akt phosphorylation is essential for nuclear translocation and retention in NGF-stimulated PC12 cells

    SciTech Connect

    Truong Le Xuan Nguyen; Choi, Joung Woo; Lee, Sang Bae; Ye, Keqiang; Woo, Soo-Dong; Lee, Kyung-Hoon; Ahn, Jee-Yin . E-mail: jyahn@med.skku.ac.kr

    2006-10-20

    Nerve growth factor (NGF) elicits Akt translocation into the nucleus, where it phosphorylates nuclear targets. Here, we describe that Akt phosphorylation can promote the nuclear translocation of Akt and is necessary for its nuclear retention. Overexpression of Akt-K179A, T308A, S473A-mutant failed to show either nuclear translocation or nuclear Akt phosphorylation, whereas expression of wild-type counterpart elicited profound Akt phosphorylation and induced nuclear translocation under NGF stimulation. Employing the PI3K inhibitor and a variety of mutants PI3K, we showed that nuclear translocation of Akt was mediated by activation of PI3K, and Akt phosphorylation status in the nucleus required PI3K activity. Thus the activity of PI3K might contribute to the nuclear translocation of Akt, and that Akt phosphorylation is essential for its nuclear retention under NGF stimulation conditions.

  2. Induction of site-specific chromosomal translocations in embryonic stem cells by CRISPR/Cas9

    PubMed Central

    Jiang, Junfeng; Zhang, Li; Zhou, Xingliang; Chen, Xi; Huang, Guanyi; Li, Fengsheng; Wang, Ruizhe; Wu, Nancy; Yan, Youzhen; Tong, Chang; Srivastava, Sankalp; Wang, Yue; Liu, Houqi; Ying, Qi-Long

    2016-01-01

    Chromosomal translocation is the most common form of chromosomal abnormality and is often associated with congenital genetic disorders, infertility, and cancers. The lack of cellular and animal models for chromosomal translocations, however, has hampered our ability to understand the underlying disease mechanisms and to develop new therapies. Here, we show that site-specific chromosomal translocations can be generated in mouse embryonic stem cells (mESCs) via CRISPR/Cas9. Mouse ESCs carrying translocated chromosomes can be isolated and expanded to establish stable cell lines. Furthermore, chimeric mice can be generated by injecting these mESCs into host blastocysts. The establishment of ESC-based cellular and animal models of chromosomal translocation by CRISPR/Cas9 provides a powerful platform for understanding the effect of chromosomal translocation and for the development of new therapeutic strategies. PMID:26898344

  3. 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

  4. Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling

    PubMed Central

    Shindo, Yuki; Iwamoto, Kazunari; Mouri, Kazunari; Hibino, Kayo; Tomita, Masaru; Kosako, Hidetaka; Sako, Yasushi; Takahashi, Koichi

    2016-01-01

    The phosphorylation cascade in the extracellular signal-regulated kinase (ERK) pathway is a versatile reaction network motif that can potentially act as a switch, oscillator or memory. Nevertheless, there is accumulating evidence that the phosphorylation response is mostly linear to extracellular signals in mammalian cells. Here we find that subsequent nuclear translocation gives rise to a switch-like increase in nuclear ERK concentration in response to signal input. The switch-like response disappears in the presence of ERK inhibitor, suggesting the existence of autoregulatory mechanisms for ERK nuclear translocation involved in conversion from a graded to a switch-like response. In vitro reconstruction of ERK nuclear translocation indicates that ERK-mediated phosphorylation of nucleoporins regulates ERK translocation. A mathematical model and knockdown experiments suggest a contribution of nucleoporins to regulation of the ERK nuclear translocation response. Taken together, this study provides evidence that nuclear translocation with autoregulatory mechanisms acts as a switch in ERK signalling. PMID:26786866

  5. 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.

  6. 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.

  7. Can Characteristics of Reciprocal Translocations Predict the Chance of Transferable Embryos in PGD Cycles?

    PubMed

    Dul, Elsbeth; van Echten-Arends, Jannie; Groen, Henk; Kastrop, Peter; Wissen, Lucie Amory-van; Engelen, John; Land, Jolande; Coonen, Edith; van Ravenswaaij-Arts, Conny

    2014-01-01

    Translocation carriers have an increased risk of miscarriage or the birth of a child with congenital anomalies. Preimplantation genetic diagnosis (PGD) is performed in translocation carriers to select for balanced embryos and, thus, increase the chance of an ongoing pregnancy. However, a common experience is that reciprocal translocation carriers produce a high percentage of unbalanced embryos, which cannot be transferred. Therefore, the pregnancy rates in PGD in this patient group are low. In a cohort of 85 reciprocal translocation carriers undergoing PGD we have searched for cytogenetic characteristics of the translocations that can predict the percentage of balanced embryos. Using shape algorithms, the most likely segregation mode per translocation was determined. Shape algorithm, breakpoint location, and relative chromosome segment sizes proved not to be independent predictors of the percentage of balanced embryos. The ratio of the relative sizes of the translocated segments of both translocation chromosomes can give some insight into the chance of transferable embryos: Very asymmetrical translocations have a higher risk of unbalanced products (p = 0.048). Counseling of the couples on the pros and cons of all their reproductive options remains very important. PMID:26237378

  8. 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.

  9. 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 120160 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

  10. A G-Protein Subunit Translocation Embedded Network Motif Underlies GPCR Regulation of Calcium Oscillations

    PubMed Central

    Giri, Lopamudra; Patel, AnilkumarK.; Karunarathne, W.K.Ajith; Kalyanaraman, Vani; Venkatesh, K.V.; Gautam, N.

    2014-01-01

    G-protein ?? subunits translocate reversibly from the plasma membrane to internal membranes on receptor activation. Translocation rates differ depending on the ? subunit type. There is limited understanding of the role of the differential rates of G?? translocation in modulating signaling dynamics in a cell. Bifurcation analysis of the calcium oscillatory network structure predicts that the translocation rate of a signaling protein can regulate the damping of system oscillation. Here, we examined whether the G?? translocation rate regulates calcium oscillations induced by G-protein-coupled receptor activation. Oscillations in HeLa cells expressing ? subunit types with different translocation rates were imaged and quantitated. The results show that differential G?? translocation rates can underlie the diversity in damping characteristics of calcium oscillations among cells. Mathematical modeling shows that a translocation embedded motif regulates damping of G-protein-mediated calcium oscillations consistent with experimental data. The current study indicates that such a motif may act as a tuning mechanism to design oscillations with varying damping patterns by using intracellular translocation of a signaling component. PMID:24988358

  11. 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.

  12. Imaging cytosolic translocation of Mycobacteria with two-photon fluorescence resonance energy transfer microscopy.

    PubMed

    Acosta, Yassel; Zhang, Qi; Rahaman, Arifur; Ouellet, Hugues; Xiao, Chuan; Sun, Jianjun; Li, Chunqiang

    2014-11-01

    Transition from latency to active tuberculosis requires Mycobacterium tuberculosis (Mtb) to penetrate the phagosomal membrane and translocate to the cytosol of the host macrophage. Quantitative two-photon fluorescence resonance energy transfer (FRET) microscopy is developed to measure cytosolic translocation using Mycobacterium marinum (Mm) as a model organism for Mtb. Macrophages were infected with Mm or non-pathogenic Mycobacterium smegmatis (Ms) as a control, then loaded with a FRET substrate. Once translocation occurs, mycobacterium-bearing β-lactamase cleaves the substrate, resulting in decrease of FRET signal. Quantification of this FRET signal change revealed that Mm, but not Ms, is capable of translocating to the cytosol. PMID:25426325

  13. Imaging cytosolic translocation of Mycobacteria with two-photon fluorescence resonance energy transfer microscopy

    PubMed Central

    Acosta, Yassel; Zhang, Qi; Rahaman, Arifur; Ouellet, Hugues; Xiao, Chuan; Sun, Jianjun; Li, Chunqiang

    2014-01-01

    Transition from latency to active tuberculosis requires Mycobacterium tuberculosis (Mtb) to penetrate the phagosomal membrane and translocate to the cytosol of the host macrophage. Quantitative two-photon fluorescence resonance energy transfer (FRET) microscopy is developed to measure cytosolic translocation using Mycobacterium marinum (Mm) as a model organism for Mtb. Macrophages were infected with Mm or non-pathogenic Mycobacterium smegmatis (Ms) as a control, then loaded with a FRET substrate. Once translocation occurs, mycobacterium-bearing β-lactamase cleaves the substrate, resulting in decrease of FRET signal. Quantification of this FRET signal change revealed that Mm, but not Ms, is capable of translocating to the cytosol. PMID:25426325

  14. Return to the wild: Translocation as a tool in conservation of the desert tortoise (Gopherus agassizii)

    USGS Publications Warehouse

    Field, K.J.; Tracy, C.R.; Medica, P.A.; Marlow, R.W.; Corn, P.S.

    2007-01-01

    Translocation could be used as a tool in conservation of the threatened Mojave Desert Tortoise (Gopherus agassizii) by moving individuals from harm's way and into areas where they could contribute to conservation of the species. Numerous factors may affect the success of translocations, including the conditions experienced by tortoises in holding facilities while awaiting translocation. The tortoises available for our translocation study had been provided supplemental water during their years spent in a captive holding facility, potentially inducing carelessness in water conservation. In addition to generally investigating the efficacy of translocation, we compared the effects of continuing with the effects of ceasing the holding facility's water supplementation regimen. After exposure to one of the two water regimens, all tortoises were given the opportunity to hydrate immediately prior to release. We examined behavior, body mass, carapace length, movement, and mortality of tortoises for two activity seasons following release to the wild. Water supplementation was correlated with high rates of carapace growth and distant movements by males after release. Lengthy movements following translocation may be problematic for conservation planning, but this should be evaluated in light of the goals and circumstances of each translocation project. Although the mortality rate was 21.4% in 1997, data suggest that drought conditions at the site rather than the translocation itself negatively affected the tortoises. None of the tortoises died during their second season at the site. Our results indicate that translocation should be considered a useful tool in conservation of the Desert Tortoise.

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

  17. 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.

  18. Direct observation of hexokinase translocation in stimulated macrophages.

    PubMed Central

    Pedley, K C; Jones, G E; Magnani, M; Rist, R J; Naftalin, R J

    1993-01-01

    1. Fluorescence imaging of antibodies was used to show that phorbol 12-myristate 13-acetate (PMA) induces a 4-fold increase in the amount of hexokinase relative to the control in the cortical shell of rat peritoneal macrophage cytosol adjacent to the plasma membrane, and a corresponding depletion in the amount of hexokinase in the central core of the cytosol. However, there was no significant PMA-dependent change in the distribution of glucose-6-phosphate dehydrogenase. 2. Cytochalasin D, an inhibitor of actin microfilament polymerization, prevented the PMA-induced hexokinase translocation and also reduced the PMA-dependent increases in 2-deoxy-D-glucose transport and glucose-dependent PMA-stimulated superoxide production. 3. PMA caused a contraction of the width of the cortical F-actin zone. Cytochalasin D caused some dispersal of F-actin within the cell, increasing the density of F-actin within the central cytosolic core and causing aggregation of the F-actin within the cortex. These data are consistent with the view that PMA induces attachment of hexokinase to microfilaments within the cortical zone adjacent to the cell membrane of macrophages, and cytochalasin D prevents this attachment. This is the first direct demonstration of the translocation of hexokinase to the plasma membrane in activated cells, and supports the view that enhanced hexokinase activity in the cortical region of the cytosol is an important early component of the macrophage activation process. Images Figure 1 Figure 2 Figure 4 Figure 9 PMID:8484732

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

    PubMed

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

    2014-08-26

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

  20. 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.

  1. DNA translocation through single-layer boron nitride nanopores.

    PubMed

    Gu, Zonglin; Zhang, Yuanzhao; Luan, Binquan; Zhou, Ruhong

    2016-01-21

    Ultra-thin nanopores have become promising biological sensors because of their outstanding signal-to-noise ratio and spatial resolution. Here, we show that boron nitride (BN), which is a new two-dimensional (2D) material similar to graphene, could be utilized for making a nanopore with an atomic thickness. Using an all-atom molecular dynamics simulation, we investigated the dynamics of DNA translocation through the BN nanopore. The results of our simulations demonstrated that it is possible to detect different double-stranded DNA (dsDNA) sequences from the recording of ionic currents through the pore during the DNA translocation. Surprisingly, opposite to results for a graphene nanopore, we found the calculated blockage current for poly(A-T)40 in a BN nanopore to be less than that for poly(G-C)40. Also in contrast with the case of graphene nanopores, dsDNA models moved smoothly and in an unimpeded manner through the BN nanopores in the simulations, suggesting a potential advantage for using BN nanopores to design stall-free sequencing devices. BN nanopores, which display several properties (such as being hydrophilic and non-metallic) that are superior to those of graphene, are thus expected to find applications in the next generation of high-speed and low-cost biological sensors. PMID:26537824

  2. Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta.

    PubMed

    Meier, R; Alessi, D R; Cron, P; Andjelković, M; Hemmings, B A

    1997-11-28

    Protein kinase B (PKB) is a member of the second messenger-dependent family of serine/threonine kinases that has been implicated in signaling pathways downstream of growth factor receptor tyrosine kinases and phosphatidylinositol 3-kinase. Here we report the characterization of the human beta-isoform of PKB (PKBbeta). PKBbeta is ubiquitously expressed in a number of human tissues, with mRNA and protein levels elevated in heart, liver, skeletal muscle, and kidney. After transfection into HEK-293 or COS-1 cells, PKBbeta is activated 2- to 12-fold by mitogens and survival factors. Activation was due to phosphorylation on Thr-309 and Ser-474, which correspond to Thr-308 and Ser-473 implicated in the regulation of PKBalpha. Both phosphorylation and activation were prevented by the phosphatidylinositol 3-kinase inhibitor wortmannin. Moreover, membrane-targeted PKBbeta was constitutively activated when overexpressed in HEK-293 cells. Although the specific activity of PKBbeta was lower than that of PKBalpha toward Crosstide as a substrate (23 nmol/min/mg compared with 178 nmol/min/mg for PKBalpha), both enzymes showed similar substrate specificities. Using confocal microscopy, we show that activation of PKBbeta results in its nuclear translocation within 20 to 30 min after stimulation. These observations provide evidence that PKBbeta undergoes nuclear translocation upon mitogenic activation and support a role for PKB in signaling from receptor tyrosine kinases to the nucleus through phosphatidylinositol 3-kinase. PMID:9374542

  3. Microscopic Mechanism of Antibiotics Translocation through a Porin.

    PubMed

    Ceccarelli, Matteo; Danelon, Christophe; Laio, Alessandro; Parrinello, Michele

    2004-07-01

    OmpF from the outer membrane of Escherichia coli is a general porin considered to be the main pathway for beta-lactam antibiotics. The availability of a high-resolution crystal structure of OmpF and new experimental techniques at the single-molecule level have opened the way to the investigation of the microscopic mechanisms that allow the passage of antibiotics through bacterial pores. We applied molecular dynamics simulations to investigate the translocation process of ampicillin (Amp) through OmpF. Using a recent algorithm capable of accelerating molecular dynamics simulations we have been able to obtain a reaction path for the translocation of Amp through OmpF. The mechanism of passage depends both on the internal degrees of freedom of Amp and on interactions of Amp with OmpF. Understanding this mechanism would help us design more efficient antibiotics and shed light on nature's way of devising channels able to enhance the transport of molecules through membranes. PMID:15240444

  4. Bringing genetic background into focus.

    PubMed

    Chow, Clement Y

    2016-02-01

    Researchers should embrace differences in genetic background to build richer disease models that more accurately reflect the level of variation in the human population, posits Clement Chow. PMID:26659016

  5. Familial Wolf's syndrome with a hidden 4p deletion by translocation of an 8p segment. Unbalanced inheritance from a maternal translocation (4;8)(p15.3;p22). Case report, review and risk estimates.

    PubMed

    Stengel-Rutkowski, S; Warkotsch, A; Schimanek, P; Stene, J

    1984-06-01

    This is the case report of a patient with Wolf's syndrome having a monosomy 4pter----p15.3 and an additional trisomy 8pter----p22, derived from a maternal balanced translocation t(4;8)(p15.3;p22) after 2:2 disjunction and adjacent-1 segregation. The patient's phenotype is presumably slightly modified by the trisomic 8p segment. Literature analyses indicate that phenotypic "hybrids" with traits of monosomy 4p and of other autosomal segment trisomies exist. The dermatoglyphics of the patient were not highly characteristic for Wolf's syndrome. Also the dermatoglyphics of the balanced translocation carriers were unspecific and did not reflect the carrier status. Pedigree analyses of 46 reported families with reciprocal translocations involving the short arm of chromosome 4 show a high risk (20.5% +/- 4.6%) for unbalanced offspring (trisomy or monosomy 4p) after 2:2 disjunction and adjacent-1 segregation, if the breakpoint in the recipient chromosome is terminal and the resulting imbalance concerns the 4p segment only. It is considerably lower (4.5% +/- 2.5%) if the breakpoint in the recipient chromosome is subterminal, as in the reported case, and the resulting imbalance concerns other chromosome segments additionally to the 4p segment. In both instances, the risk decreases with increasing segment length. The risk for unidentified abortions, stillbirths or neonatal deaths is also high in these families (about 40%). The frequency of progeny with balanced compared to progeny with normal karyotype corresponds to the expected 50% for alternate segregation. PMID:6539659

  6. Low Background Counting at LBNL

    NASA Astrophysics Data System (ADS)

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

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory 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 cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to 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, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3? anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  7. Low Background Counting at LBNL

    SciTech Connect

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

    2015-03-24

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory 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 cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to 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, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3π anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  8. Low Background Counting at LBNL

    DOE PAGESBeta

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

    2015-03-24

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory 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 cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to 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)more » or common cosmogenic/anthropogenic products, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3π anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.« less

  9. 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

  10. Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

    PubMed

    Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Kppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trmper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

    2014-04-01

    Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics. PMID:24179151

  11. Low Background Micromegas in CAST

    NASA Astrophysics Data System (ADS)

    Garza, J. G.; Aune, S.; Aznar, F.; Calvet, D.; Castel, J. F.; Christensen, F. E.; Dafni, T.; Davenport, M.; Decker, T.; Ferrer-Ribas, E.; Galán, J.; García, J. A.; Giomataris, I.; Hill, R. M.; Iguaz, F. J.; Irastorza, I. G.; Jakobsen, A. C.; Jourde, D.; Mirallas, H.; Ortega, I.; Papaevangelou, T.; Pivovaroff, M. J.; Ruz, J.; Tomás, A.; Vafeiadis, T.; Vogel, J. K.

    2015-11-01

    Solar axions could be converted into x-rays inside the strong magnetic field of an axion helioscope, triggering the detection of this elusive particle. Low background x-ray detectors are an essential component for the sensitivity of these searches. We report on the latest developments of the Micromegas detectors for the CERN Axion Solar Telescope (CAST), including technological pathfinder activities for the future International Axion Observatory (IAXO). The use of low background techniques and the application of discrimination algorithms based on the high granularity of the readout have led to background levels below 10-6 counts/keV/cm2/s, more than a factor 100 lower than the first generation of Micromegas detectors. The best levels achieved at the Canfranc Underground Laboratory (LSC) are as low as 10-7 counts/keV/cm2/s, showing good prospects for the application of this technology in IAXO. The current background model, based on underground and surface measurements, is presented, as well as the strategies to further reduce the background level. Finally, we will describe the R&D paths to achieve sub-keV energy thresholds, which could broaden the physics case of axion helioscopes.

  12. Illuminating the Background: Topics in Cosmic Microwave Background Polarization Research

    NASA Astrophysics Data System (ADS)

    Miller, Nathan J.

    The cosmic microwave background provides a wealth of information about the origin and history of the universe. The statistics of the anisotropy and the polarization of the cosmic microwave background, among other things, can tell us about the distribution of matter, the redshift of reionization, and the nature of the primordial uctuations. From the lensing of cosmic microwave background due to intervening matter, we can extract information about neutrinos and the equation of state of dark energy. A measurement of the large angular scale B-mode polarization has been called the "smoking gun" of in ation, a theory that describes a possible early rapid expansion of the universe. The focus of current experiments is to measure this B-mode polarization, while several experiments, such as POLARBEAR, are also looking to measure the lensing of the cosmic microwave background. This dissertation will discuss several different topics in cosmic microwave background polarization research. I will make predictions for future experiments and I will also show analysis for two current experiments, POLARBEAR and BICEP. I will show how beam systematics affect the measurement of cosmological parameters and how well we must limit these systematics in order to get unbiased constraints on cosmological parameters for future experiments. I will discuss a novel way of using the temperature-polarization cross correlation to constrain the amount of inflationary gravitational waves. Through Markov Chain Monte Carlo methods, I will determine how well future experiments will be able to constrain the neutrino masses and their degeneracy parameters. I will show results from current data analysis and calibration being done on the Cedar Flat deployment for the POLARBEAR experiment which is currently being constructed in the Atacama desert in Chile. Finally, I will analyze the claim of detection of cosmological birefringence in the BICEP data and show that there is reason to believe it is due to systematic effects in the data.

  13. 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.

  14. Background simulations and shielding calculations

    SciTech Connect

    Kudryavtsev, Vitaly A.

    2011-04-27

    Key improvements in the sensitivity of the underground particle astrophysics experiments can only be achieved if the radiation causing background events in detectors is well understood and proper measures are taken to suppress it. The background radiation arising from radioactivity and cosmic-ray muons is discussed here together with the methods of its suppression. Different shielding designs are considered to attenuate gamma-rays and neutrons coming from radioactivity in rock and lab walls. Purity of materials used in detector construction is analysed and the background event rates due to the presence of radioactive isotopes in detector components are discussed. Event rates in detectors caused by muon-induced neutrons with and without active veto systems are presented leading to the requirements for the depth of an underground laboratory and the efficiency of the veto system.

  15. Stochastic background search correlating ALLEGRO with LIGO engineering data

    NASA Astrophysics Data System (ADS)

    Whelan, John T.; Daw, Edward; Heng, Ik Siong; McHugh, Martin P.; Lazzarini, Albert

    2003-09-01

    We describe the role of correlation measurements between the LIGO interferometer in Livingston, LA, and the ALLEGRO resonant bar detector in Baton Rouge, LA, in searches for a stochastic background of gravitational waves. Such measurements provide a valuable complement to correlations between interferometers at the two LIGO sites, since they are sensitive in a different, higher, frequency band. Additionally, the variable orientation of the ALLEGRO detector provides a means to distinguish gravitational wave correlations from correlated environmental noise. We describe the analysis underway to set a limit on the strength of a stochastic background at frequencies near 900 Hz using ALLEGRO data and data from LIGO's E7 Engineering Run.

  16. Generative electronic background music system

    SciTech Connect

    Mazurowski, Lukasz

    2015-03-10

    In this short paper-extended abstract the new approach to generation of electronic background music has been presented. The Generative Electronic Background Music System (GEBMS) has been located between other related approaches within the musical algorithm positioning framework proposed by Woller et al. The music composition process is performed by a number of mini-models parameterized by further described properties. The mini-models generate fragments of musical patterns used in output composition. Musical pattern and output generation are controlled by container for the mini-models - a host-model. General mechanism has been presented including the example of the synthesized output compositions.

  17. Exotic branes and nongeometric backgrounds.

    PubMed

    de Boer, Jan; Shigemori, Masaki

    2010-06-25

    When string or M theory is compactified to lower dimensions, the U-duality symmetry predicts so-called exotic branes whose higher-dimensional origin cannot be explained by the standard string or M-theory branes. We argue that exotic branes can be understood in higher dimensions as nongeometric backgrounds or Ufolds, and that they are important for the physics of systems which originally contain no exotic charges, since the supertube effect generically produces such exotic charges. We discuss the implications of exotic backgrounds for black hole microstate (non-)geometries. PMID:20867363

  18. Detector Background at Muon Colliders

    SciTech Connect

    Mokhov, N.V.; Striganov, S.I.; /Fermilab

    2011-09-01

    Physics goals of a Muon Collider (MC) can only be reached with appropriate design of the ring, interaction region (IR), high-field superconducting magnets, machine-detector interface (MDI) and detector. Results of the most recent realistic simulation studies are presented for a 1.5-TeV MC. It is shown that appropriately designed IR and MDI with sophisticated shielding in the detector have a potential to substantially suppress the background rates in the MC detector. The main characteristics of backgrounds are studied.

  19. 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... chromosomes during cell division. (2) Reciprocal translocations are chromosomal translocations resulting from... chemical, it is enough to sample one germ cell stage, either mature sperm or spermatids (for...

  20. 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... chromosomes during cell division. (2) Reciprocal translocations are chromosomal translocations resulting from... chemical, it is enough to sample one germ cell stage, either mature sperm or spermatids (for...

  1. 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... chromosomes during cell division. (2) Reciprocal translocations are chromosomal translocations resulting from... chemical, it is enough to sample one germ cell stage, either mature sperm or spermatids (for...

  2. Translocation of Shiga-toxin producting cells of Escherichia coli in chemically-injected beef subprimals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Relatively little information is available regarding the translocation of Escherichia coli O157:H7 (ECOH) and non-O157:H7 verocytotoxigenic E. coli (STEC) into beef subprimals following chemical tenderization. Purpose: Quantify translocation of ECOH or STEC from the surface into the i...

  3. Cytotoxic Necrotizing Factor-Y Boosts Yersinia Effector Translocation by Activating Rac Protein*

    PubMed Central

    Wolters, Manuel; Boyle, Erin C.; Lardong, Kerstin; Trlzsch, Konrad; Steffen, Anika; Rottner, Klemens; Ruckdeschel, Klaus; Aepfelbacher, Martin

    2013-01-01

    Pathogenic Yersinia spp. translocate the effectors YopT, YopE, and YopO/YpkA into target cells to inactivate Rho family GTP-binding proteins and block immune responses. Some Yersinia spp. also secrete the Rho protein activator cytotoxic necrotizing factor-Y (CNF-Y), but it has been unclear how the bacteria may benefit from Rho protein activation. We show here that CNF-Y increases Yop translocation in Yersinia enterocolitica-infected cells up to 5-fold. CNF-Y strongly activated RhoA and also delayed in time Rac1 and Cdc42, but when individually expressed, constitutively active mutants of Rac1, but not of RhoA, increased Yop translocation. Consistently, knock-out or knockdown of Rac1 but not of RhoA, -B, or -C inhibited Yersinia effector translocation in CNF-Y-treated and control cells. Activation or knockdown of Cdc42 also affected Yop translocation but much less efficiently than Rac. The increase in Yop translocation induced by CNF-Y was essentially independent of the presence of YopE, YopT, or YopO in the infecting Yersinia strain, indicating that none of the Yops reported to inhibit translocation could reverse the CNF-Y effect. In summary, the CNF-Y activity of Yersinia strongly enhances Yop translocation through activation of Rac. PMID:23803609

  4. Charge requirements for proton gradient-driven translocation of anthrax toxin.

    PubMed

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

    2011-07-01

    Anthrax lethal toxin is used as a model system to study protein translocation. The toxin is composed of a translocase channel, called protective antigen (PA), and an enzyme, called lethal factor (LF). A proton gradient (?pH) can drive LF unfolding and translocation through PA channels; however, the mechanism of ?pH-mediated force generation, substrate unfolding, and establishment of directionality are poorly understood. One recent hypothesis suggests that the ?pH may act through changes in the protonation state of residues in the substrate. Here we report the charge requirements of LF's amino-terminal binding domain (LF(N)) using planar lipid bilayer electrophysiology. We found that acidic residues are required in LF(N) to utilize a proton gradient for translocation. Constructs lacking negative charges in the unstructured presequence of LF(N) translocate independently of the ?pH driving force. Acidic residues markedly increase the rate of ?pH-driven translocation, and the presequence is optimized in its natural acidic residue content for efficient ?pH-driven unfolding and translocation. We discuss a ?pH-driven charge state Brownian ratchet mechanism for translocation, where glutamic and aspartic acid residues in the substrate are the "molecular teeth" of the ratchet. Our Brownian ratchet model includes a mechanism for unfolding and a novel role for positive charges, which we propose chaperone negative charges through the PA channel during ?pH translocation. PMID:21507946

  5. Vesicle transmembrane potential is required for translocation to the cytosol of externally added FGF-1

    PubMed Central

    Ma?ecki, J?drzej; Wi?d?ocha, Antoni; Wesche, Jrgen; Olsnes, Sjur

    2002-01-01

    Externally added fibroblast growth factor-1 (FGF-1) is capable of crossing cellular membranes to reach the cytosol and the nucleus in a number of cell types. We have monitored the translocation of the growth factor by two methods: phosphorylation of FGF-1, and prenylation of an FGF-1 mutant that contains a C-terminal prenylation signal. Inhibition of endosomal acidification by ammonium chloride or monensin did not block the translocation of FGF-1, whereas bafilomycinA1, a specific inhibitor of vacuolar proton pumps, blocked translocation completely. A combination of ionophores expected to dissipate the vesicular membrane potential (valinomycin plus monensin) also fully inhibited the translocation. The inhibition of translocation by bafilomycinA1 was overcome in the presence of monensin or nigericin, while ouabain blocked translocation under these conditions. The data indicate that translocation of FGF-1 to cytosol occurs from the lumen of intracellular vesicles possessing vacuolar proton pumps, and that a vesicular membrane potential is required. Apparently, activation of vesicular Na+/K+-ATPase by monensin or nigericin generates a membrane potential that can support translocation when the proton pump is blocked. PMID:12198150

  6. Chromosome aberrations and spermatogenic disorders in mice with Robertsonian translocation (11; 13)

    PubMed Central

    Zhuang, Xinjie; Huang, Jin; Jin, Xiaohu; Yu, Yang; Li, Junsheng; Qiao, Jie; Liu, Ping

    2014-01-01

    Objective: To determine the diagnostic features of Robertsonian (Rob) translocation (11; 13) in mice and the mechanisms underlying the effect on spermatogenesis and reproductive decline. Methods: A Rob translocation (11; 13) mouse model was established by cross-breeding, and confirmed by chromosome analysis. Chromosome aberrations and translocation patterns were identified in mice with Rob translocation (11; 13) by fluorescence in situ hybridization (FISH). Spermatogenic disorders were investigated at different stages of spermatogenesis. Immunofluorescent analysis was performed on sections of testis and epididymis specimens during spermatogenic meiosis. The weight of the testes and reproductive decline were recorded. Results: The crossed Rob translocation (11; 13) mouse has 39 chromosomes, including a fusion chromosome (included chromosomes 11 and 13) using dual color FISH. There was no difference in the distribution pattern of SYCP3 and ?H2AX in spermatocytes between Rob translocation and wild-type mice; however, round haploid spermatids presented characteristic morphologic changes of apoptosis and the number of haploid spermatids was decreased. Furthermore, the immature germ cells were released into the epididymis and the number of mature sperm was reduced. Conclusions: Chromosome aberrations and spermatogenic disorders may result from apoptosis of round haploid spermatids and a reduced number of mature sperm in Rob translocation (11; 13) mice. Abnormal sperm and reduced number of sperm may be one of the main reasons for reproductive decline and male infertility in Rob translocation (11; 13) mice. PMID:25550810

  7. A genomic comparison of homoeologous recombinants of the Lr19 (T4) translocation in wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Lr19 translocation continues to provide broad resistance to Puccinia triticina in many parts of the world and can be particularly useful when employed in resistance gene pyramids. Previously, an associated gene for yellow endosperm pigmentation precluded the use of the translocation in many coun...

  8. 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...

  9. 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.

  10. Digital simulation of hybrid loop operation in RFI backgrounds.

    NASA Technical Reports Server (NTRS)

    Ziemer, R. E.; Nelson, D. R.

    1972-01-01

    A digital computer model for Monte-Carlo simulation of an imperfect second-order hybrid phase-locked loop (PLL) operating in radio-frequency interference (RFI) and Gaussian noise backgrounds has been developed. Characterization of hybrid loop performance in terms of cycle slipping statistics and phase error variance, through computer simulation, indicates that the hybrid loop has desirable performance characteristics in RFI backgrounds over the conventional PLL or the costas loop.

  11. 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.

  12. 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 1.7 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

  13. Uniparental disomy in Robertsonian translocations: strategies for uniparental disomy testing

    PubMed Central

    2014-01-01

    Robertsonian translocations (ROBs) are whole arm rearrangements involving the acrocentric chromosomes 13-15 and 21-22 and carriers are at increased risk for aneuploidy and thus uniparental disomy (UPD). Chromosomes 14 and 15 are imprinted with expression of genes dependent on the parental origin of the chromosome. Correction of a trisomic or monosomic conceptus for chromosomes 14 or 15 would lead to one of the established UPD 14mat/pat or UPD 15 (Prader-Willi/Angelman) syndromes (PWS/AS). In view of this, prenatal UPD testing should be considered for balanced carriers of a ROB, fetuses with a familial or de novo balanced ROB that contains chromosome 14 or 15 or with a normal karyotype when a parent is a carrier of a balanced ROB with a 14 or 15. Individuals with congenital anomalies and an abnormal phenotype and carry a ROB involving the two imprinted chromosomes should also be UPD tested.

  14. Heterologous protein production using the twin arginine translocation pathway

    DOEpatents

    Pohlschroder, Mechtild; Kissinger, Jessica C; Rose, R. Wesley; Brueser, Thomas; Dilks, Kieran

    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.

  15. Farnesylation of Retinal Transducin Underlies Its Translocation during Light Adaptation

    PubMed Central

    Kassai, Hidetoshi; Aiba, Atsu; Nakao, Kazuki; Nakamura, Kenji; Katsuki, Motoya; Xiong, Wei-Hong; Yau, King-Wai; Imai, Hiroo; Shichida, Yoshinori; Satomi, Yoshinori; Takao, Toshifumi; Okano, Toshiyuki; Fukada, Yoshitaka

    2010-01-01

    Summary G proteins are posttranslationally modified by isoprenylation: either farnesylation or geranylgeranylation. The ? subunit of retinal transducin (T?/T??) is selectively farnesylated, and the farnesylation is required for light signaling mediated by transducin in rod cells. However, whether and how this selective isoprenylation regulates cellular functions remain poorly understood. Here we report that knockin mice expressing geranylgeranylated T? showed normal rod responses to dim flashes under dark-adapted conditions but exhibited impaired properties in light adaptation. Of note, geranylgeranylation of T? suppressed light-induced transition of T?? from membrane to cytosol, and also attenuated its light-dependent translocation from the outer segment to the inner region, an event contributing to retinal light adaptation. These results indicate that, while the farnesylation of transducin is interchangeable with the geranylgeranylation in terms of the light signaling, the selective farnesylation is important for visual sensitivity regulation by providing sufficient but not excessive membrane anchoring of T??. PMID:16102536

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

    PubMed

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

    2015-06-15

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

  17. Logic Gate Operation by DNA Translocation through Biological Nanopores.

    PubMed

    Yasuga, Hiroki; Kawano, Ryuji; Takinoue, Masahiro; Tsuji, Yutaro; Osaki, Toshihisa; Kamiya, Koki; Miki, Norihisa; Takeuchi, Shoji

    2016-01-01

    Logical operations using biological molecules, such as DNA computing or programmable diagnosis using DNA, have recently received attention. Challenges remain with respect to the development of such systems, including label-free output detection and the rapidity of operation. Here, we propose integration of biological nanopores with DNA molecules for development of a logical operating system. We configured outputs "1" and "0" as single-stranded DNA (ssDNA) that is or is not translocated through a nanopore; unlabeled DNA was detected electrically. A negative-AND (NAND) operation was successfully conducted within approximately 10 min, which is rapid compared with previous studies using unlabeled DNA. In addition, this operation was executed in a four-droplet network. DNA molecules and associated information were transferred among droplets via biological nanopores. This system would facilitate linking of molecules and electronic interfaces. Thus, it could be applied to molecular robotics, genetic engineering, and even medical diagnosis and treatment. PMID:26890568

  18. Logic Gate Operation by DNA Translocation through Biological Nanopores

    PubMed Central

    Takinoue, Masahiro; Tsuji, Yutaro; Osaki, Toshihisa; Kamiya, Koki; Miki, Norihisa; Takeuchi, Shoji

    2016-01-01

    Logical operations using biological molecules, such as DNA computing or programmable diagnosis using DNA, have recently received attention. Challenges remain with respect to the development of such systems, including label-free output detection and the rapidity of operation. Here, we propose integration of biological nanopores with DNA molecules for development of a logical operating system. We configured outputs “1” and “0” as single-stranded DNA (ssDNA) that is or is not translocated through a nanopore; unlabeled DNA was detected electrically. A negative-AND (NAND) operation was successfully conducted within approximately 10 min, which is rapid compared with previous studies using unlabeled DNA. In addition, this operation was executed in a four-droplet network. DNA molecules and associated information were transferred among droplets via biological nanopores. This system would facilitate linking of molecules and electronic interfaces. Thus, it could be applied to molecular robotics, genetic engineering, and even medical diagnosis and treatment. PMID:26890568

  19. Periodic forces trigger knot untying during translocation of knotted proteins

    PubMed Central

    Szymczak, Piotr

    2016-01-01

    Proteins need to be unfolded when translocated through the pores in mitochondrial and other cellular membranes. Knotted proteins, however, might get stuck during this process, jamming the pore, since the diameter of the pore is smaller than the size of maximally tightened knot. The jamming probability dramatically increases as the magnitude of the driving force exceeds a critical value, Fc. In this numerical study, we show that for deep knots Fc lies below the force range over which molecular import motors operate, which suggest that in these cases the knots will tighten and block the pores. Next, we show how such topological traps might be prevented by using a pulling protocol of a repetitive, on-off character. Such a repetitive pulling is biologically relevant, since the mitochondrial import motor, like other molecular motors transforms chemical energy into directed motions via nucleotide-hydrolysis-mediated conformational changes, which are cyclic in character. PMID:26996878

  20. Nomadic genetic elements contribute to oncogenic translocations: Implications in carcinogenesis.

    PubMed

    Dhivya, Sridaran; Premkumar, Kumpati

    2016-02-01

    Chromosomal translocations as molecular signatures have been reported in various malignancies but, the mechanism behind which is largely unknown. Swapping of chromosomal fragments occurs by induction of double strand breaks (DSBs), most of which were initially assumed de novo. However, decoding of human genome proved that transposable elements (TE) might have profound influence on genome integrity. TEs are highly conserved mobile genetic elements that generate DSBs, subsequently resulting in large chromosomal rearrangements. Previously TE insertions were thought to be harmless, but recently gains attention due to the origin of spectrum of post-insertional genomic alterations and subsequent transcriptional alterations leading to development of deleterious effects mainly carcinogenesis. Though the existing knowledge on the cancer-associated TE dynamics is very primitive, exploration of underlying mechanism promises better therapeutic strategies for cancer. Thus, this review focuses on the prevalence of TE in the genome, associated genomic instability upon transposition activation and impact on tumorigenesis. PMID:26548742

  1. Effect of acid-adaptation on Listeria monocytogenes survival and translocation in a murine intragastric infection model.

    PubMed

    Saklani-Jusforgues, H; Fontan, E; Goossens, P L

    2000-12-01

    Acid tolerance response mechanisms can greatly influence Listeria monocytogenes survival in low pH foods. In the present paper, the effect of acid-adaptation together with control of gastric pH level on L. monocytogenes survival and translocation was analyzed after intragastric inoculation in the BALB/c mouse model. Our results showed that acid-adaptation led to an increase in resistance to the first barrier constituted by the low gastric pH and that inoculation at alkaline pH had a synergistic effect. It resulted in a higher live bacterial load reaching the next intestinal compartments and was correlated with increased translocation rates to the mesenteric lymph nodes, both at the frequency and quantitative levels. Our results in this murine model suggest that acid-adaptation of L. monocytogenes in low pH foods, together with control of gastric pH level through dietary practices, or use of inhibitors of gastric acid secretion, may be potential aggravating risk factors to food-borne listeriosis. PMID:11094295

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

    PubMed

    Musatov, Andrej; Robinson, Neal C

    2014-10-01

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

  3. 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.

  4. 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

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

    PubMed Central

    Belardinelli, Juan Manuel; Larrouy-Maumus, Grald; 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. The Translocation of Nuclear Molecules During Inflammation and Cell Death

    PubMed Central

    2014-01-01

    Abstract Significance: Inflammation is a complex biological process that represents the body's response to infection and/or injury. Endogenous molecules that induce inflammation are called death- or damage-associated molecular patterns (DAMPs). Among cellular constituents with DAMP activity, nuclear molecules can stimulate pattern recognition receptors, including toll-like receptors (TLRs). Current research is elucidating the translocation of nuclear molecules during cell death and identifying novel anti-inflammatory approaches to block their DAMP activity. Recent Advances: High mobility group box protein 1 (HMGB1), a non-histone nuclear protein, can translocate from cells during immune cell activation and cell death. Depending on redox state, HMGB1 can interact with TLR4 although it can bind to molecules such as cytokines to trigger other receptors. DNA and histones, which are bound together in the nucleus, also have important immunological activity. For DNA, DAMP activity may vary depending upon the binding to molecules that affect cell entry and intracellular location. The role of nuclear molecules in disease has been established in animal models using antibodies as inhibitors. Critical Issues: Key issues about the DAMP activity of nuclear molecules relate to (i) the impact on function of biochemical modifications such as redox state and post-translational modification, and (ii) the composition and properties of complexes that nuclear molecules may form with other blood components to affect immunological activity. Future Directions: With the recognition of the immunological activity of the products of dead cells, future studies will define the diversity and properties of nuclear molecules in the extracellular space and develop strategies to block their activity during inflammation. Antioxid. Redox Signal. 20, 11171125. PMID:23373769

  7. Chlordane uptake and its translocation in food crops.

    PubMed

    Mattina, M J; Iannucci-Berger, W; Dykas, L

    2000-05-01

    Chlordane is a member of the persistent organic pollutants (POPs), a group of chemicals characterized by extremely long residence in the environment after application. Technical chlordane, composed of a large number of components, is a synthetic organochlorine substance that was used primarily as an insecticide. Uptake by root crops of persistent soil residues of chlordane was noted early in the chronology of the material. The present report is the first comprehensive study of the uptake of weathered soil residues of chlordane and its translocation throughout the tissues of food crops under both greenhouse and field conditions. The data show that for all 12 crops chlordane is not limited to root tissue but is translocated from the root to some of the aerial tissues. Chlordane accumulation in edible aerial tissue appears to be dependent on plant physiology. As expected, chlordane was detected in the edible root tissue of the three root crops examined, carrots, beets, and potatoes. In the remaining crops chlordane was detected in the edible aerial tissue of spinach, lettuce, dandelion, and zucchini, whereas it was not detected in edible aerial tissue of tomatoes, peppers, and corn; trace amounts of chlordane were detected in the edible aerial tissue of bush beans and eggplant. Under the conditions of the field trial the data indicate that for weathered chlordane residues, the soil-to-plant uptake route dominates over the air-to-plant uptake route. This is the case even when the soil concentration of the recalcitrant, weathered residues, for which volatilization is expected to be minimal, is as high as it would be directly following application. Greenhouse trials confirm this observation for zucchini, a member of the Cucurbitaceae family, which bioaccumulates weathered chlordane very efficiently in its edible fruits. PMID:10820114

  8. Controlling protein translocation through nanopores with bio-inspired fluid walls

    NASA Astrophysics Data System (ADS)

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

    2011-04-01

    Synthetic nanopores have been used to study individual biomolecules in high throughput, but their performance as sensors does not match that of biological ion channels. Challenges include control of nanopore diameters and surface chemistry, modification of the translocation times of single-molecule analytes through nanopores, and prevention of non-specific interactions with pore walls. Here, inspired by the olfactory sensilla of insect antennae, we show that coating nanopores with a fluid lipid bilayer tailors their surface chemistry and allows fine-tuning and dynamic variation of pore diameters in subnanometre increments. Incorporation of mobile ligands in the lipid bilayer conferred specificity and slowed the translocation of targeted proteins sufficiently to time-resolve translocation events of individual proteins. Lipid coatings also prevented pores from clogging, eliminated non-specific binding and enabled the translocation of amyloid-beta (Aβ) oligomers and fibrils. Through combined analysis of their translocation time, volume, charge, shape and ligand affinity, different proteins were identified.

  9. Time-dependent Behavior of a Mathematical Model for Munch Translocation

    PubMed Central

    Ferrier, Jack M.; Christy, A. Lawrence

    1975-01-01

    The time evolution of a Munch pressure-flow translocation system is calculated using a numerical computer method. Results are obtained for the time course of the system variables following application of a large resistance in the translocation path, intended to simulate a cold block. The resistance factor required to produce translocation inhibition indicates that even moderate inhibition is primarily due to sieve plate pore block-age, rather than to the viscosity increase. The calculated time for recovery from cold inhibition and the shape of the translocation recovery curve agree with experimental results. The time for translocation recovery and the level of velocity recovery depend on the rate of sucrose unloading in the sink; on the sucrose concentration in the sieve tube; on the position, length, and resistance factor of the cold block; and on the hydraulic conductivities. PMID:16659112

  10. A mobile aviary to enhance translocation success of red-cockaded woodpeckers.

    SciTech Connect

    Edwards, John W.; Mari, Yvett; Smathers, Webb

    2004-12-31

    Edwards, John W., Yvette Mari, and Webb Smathers. 2004. A mobile aviary to enhance 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 335-336. Abstract: Because translocations of male red-cockaded woodpeckers have been less successful (Costa and Kennedy 1994) and because translocations of females are dependent on the availability of established males, a technique to increase the success of translocations would be an important contribution to conservation efforts. Researchers from the U.S. Forest Service Southern Research Station hypothesized that by maintaining red-cockaded woodpeckers in an aviary prior to release the birds would develop an affinity for, and possibly imprint (Scott and Carpenter 1987) on their surroundings, and that this would increase their likelyhood of remaining in the cluster upon their release.

  11. Cardiac contraction-induced GLUT4 translocation requires dual signaling input.

    PubMed

    Luiken, Joost J F P; Glatz, Jan F C; Neumann, Dietbert

    2015-08-01

    Contraction-induced translocation of glucose transporter type-4 (GLUT4) to the sarcolemma is essential to stimulate cardiac glucose uptake during increased energy demand. As such, this process is a target for therapeutic strategies aiming at increasing glucose uptake in insulin-resistant and/or diabetic hearts. AMP-activated protein kinase (AMPK) and its upstream kinases form part of a signaling axis essential for contraction-induced GLUT4 translocation. Recently, activation of protein kinase-D1 (PKD1) was also shown to be as obligatory for contraction-induced GLUT4 translocation in cardiac muscle. However, contraction-induced PKD1 activation in this context occurs independently from AMPK signaling, suggesting that contraction-induced GLUT4 translocation requires the input of two separate signaling pathways. Necessity for dual input would more tightly couple GLUT4 translocation to stimuli that are inherent to cardiac contraction. PMID:26138758

  12. Determination of Molecular Weights in Polyelectrolyte Mixtures Using Polymer Translocation through a Protein Nanopore

    PubMed Central

    2015-01-01

    We introduce a single molecular analysis technique for the evaluation of molecular weight distributions of polyelectrolyte solutions by measuring translocation times of sodium polystyrenesulfonate (NaPSS) chains in a mixture passing through an ?-hemolysin protein nanopore. The ionic current through an ?-hemolysin nanopore is partially blocked transiently when the pore is occupied by a polymer chain with an average residence time proportional to the molecular weight of the polymer chain. We have measured the translocation times for an equimolar mixture of four different molecular weight NaPSS standards and observed distinct translocation time distribution peaks, each of which corresponding to the different components in the mixture. Size exclusion chromatography analyses were performed on the equimolar and equiweight NaPSS mixtures of the same components and compared with the translocation time measurements. The experimental results demonstrate that measuring translocation times can be a competitive technique for estimating the broad molecular weight distributions of polyelectrolytes. PMID:25243100

  13. The amino terminus of opsin translocates "posttranslationally" as efficiently as cotranslationally.

    PubMed

    Kanner, Elliott M; Klein, Irene K; Friedlander, Martin; Simon, Sanford M

    2002-06-18

    Opsin, a member of the G-protein-coupled receptor family, is a polytopic membrane protein that does not encode a cleaved amino-terminal signal sequence. The amino terminus of opsin precedes the first known targeting information, suggesting that it translocates across the endoplasmic reticulum (ER) membrane after synthesis, uncoupled from translation. However, translocation across the mammalian ER is believed to be coupled to protein synthesis. In this study we show that opsin, within a range of nascent peptide lengths, targets and translocates equally efficiently co- and posttranslationally. Longer nascent opsin peptides have a lower efficiency of cotranslational translocation but an even lower efficiency of posttranslational translocation. We also show that SRP is required for both co- and posttranslational targeting. PMID:12056902

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

    PubMed

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

    2015-07-01

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

  15. 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

  16. Quantitative Analysis of Protein Translocations by Microfluidic Total Internal Reflection Fluorescence Flow Cytometry

    PubMed Central

    Wang, Jun; Fei, Bei; Geahlen, Robert L.

    2010-01-01

    Protein translocation, or the change in a proteins location between different subcellular compartments, is a critical process by which intracellular proteins carry out their cellular functions. Aberrant translocation events contribute to various diseases ranging from metabolic disorders to cancer. In this study, we demonstrate the use of a newly developed single-cell tool, microfluidic total internal reflection fluorescence flow cytometry (TIRF-FC), for detecting both cytosol to plasma membrane and cytosol to nucleus translocations using the tyrosine kinase Syk and the transcription factor NF-?B as models. This technique detects fluorescent molecules at the plasma membrane and in the membrane-proximal cytosol in single cells. We were able to record quantitatively changes in the fluorescence density in the evanescent field associated with these translocation processes for large cell populations with single cell resolution. We envision that TIRF-FC will provide a new approach to explore the molecular biology and clinical relevance of protein translocations. PMID:20820633

  17. Ambient background particulate composition, outdoor natural background: interferents/clutter

    NASA Astrophysics Data System (ADS)

    Paterno, Dorothea

    2012-06-01

    It has proven a very difficult task to discriminate an actual BW threat from the natural occurring ambient particulate aerosol, which includes a significant fraction of particles consisting of mixed mineral and biological material. The interferent particles [clutter] (bio and non bio) concentration varies widely both by location, weather and season and diurnally. Naturally occurring background particulates are composed of fungal and bacterial spores both fragments and components, plant fragments and debris, animal fragments and debris, all of which may be associated with inert dust or combustion material. Some or all of which could also be considered to be an interferent to a biological warfare detector and cause these biodector systems to cause False Alarms by non specific BW bio detectors. I will share analysis of current long term background data sets.

  18. 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.

  19. Teaching about Natural Background Radiation

    ERIC Educational Resources Information Center

    Al-Azmi, Darwish; Karunakara, N.; Mustapha, Amidu O.

    2013-01-01

    Ambient gamma dose rates in air were measured at different locations (indoors and outdoors) to demonstrate the ubiquitous nature of natural background radiation in the environment and to show that levels vary from one location to another, depending on the underlying geology. The effect of a lead shield on a gamma radiation field was also…

  20. Teaching about Natural Background Radiation

    ERIC Educational Resources Information Center

    Al-Azmi, Darwish; Karunakara, N.; Mustapha, Amidu O.

    2013-01-01

    Ambient gamma dose rates in air were measured at different locations (indoors and outdoors) to demonstrate the ubiquitous nature of natural background radiation in the environment and to show that levels vary from one location to another, depending on the underlying geology. The effect of a lead shield on a gamma radiation field was also

  1. Low background techniques in CANDLES

    NASA Astrophysics Data System (ADS)

    Nakajima, K.; Iida, T.; Kishimoto, T.; Matsuoka, K.; Nomachi, M.; Umehara, S.; Chan, W. M.; Kakubata, H.; Li, X.; Maeda, T.; Ohata, T.; Temuge, B.; Tetsuno, K.; Trang, V. T. T.; Uehara, T.; Yoshida, S.; Morishita, K.; Ogawa, I.; Sakamoto, K.; Tamagawa, Y.; Yoshizawa, M.; Fushimi, K.; Hazama, R.; Naktani, N.; Suzuki, K.

    2015-08-01

    CANDLES is a double beta decay experiment using 48Ca in CaF2 crystals. The measurement is being performed with prototype detector (CANDLES III) for high sensitive measurement in the future. Recent status of detector improvements and background reduction techniques are described in this paper.

  2. A Little Background Music, Please.

    ERIC Educational Resources Information Center

    Giles, Martha Mead

    1991-01-01

    Background music could be used to provide a pleasant beginning for the school day, to help keep students quiet and relaxed in the school cafeteria at lunchtime, and to provide a midafternoon lift for bored and tired children. The most effective music pleases children without overly exciting them through jarring rhythms and loud dynamics. (nine…

  3. Teacher Pensions: A Background Paper

    ERIC Educational Resources Information Center

    Hansen, Janet S.

    2008-01-01

    Pensions are an important but comparatively unexamined component of human resource policies in education. In an increasingly competitive world where employees are more mobile than ever, pension policies that were designed in the last century may be out of step with the needs of both individuals and schools. This background paper aims to foster…

  4. Mathematical background of Parrondo's paradox

    NASA Astrophysics Data System (ADS)

    Behrends, Ehrhard

    2004-05-01

    Parrondo's paradox states that there are losing gambling games which, when being combined stochastically or in a suitable deterministic way, give rise to winning games. Here we investigate the probabilistic background. We show how the properties of the equilibrium distributions of the Markov chains under consideration give rise to the paradoxical behavior, and we provide methods how to find the best a priori strategies.

  5. Cultural Backgrounds and Textual Appropriation

    ERIC Educational Resources Information Center

    Shi, Ling

    2006-01-01

    This study examines interviews with 46 undergraduates to explore if participants with differing language and cultural backgrounds view plagiarism or textual appropriation primarily as a) a language problem because of a lack of words of one's own, or b) a cultural challenge as a result of either some first language (L1) cultural training to

  6. Integrated Global Background Monitoring Network

    SciTech Connect

    Wiersma, G.B.; Franklin, J.F.; Kohler, A.; Croze, H.; Boelcke, C.

    1986-12-01

    One of the more significant problems when trying to determine what impact is having on global cycles is not knowing what ''natural'' levels should be for both abiotic (gases, trace elements) and biotic (ecosystem functions) processes. The authors believe that a well designed, coordinated network of baseline stations in remote areas around the world can provide a data base will allow best current estimates to be made of biotic and abiotic baseline conditions. These baseline conditions will then help us make better comparisons with more impacted areas, and thus help us more fully understand the impact man is having on his world. This paper examines the history of background pollution monitoring at the international level, describes current activities in the field of ''integrated'' background monitoring, and proposes criteria for the development of a global network of baseline stations to coordinate background monitoring for the presence, accumulation and behavior of pollutants in remote ecosystems. In this paper, this network is called the Integrated Global Background Monitoring Network.

  7. Simulation of HEAO 3 background

    NASA Astrophysics Data System (ADS)

    Graham, B. L.; Phlips, B. F.; Kroeger, R. A.; Kurfess, J. D.

    1997-05-01

    A Monte Carlo technique for modeling background in space-based gamma-ray telescopes has been developed. The major background components included in this modeling technique are the diffuse cosmic gamma-ray flux, the Earth's atmospheric flux, and decay of nuclei produced by spallation of cosmic rays, trapped protons and their secondaries, the decay of nuclei produced by neutron capture, and the de-excitation of excited states produced by inelastic scattering of neutrons. The method for calculating the nuclear activation and decay component of the background combines the low Earth orbit proton and neutron spectra, the spallation cross sections from Alice91 [2], nuclear decay data from the National Nuclear Data Center's (NNDC) Evaluated Nuclear Structure Data File (ENSDF) database [3], and three-dimensional gamma-ray and beta transport with Electron Gamma-ray Shower version 4 (EGS4) [4] using MORSE combinatorial geometry. This Monte Carlo code handles the following decay types: electron capture, ?-, ?+, meta-stable isotope and short lived intermediate states, and isotopes that have branchings to both ?- and ?+. Actual background from the HEAO 3 space instrument are used to validate the code.

  8. Regional Background Fine Particulate Matter

    EPA Science Inventory

    A modeling system composed of the global model GEOS-Chem providing hourly lateral boundary conditions to the regional model CMAQ was used to calculate the policy relevant background level of fine particulate: matter. Simulations were performed for the full year of 2004 over the d...

  9. 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

  10. 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

  11. Detection of the AML translocation (8;21) by two-color fluorescent in situ hybridization

    SciTech Connect

    Sacchi, N.; Magnani, I.; Kearney, L.

    1994-09-01

    In the translocation (8;21)(q22;q22) associated with acute myelogenous leukemia (AML), part of the long arm of chromosome 8 is reciprocally translocated onto chromosome 21. At the molecular level the translocation results in the fusion of the 5{prime} region of the AML1 gene on chromosome 21 and almost the entire CDR gene (also ETO or MTG8) on chromosome 8. To detection the translocation at the single cell level, we used two probes, a cosmid clone containing the first five exons of AML1 and a P1 clone containing the entire CDR gene. Hybridization of the two probes to the distal and proximal sides of the translocation breakpoint was expected to highlight the derivative 8q-chromosome in an interphase cell. To demonstrate the ability to identify the translocation in interphase cells using two-color FISH, these two probes were hybridized simultaneously to a cell line containing the 8;21 translocation, Kasumi-1. Each probe was detected with a different color so that their relationship in the sample could be determined within the same interphase cell. Simultaneous hybridization of the CDR and AML1 probes to interphase Kasumi-1 cells resulted in one orange and one green hybridization signal randomly located in the cell, from the hybridization to the normal 8 and 21 chromosomes, and one orange-green pair of signals from the close hybridization of the two probes to the fusion gene on the derivative 8q-chromosome, indicating the translocation. The translocation was identified by an abnormal pairing of the two differently colored signals in the same interphase cell. This technique allows for the detection of the translocation in all cells, not just those arrested in metaphase, and also permits the analysis of a small number of cells. Therefore, useful information can still be obtained from samples not suited for RT-PCR analysis and conventional cytogenetic techniques.

  12. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. Anisotropy in nonprimordial cosmic background radiation

    SciTech Connect

    Hogan, C.J.

    1982-05-15

    In the standard cosmological model, large-scale anisotropy in microwave background temperature is generally attributed to primordial fluctuations. However, anisotropy may also be produced by radiation emitted inhomogeneously at relatively recent epochs (z< or approx. =200) and thermalized by grains or molecules. This hypothesis predicts a white noise angular distribution of deltaT/T on large scales, with amplitude determined by the inhomogeneity of the sources of radiation, and a smooth distribution below an angle theta/sub 1/roughly-equal3/sup 0/--15/sup 0/ where scattering becomes important. The angular scale of the smoothing may increase with frequency if dust or molecular opacity dominates over Thomson scattering. Nonstandard big bangs or theories of galaxy formation which have smooth initial conditions may be tested by current observations of anisotropy at roughly-equal6/sup 0/ and roughly-equal90/sup 0/.

  16. Electromagnetic PIC modeling with a background gas

    SciTech Connect

    Verboncoeur, J.P.; Cooperberg, D.

    1997-02-01

    Modeling the interaction of relativistic electromagnetic plasmas with a background gas is described. The timescales range over many orders of magnitude, from the electromagnetic Courant condition ({approximately}10{sup {minus}12}sec) to electron-neutral collision times ({approximately}10{sup {minus}7}sec) to ion transit times ({approximately}10{sup {minus}5}sec). For this work, the traditional Monte Carlo algorithm [1] is described for relativistic electrons. Subcycling is employed to improve efficiency, and smoothing is employed to reduce particle noise. Applications include plasma-focused electron guns, gas-filled microwave tubes, surface wave discharges driven at microwave frequencies, and electron-cyclotron resonance discharges. The method is implemented in the OOPIC code [2]. {copyright} {ital 1997 American Institute of Physics.}

  17. 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.

  18. Diversity of hepatocellular carcinoma clones bearing hematopoietic malignancies-related chromosomal translocation.

    PubMed

    Parent, Romain; Plissonnier, Marie-Laure; Bancel, Brigitte; Liao, Wan-Li; Rumin, Sylvie; Asaad, Remal; Till, Marianne; Sanlaville, Damien; Zoulim, Fabien; Trpo, Christian; Marion, Marie-Jeanne

    2014-04-01

    Interpatient heterogeneity of hepatocellular carcinoma has been in-depth addressed. Intrapatient heterogeneity is less known. Four clones were freshly isolated from an Edmondson grade I HCV-associated hepatocellular carcinoma. Biochemical approaches, functional assays and cytogenetics were used. Albumin inducibility was uncoupled from canonical cytokeratin profiles, suggesting pathological combinations of hepatospecific and biliary markers. Poor differentiation and TGF?'s proproliferative effect on all clones were observed. TGF?, Interferon ? and doxorubicin sensitivity levels were found highly heterogeneous. Progenitor and stem cells markers OV6 and EpCAM were mutually exclusively expressed. All clones were CD44+, while none expressed CD90, CD133, or CD117. Three clones displayed a liver progenitor OV6+ phenotype, and were susceptible to hepatocytic differentiation, among which one fibroblastoid clone displayed intrahepatic parenchymal engraftment capability. A fourth clone, the less motile, displayed a cancer stem cell EpCAM+ phenotype, was essentially ?-catenin negative, and was as expected devoid of hepatocytic differentiation capability, yet the most sensitive to doxorubicin treatment. Cytogenetics evidenced in all clones a t(12;22)(p11;q11) translocation found in several myelodysplastic syndromes. All clones, that probably derive from EpCAM+ tumor cells, display aberrant E-cadherin cytosolic localization. Because of their diverse pathophysiolocal features, these freshly isolated, low population doubling-defined, HCC clones may provide novel opportunities to tackle HCC heterogeneity in a single patient background for therapy improvement purposes, especially regarding recently developed targeted strategies. PMID:24453043

  19. WFC3/UVIS Sky Backgrounds

    NASA Astrophysics Data System (ADS)

    Baggett, Sylvia; Anderson, Jay

    2012-06-01

    This report summarizes the on-orbit background levels present in WFC3/UVIS full-frame images. The results are based on nearly all standard readout images taken since the installation of WFC3 on HST in May 2009, with a relatively small number of exclusions e.g. images with obvious anomalous backgrounds (such as extended targets filling the field of view) or those taken with the quad filters (different bandpass in each amp). Comparisons are provided to estimates from the Exposure Time Calculator (ETC). We anticipate these results to be helpful in fine-tuning the level of post-flash required to achieve the optimum balance of charge transfter efficiency (CTE) loss mitigation versus noise penalty. Observers considering the use of post-flash should refer to the White Paper (MacKenty & Smith 2012) on the CTE WWW page (http://www.stsci.edu/hst/wfc3/ins_performance/CTE/).

  20. Background stratospheric aerosol reference model

    NASA Technical Reports Server (NTRS)

    Mccormick, M. P.; Wang, P.

    1989-01-01

    In this analysis, a reference background stratospheric aerosol optical model is developed based on the nearly global SAGE 1 satellite observations in the non-volcanic period from March 1979 to February 1980. Zonally averaged profiles of the 1.0 micron aerosol extinction for the tropics and the mid- and high-altitudes for both hemispheres are obtained and presented in graphical and tabulated form for the different seasons. In addition, analytic expressions for these seasonal global zonal means, as well as the yearly global mean, are determined according to a third order polynomial fit to the vertical profile data set. This proposed background stratospheric aerosol model can be useful in modeling studies of stratospheric aerosols and for simulations of atmospheric radiative transfer and radiance calculations in atmospheric remote sensing.

  1. Quantum chromodynamics in background fields

    NASA Astrophysics Data System (ADS)

    Huang, Tao; Huang, Zheng

    1989-02-01

    We try to build a framework for quantum chromodynamics in background fields. The nonvanishing vacuum condensates are described by the classical fields, while the corresponding quantum fields are quantized in the Furry representation and the physical states are defined in the physical QCD vacuum. The complete quark and gluon propagators are discussed in this framework and running condensate parameters are introduced by the renormalization requirement. A modified Callan-Symanzik equation is derived by taking account of the nonperturbative corrections.

  2. Backgrounds and characteristics of arsonists.

    PubMed

    Labree, Wim; Nijman, Henk; van Marle, Hjalmar; Rassin, Eric

    2010-01-01

    The aim of this study was to gain more insight in the backgrounds and characteristics of arsonists. For this, the psychiatric, psychological, personal, and criminal backgrounds of all arsonists (n=25), sentenced to forced treatment in the maximum security forensic hospital "De Kijvelanden", were compared to the characteristics of a control group of patients (n=50), incarcerated at the same institution for other severe crimes. Apart from DSM-IV Axis I and Axis II disorders, family backgrounds, level of education, treatment history, intelligence (WAIS scores), and PCL-R scores were included in the comparisons. Furthermore, the apparent motives for the arson offences were explored. It was found that arsonists had more often received psychiatric treatment, prior to committing their index offence, and had a history of severe alcohol abuse more often in comparison to the controls. The arsonists turned out to be less likely to suffer from a major psychotic disorder. Both groups did not differ significantly on the other variables, among which the PCL-R total scores and factor scores. Exploratory analyses however, did suggest that arsonists may differentiate from non-arsonists on three items of the PCL-R, namely impulsivity (higher scores), superficial charm (lower scores), and juvenile delinquency (lower scores). Although the number of arsonists with a major psychotic disorder was relatively low (28%), delusional thinking of some form was judged to play a role in causing arson crimes in about half of the cases (52%). PMID:20434774

  3. The isotropic radio background revisited

    SciTech Connect

    Fornengo, Nicolao; Regis, Marco; Lineros, Roberto A.

    2014-04-01

    We present an extensive analysis on the determination of the isotropic radio background. We consider six different radio maps, ranging from 22 MHz to 2.3 GHz and covering a large fraction of the sky. The large scale emission is modeled as a linear combination of an isotropic component plus the Galactic synchrotron radiation and thermal bremsstrahlung. Point-like and extended sources are either masked or accounted for by means of a template. We find a robust estimate of the isotropic radio background, with limited scatter among different Galactic models. The level of the isotropic background lies significantly above the contribution obtained by integrating the number counts of observed extragalactic sources. Since the isotropic component dominates at high latitudes, thus making the profile of the total emission flat, a Galactic origin for such excess appears unlikely. We conclude that, unless a systematic offset is present in the maps, and provided that our current understanding of the Galactic synchrotron emission is reasonable, extragalactic sources well below the current experimental threshold seem to account for the majority of the brightness of the extragalactic radio sky.

  4. Bayesian Analysis of the Cosmic Microwave Background

    NASA Technical Reports Server (NTRS)

    Jewell, Jeffrey

    2007-01-01

    There is a wealth of cosmological information encoded in the spatial power spectrum of temperature anisotropies of the cosmic microwave background! Experiments designed to map the microwave sky are returning a flood of data (time streams of instrument response as a beam is swept over the sky) at several different frequencies (from 30 to 900 GHz), all with different resolutions and noise properties. The resulting analysis challenge is to estimate, and quantify our uncertainty in, the spatial power spectrum of the cosmic microwave background given the complexities of "missing data", foreground emission, and complicated instrumental noise. Bayesian formulation of this problem allows consistent treatment of many complexities including complicated instrumental noise and foregrounds, and can be numerically implemented with Gibbs sampling. Gibbs sampling has now been validated as an efficient, statistically exact, and practically useful method for low-resolution (as demonstrated on WMAP 1 and 3 year temperature and polarization data). Continuing development for Planck - the goal is to exploit the unique capabilities of Gibbs sampling to directly propagate uncertainties in both foreground and instrument models to total uncertainty in cosmological parameters.

  5. DNA sequencing using fluorescence background electroblotting membrane

    DOEpatents

    Caldwell, K.D.; Chu, T.J.; Pitt, W.G.

    1992-05-12

    A method for the multiplex sequencing on DNA is disclosed which comprises the electroblotting or specific base terminated DNA fragments, which have been resolved by gel electrophoresis, onto the surface of a neutral non-aromatic polymeric microporous membrane exhibiting low background fluorescence which has been surface modified to contain amino groups. Polypropylene membranes are preferably and the introduction of amino groups is accomplished by subjecting the membrane to radio or microwave frequency plasma discharge in the presence of an aminating agent, preferably ammonia. The membrane, containing physically adsorbed DNA fragments on its surface after the electroblotting, is then treated with crosslinking means such as UV radiation or a glutaraldehyde spray to chemically bind the DNA fragments to the membrane through amino groups contained on the surface. The DNA fragments chemically bound to the membrane are subjected to hybridization probing with a tagged probe specific to the sequence of the DNA fragments. The tagging may be by either fluorophores or radioisotopes. The tagged probes hybridized to the target DNA fragments are detected and read by laser induced fluorescence detection or autoradiograms. The use of aminated low fluorescent background membranes allows the use of fluorescent detection and reading even when the available amount of DNA to be sequenced is small. The DNA bound to the membranes may be reprobed numerous times. No Drawings

  6. DNA sequencing using fluorescence background electroblotting membrane

    DOEpatents

    Caldwell, Karin D.; Chu, Tun-Jen; Pitt, William G.

    1992-01-01

    A method for the multiplex sequencing on DNA is disclosed which comprises the electroblotting or specific base terminated DNA fragments, which have been resolved by gel electrophoresis, onto the surface of a neutral non-aromatic polymeric microporous membrane exhibiting low background fluorescence which has been surface modified to contain amino groups. Polypropylene membranes are preferably and the introduction of amino groups is accomplished by subjecting the membrane to radio or microwave frequency plasma discharge in the presence of an aminating agent, preferably ammonia. The membrane, containing physically adsorbed DNA fragments on its surface after the electroblotting, is then treated with crosslinking means such as UV radiation or a glutaraldehyde spray to chemically bind the DNA fragments to the membrane through said smino groups contained on the surface thereof. The DNA fragments chemically bound to the membrane are subjected to hybridization probing with a tagged probe specific to the sequence of the DNA fragments. The tagging may be by either fluorophores or radioisotopes. The tagged probes hybridized to said target DNA fragments are detected and read by laser induced fluorescence detection or autoradiograms. The use of aminated low fluorescent background membranes allows the use of fluorescent detection and reading even when the available amount of DNA to be sequenced is small. The DNA bound to the membrances may be reprobed numerous times.

  7. 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 ~20nm 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 1.4nm, 18nm and 80nm 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 24hours. 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 1.4nm 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 (30ng) and 0.00004 (0.1ng) of 1.4nm and 18nm AuNP, respectively, were detected, but no 80nm AuNP (<0.000004 (<0.1ng)). These data show that no AuNP entered the fetuses from amniotic fluids within 24hours 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

  8. Using Correlated Photons to Suppress Background Noise

    NASA Technical Reports Server (NTRS)

    Jackson, Deborah; Hockney, George; Dowling, Jonathan

    2003-01-01

    A proposed method of suppressing the effect of background noise in an optical communication system would exploit the transmission and reception of correlated photons at the receiver. The method would not afford any advantage in a system in which performance is limited by shot noise. However, if the performance of the system is limited by background noise (e.g., sunlight in the case of a free-space optical communication system or incoherently scattered in-band photons in the case of a fiber-optic communication system), then the proposed method could offer an advantage: the proposed method would make it possible to achieve a signal-to-noise ratio (S/N) significantly greater than that of an otherwise equivalent background- noise-limited optical communication system based on the classical transmission and reception of uncorrelated photons. The figure schematically depicts a classical optical-communication system and a system according to the proposed method. In the classical system, a modulated laser beam is transmitted along an optical path to a receiver, the optics of which include a narrow-band-pass filter that suppresses some of the background noise. A photodetector in the receiver detects the laser-beam and background photons, most or all of which are uncorrelated. In the proposed system, correlated photons would be generated at the transmitter by making a modulated laser beam pass through a nonlinear parametric down-conversion crystal. The sum of frequencies of the correlated photons in each pair would equal the frequency of the incident photon from which they were generated. As in the classical system, the correlated photons would travel along an optical path to a receiver, where they would be band-pass filtered and detected. Unlike in the classical system, the photodetector in the receiver in this system would be one that intrinsically favors the detection of pairs of correlated photons over the detection of uncorrelated photons. Even though there would be no way of knowing the precise location and time of creation of a given pair of correlated signal photons in the nonlinear down-conversion crystal, the fact that the photons are necessarily created at the same time and place makes it possible to utilize conventional geometrical imaging optics to reunite the photons in coincidence in the receiving photodetector. Because most or all of the signal photons would be correlated while most or all of the noise photons would be uncorrelated, the S/N would be correspondingly enhanced in the photodetector output. An additional advantage to be gained by use of a correlated-photon detector is that it could be capable of recovering the signal even in the presence of background light so bright that a classical uncorrelated-photon detector would be saturated. A blocked-impurity-band (BIB) photodetector that preferentially detects pairs of correlated photons over uncorrelated ones and that operates at a quantum efficiency of 88 percent is commercially available. This detector must be cooled to the temperature of liquid helium to obtain the desired low-noise performance. It is planned to use this detector in a proof-of-principle demonstration. In addition, it may be possible to develop GaN-based photodetectors that could offer the desired low-noise performance at room temperature.

  9. Extensive nonhomologous meiotic synapsis between normal chromosome axes of an rcp(3;6)(p14;q21) translocation in a hairless Mexican boar.

    PubMed

    Villagmez, D A F; Ayala-Valdovinos, M A; Galindo-Garca, J; Snchez-Chipres, D R; Mora-Galindo, J; Taylor-Preciado, J J

    2008-01-01

    Due to its low fertility, expressed as small litter size, a Mexican hairless boar was subjected to cytogenetic investigation. Analysis of G-banded mitotic chromosomes revealed a reciprocal chromosome translocation, rcp(3;6) (p14;q21). Synaptonemal complex analysis showed a regular pairing behavior of the translocation chromosome axes, always resulting in a quadrivalent configuration. However, due to extensive nonhomologous pairing between the axes of nonderivative chromosomes 3 and 6, the quadrivalent mostly had an asymmetrical cross-shaped morphology. The nonhomologous pairing occurred not only at mid and late pachytene, but also at the earliest stage of pachytene. It seems that early pachytene heterosynapsis is a common phenomenon in the pairing behavior of pig reciprocal translocations. Therefore, heterosynapsis may reduce apoptosis of germ cells due to partial absence of homologous synapsis during the pairing phase of meiosis. The frequency of spermatocytes showing quadrivalent configurations with unpaired axial segments apparently did not affect germ cell progression in the boar, since fairly normal testicular histology was noticed. PMID:18467833

  10. 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.

  11. 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.

  12. Probing the Influence of Coil Configuration on DNA Translocation Dynamics in Solid-State Nanopores

    NASA Astrophysics Data System (ADS)

    Liu, Xu; Dipetrillo, Karri; Chan, Jason; Eggers, Lucas; McMullen, Angus; Stein, Derek

    2013-03-01

    We studied electrophoretic DNA translocations of asymmetric nanopore-cavity structures designed to control the initial configurations of molecules. The structures comprise a thin SiN membrane with a nanopore that leads into a 400 nm-high cavity, which is in turn covered by a 400-nm thick SiN membrane with a circular opening whose diameter ranged from 150 nm to 1.5 ?m. These structures maintain a gap between the nanopore and a DNA coil translocating from above, but not one translocating from below. The viscous drag on the DNA segment extending from the coil to the nanopore significantly slowed translocations from above. The mean translocation times for those events were 2.5 times longer than for tranlocations from below when the upper opening of the cavity was only 200 nm wide. The translocation times converged as the opening was increased to micrometer diameters. This last result can be explained by the DNA coil, whose radius of gyration is ~600 nm, squeezing into the upper opening by increasing amounts. Our experimental results compare favourably with a quantitative model of DNA translocation speeds, similar to models by Lu et al. and by Grosberg, which accounts for the initial configuration of the DNA coil. This work was supported by the National Science Foundation under Grant No. CBET0846505.

  13. 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.

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

    PubMed

    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)PNASA60027-842410.1073/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 (???/N^{1.5}?^{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. PMID:26465502

  15. 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

  16. Quantitative Analysis of the Nanopore Translocation Dynamics of Simple Structured Polynucleotides

    PubMed Central

    Schink, Severin; Renner, Stephan; Alim, Karen; Arnaut, Vera; Simmel, Friedrich C.; Gerland, Ulrich

    2012-01-01

    Nanopore translocation experiments are increasingly applied to probe the secondary structures of RNA and DNA molecules. Here, we report two vital steps toward establishing nanopore translocation as a tool for the systematic and quantitative analysis of polynucleotide folding: 1), Using α-hemolysin pores and a diverse set of different DNA hairpins, we demonstrate that backward nanopore force spectroscopy is particularly well suited for quantitative analysis. In contrast to forward translocation from the vestibule side of the pore, backward translocation times do not appear to be significantly affected by pore-DNA interactions. 2), We develop and verify experimentally a versatile mesoscopic theoretical framework for the quantitative analysis of translocation experiments with structured polynucleotides. The underlying model is based on sequence-dependent free energy landscapes constructed using the known thermodynamic parameters for polynucleotide basepairing. This approach limits the adjustable parameters to a small set of sequence-independent parameters. After parameter calibration, the theoretical model predicts the translocation dynamics of new sequences. These predictions can be leveraged to generate a baseline expectation even for more complicated structures where the assumptions underlying the one-dimensional free energy landscape may no longer be satisfied. Taken together, backward translocation through α-hemolysin pores combined with mesoscopic theoretical modeling is a promising approach for label-free single-molecule analysis of DNA and RNA folding. PMID:22225801

  17. 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

  18. Calcium-dependent translocation of S100A11 requires tubulin filaments.

    PubMed

    Davey, G E; Murmann, P; Hoechli, M; Tanaka, T; Heizmann, C W

    2000-12-20

    Protein translocation between different subcellular compartments might play a significant role in various signal transduction pathways. The S100 family is comprised of the multifunctional, small, acidic proteins, some of which translocate in the form of vesicle-like structures upon increase in intracellular Ca(2+) levels. Previously, cells were fixed before and after calcium activation in order to examine the possible relocation of S100 proteins. In this study, we were able to track the real-time translocation. We compared the localization of endogenous S100A11 to that of the S100A11-green fluorescent protein. The application of thapsigargin, an agent increasing intracellular Ca(2+) levels, resulted in the relocation of the S100A11. In contrast, addition of EGTA, which specifically binds Ca(2+), either inhibited the ongoing process of translocation or prevented its induction. Since translocation was not affected by treatment with brefeldin A, it appears that S100A11 relocates in an endoplasmic reticulum-Golgi-independent pathway. Furthermore, the depolymerization of actin filaments by amlexanox did not affect the capacity of S100A11 to translocate. However, the time course treatment with demecolcine, which depolymerizes tubulin filaments, resulted in cease of translocation, suggesting that the tubulin network is required for this process. PMID:11108965

  19. 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.

  20. 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.

  1. Confirmation of CHD7 as a cause of CHARGE association identified by mapping a balanced chromosome translocation in affected monozygotic twins

    PubMed Central

    Johnson, D; Morrison, N; Grant, L; Turner, T; Fantes, J; Connor, J M; Murday, V

    2006-01-01

    Background CHARGE syndrome has an estimated prevalence of 1/10?000. Most cases are sporadic which led to hypotheses of a non?genetic aetiology. However, there was also evidence for a genetic cause with reports of multiplex families with presumed autosomal dominant, possible autosomal recessive inheritance and concordant twin pairs. We identified a monozygotic twin pair with CHARGE syndrome and a de novo balanced chromosome rearrangement t(8;13)(q11.2;q22). Methods Fluorescence in situ hybridisation was performed with BAC and PAC probes to characterise the translocation breakpoints. The breakpoint on chromosome 8 was further refined using 10?kb probes we designed and produced using sequence data for clone RP11 33I11, the Primer3 website, and a long range PCR kit. Results BAC and PAC probe hybridisation redefined the breakpoints to 8q12.2 and 13q31.1. Probe RP11 33I11 spanned the breakpoint on chromosome 8. Using our 10?kb probes we demonstrated that the chromodomain gene CHD7 was disrupted by the translocation between exons 3 and 8. Discussion Identifying that the translocation breakpoint in our patients occurred between exons 3 and 8 of CHD7 suggests that disruption of this gene is the cause of CHARGE syndrome in the twins and independently confirms the role of CHD7 in CHARGE syndrome. PMID:16118347

  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. Organic Acids and Iron Translocation in Maize Genotypes

    PubMed Central

    Clark, R. B.; Tiffin, L. O.; Brown, J. C.

    1973-01-01

    Translocation of Fe was studied in WF9 (Fe-efficient) and ys1/ys1 (Fe-inefficient) maize (Zea mays L.) genotypes. Iron-deficient WF9 translocated more Fe to the tops than Fe-deficient ys1/ys1. Malate and citrate contents of root saps increased nearly 2-fold and aconitate increased over 4-fold in both genotypes as Fe of nutrient solutions increased from 0.1 to 3 milligrams per liter. Relative acid contents in root saps were as follows: malate > aconitate > citrate. Citric acid concentrations in stem exudates were nearly the same as in root sap. Malic acid concentrations were considerably lower in exudates than in root saps, and only a trace of aconitic acid was detected in the exudates. The concentration of Fe was 7-fold higher in exudate of WF9 than in exudate of ys1/ys1 and the concentration of exudate P was about the same for both genotypes. Electropherograms of WF9 stem exudates showed that 59Fe moved toward the anode as 59Fe-citrate. Exudates of ys1/ys1 contained insufficient 59Fe to produce radiographs. When 59Fe was added in vitro to ys1/ys1 stem exudate, the 59Fe moved as 59Fe-citrate, indicating that sufficient citric acid was present in the exudate to chelate the Fe. Effectiveness of citric, isocitric, trans-aconitic, and malic acids in moving 59Fe electrophoretically in acetate, citrate, isocitrate, trans-aconitate, and malate buffers was studied. Malic, acetic, and trans-aconitic acids were ineffective in moving Fe from the origin. Citric acid moved Fe anodically whenever present on the electropherogram and successfully competed with the other acids for Fe. Results with ys1/ys1 roots indicate an absence of an efficient mechanism for transporting Fe from cortical cells to the xylem. If Fe can reach the xylem stream, the ys1/ys1 genotype should be as efficient as WF9 in moving Fe to the leaves. Images PMID:16658516

  4. 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.

  5. Production and Identification of Wheat-Agropyron cristatum 2P Translocation Lines

    PubMed Central

    Li, Huanhuan; Lv, Mingjie; Song, Liqiang; Zhang, Jinpeng; Gao, Ainong; Li, Lihui; Liu, Weihua

    2016-01-01

    Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), a wild relative of common wheat, possesses many potentially valuable traits that can be transferred to common wheat through breeding programs. The wheat-A. cristatum disomic addition and translocation lines can be used as bridge materials to introduce alien chromosomal segments to wheat. Wheat-A. cristatum 2P disomic addition line II-9-3 was highly resistant to powdery mildew and leaf rust, which was reported in our previous study. However, some translocation lines induced from II-9-3 have not been reported. In this study, some translocation lines were induced from II-9-3 by 60Co-γ irradiation and gametocidal chromosome 2C and then identified by cytological methods. Forty-nine wheat-A. cristatum translocation lines were obtained and various translcoation types were identified by GISH (genomic in situ hybridization), such as whole-arm, segmental and intercalary translocations. Dual-color FISH (fluorescent in situ hybridization) was applied to identify the wheat chromosomes involved in the translocations, and the results showed that A. cristatum 2P chromosome segments were translocated to the different wheat chromosomes, including 1A, 2A, 3A, 4A, 5A, 6A, 7A, 3B, 5B, 7B, 1D, 4D and 6D. Many different types of wheat-A. cristatum alien translocation lines would be valuable for not only identifying and cloning A. cristatum 2P-related genes and understanding the genetics and breeding effects of the translocation between A. cristatum chromosome 2P and wheat chromosomes, but also providing new germplasm resources for the wheat genetic improvement. PMID:26731742

  6. Cytometric analysis of an epitope-tagged transit peptide bound to the chloroplast translocation apparatus.

    PubMed

    Subramanian, C; Ivey, R; Bruce, B D

    2001-02-01

    Chloroplast transit peptides are necessary and sufficient for the targeting and translocation of precursor proteins across the chloroplast envelope. However, the mechanism by which transit peptides engage the translocation apparatus has not been investigated. To analyse this interaction, we have developed a novel epitope-tagged transit peptide derived from the precursor of the small subunit of pea Rubisco. The recombinant transit peptide, His-S-SStp, contains a removable dual-epitope tag, His-S, at its N-terminus that permits both rapid purification via immobilized metal affinity chromatography and detection by blotting, flow cytometry and laser-scanning confocal microscopy. Unlike other chimeric precursors, which place the passenger protein C-terminal to the transit peptide, His-S-SStp bound to the translocation apparatus yet did not translocate across the chloroplast envelope. This early translocation intermediate allowed non-radioactive detection using fluorescent and chemiluminescent reporters. The physiological relevance of this interaction was confirmed by protein import competitions, sensitivity to pre- and post-import thermolysin treatment, photochemical cross-linking and organelle fractionation. The interaction was specific for the transit peptide since His-S alone did not engage the chloroplast translocation apparatus. Quantitation of the bound transit peptide was determined by flow cytometry, showing saturation of binding yet only slight ATP-dependence. The addition of GTP showed inhibition of the binding of His-S-SStp to the chloroplasts indicating an involvement of GTP in the formation of this early translocation intermediate. In addition, direct visualization of His-S-SStp and Toc75 by confocal microscopy revealed a patch-like labeling, suggesting a co-ordinate localization to discrete regions on the chloroplast envelope. These findings represent the first direct visualization of a transit peptide interacting with the chloroplast translocation apparatus. Furthermore, identification of a chloroplast-binding intermediate may provide a novel tool to dissect interactions between a transit peptide and the chloroplast translocation apparatus. PMID:11208026

  7. The Haemophilus influenzae Hia autotransporter contains an unusually short trimeric translocator domain.

    PubMed

    Surana, Neeraj K; Cutter, David; Barenkamp, Stephen J; St Geme, Joseph W

    2004-04-01

    Gram-negative bacterial autotransporter proteins are a growing group of virulence factors that are characterized by their ability to cross the outer membrane without the help of accessory proteins. A conserved C-terminal beta-domain is critical for targeting of autotransporters to the outer membrane and for translocation of the N-terminal "passenger" domain to the bacterial surface. We have demonstrated previously that the Haemophilus influenzae Hia adhesin belongs to the autotransporter family, with translocator activity residing in the C-terminal 319 residues. To gain further insight into the mechanism of autotransporter protein translocation, we performed a structure-function analysis on Hia. In initial experiments, we generated a series of in-frame deletions and a set of chimeric proteins containing varying regions of the Hia C terminus fused to a heterologous passenger domain and discovered that the final 76 residues of Hia are both necessary and sufficient for translocation. Analysis by flow cytometry revealed that the region N-terminal to this shortened translocator domain is surface localized, further suggesting that this region is not involved in beta-barrel formation or in translocation of the passenger domain. Western analysis demonstrated that the translocation-competent regions of the C terminus migrated at masses consistent with trimers, suggesting that the Hia C terminus oligomerizes. Furthermore, fusion proteins containing a heterologous passenger domain demonstrated that similarly small C-terminal regions of Yersinia sp. YadA and Neisseria meningitidis NhhA are translocation-competent. These data provide experimental support for a unique subclass of autotransporters characterized by a short trimeric translocator domain. PMID:14726537

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

    PubMed

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

    2015-01-01

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

  9. A Role for Cytoskeletal Elements in the Light-Driven Translocation of Proteins in Rod Photoreceptors

    PubMed Central

    Peterson, James J.; Orisme, Wilda; Fellows, Jonathan; McDowell, J. Hugh; Shelamer, Charles L.; Dugger, Donald R.; Clay Smith, W.

    2006-01-01

    PURPOSE. Light-driven protein translocation is responsible for the dramatic redistribution of some proteins in vertebrate rod photoreceptors. In this study, the involvement of microtubules and microfilaments in the light-driven translocation of arrestin and transducin was investigated. METHODS. Pharmacologic reagents were applied to native and transgenic Xenopus tadpoles, to disrupt the microtubules (thiabendazole) and microfilaments (cytochalasin D and latrunculin B) of the rod photoreceptors. Quantitative confocal imaging was used to assess the impact of these treatments on arrestin and transducin translocation. A series of transgenic tadpoles expressing arrestin truncations were also created to identify portions of arrestin that enable arrestin to translocate. RESULTS. Application of cytochalasin D or latrunculin B to disrupt the microfilament organization selectively slowed only transducin movement from the inner to the outer segments. Perturbation of the microtubule cytoskeleton with thiabendazole slowed the translocation of both arrestin and transducin, but only in moving from the outer to the inner segments. Transgenic Xenopus expressing fusions of green fluorescent protein (GFP) with portions of arrestin implicates the C terminus of arrestin as an important portion of the molecule for promoting translocation. This C-terminal region can be used independently to promote translocation of GFP in response to light. CONCLUSIONS. The results show that disruption of the cytoskeletal network in rod photoreceptors has specific effects on the translocation of arrestin and transducin. These effects suggest that the light-driven translocation of visual proteins at least partially relies on an active motor-driven mechanism for complete movement of arrestin and transducin. PMID:16249472

  10. Production and Identification of Wheat-Agropyron cristatum 2P Translocation Lines.

    PubMed

    Li, Huanhuan; Lv, Mingjie; Song, Liqiang; Zhang, Jinpeng; Gao, Ainong; Li, Lihui; Liu, Weihua

    2016-01-01

    Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), a wild relative of common wheat, possesses many potentially valuable traits that can be transferred to common wheat through breeding programs. The wheat-A. cristatum disomic addition and translocation lines can be used as bridge materials to introduce alien chromosomal segments to wheat. Wheat-A. cristatum 2P disomic addition line II-9-3 was highly resistant to powdery mildew and leaf rust, which was reported in our previous study. However, some translocation lines induced from II-9-3 have not been reported. In this study, some translocation lines were induced from II-9-3 by 60Co-γ irradiation and gametocidal chromosome 2C and then identified by cytological methods. Forty-nine wheat-A. cristatum translocation lines were obtained and various translcoation types were identified by GISH (genomic in situ hybridization), such as whole-arm, segmental and intercalary translocations. Dual-color FISH (fluorescent in situ hybridization) was applied to identify the wheat chromosomes involved in the translocations, and the results showed that A. cristatum 2P chromosome segments were translocated to the different wheat chromosomes, including 1A, 2A, 3A, 4A, 5A, 6A, 7A, 3B, 5B, 7B, 1D, 4D and 6D. Many different types of wheat-A. cristatum alien translocation lines would be valuable for not only identifying and cloning A. cristatum 2P-related genes and understanding the genetics and breeding effects of the translocation between A. cristatum chromosome 2P and wheat chromosomes, but also providing new germplasm resources for the wheat genetic improvement. PMID:26731742

  11. Timing of translocation influences birth rate and population dynamics in a forest carnivore

    USGS Publications Warehouse

    Facka, Aaron N; Lewis, Jeffrey C.; Happe, Patricia; Jenkins, Kurt J.; Callas, Richard; Powell, Roger A.

    2016-01-01

    Timing can be critical for many life history events of organisms. Consequently, the timing of management activities may affect individuals and populations in numerous and unforeseen ways. Translocations of organisms are used to restore or expand populations but the timing of translocations is largely unexplored as a factor influencing population success. We hypothesized that the process of translocation negatively influences reproductive rates of individuals that are moved just before their birthing season and, therefore, the timing of releases could influence translocation success. Prior to reintroducing fishers (Pekania pennanti) into northern California and onto the Olympic Peninsula of Washington, we predicted that female fishers released in November and December (early) would have a higher probability of giving birth to kits the following March or April than females released in January, February, and March (late), just prior to or during the period of blastocyst implantation and gestation. Over four winters (2008–2011), we translocated 56 adult female fishers that could have given birth in the spring immediately after release. Denning rates, an index of birth rate, for females released early were 92% in California and 38% in Washington. In contrast, denning rates for females released late were 40% and 11%, in California and Washington, a net reduction in denning rate of 66% across both sites. To understand how releasing females nearer to parturition could influence population establishment and persistence, we used stochastic population simulations using three-stage Lefkovitch matrices. These simulations showed that translocating female fishers early had long-term positive influences on the mean population size and on quasi-extinction thresholds compared to populations where females were released late. The results from both empirical data and simulations show that the timing of translocation, with respect to life history events, should be considered during planning of translocations