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. [Univ. of Southern California, Los Angeles, CA (United States)

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

    PubMed Central

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

    2008-01-01

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

  4. 1/29 Robertsonian translocation in Blonde d'Aquitaine bulls: frequency and

    E-print Network

    Boyer, Edmond

    1/29 Robertsonian translocation in Blonde d'Aquitaine bulls: frequency and effects on semen; Toulouse-Auzeville, 10-13 July 1990) bull / Robertsonian translocation / 1/29 / frequency / semen of the 1/29 centric fusion in Blonde d'Aquitaine bulls and its effects upon semen characteristics

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

    PubMed

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

    2006-01-01

    Hypomagnesemia with secondary hypocalcemia (HSH) is a rare inherited disease, characterised by neurological symptoms, such as tetany, muscle spasms and seizures, due to hypocalcemia. It has been suggested that HSH is genetically heterogeneous, but only one causative gene, TRPM6, on chromosome 9 has so far been isolated. We have now studied the genetic background of HSH in four Polish patients belonging to three families, and a HSH patient carrying an apparently balanced X;9 translocation. The translocation patient has long been considered as an example of the X-linked form of HSH. We identified six TRPM6 gene mutations, of which five were novel, in the Polish patients. All the alterations were either nonsense/splicing or missense mutations. The clinical picture of the patients was similar to the HSH patients reported earlier. No genotype-phenotype correlation could be detected. Sequencing did not reveal any TRPM6 or TRPM7 gene mutations in the female HSH patient with an X;9 translocation. Isolation of the translocation breakpoint showed that the chromosome 9 specific breakpoint mapped within satellite III repeat sequence. The X-chromosomal breakpoint was localised to the first intron of the vascular endothelial growth factor gene, VEGFD. No other sequence alterations were observed within the VEGFD gene. Even though the VEGFD gene was interrupted by the X;9 translocation, it seems unlikely that VEGFD is causing the translocation patient's HSH-like phenotype. Furthermore, re-evaluation of patient's clinical symptoms suggests that she did not have a typical HSH. PMID:16267500

  6. High Frequency of BCL2 Translocation in Thai Patients with Follicular Lymphomas

    Microsoft Academic Search

    Ponlapat Rojnuckarin; Thamatorn Assanasen; Atcharaporn Chotipuech; Preecha Ruangvejvorachai; Montakarn Tansatit; Pongsak Wannakrairot; Tanin Intragumtornchai

    2007-01-01

    Follicular lymphoma is characterized by chromosomal translocation involvingBCL2 and immunoglobulin heavy chain genes (IgH). That the incidence of follicular lymphoma and the previously reported frequency\\u000a ofBCL2 translocation are lower in Asians than in Caucasians implies a different molecular pathology. The study ofBCL2 rearrangement will yield deeper insights into the pathogenesis of follicular lymphomas and into clinical applications of\\u000a molecular diagnosis

  7. Background

    E-print Network

    Grozdanko Grbesa; Maja Simonovic; Dorjanka Jankovic

    Efficiency of the EMDR procedure is based on a presumption of neuropsychological changes in therapeutic process.The aim of the investigation is to scann and give evidence of electroactivity changes, during the process of EMDR procedure and after finishing it. Materials and methods We have recorded a continual polygraph EEG, before, during and after EMDR therapy, in patient with combat-related PTSD. Results Before the treatment, EEG recorded basic activity of low voltage (attenuation) of 20 ?V, frequency of beta range (17-26 Hz), bioccipital, with no pathologic activity. Patient had prominent vegetative symptoms (anxiety, heart rate 100/min). Background activity immediately

  8. Reciprocal translocations

    SciTech Connect

    NONE

    1993-12-31

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

  9. 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

  10. Limits on high-frequency gravitational wave background from its interplay with large scale magnetic fields

    SciTech Connect

    Pshirkov, M. S.; Baskaran, D. [Pushchino Radio Astronomy Observatory, Astro Space Center, Lebedev Physical Institute, Pushchino (Russian Federation); School of Physics and Astronomy, Cardiff University, Cardiff CF24 3AA, United Kingdom and Wales Institute of Mathematical and Computational Sciences, Swansea SA2 8PP (United Kingdom)

    2009-08-15

    In this work, we analyze the implications of graviton-to-photon conversion in the presence of large scale magnetic fields. We consider the magnetic fields associated with galaxy clusters, filaments in the large scale structure, as well as primordial magnetic fields. We analyze the interaction of these magnetic fields with an exogenous high-frequency gravitational wave (HFGW) background which may exist in the Universe. We show that, in the presence of the magnetic fields, a sufficiently strong HFGW background would lead to an observable signature in the frequency spectrum of the cosmic microwave background. The sensitivity of current day cosmic microwave background experiments allows one to place significant constraints on the strength of the HFGW background, {omega}{sub GW} < or approx. 1. These limits are about 25 orders of magnitude stronger than currently existing direct constraints in this frequency region.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  13. Theta Frequency Background Tunes Transmission but Not Summation of Spiking Responses

    PubMed Central

    Parameshwaran, Dhanya; Bhalla, Upinder S.

    2013-01-01

    Hippocampal neurons are known to fire as a function of frequency and phase of spontaneous network rhythms, associated with the animal's behaviour. This dependence is believed to give rise to precise rate and temporal codes. However, it is not well understood how these periodic membrane potential fluctuations affect the integration of synaptic inputs. Here we used sinusoidal current injection to the soma of CA1 pyramidal neurons in the rat brain slice to simulate background oscillations in the physiologically relevant theta and gamma frequency range. We used a detailed compartmental model to show that somatic current injection gave comparable results to more physiological synaptically driven theta rhythms incorporating excitatory input in the dendrites, and inhibitory input near the soma. We systematically varied the phase of synaptic inputs with respect to this background, and recorded changes in response and summation properties of CA1 neurons using whole-cell patch recordings. The response of the cell was dependent on both the phase of synaptic inputs and frequency of the background input. The probability of the cell spiking for a given synaptic input was up to 40% greater during the depolarized phases between 30–135 degrees of theta frequency current injection. Summation gain on the other hand, was not affected either by the background frequency or the phasic afferent inputs. This flat summation gain, coupled with the enhanced spiking probability during depolarized phases of the theta cycle, resulted in enhanced transmission of summed inputs during the same phase window of 30–135 degrees. Overall, our study suggests that although oscillations provide windows of opportunity to selectively boost transmission and EPSP size, summation of synaptic inputs remains unaffected during membrane oscillations. PMID:23383242

  14. Background

    Cancer.gov

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

  15. Background frequency, information content, and the scoring matrix in sequence alignment

    NASA Astrophysics Data System (ADS)

    Yu, Yi-Kuo; Altschul, Stephen

    2003-03-01

    Sequence alignment tools for protein/DNA sequences have been widely used to find homologous biosequences over the past few decades. In these automated procedures, the target similarity between the two sequences compared is largely determined by the scoring matrix used. Theoretically, each matrix element of the scoring matrix is a log-odd ratio, i.e., the logarithm of the target frequency over the background frequency. In real alignment applications, however, the theoretical criterion is often overlooked. In this talk, we will present a sensible solution to forcibly maintain the theoretical criterion. We will also discuss the information content of the scoring matrix.

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

    Microsoft Academic Search

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

    1988-01-01

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

  17. 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.

  18. Consistency In Time And Frequency Domains In Presentation Of Measured Infrared Background Data

    NASA Astrophysics Data System (ADS)

    Klein, Harold J.

    1985-06-01

    Infrared background data are usually presented in the form of time histories and various statistics. The statistics in the time domain include means, variances, a utocorrelations, and histograms of various types. The statistic usually presented in the frequency domain is power spectral density. The data in either the time or the frequency domain may be useful, depending on how the system designer chooses to implement his filtering system and perform his system calculation. This paper examines the requirement for consistency in the two domains and shows how well certain windowing techniques assure con-sistency between the time and frequency domains. A particular technique is shown to give virtually perfect consistency. Data from the Balloon Altitude Mosaic Measurement (BAMM) are used to illustrate the results.

  19. Consistency In Time And Frequency Domains In Presentation Of Measured Infrared Background Data

    NASA Astrophysics Data System (ADS)

    Klein, Harold J.

    1985-01-01

    Infrared background data are usually presented in the form of time histories and various statistics. The statistics in the time domain include means, variances, autocorrelations, and histograms of various types. The statistic usually presented in the frequency domain is power spectral density (PSD). The data in either time or frequency domain may be useful depending on how the system designer chooses to implement his filtering system and perform his system calculation. This paper examines the requirement for consistency in the two domains and shows how well certain windowing techniques assure consistency between time and frequency domains. A particular technique is shown to give virtually perfect consistency. Data from the Balloon Altitude Mosaic Measurement (BAMM) are used to illustrate the results.

  20. 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

  1. Background

    E-print Network

    Jui-min Chang; Nai-jen Liu; Betty Chien-jung Pai; Yun-hen Liu; Ming-hung Tsai; Ching-song Lee; Yin-yi Chu; Chih-chuan Lin; Cheng-tang Chiu; Hao-tsai Cheng

    Background: Although the outcomes of caustic ingestion differ between children and adults, it is unclear whether such outcomes differ among adults as a function of their age. This retrospective study was performed to ascertain whether the clinical outcomes of caustic ingestion differ significantly between elderly and non-elderly adults. Methods: Medical records of patients hospitalized for caustic ingestion between June 1999 and July 2009 were reviewed retrospectively. Three hundred eighty nine patients between the ages of 17 and 107 years were divided into two groups: non-elderly (ingestion, substance ingested, systemic and gastrointestinal complications, psychological and systemic comorbidities, severity of mucosal injury, and time to expiration. Results: The incidence of psychological comorbidities was higher for the non-elderly group. By contrast, the incidence of systemic comorbidities, the grade of severity of mucosal damage, and the incidence of systemic complications were higher for the elderly group. The percentages of ICU admissions and deaths in the ICU were higher and the cumulative survival rate was lower for the elderly group. Elderly subjects, those with systemic complications had the greatest mortality risk due to caustic ingestion. Conclusions: Caustic ingestion by subjects ?65 years of age is associated with poorer clinical outcomes as compared to subjects < 65 years of age; elderly subjects with systemic complications have the poorest clinical outcomes. The severity of gastrointestinal tract injury appears to have no impact on the survival of elderly subjects.

  2. Propagation of the two-frequency coherence function in an inhomogeneous background random medium

    NASA Astrophysics Data System (ADS)

    Kalugin, Alexander; Bronshtein, Alexander; Mazar, Reuven

    2004-07-01

    The spatial and temporal structures of time-dependent signals can be appreciably affected by random changes of the parameters of the medium characteristic of almost all geophysical environments. The dispersive properties of random media cause distortions in the propagating signal, particularly in pulse broadening and time delay. When there is also spatial variation of the background refractive index, the observer can be accessed by a number of background rays. In order to compute the pulse characteristics along each separate ray, there is a need to know the behaviour of the two-frequency mutual coherence function. In this work, we formulate the equation of the two-frequency mutual coherence function along a curved background ray trajectory. To solve this equation, a recently developed reference-wave method is applied. This method is based on embedding the problem into a higher dimensional space and is accompanied by the introduction of additional coordinates. Choosing a proper transform of the extended coordinate system allows us to emphasize 'fast' and 'slow' varying coordinates which are consequently normalized to the scales specific to a given type of problem. Such scaling usually reveals the important expansion parameters defined as ratios of the characteristic scales and allows us to present the proper ordering of terms in the desired equation. The performance of the main order solution is demonstrated for the homogeneous background case when the transverse structure function of the medium can be approximated by a quadratic term. This article is dedicated to the memory of Professor Reuven Mazar, a top notch scientist, whose creativity influenced many random media researchers. Professor Mazar passed away suddenly a few weeks before the publication of this paper.

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

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

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

    PubMed

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

    2010-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  6. 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

  7. 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

  8. Robertsonian translocations

    SciTech Connect

    NONE

    1993-12-31

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

  9. Microbiology of bacterial translocation in humans

    Microsoft Academic Search

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

    1998-01-01

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

  10. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

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

    E-print Network

    Sarkissian, John M.

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

  13. High-Frequency Ambient Noise as Background to Deep Ocean Transient Signal Detection

    E-print Network

    Kurahashi, Naoko

    2007-01-01

    Ambient noise measured in the deep ocean is studied in the context of a search for high frequency transient signals. The spectral shape of the noise is found to be very stable for an extensive data set collected over several months from 49 hydrophones mounted near the bottom of the ocean at ~1600 m depth. The slopes of the ambient noise spectra above 15 kHz are found to roll-off faster than the -6 dB/octave seen in Knudsen spectra. A model including frequency-dependent absorption at large depth is found to fit the data well up to 25 kHz. For a subset of the data a correlation is observed between the overall noise level and the wind intensity. These measurements confirm that ambient noise, even at large depths, is still modeled well over a large frequency band by a uniform distribution of surface sources related to wind conditions.

  14. Removal of coherent Extremely Low Frequency (ELF) background noise by adaptive noise cancellation

    Microsoft Academic Search

    Samuel J. Strange

    1993-01-01

    The use of the sequential regression algorithm (SER) to coherently remove background noise from an ELF sensor is presented. The SER algorithm is described for a multichannel application in order to cancel coherent portions of reference sensors from a primary sensor. The algorithm adaptively accounts for differences between two parallel array platforms for the purpose of coherent subtraction. A section

  15. Generation of frequency degenerate twin photons in pulse pumped fiber optical parametric amplifiers: influence of background noise.

    PubMed

    Yang, Lei; Sun, Fengwei; Zhao, Ningbo; Li, Xiaoying

    2014-02-10

    Using a Sagnac fiber loop functions as a deterministic splitter of photon pairs produced by the frequency degenerate four wave mixing, we show that the background noise of the degenerate photon pairs is contributed by both Raman scattering and frequency non-degenerate four wave mixing. To improve the purity of photon pairs in the high gain regime, in addition to suppressing the noise photons by cooling the nonlinear fiber and by optimizing the detuning between the frequencies of the pump and photon pairs, the walk-off effect of the two pulsed pump fields should be mitigated by managing the dispersion of the fiber. Our investigation is not only the first step towards the generation of multi-mode squeezed vacuum in fiber optical parametric amplifiers pumped with pulsed lights, but also contributes to improving the purity of the fiber sources of degenerate photon pairs. PMID:24663548

  16. Low frequency association of the t(2;5)(p23;q35) chromosomal translocation with CD30+ lymphomas from American and Asian patients. A reverse transcriptase-polymerase chain reaction study.

    PubMed Central

    Lopategui, J. R.; Sun, L. H.; Chan, J. K.; Gaffey, M. J.; Frierson, H. F.; Glackin, C.; Weiss, L. M.

    1995-01-01

    Although cytogenetic data suggest that the t(2;5)-(p23;q35) translocation occurs in many cases of CD30+ lymphomas, the exact frequency of this event is still unknown. To clarify this issue and its epidemiological characteristics, we examined 37 formalin-fixed, paraffin-embedded specimens of CD30+ lymphomas from the United States and Hong Kong by reverse transcriptase-polymerase chain reaction (RT-PCR) for the status of the NPM and ALK genes, which are typically juxtaposed by the t(2;5) translocation. Thirty-four cases were classified as anaplastic large cell lymphomas (ALCL), 2 cases as non-anaplastic large cell lymphomas (LCL), and 1 case as the small cell variant of CD30+ lymphoma. The t(2;5) translocation was detected in 6 cases (16%), including 3 of 18 American patients and 3 of 19 cases from Hong Kong. All cases had a 185-bp NPM RT-PCR product as detected by Southern blot analysis, indicating adequate preservation of mRNA. The 6 positive cases were among 4 of 34 adult lymphomas, as compared with 2 of 3 childhood cases. Five of 17 T-lineage cases were t(2;5)-positive, compared with 1 of 15 B-lineage cases and none of the 5 null-cell or mixed lineage cases. Our results therefore show that t(2;5) occurs at a low frequency among CD30+ lymphomas, at least in our adult-dominated series. Images Figure 1 Figure 2 PMID:7856744

  17. A real time index of geomagnetic background noise for the MAD (Magnetic Anomaly Detection) frequency band

    NASA Astrophysics Data System (ADS)

    Bernardi, A.; Fraser-Smith, A. C.; Villard, O. G.

    1985-02-01

    An index of geomagnetic activity in the upper part of the ultra low frequency (ULF) range (less than 4.55 Hz) has been developed. This index will be referred to as the MA index (magnetic activity index). The MA index is prepared every half hour and is a measure of the strength of the geomagnetic activity in the Pc1-Pc3 pulsation frequency range during that half hour period. Activity in the individual Pc pulsation ranges can also be measured, if desired. The index is calculated from the running average of the full-wave rectified values of the band pass filtered geomagnetic signals and thus it provides a better indication of the magnitude of these band pass filtered magnetic pulsations than does the ap index, for example. Daily variations of the band pass filtered magnetic signals are also better captured by the MA index. To test this system we used analog tape recordings of wide-band geomagnetic signals. The indices for these tapes are presented in the form of plots, together with a comparison with the ap indices of the same time intervals. The MA index shows the daily variation of the geometric signals quite clearly during times when there is strong activity, i.e., when the ap index values are large. Because impulsive signals, such as lightning discharges, tend to be suppressed in the averaging process, the MA index is insensitive to impulsive noise. It is found that the time variation of the MA index is in general markedly different from the variation of the ap index for the same time intervals.

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

    PubMed

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

    2010-06-01

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

  19. Whole blood thallium determination by GFAAS with high-frequency modulation polarization Zeeman effect background correction.

    PubMed

    Solovyev, Nikolay D; Ivanenko, Natalya B; Ivanenko, Anatoly A

    2011-10-01

    A new technique of blood thallium direct determination based on graphite furnace atomic absorption spectrometry with Zeeman background absorption correction system was designed. The developed technique does not require sample digestion. Sample treatment includes only a fivefold per volume dilution of blood sample with 0.1% (m/v) Triton X-100. L'vov integrated platform was modified with 400 ?g of Rh. Matrix modifier (200 ?g NH(4)NO(3) and 160 ?g Pd(NO(3))(2)) was suggested for coping chloride and blood organic matter interferences. Standard reference material (Clincheck® Plasma Control for trace elements) analysis was used for validation. Additional validation was performed by analyzing spiked blood samples in the whole dynamic range. The dynamic range was 2-50 ?g/L. Precision (RSD) was found <12%. Blood thallium limit of detection was 0.2 ?g/L. PMID:20922499

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  1. Mode of ATM-dependent suppression of chromosome translocation

    SciTech Connect

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

    2011-12-09

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

  2. 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).

  3. 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 [Department of Physics, Chongqing University, Chongqing 400044 (China); Baker, Robert M. L. Jr. [GRAWAVE registered LLC, 8123 Tuscany Avenue, Playa del Rey, California 90293 (United States); Stephenson, Gary V. [Seculine Consulting, P.O. Box 925, Redondo Beach, California 90277 (United States)

    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.

  4. 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. ...

  5. Fluctuations in polymer translocation

    NASA Astrophysics Data System (ADS)

    Krapivsky, P. L.; Mallick, K.

    2010-07-01

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

  6. Active polymer translocation in the three-dimensional domain

    NASA Astrophysics Data System (ADS)

    Fiasconaro, A.; Mazo, J. J.; Falo, F.

    2015-02-01

    In this work we study the translocation process of a polymer through a nanochannel where a time dependent force is acting. Two conceptually different types of driving are used: a deterministic sinusoidal one and a random telegraph noise force. The mean translocation time presents interesting resonant minima as a function of the frequency of the external driving. For the computed sizes, the translocation time scales with the polymer length according to a power law with the same exponent for almost all the frequencies of the two driving forces. The dependence of the translocation time with the polymer rigidity, which accounts for the persistence length of the molecule, shows a different low frequency dependence for the two drivings.

  7. 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

  8. Investigation of radio frequency discharges and Langmuir probe diagnostic methods in a fast flowing electronegative background gas

    Microsoft Academic Search

    Nathaniel P. Lockwood

    2007-01-01

    Discharges in a flowing background gas are used to produce charged and excited atomic and molecular species for numerous applications including etching semiconductors, pumping gas discharge lasers, and a variety of other applications (Pinhero and others, 1998). The effect of a flowing background gas on the charged and excited neutral species generation by an RF discharge in a flow tube

  9. Simulations of Polymer Translocation

    NASA Astrophysics Data System (ADS)

    Vocks, H.

    2008-07-01

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

  10. Dicentric Robertsonian translocations in man

    Microsoft Academic Search

    M. G. Mattei; J. F. Mattei; S. Ayme; F. Giraud

    1979-01-01

    The authors studies 17 cases of Robertsonian translocations. In all cases but one C banding showed that a dicentric translocation was involved. Silver staining demonstrated the presence of an NOR between the two centromeres in only one case.

  11. Polymer Translocation in Crowded Environments

    NASA Astrophysics Data System (ADS)

    Gopinathan, Ajay; Kim, Yong Woon

    2007-11-01

    We study the effect of the crowded environments on the translocation of a polymer through a pore in a membrane. By systematically treating the entropic penalty due to crowding, we show that the translocation dynamics are significantly altered, leading to novel scaling behaviors of the translocation time. We also observe new and qualitatively different translocation regimes depending upon the extent of crowding, transmembrane chemical potential asymmetry, and polymer length.

  12. Synaptonemal complex analysis of reciprocal chromosome translocations

    E-print Network

    Paris-Sud XI, Université de

    Synaptonemal complex analysis of reciprocal chromosome translocations in the domestic pig DAF analysis/ reciprocal chromosome translocation/ domestic pig One main feature of chromosome translocations especially when acrocentric chromosomes are involved and unpaired segments of the translocation configuration

  13. Protein Translocation Across Biological Membranes

    NSDL National Science Digital Library

    William Wickner (Dartmouth Medical School; Department of Biological Chemistry)

    2005-12-02

    This article provides a review of progress made in the study of protein translocation. 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.

  14. 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

  15. DESIGN NOTE: A new set-up for nonlinear polarization spectroscopy in the frequency domain: experimental examples and theoretical background

    NASA Astrophysics Data System (ADS)

    Voigt, B.; Nowak, F. R.; Beenken, W.

    1999-01-01

    The advantages of a new experimental geometry for nonlinear polarization spectroscopy in the frequency domain (NLPF) are demonstrated. First, homogeneous illumination of the sample allows one to use lower pump intensities, so that the 0957-0233/10/1/014/img1 approach to describing the NLPF signal is valid. Secondly, there being fewer artefacts from competitive scattering processes results in distortionless NLPF spectra. These experimental improvements are illustrated by experimental results concerning pinacyanol.

  16. 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

  17. Translocations in epithelial cancers

    PubMed Central

    Chad Brenner, J.; Chinnaiyan, Arul M.

    2009-01-01

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

  18. Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo

    Microsoft Academic Search

    Raymond R. Russell III; Renfu Yin; Michael J. Caplan; Xiaoyue Hu; Jianming Ren; Gerald I. Shulman; Albert J. Sinusas; Lawrence H. Young

    2010-01-01

    Background—Myocardial ischemia increases glucose uptake through the translocation of GLUT1 and GLUT4 from an intracellular compartment to the sarcolemma. The present study was performed to determine whether hyperinsulinemia causes translocation of myocardial GLUT1 as well as GLUT4 in vivo and whether there are additive effects of insulin and ischemia on GLUT1 and GLUT4 translocation. Methods and Results—Myocardial glucose uptake and

  19. Polymer translocation facilitated by Chaperones

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Aniket; Ala-Nissila, Tapio; Sung, Wokyung

    2011-03-01

    We study translocation of biopolymers through a nanopore in a membrane facilitated by attractive binding particles (Chaperones) using Langevin dynamics simulation. Specifically we study how the density and attractive strength of these bindings particles affect the chain conformations at the trans side and mean first passage time (MFPT). We also consider model larger chaperone that can bind reversibly on the multiple units of the translocating chain. Finally, we consider translocation of heteropolymers and how a specific sequence affect the translocation process. We discuss relevance of our studies in biological translocation processes.^1R. Zandi, D. Reguera, J. Rudnick and W. M. Gelbart, Proc. Natl. Acad. Sci. USA 100 8649 (2003).^2W. Sung and P. J. Park, Phys. Rev. Lett. 77, 783 (1996).

  20. A Specific Nuclear DNA Background Is Required for High Frequency Lymphoma Development in Transmitochondrial Mice with G13997A mtDNA

    PubMed Central

    Taketo, Makoto M.; Nakada, Kazuto; Hayashi, Jun-Ichi

    2015-01-01

    We previously found that mouse mitochondrial DNA (mtDNA) with a G13997A mutation (G13997A mtDNA) controls not only the transformation of cultured lung carcinoma cells from poorly metastatic into highly metastatic cells, but also the transformation of lymphocytes into lymphomas in living C57BL/6 (B6) mice. Because the nuclear genetic background of the B6 strain makes the strain prone to develop lymphomas, here we examined whether G13997A mtDNA independently induces lymphoma development even in mice with the nuclear genetic background of the A/J strain, which is not prone to develop lymphomas. Our results showed that the B6 nuclear genetic background is required for frequent lymphoma development in mice with G13997A mtDNA. Moreover, G13997A mtDNA in mice did not enhance the malignant transformation of lung adenomas into adenocarcinomas or that of hepatocellular carcinomas from poorly metastatic into highly metastatic carcinomas. Therefore, G13997A mtDNA enhances the frequency of lymphoma development under the abnormalities in the B6 nuclear genome, and does not independently control tumor development and tumor progression. PMID:25738506

  1. Prenatal Origin of Chromosomal Translocations in Acute Childhood Leukemia: Implications and Future Directions

    E-print Network

    California at Berkeley, University of

    Prenatal Origin of Chromosomal Translocations in Acute Childhood Leukemia: Implications and Future an in utero origin for translocations associated with childhood leukemia, with latency periods in some cases birth) at a frequency that is 100-fold greater than the risk of developing the corresponding leukemia

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

    PubMed

    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

  3. Cord Blood Stem Cells Inhibit Epidermal Growth Factor Receptor Translocation to Mitochondria in Glioblastoma

    Microsoft Academic Search

    Venkata Ramesh Dasari; Kiran Kumar Velpula; Kiranmai Alapati; Meena Gujrati; Andrew J. Tsung

    2012-01-01

    BackgroundOverexpression of EGFR is one of the most frequently diagnosed genetic aberrations of glioblastoma multiforme (GBM). EGFR signaling is involved in diverse cellular functions and is dependent on the type of preferred receptor complexes. EGFR translocation to mitochondria has been reported recently in different cancer types. However, mechanistic aspects of EGFR translocation to mitochondria in GBM have not been evaluated

  4. 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.

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

    E-print Network

    Mayer, Michael

    walls1,3,29 and prevent pore clogging3 . Finally, the low frequency of translocation events at low, volume, charge, shape and ligand affinity, different proteins were identified. N anopores hold tremendous

  6. Mechanism of helicase translocation along nucleic acid

    E-print Network

    Zhang, Yunxin

    2012-01-01

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

  7. Nonequilibrium Dynamics of Polymer Translocation

    NASA Astrophysics Data System (ADS)

    Sakaue, Takahiro

    2013-03-01

    When a flexible chain is pulled or sucked, it can initially respond only locally, and sequential nonequilibrium processes with large conformational distortion follow in line with the propagation of tensile force along the chain backbone. This is a generic dynamical response property of polymers, the understanding of which provides us with a viewpoint to capture an essential aspect of the driven translocation process. In the meeting, I will summarize a basic framework to analyze the nonequilibrium dynamics of driven translocation process alongside of recent progresses. [4pt] References:[0pt] T. Sakaue, Phys. Rev. E, 76, 021803 (2007) ``Nonequilibrium dynamics of polymer translocation and straightening''[0pt] T. Sakaue, Phys. Rev. E, 81, 041808 (2010) ``Sucking genes into pores: Insight into driven translocation''[0pt] T. Saito and T. Sakaue, Eur. Phys. J. E, 34, 145 (2011) ``Dynamical diagram and scaling in polymer driven translocation''[0pt] T. Saito and T. Sakaue, Phys. Rev. E, 85, 061803 (2012) ``Process time distribution of driven polymer transport''

  8. BCR-ABL Translocation in Pediatric Acute Lymphoblastic Leukemia in Southern India.

    PubMed

    Sugapriya, D; Preethi, S; Shanthi, P; Chandra, N; Jeyaraman, G; Sachdanandam, P; Thilagavathy, S; Venkatadesilalu, S

    2012-03-01

    Cytogenetics and polymerase chain reaction (PCR) based assays provide important information regarding biologically defined and prognostically relevant subgroups in acute leukemias. We utilized karyotyping and molecular analysis by reverse transcriptase PCR for the BCR-ABL translocation, in addition to morphological study, cytochemistry and immunophenotyping, to study 24 cases of pediatric acute lymphoblastic leukemia (ALL). Our objective was to determine the frequency of the BCRABL translocation in childhood ALL from southern India. Karyotyping showed one case of hyperdiploidy, one case of t (12; 21) translocation and one case of 46, XY-21+mar. The BCR-ABL translocation was found in 8.3% of these cases. One of these was a cryptic translocation, the karyotype being normal. BCR-ABL positivity in ALL is associated with aggressive disease and has been shown to be a poor prognostic factor, especially in children. PMID:23449388

  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 [Physics Department, Udine University, via delle Scienze 208, I-33100 Udine (Italy); Persic, Massimo [INAF-Trieste, via G. B. Tiepolo 11, I-34143 Trieste (Italy); Tavecchio, Fabrizio [INAF-Brera, via E. Bianchi 46, I-23807 Merate (Italy)

    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. Intestinal obstruction promotes gut translocation of bacteria

    Microsoft Academic Search

    P. M. Sagar; J. MacFie; P. Sedman; J. May; B. Mancey-Jones; D. Johnstone

    1995-01-01

    PURPOSE: Translocation of enteric organisms has been implicated as a possible source of sepsis in susceptible patients. Animal studies have suggested that intestinal obstruction promotes bacterial translocation from the gut lumen. The aim of this study was to study the prevalence of bacterial translocation in patients with and without intestinal obstruction. METHODS: Serosal scrapings, mesenteric lymph nodes, and peripheral blood

  11. 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.

  12. Creating cancer translocations in human cells using Cas9 DSBs and nCas9 paired nicks

    PubMed Central

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

    2015-01-01

    Recurrent chromosomal translocations are found in numerous of tumor types, often leading to the formation and expression of fusion genes with oncogenic potential. Creating chromosomal translocations at the relevant endogenous loci, rather than just ectopically expressing the fusion genes, opens new possibilities for better characterizing molecular mechanisms driving tumor formation. In this chapter, we describe methods to create cancer translocations in human cells. DSBs or paired nicks generated by either wild-type Cas9 or the Cas9 nickase, respectively, are used to induce translocations at the relevant loci. Using different PCR-based methods, we also explain how to quantify translocation frequency and to analyze breakpoint junctions in the cells of interest. In addition, PCR detection of translocations is used as a very sensitive method to detect off-target effects, which has general utility. PMID:25398344

  13. PARP1 is required for chromosomal translocations

    PubMed Central

    Wray, Justin; Williamson, Elizabeth A.; Singh, Sudha B.; Wu, Yuehan; Cogle, Christopher R.; Weinstock, David M.; Zhang, Yu; Lee, Suk-Hee; Zhou, Daohong; Shao, Lijian; Hauer-Jensen, Martin; Pathak, Rupak; Klimek, Virginia; Nickoloff, Jac A.

    2013-01-01

    Chromosomal translocations are common contributors to malignancy, yet little is known about the precise molecular mechanisms by which they are generated. Sequencing translocation junctions in acute leukemias revealed that the translocations were likely mediated by a DNA double-strand break repair pathway termed nonhomologous end-joining (NHEJ). There are major 2 types of NHEJ: (1) the classical pathway initiated by the Ku complex, and (2) the alternative pathway initiated by poly ADP-ribose polymerase 1 (PARP1). Recent reports suggest that classical NHEJ repair components repress translocations, whereas alternative NHEJ components were required for translocations. The rate-limiting step for initiation of alternative NHEJ is the displacement of the Ku complex by PARP1. Therefore, we asked whether PARP1 inhibition could prevent chromosomal translocations in 3 translocation reporter systems. We found that 2 PARP1 inhibitors or repression of PARP1 protein expression strongly repressed chromosomal translocations, implying that PARP1 is essential for this process. Finally, PARP1 inhibition also reduced both ionizing radiation–generated and VP16-generated translocations in 2 cell lines. These data define PARP1 as a critical mediator of chromosomal translocations and raise the possibility that oncogenic translocations occurring after high-dose chemotherapy or radiation could be prevented by treatment with a clinically available PARP1 inhibitor. PMID:23568489

  14. PARP1 is required for chromosomal translocations.

    PubMed

    Wray, Justin; Williamson, Elizabeth A; Singh, Sudha B; Wu, Yuehan; Cogle, Christopher R; Weinstock, David M; Zhang, Yu; Lee, Suk-Hee; Zhou, Daohong; Shao, Lijian; Hauer-Jensen, Martin; Pathak, Rupak; Klimek, Virginia; Nickoloff, Jac A; Hromas, Robert

    2013-05-23

    Chromosomal translocations are common contributors to malignancy, yet little is known about the precise molecular mechanisms by which they are generated. Sequencing translocation junctions in acute leukemias revealed that the translocations were likely mediated by a DNA double-strand break repair pathway termed nonhomologous end-joining (NHEJ). There are major 2 types of NHEJ: (1) the classical pathway initiated by the Ku complex, and (2) the alternative pathway initiated by poly ADP-ribose polymerase 1 (PARP1). Recent reports suggest that classical NHEJ repair components repress translocations, whereas alternative NHEJ components were required for translocations. The rate-limiting step for initiation of alternative NHEJ is the displacement of the Ku complex by PARP1. Therefore, we asked whether PARP1 inhibition could prevent chromosomal translocations in 3 translocation reporter systems. We found that 2 PARP1 inhibitors or repression of PARP1 protein expression strongly repressed chromosomal translocations, implying that PARP1 is essential for this process. Finally, PARP1 inhibition also reduced both ionizing radiation-generated and VP16-generated translocations in 2 cell lines. These data define PARP1 as a critical mediator of chromosomal translocations and raise the possibility that oncogenic translocations occurring after high-dose chemotherapy or radiation could be prevented by treatment with a clinically available PARP1 inhibitor. PMID:23568489

  15. 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

  16. Dynamics of polymer translocation through kinked nanopores

    NASA Astrophysics Data System (ADS)

    Wang, Junfang; Wang, Yilin; Luo, Kaifu

    2015-02-01

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

  17. Facilitated Translocation of Polypeptides Through A Single Nanopore

    PubMed Central

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

    2011-01-01

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

  18. Nanoelectropulse-Induced Phosphatidylserine Translocation

    Microsoft Academic Search

    P. Thomas Vernier; Yinghua Sun; Laura Marcu; Cheryl M. Craft; Martin A. Gundersen

    2004-01-01

    Nanosecond, megavolt-per-meter, pulsed electric fields induce phosphatidylserine (PS) externalization, intracellular calcium redistribution, and apoptosis in Jurkat T-lymphoblasts, without causing immediately apparent physical damage to the cells. Intracellular calcium mobilization occurs within milliseconds of pulse exposure, and membrane phospholipid translocation is observed within minutes. Pulsed cells maintain cytoplasmic membrane integrity, blocking propidium iodide and Trypan blue. Indicators of apoptosis—caspase activation and

  19. Cytological study of Searle's X-autosome translocation in Mus musculus

    Microsoft Academic Search

    Susumu Ohno; Mary F. Lyon

    1965-01-01

    Genetic studies on Searle'S X-autosome translocation of Mus musculus have shown that a segment of the X carrying the loci for two sex-linked genes, Ta and Blo, has been translocated to an autosome. Females heterozygous for Tabby normally have variegated hair structures, with transverse Ta bands visible against a background of wildtype fur. When the wild-type allele of Ta or

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

    PubMed Central

    Bunce, James A.

    2007-01-01

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

  1. 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

  2. Translocation of Copolymers through a Nanopore

    NASA Astrophysics Data System (ADS)

    Matsuyama, Akihiko; Ohno, Kyoko; Nishiono, Makoto

    2013-02-01

    Translocation of copolymers (AB, ABA, BAB, ABAB, random, etc.), consisting of hydrophilic (monomer A) and hydrophobic (monomer B) groups, threading a nanopore is studied by using a three-dimensional dynamic Monte Carlo simulation. We focus on the orientation of a copolymer, namely the monomer A enters the pore first or the monomer B first. We find that there are two characteristic translocation times and waiting time distributions associated with translocation of these copolymers.

  3. Nitrate Translocation by Detopped Corn Seedlings 1

    PubMed Central

    Ezeta, Fernando N.; Jackson, William A.

    1975-01-01

    Five-day-old seedlings of corn (Ze? mays L.) grown without nitrate were decapitated and exposed to 0.5 mm KNO3 or 0.5 mm KCl in aerated solutions at 30 C. Uptake of nitrate, chloride, and potassium was determined by replacing solutions hourly and measuring their depletion. Translocation of these ions and of organic nitrogen was determined by hourly analysis of the vascular exudate. Nitrate reduction was estimated by the difference between nitrate uptake and nitrate recovered in the tissue and exudate. Nitrate uptake exhibited its usual pattern of apparent induction resulting in the development of an accelerated uptake phase. Chloride uptake remained fairly constant throughout the experimental period. Translocation of nitrate increased progressively for at least 7 hours whereas chloride translocation reached a maximum about the 3d hour and then declined to a lower rate than nitrate translocation. Nitrate uptake and translocation were restricted by anaerobiosis, by 20 and 40 C relative to 30 C, and by 0.05 mm 6-methylpurine, an RNA-synthesis inhibitor. Accumulation, reduction and translocation of nitrate had different sensitivities to all these factors. The effect of 0.05 mm 6-methylpurine was more detrimental to nitrate translocation and nitrate reduction than to nitrate uptake. Ambient nitrate, relative to chloride, enhanced the exudation volume and the translocation of organic nitrogen within 4 hours from initiation of the experiments. Translocation of nitrate and organic nitrogen decreased shortly after removal of external nitrate. The higher rates of organic nitrogen translocation which occurred during nitrate uptake indicates either (a) rapid translocation of amino acids synthesized from the entering nitrate, or (b) an accelerated rate of protein turnover and a resulting enhancement in translocation of endogenous amino acids. PMID:16659246

  4. A De Novo Case of Floating Chromosomal Polymorphisms by Translocation in Quasipaa boulengeri (Anura, Dicroglossidae)

    PubMed Central

    Qing, Liyan; Xia, Yun; Zheng, Yuchi; Zeng, Xiaomao

    2012-01-01

    Very few natural polymorphisms involving interchromosomal reciprocal translocations are known in amphibians even in vertebrates. In this study, thirty three populations, including 471 individuals of the spiny frog Quasipaa boulengeri, were karyotypically examined using Giemsa stain or FISH. Five different karyomorphs were observed. The observed heteromorphism was autosomal but not sex-related, as the same heteromorphic chromosomes were found both in males and females. Our results indicated that the variant karyotypes resulted from a mutual interchange occurring between chromosomes 1 and 6. The occurrence of a nearly whole-arm translocation between chromosome no. 1 and no. 6 gave rise to a high frequency of alternate segregation and probably resulted in the maintenance of the translocation polymorphisms in a few populations. The translocation polymorphism is explained by different frequencies of segregation modes of the translocation heterozygote during meiosis. Theoretically, nine karyomorphs should be investigated, however, four expected karyotypes were not found. The absent karyomorphs may result from recessive lethal mutations, position effects, duplications and deficiencies. The phylogenetic inference proved that all populations of Q. boulengeri grouped into a monophyletic clade. The mutual translocation likely evolved just once in this species and the dispersal of the one karyomorph (type IV) can explain the chromosomal variations among populations. PMID:23056254

  5. Rare Robertsonian translocations and meiotic behaviour: sperm FISH analysis of t(13;15) and t(14;15) translocations: a case report.

    PubMed

    Moradkhani, K; Puechberty, J; Bhatt, S; Lespinasse, J; Vago, P; Lefort, G; Sarda, P; Hamamah, S; Pellestor, F

    2006-12-01

    t(13;15) and t(14;15) are two rare Robertsonian translocations. Meiotic segregation was studied in four males heterozygous for the rare Robertsonian translocations t(13;15) and t(14;15). Both locus-specific probes (LSPs) and whole chromosome painting (WCP) probes, specific to chromosomes 13, 14 and 15, were used in this study. The number of spermatozoa scored for each carrier ranged from 891 to 5000. The frequencies of normal and balanced sperm resulting from the alternate mode of segregation ranged from 77.6 to 92.8%, confirming the prevalence of alternate segregation over other segregation modes in all Robertsonian translocations. The incidences of unbalanced complements ranged from 6.7 to 20.4%, with a significant excess of disomy rates over the complementary frequencies of nullisomy. This variability might reflect differences in the location of breakpoints in translocated chromosomes, leading to the variable production of unbalanced gametes and the variable alterations of semen parameters in Robertsonian translocation carriers. PMID:16917122

  6. 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.

  7. Translocations among Antibody Genes in Human Cancer

    Microsoft Academic Search

    Philip Leder; Jim Battey; Gilbert Lenoir; Christopher Moulding; William Murphy; Huntington Potter; Timothy Stewart; Rebecca Taub

    1983-01-01

    The characteristic chromosomal translocations that occur in certain human malignancies offer opportunities to understand how two gene systems can affect one another when they are accidentally juxtaposed. In the case of Burkitt lymphoma, such a translocation joins the cellular oncogene, c-myc, to a region encoding one of the immunoglobulin genes. In at least one example, the coding sequence of the

  8. The regulation of ammonium translocation in plants

    Microsoft Academic Search

    J. K. Schjoerring; S. Husted; G. Mack; M. Mattsson

    2010-01-01

    Much controversy exists about whether or not NHq 4 is translocated in the xylem from roots to shoots. In this paper it is shown that such translocation can indeed take place, but that interference from other meta- bolites such as amino acids and amines may give rise to large uncertainties about the magnitude of xylem NHq 4 concentrations. Elimination of

  9. New and Notable How Polymers Translocate

    E-print Network

    New and Notable How Polymers Translocate Through Pores: Memory is Important Anatoly B. Kolomeisky cellular membranes, involve the motion of polymer molecules across nar- row channels (1). Translocation the entropic barriers. These barriers ap- pear due to the decrease in the number of available polymer

  10. Complications associated with limited macular translocation

    Microsoft Academic Search

    Gildo Y Fujii; Dante J Pieramici; Mark S Humayun; Andrew P Schachat; Sandra M Reynolds; Michele Melia; Eugene De Juan

    2000-01-01

    PURPOSE: To report the ocular complications associated with the limited macular translocation procedure.METHODS: Retrospective review of 153 consecutive eyes of 151 patients that had the limited macular translocation procedure for subfoveal choroidal neovascularization between April 1996 and February 1999. The major study variables investigated included the incidence of specific ocular complications and their impact on visual acuity at 3 months

  11. Twin arginine translocation in Yersinia.

    PubMed

    Lavander, Moa; Ericsson, Solveig K; Bröms, Jeanette E; Forsberg, Ake

    2007-01-01

    Bacteria utilise Twin arginine translocation (Tat) to deliver folded proteins across the cytoplasmic membrane. Disruption of Tat typically results in pleiotropic effects on e.g. growth, stress resistance, bacterial membrane biogenesis, motility and cell morphology. Further, Tat is coupled to virulence in a range of pathogenic bacteria, including species of Pseudomonas, Legionella, Agrobacterium and Mycobacterium. We have investigated this, for Yersinia, previously unexplored system, and have shown that the Tat pathway is functional and absolutely required for virulence of Yersinia pseudotuberculosis. A range of putative Yersinia Tat substrates have been predicted in silico, which together with the Tat system itself may be interesting targets for future development of antimicrobial treatments. Here we present a brief review of bacterial Tat and discuss our results concerning this system in Yersinia. PMID:17966422

  12. Electrically facilitated translocation of protein through solid nanopore

    PubMed Central

    2014-01-01

    Nanopores have been proven as versatile single-molecule sensors for individual unlabeled biopolymer detection and characterization. In the present work, a relative large nanopore with a diameter of about 60 nm has been used to detect protein translocation driven by a series of applied voltages. Compared with previous studied small nanopores, a distinct profile of protein translocation through a larger nanopore has been characterized. First, a higher threshold voltage is required to drive proteins into the large nanopore. With the increase of voltages, the capture frequency of protein into the nanopore has been markedly enhanced. And the distribution of current blockage events is characterized as a function of biased voltages. Due to the large dimension of the nanopore, the adsorption and desorption phenomenon of proteins observed with a prolonged dwell time has been weakened in our work. Nevertheless, the protein can still be stretched into an unfolded state by increased electric forces at high voltages. In consideration of the high throughput of the large nanopore, a couple of proteins passing through the nanopore simultaneously occur at high voltage. As a new feature, the feasibility and specificity of a nanopore with distinct geometry have been demonstrated for sensing protein translocation, which broadly expand the application of nanopore devices. PMID:24661490

  13. Detection of chemical agents in the atmosphere by open-path FT-IR spectroscopy under conditions of background interference: I. High-frequency flashes.

    PubMed

    Shao, Limin; Roske, Christopher W; Griffiths, Peter R

    2010-06-01

    Open-path FT-IR spectra were measured while fireworks were emitting smoke and incandescent particles into the infrared beam. These conditions were designed to simulate the appearance of smoke and explosions in a battlefield. Diethyl ether was used to simulate the vapor-phase spectra of G agents such as sarin. The measured interferograms were corrected by a high-pass filter and were rejected when interfering features were of such high frequency that they could not be removed by application of this filter. The concentration of diethyl ether was calculated correctly by partial least squares regression in the absence of fireworks but significant errors were encountered when the spectra of the oxide particles were not included in the calibration set. Target factor analysis allowed the presence of the analyte to be detected even when the incandescent particles were present in the beam. PMID:20401469

  14. Double Translocation: An Interesting Family History

    PubMed Central

    Uysal, A; Uluda?, A; S?lan, F; Erçelen, N; Zafer, C; Özdemir, Ö

    Double balanced translocations are particularly rare and the risk of a fetus with an unbalanced chromosomal anomaly is greater than for single translocation carriers. In this present case, we describe an interesting family history which included three generations. A couple, married for 4 years, was referred to the genetic clinic due to infertility and family chromosome anomalies. A GTG-band chromosome analysis indicated that the male partner’s karyotype was 45,XY, t(3;18)(q11;ptel)t(13;14)(q10;q10). The same double balanced translocation was found in two others family members. PMID:24265590

  15. Arsenic translocation in rice investigated using radioactive 73 As tracer

    Microsoft Academic Search

    Fang-Jie Zhao; M. Asaduzzaman Khan; Steve P. McGrath

    Background and aims  Excessive accumulation of arsenic (As) in rice (Oryza sativa L.) may pose a health risk to rice consumers. Long-distance transport of As within plant tissues is not well understood.\\u000a The aim of our study was to evaluate As translocation from roots to shoots and from shoot tissues to rice grain.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  At the grain filling stage, 73As-labelled arsenite was

  16. High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers

    E-print Network

    Newman, Scott; Edwards, Paul A W

    2010-03-17

    . Howarth KD, Blood KA, Ng BL, Beavis JC, Chua Y, Cooke SL, Raby S, Ichimura K, Collins VP, Carter NP, Edwards PA: Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer- relevant genes. Oncogene...

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

    E-print Network

    Nicchitta, Chris

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  19. Nanoelectropulse-Induced Phosphatidylserine Translocation

    PubMed Central

    Vernier, P. Thomas; Sun, Yinghua; Marcu, Laura; Craft, Cheryl M.; Gundersen, Martin A.

    2004-01-01

    Nanosecond, megavolt-per-meter, pulsed electric fields induce phosphatidylserine (PS) externalization, intracellular calcium redistribution, and apoptosis in Jurkat T-lymphoblasts, without causing immediately apparent physical damage to the cells. Intracellular calcium mobilization occurs within milliseconds of pulse exposure, and membrane phospholipid translocation is observed within minutes. Pulsed cells maintain cytoplasmic membrane integrity, blocking propidium iodide and Trypan blue. Indicators of apoptosis—caspase activation and loss of mitochondrial membrane potential—appear in nanoelectropulsed cells at later times. Although a theoretical framework has been established, specific mechanisms through which external nanosecond pulsed electric fields trigger intracellular responses in actively growing cells have not yet been experimentally characterized. This report focuses on the membrane phospholipid rearrangement that appears after ultrashort pulse exposure. We present evidence that the minimum field strength required for PS externalization in actively metabolizing Jurkat cells with 7-ns pulses produces transmembrane potentials associated with increased membrane conductance when pulse widths are microseconds rather than nanoseconds. We also show that nanoelectropulse trains delivered at repetition rates from 2 to 2000 Hz have similar effects, that nanoelectropulse-induced PS externalization does not require calcium in the external medium, and that the pulse regimens used in these experiments do not cause significant intra- or extracellular Joule heating. PMID:15189899

  20. Gene Translocations in Musculoskeletal Neoplasms

    PubMed Central

    Krishnan, Balaji; Khanna, Gaurav

    2008-01-01

    Establishing the best diagnosis for musculoskeletal neoplasms requires a multidisciplinary approach using clinical, radiographic, and histologic analyses. Despite this rigorous approach, establishing accurate diagnoses and prognoses remains challenging. Improved diagnostic methods are expected as unique molecular signals for specific bone and soft tissue cancers are identified. We performed a systematic review of the best available evidence to explore three major applications of molecular genetics that will best benefit clinical management of musculoskeletal neoplasms: diagnostic, prognostic, and therapeutic applications. The specific questions addressed in this systematic review are: (1) What sets of histopathologic sarcoma subtypes will benefit from molecular evaluation and diagnosis? (2) What molecular methods are best applied to histopathologic sarcomas to distinguish between major subtypes? (3) How do the molecular patterns discovered on genetic diagnosis affect prognosis of certain sarcomas? (4) Which sarcoma translocations can benefit from an improved response and outcome using existing and forthcoming pharmacogenetic approaches targeting molecular events? This review summarizes recent advances in molecular genetics that are available and will soon be available to clinicians to better predict outcomes and subsequently help make future treatment decisions. Level of Evidence: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18566876

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2009-06-01

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

  3. Cosmic microwave background radiation

    Microsoft Academic Search

    Lyman Page; David Wilkinson

    1999-01-01

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

  4. Hemorrhage Exacerbates Bacterial Translocation at Low Levels of Intra-abdominal Pressure

    Microsoft Academic Search

    Nicholas J. Gargiulo III; Ronald J. Simon; Walter Leon; George W. Machiedo

    1998-01-01

    Background: It has been shown previously that the ad- verse cardiopulmonary sequelae of increased intra- abdominal pressure (IAP) are worsened by hemorrhage and resuscitation. Bacterial translocation (BT) to the mes- enteric lymph nodes (MLNs), liver, and spleen has also been shown to occur with increased IAP. Objective: To investigate the hypothesis that BT asso- ciated with elevated IAP would be

  5. Translocation of polymers in a lattice model.

    PubMed

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

    2012-06-01

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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Bax translocation and mitochondrial fragmentation induced by Helicobacter pylori

    PubMed Central

    Ashktorab, H; Frank, S; Khaled, A R; Durum, S K; Kifle, B; Smoot, D T

    2004-01-01

    Background and aims: Previous in vitro and in vivo studies have revealed an association between Helicobacter pylori infection and apoptosis in gastric epithelial cells. Although involvement of the Bcl-2 family of proteins as well as cytochrome c release has been demonstrated in H pylori induced cell death, the exact role of the mitochondria during this type of programmed cell death has not been fully elucidated. Therefore, we sought to determine whether or not Bax translocation and mitochondrial fragmentation occur on exposure of gastric epithelial cells to H pylori, resulting in cell death. Methods: Experiments were performed with human gastric adenocarcinoma (AGS) cells, AGS cells transfected with the HPV-E6 gene (which inactivates p53 function), AGS-neo cells (transfected with the backbone construct), mouse embryonic fibroblasts (MEFs), and p19ARF null (ARF?/?) MEFs. Cells were incubated with a cag positive H pylori strain for up to 24 hours, lysed, and cytoplasmic and mitochondrial membrane fractions were analysed by western blot for Bax translocation. Results: Bax translocation was detected in AGS, AGS-neo, and normal MEF cells after exposure to H pylori for three hours, but not in ARF?/? MEFs cells. Translocation of Bax after H pylori incubation was also detected in AGS-E6 cells (inactive p53 gene) but to a lesser degree than in AGS-neo cells. In parallel studies, the mitochondrial morphology of living cells infected with H pylori was assessed by confocal microscopy. Mitochondrial fragmentation was detectable after 10 hours of H pylori incubation with AGS cells and after seven hours with MEF cells. In wild-type MEFs, mitochondrial fragmentation was significantly increased in comparison with ARF null MEFs (43% v 10.4%, respectively). Furthermore, mitochondrial depolarisation and caspase-3 activity were initiated within four hours in cells incubated with H pylori, and these events were inhibited by forced expression of Bcl-2. Conclusions: These data suggest that during H pylori induced apoptosis, Bax translocates to the mitochondria which subsequently undergo depolarisation and profound fragmentation. Functional ARF and p53 proteins may play an important role in H pylori induced mitochondrial modification. PMID:15138206

  11. The effect of interleukin-6 on bacterial translocation in acute canine pancreatitis

    Microsoft Academic Search

    Qiang Liu; Goldie Djuricin; Catherine Nathan; Paolo Gattuso; Robert A. Weinstein; Richard A. Prinz

    2000-01-01

    Summary  \\u000a Background. Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of\\u000a infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6)\\u000a is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis.\\u000a \\u000a \\u000a Methods. Twenty-four mongrel dogs (18–29 kg) were studied in four equal

  12. Chemical mutagenesis testing in Drosophila. I. Comparison of positive and negative control data for sex-linked recessive lethal mutations and reciprocal translocations in three laboratories

    SciTech Connect

    Woodruff, R.C.; Mason, J.M.; Valencia, R.; Zimmering, S.

    1984-01-01

    As part of the validation phase of the Drosophila melanogaster segment of the National Toxicology Program, a comparison has been made of positive and negative controls for sex-linked recessive lethal mutations and reciprocal translocations from three laboratories. This comparison involves approximately 700,000 spontaneous recessive lethal mutation tests, 70,000 spontaneous translocation tests, and screens for genetic damage induced by N-nitrosodimethylamine and ..beta..-propiolactone. Spontaneous frequencies for lethal mutations and translocations were homogeneous in the laboratories regardless of solvent or broods sampled. Inhomogeneity was observed in induced frequencies among laboratories, but the variation was no greater than that found within a laboratory.

  13. A recurrent translocation is mediated by homologous recombination between HERV-H elements

    PubMed Central

    2012-01-01

    Background Chromosome rearrangements are caused by many mutational mechanisms; of these, recurrent rearrangements can be particularly informative for teasing apart DNA sequence-specific factors. Some recurrent translocations are mediated by homologous recombination between large blocks of segmental duplications on different chromosomes. Here we describe a recurrent unbalanced translocation casued by recombination between shorter homologous regions on chromosomes 4 and 18 in two unrelated children with intellectual disability. Results Array CGH resolved the breakpoints of the 6.97-Megabase (Mb) loss of 18q and the 7.30-Mb gain of 4q. Sequencing across the translocation breakpoints revealed that both translocations occurred between 92%-identical human endogenous retrovirus (HERV) elements in the same orientation on chromosomes 4 and 18. In addition, we find sequence variation in the chromosome 4 HERV that makes one allele more like the chromosome 18 HERV. Conclusions Homologous recombination between HERVs on the same chromosome is known to cause chromosome deletions, but this is the first report of interchromosomal HERV-HERV recombination leading to a translocation. It is possible that normal sequence variation in substrates of non-allelic homologous recombination (NAHR) affects the alignment of recombining segments and influences the propensity to chromosome rearrangement. PMID:22260357

  14. 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.

  15. A girl with the Prader-Willi Syndrome and Robertsonian translocation 45,XX,t(14;15)(p11;q11) which was present in three normal family members

    Microsoft Academic Search

    Arabella Smith; Michael Noel

    1980-01-01

    A 21-year-old girl with classical Prader-Willi Syndrome was found to have a 14;15 Robertsonian translocation—45,XX,t(14;15)(p11;q11). This type of Robertsonian translocation was not found in any patient from 8 surveys covering 6144 patients with mental retardation. Chromosome 15 has been involved in translocations in patients with the Prader-Willi Syndrome with greater than expected frequency. This is the first report of a

  16. Analyzing disease risks associated with translocations.

    PubMed

    Sainsbury, Anthony W; Vaughan-Higgins, Rebecca J

    2012-06-01

    Translocations of species are expected to be used increasingly to counter the undesirable effects of anthropogenic changes to ecosystems, including loss of species. Methods to assess the risk of disease associated with translocations have been compiled in a comprehensive manual of disease-risk analysis for movement of domestic animals. We used this manual to devise a qualitative method for assessing the probability of the occurrence of disease in wild animals associated with translocations. We adapted the method such that we considered a parasite (any agent of infectious or noninfectious disease) a hazard if it or the host had crossed an ecological or geographical barrier and was novel to the host. We included in our analyses hazards present throughout the translocation pathway derived from the interactions between host immunity and the parasite, the effect of parasites on populations, the effect of noninfectious disease agents, and the effect of stressors on host-parasite interactions. We used the reintroduction of Eurasian Cranes (Grus grus) to England to demonstrate our method. Of the 24 hazards identified, 1 was classified as high risk (coccidia) and 5 were medium risk (highly pathogenic avian influenza virus, Mycobacterium avium, Aspergillus fumigatus, tracheal worms [Syngamus sp. and Cyathostoma sp.], and Tetrameres spp.). Seventeen other hazards were considered low or very low risk. In the absence of better information on the number, identity, distribution, and pathogenicity of parasites of wild animals, there is uncertainty in the risk of disease to translocated animals and recipient populations. Surveys of parasites in source and destination populations and detailed health monitoring after release will improve the information available for future analyses of disease risk. We believe our method can be adapted to assess the risks of disease in other translocated populations. PMID:22533691

  17. Dynamics of Translocation and Substrate Binding in Individual Complexes Formed with Active Site Mutants of ?29 DNA Polymerase*

    PubMed Central

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

    2014-01-01

    The ?29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual ?29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the ?29 DNAP-DNA binary complex and the ?29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation. Here, we have examined the dynamics of translocation and substrate binding in complexes formed with the Y226F and Y390F mutants. The Y226F mutation diminished the forward and reverse rates of translocation, increased the affinity for dNTP in the post-translocation state by decreasing the dNTP dissociation rate, and increased the affinity for pyrophosphate in the pre-translocation state. The Y390F mutation significantly decreased the affinity for dNTP in the post-translocation state by decreasing the association rate ?2-fold and increasing the dissociation rate ?10-fold, implicating this as a mechanism by which this mutation impedes DNA synthesis. The Y390F dissociation rate increase is suppressed when complexes are examined in the presence of Mn2+ rather than Mg2+. The same effects of the Y226F or Y390F mutations were observed in the background of the D12A/D66A mutations, located in the exonuclease active site, ?30 ? from the polymerase active site. Although translocation rates were unaffected in the D12A/D66A mutant, these exonuclease site mutations caused a decrease in the dNTP dissociation rate, suggesting that they perturb ?29 DNAP interdomain architecture. PMID:24464581

  18. Translocation pathways for inhaled asbestos fibers

    Microsoft Academic Search

    G Miserocchi; G Sancini; F Mantegazza; Gerolamo Chiappino

    2008-01-01

    We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by

  19. 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 processes—rapid directional translocations—that 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

  20. Original article Grooming behaviors and the translocation

    E-print Network

    Paris-Sud XI, Université de

    to the abdomen of honey bee workers. The several observed grooming behaviors do not appear to function solely translocated in substantial amounts to the legs, thorax, and abdomen of reti- nue workers after contracting of QMC to the feet and abdomen of retinue workers may increase the rate at which pheromone can be passed

  1. Geographic Translocation of Bats: Known and Potential Problems

    Microsoft Academic Search

    Denny G. Constantine

    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 dis- eases, 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

  2. Slowing DNA Translocation in a Solid-State Nanopore

    E-print Network

    Li, Jiali

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

  3. 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

  4. Post-release dispersal in animal translocations: social attraction and the "vacuum effect".

    PubMed

    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

  5. A Novel de novo Balanced Reciprocal Translocation t(18;22) Associated with Recurrent Miscarriages: A Case Report

    PubMed Central

    Dutta, Usha R.; Ponnala, Rajitha; Dalal, Ashwin

    2014-01-01

    Background Recurrent miscarriage is a major concern in the couples with reproductive problems. The chromosomal abnormalities, mainly balanced rearrangements are reported in variable phenotypes and the prevalence of them is 2-8% in such couples. Case Presentation In this study, the clinical, cytogenetic and molecular cytogenetic evaluations were performed on a couple with RM. The cytogenetic analysis of the husband revealed a balanced reciprocal translocation of t(18;22)(q21.1;q12) whereas wife had a normal karyotype of 46,XX. Further spectral karyotyping was performed to rule out the involvement of any other chromosomal aberrations present in the genome. Additional whole chromosome paint FISH (Fluorescence in situ hybridization) with paint probes 18 and 22 confirmed the translocation. Conclusion To our knowledge, this is the first report of a novel (18;22) translocation with unique breakpoints and their association with RM. The reciprocal translocations provide a good opportunity for the identification of disease associated genes. However, in recurrent miscarriages, most of them do not disrupt any gene at the breakpoint but can lead to unbalanced gametes and hence poor reproductive outcome like RM or birth of a child with malformations and intellectual disability. The translocation breakpoints might be risk factors for RM. Moreover, the impact of the balanced translocations in association with RM is discussed in this report. PMID:24918085

  6. 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

  7. Translocation and encapsulation of siRNA inside carbon nanotubes

    E-print Network

    Santosh Mogurampelly; Prabal K. Maiti

    2012-12-11

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

  8. Translocation and encapsulation of siRNA inside carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Mogurampelly, Santosh; Maiti, Prabal K.

    2013-01-01

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

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

    PubMed

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

    2010-12-01

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

  10. 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

  11. The Bacterial Twin-Arginine Translocation Pathway

    PubMed Central

    Lee, Philip A.; Tullman-Ercek, Danielle; Georgiou, George

    2009-01-01

    The twin-arginine translocation (Tat) pathway is responsible for the export of folded proteins across the cytoplasmic membrane of bacteria. Substrates for the Tat pathway include redox enzymes requiring cofactor insertion in the cytoplasm, multimeric proteins that have to assemble into a complex prior to export, certain membrane proteins, and proteins whose folding is incompatible with Sec export. These proteins are involved in a diverse range of cellular activities including anaerobic metabolism, cell envelope biogenesis, metal acquisition and detoxification, and virulence. The Escherichia coli translocase consists of the TatA, TatB, and TatC proteins, but little is known about the precise sequence of events that leads to protein translocation, the energetic requirements, or the mechanism that prevents the export of misfolded proteins. Owing to the unique characteristics of the pathway, it holds promise for biotechnological applications. PMID:16756481

  12. Regulating DNA translocation through functionalized soft nanopores

    NASA Astrophysics Data System (ADS)

    Yeh, Li-Hsien; Zhang, Mingkan; Qian, Shizhi; Hsu, Jyh-Ping

    2012-03-01

    Nanopores have emerged as promising next-generation devices for DNA sequencing technology. The two major challenges in such devices are: (i) find an efficient way to raise the DNA capture rate prior to funnelling a nanopore, and (ii) reduce the translocation velocity inside it so that single base resolution can be attained efficiently. To achieve these, a novel soft nanopore comprising a solid-state nanopore and a functionalized soft layer is proposed to regulate the DNA electrokinetic translocation. We show that, in addition to the presence of an electroosmotic flow (EOF), which reduces the DNA translocation velocity, counterion concentration polarization (CP) occurs near the entrance of the nanopore. The latter establishes an enrichment of the counterion concentration field, thereby electrostatically enhancing the capture rate. The dependence of the ionic current on the bulk salt concentration, the soft layer properties, and the length of the nanopore are investigated. We show that if the salt concentration is low, the ionic current depends largely upon the length of the nanopore, and the density of the fixed charge of the soft layer, but not upon its degree of softness. On the other hand, if it is high, ionic current blockade always occurs, regardless of the levels of the other parameters. The proposed soft nanopore is capable of enhancing the performance of DNA translocation while maintaining its basic signature of the ionic current at high salt concentration. The results gathered provide the necessary information for designing devices used in DNA sequencing.Nanopores have emerged as promising next-generation devices for DNA sequencing technology. The two major challenges in such devices are: (i) find an efficient way to raise the DNA capture rate prior to funnelling a nanopore, and (ii) reduce the translocation velocity inside it so that single base resolution can be attained efficiently. To achieve these, a novel soft nanopore comprising a solid-state nanopore and a functionalized soft layer is proposed to regulate the DNA electrokinetic translocation. We show that, in addition to the presence of an electroosmotic flow (EOF), which reduces the DNA translocation velocity, counterion concentration polarization (CP) occurs near the entrance of the nanopore. The latter establishes an enrichment of the counterion concentration field, thereby electrostatically enhancing the capture rate. The dependence of the ionic current on the bulk salt concentration, the soft layer properties, and the length of the nanopore are investigated. We show that if the salt concentration is low, the ionic current depends largely upon the length of the nanopore, and the density of the fixed charge of the soft layer, but not upon its degree of softness. On the other hand, if it is high, ionic current blockade always occurs, regardless of the levels of the other parameters. The proposed soft nanopore is capable of enhancing the performance of DNA translocation while maintaining its basic signature of the ionic current at high salt concentration. The results gathered provide the necessary information for designing devices used in DNA sequencing. Electronic supplementary information (ESI) available: Details of the theoretical derivation, numerical implementation, code validation, and the results of the normalized DNA translational velocity for the case of Fig. 5. See DOI: 10.1039/c2nr30102d

  13. Facial Translocation Approach to the Cranial Base

    PubMed Central

    Arriaga, Moises A.; Janecka, Ivo P.

    1991-01-01

    Surgical exposure of the nasopharyngeal region of the cranial base is difficult because of its proximity to key anatomic structures. Our laboratory study outlines the anatomic basis for a new approach to this complex topography. Dissections were performed on eight cadaver halves and two fresh specimens injected with intravascular silicone rubber compound. By utilizing facial soft tissue translocation combined with craniofacial osteotomies; a wide surgical field can be obtained at the skull base. The accessible surgical field extends from the contralateral custachian tube to the ipsilateral geniculate ganglion, including the nasopharyax; clivus, sphonoid, and cavernous sinuses, the entire infratemporal fossa, and superior orbital fissure. The facial translocation approach offers previously unavailable wide and direct exposure, with a potential for immediate reconstruction, of this complex region of the cranial base. ImagesFigure 4Figure 5Figure 7Figure 8Figure 9 PMID:17170817

  14. Translocation of Thorotrast in the body.

    PubMed

    Spiethoff, A; Wesch, H; Wegener, K; Hanisch, E; Kaul, A

    1994-06-01

    To investigate whether there is a permanent translocation of Thorotrast in the body, the liver of male Lewis rats was removed 4 weeks after injection of Thorotrast (300 microliters) and replaced by a donor liver. In half of the animals the spleen was removed as well. Measuring the 232Th content in the donor liver at different times after implantation demonstrated a permanent transport of 232Th into the surrogate organ. After 231 days a 232Th depot of about 1.1 mg was found, representing about 3% of the total body burden. The additional removal of the spleen resulted in a significantly lower transport of 232Th into the implanted liver. Histological examinations of the donated livers revealed increasing local concentration of Thorotrast granules, leading to the development of conglomerates. A comparable translocation of Thorotrast was verified in two humans who required liver transplantation more than 40 years after Thorotrast injection. PMID:8184016

  15. Iron translocation by free fatty acids.

    PubMed

    Qian, M W; Eaton, J W

    1991-12-01

    Organic extracts of cigarette smoke and uncombusted tobacco contain substances capable of translocating iron from aqueous solutions into immiscible organic solvents. Such extracts will also effect the organic solvation of iron present in ferruginous forms of asbestos such as amosite and crocidolite (Qian and Eaton, Arch Biochem Biophys 1989, 275:280). These substances, previously detected by their iron-translocating properties, have now been purified and identified by mass spectroscopy as saturated fatty acids, predominantly stearic and palmitic acids. Organic extracts of tobacco smoke, as well as the pure fatty acids, also transfer ferrous iron into both isolated red cell membranes and intact human erythrocytes. The increased membrane iron may enhance cellular susceptibility to exogenous oxidants; erythrocyte membranes subject to fatty acid-mediated iron accumulation show elevated peroxidation of endogenous polyunsaturated fatty acids. These observations may help explain the phlogistic effects of tobacco use and suggest, in a broader context, that free fatty acids may act as physiologic and pathologic mediators of metal translocation. PMID:1750512

  16. Determination of RNA orientation during translocation through a biological nanopore.

    PubMed

    Butler, Tom Z; Gundlach, Jens H; Troll, Mark A

    2006-01-01

    We investigate single-molecule electrophoretic translocation of A(50), C(50), A(25)C(50), and C(50)A(25) RNA molecules through the alpha-hemolysin transmembrane protein pore. We observe pronounced bilevel current blockages during translocation of A(25)C(50) and C(50)A(25) molecules. The two current levels observed during these bilevel blockages are very similar to the characteristic current levels observed during A(50) and C(50) translocation. From the temporal ordering of the two levels within the bilevel current blockages, we infer whether individual A(25)C(50) and C(50)A(25) molecules pass through the pore in a 3'-->5' or 5'-->3' orientation. Correlation between the level of current obstruction and the inferred A(25)C(50) or C(50)A(25) orientation indicates that 3'-->5' translocation of a poly C segment causes a significantly deeper current obstruction than 5'-->3' translocation. Our analysis also suggests that the 3' ends of C(50) and A(25)C(50) RNA molecules are more likely to initiate translocation than the 5' ends. Orientation dependent differences in a smaller current blockage that immediately precedes many translocation events suggest that this blockage also contains information about RNA orientation during translocation. These findings emphasize that the directionality of polynucleotide molecules is an important factor in translocation and demonstrate how structure within ionic current signals can give new insights into the translocation process. PMID:16214857

  17. Formation of complex and unstable chromosomal translocations in yeast.

    PubMed

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

    2010-01-01

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

  18. 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

  19. Genomic Hallmarks of Genes Involved in Chromosomal Translocations in Hematological Cancer

    PubMed Central

    Shugay, Mikhail; Ortiz de Mendíbil, Iñigo; Vizmanos, José L.; Novo, Francisco J.

    2012-01-01

    Reciprocal chromosomal translocations (RCTs) leading to the formation of fusion genes are important drivers of hematological cancers. Although the general requirements for breakage and fusion are fairly well understood, quantitative support for a general mechanism of RCT formation is still lacking. The aim of this paper is to analyze available high-throughput datasets with computational and robust statistical methods, in order to identify genomic hallmarks of translocation partner genes (TPGs). Our results show that fusion genes are generally overexpressed due to increased promoter activity of 5? TPGs and to more stable 3?-UTR regions of 3? TPGs. Furthermore, expression profiling of 5? TPGs and of interaction partners of 3? TPGs indicates that these features can help to explain tissue specificity of hematological translocations. Analysis of protein domains retained in fusion proteins shows that the co-occurrence of specific domain combinations is non-random and that distinct functional classes of fusion proteins tend to be associated with different components of the gene fusion network. This indicates that the configuration of fusion proteins plays an important role in determining which 5? and 3? TPGs will combine in specific fusion genes. It is generally accepted that chromosomal proximity in the nucleus can explain the specific pairing of 5? and 3? TPGS and the recurrence of hematological translocations. Using recently available data for chromosomal contact probabilities (Hi-C) we show that TPGs are preferentially located in early replicated regions and occupy distinct clusters in the nucleus. However, our data suggest that, in general, nuclear position of TPGs in hematological cancers explains neither TPG pairing nor clinical frequency. Taken together, our results support a model in which genomic features related to regulation of expression and replication timing determine the set of candidate genes more likely to be translocated in hematological tissues, with functional constraints being responsible for specific gene combinations. PMID:23236267

  20. 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

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

    PubMed

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

    2015-02-26

    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. PMID:25685900

  2. The regulation of ammonium translocation in plants.

    PubMed

    Schjoerring, J K; Husted, S; Mäck, G; Mattsson, M

    2002-04-01

    Much controversy exists about whether or not NH(+)(4) is translocated in the xylem from roots to shoots. In this paper it is shown that such translocation can indeed take place, but that interference from other metabolites such as amino acids and amines may give rise to large uncertainties about the magnitude of xylem NH(+)(4) concentrations. Elimination of interference requires sample stabilization by, for instance, formic acid or methanol. Subsequent quantification of NH(+)(4) should be done by the OPA-fluorometric method at neutral pH with 2-mercaptoethanol as the reducing agent since this method is sensitive and reliable. Colorimetric methods based on the Berthelot reaction should never be used, as they are prone to give erroneous results. Significant concentrations of NH(+)(4), exceeding 1 mM, were measured in both xylem sap and leaf apoplastic solution of oilseed rape and tomato plants growing with NO(-)(3) as the sole N source. When NO(-)(3) was replaced by NH(+)(4), xylem sap NH(+)(4) concentrations increased with increasing external concentrations and with time of exposure to NH(+)(4). Up to 11% of the translocated N was constituted by NH(+)(4). Glutamine synthetase (GS) incorporates NH(+)(4) into glutamine, but root GS activity and expression were repressed when high levels of NH(+)(4) were supplied. Ammonium concentrations measured in xylem sap sampled just above the stem base were highly correlated with NH(+)(4) concentrations in apoplastic solution from the leaves. Young leaves tended to have higher apoplastic NH(+)(4) concentrations than older non-senescing leaves. The flux of NH(+)(4) (concentration multiplied by transpirational water flow) increased with temperature despite a decline in xylem NH(+)(4) concentration. Retrieval of leaf apoplastic NH(+)(4) involves both high and low affinity transporters in the plasma membrane of mesophyll cells. Current knowledge about these transporters and their regulation is discussed. PMID:11912231

  3. 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

  4. Assessing translocation outcome: Comparing behavioral and physiological aspects of translocated and resident African elephants (Loxodonta africana)

    E-print Network

    Pinter-Wollman, Noa

    - bwa et al., 2001), and for humanely reducing overpopulation at the source site (Garai and Carr, 2001. (2000), and Edgar et al. (2005)), for solving human-wildlife conflicts (Jones and Nealson, 2003; Wam (Griffith et al., 1989) and most translocations aimed at solving human­animal conflicts have failed (Fischer

  5. Evaluation of translocation criteria: case study with trumpeter swans ( Cygnus buccinator)

    Microsoft Academic Search

    Katharina A. M Engelhardt; John A Kadlec; Victoria L Roy; James A Powell

    2000-01-01

    Translocations are a common conservation technique; however, the feasibility and success of translocations are evaluated rarely. We translocated 57 trumpeter swans (Cygnus buccinator) from Idaho to Utah during 1996 to encourage migration to more southern wintering areas. We evaluated the feasibility and success of the translocation by studying biological and socio-political criteria prior to and during the translocation. Lack of

  6. Mineralocorticoid and glucocorticoid receptor mRNA expression in the brain of translocated chukar ( Alectoris chukar)

    Microsoft Academic Search

    Molly J. Dickens; Simone L. Meddle; L. Michael Romero

    2011-01-01

    Although translocation is an important conservation tool in the effort to create self-sustaining wild populations of threatened species, avian translocations have a high failure rate and causes for failure are poorly understood. While “stress” is considered to play a major role in translocation failure, the physiological changes associated with chronic stress resulting from translocation have been investigated only recently. Translocation

  7. Mitochondrial BNIP3 upregulation precedes endonuclease G translocation in hippocampal neuronal death following oxygen-glucose deprivation

    PubMed Central

    Zhao, Shen-Ting; Chen, Ming; Li, Shu-Ji; Zhang, Ming-Hai; Li, Bo-Xing; Das, Manas; Bean, Jonathan C; Kong, Ji-Ming; Zhu, Xin-Hong; Gao, Tian-Ming

    2009-01-01

    Background Caspase-independent apoptotic pathways are suggested as a mechanism for the delayed neuronal death following ischemic insult. However, the underlying signalling mechanisms are largely unknown. Recent studies imply the involvement of several mitochondrial proteins, including endonuclease G (EndoG) and Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP3), in the pathway of non-neuronal cells. Results In this report, using western blot analysis and immunocytochemistry, we found that EndoG upregulates and translocates from mitochondria to nucleus in a time-dependent manner in cultured hippocampal neurons following oxygen-glucose deprivation (OGD). Moreover, the translocation of EndoG occurs hours before the observable nuclear pyknosis. Importantly, the mitochondrial upregulation of BNIP3 precedes the translocation of EndoG. Forced expression of BNIP3 increases the nuclear translocation of EndoG and neuronal death while knockdown of BNIP3 decreases the OGD-induced nuclear translocation of EndoG and neuronal death. Conclusion These results suggest that BNIP3 and EndoG play important roles in hippocampal neuronal apoptosis following ischemia, and mitochondrial BNIP3 is a signal protein upstream of EndoG that can induce neuronal death. PMID:19737385

  8. Microbial Translocation in Chronic Liver Diseases

    PubMed Central

    Pinzone, Marilia Rita; Celesia, Benedetto Maurizio; Di Rosa, Michele; Cacopardo, Bruno; Nunnari, Giuseppe

    2012-01-01

    The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products (i.e., LPS, lipopeptides) from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. The most recent evidence suggests that microbial translocation (MT) may occur not only in cirrhosis, but also in the early stage of several liver diseases, including alcoholic hepatopathy and nonalcoholic fatty liver disease. Different mechanisms, such as small intestinal bacterial overgrowth, increased permeability of intestinal mucosa, and impaired immunity, may favor MT. Furthermore, MT has been implicated in the pathogenesis of the complications of cirrhosis, which are a significant cause of morbidity and mortality in cirrhotic subjects. Therapeutic strategies aiming at modulating the gut microflora and reducing MT have focused on antibiotic-based options, such as selective intestinal decontamination, and nonantibiotic-based options, such as prokinetics and probiotics. In particular, probiotics may represent an attractive strategy, even though the promising results of experimental models and limited clinical studies need to be confirmed in larger randomized trials. PMID:22848224

  9. Microbial translocation in chronic liver diseases.

    PubMed

    Pinzone, Marilia Rita; Celesia, Benedetto Maurizio; Di Rosa, Michele; Cacopardo, Bruno; Nunnari, Giuseppe

    2012-01-01

    The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products (i.e., LPS, lipopeptides) from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. The most recent evidence suggests that microbial translocation (MT) may occur not only in cirrhosis, but also in the early stage of several liver diseases, including alcoholic hepatopathy and nonalcoholic fatty liver disease. Different mechanisms, such as small intestinal bacterial overgrowth, increased permeability of intestinal mucosa, and impaired immunity, may favor MT. Furthermore, MT has been implicated in the pathogenesis of the complications of cirrhosis, which are a significant cause of morbidity and mortality in cirrhotic subjects. Therapeutic strategies aiming at modulating the gut microflora and reducing MT have focused on antibiotic-based options, such as selective intestinal decontamination, and nonantibiotic-based options, such as prokinetics and probiotics. In particular, probiotics may represent an attractive strategy, even though the promising results of experimental models and limited clinical studies need to be confirmed in larger randomized trials. PMID:22848224

  10. A translocation, insertion and deletion distance formula for sorting genomes

    Microsoft Academic Search

    Hao Fanchang; Luan Junfeng; Zhu Daming; Feng Haodi

    2009-01-01

    Sorting genomes by translocation, insertion and deletions has already been researched for years such as in. However, the authors in did not consider the case that a gene in the target genome does not appear in the source genome. Translocation is a reciprocal operation in sorting genomes, and deletion and insertion are reciprocal to each other. In this paper, we

  11. Anomalous dynamics of forced translocation Yacov Kantor1,

    E-print Network

    Kantor, Yacov

    . INTRODUCTION Translocation of a polymer through a narrow pore in a membrane is important to many biological, and gene swapping through bacterial pili 1 . Translocation also has practical applica- tions in genetics as in cell transformation by DNA electropo- ration 1 , and in gene therapy 2 . This has inspired a num- ber

  12. Mechanisms of chromosomal translocations in B cell lymphomas

    Microsoft Academic Search

    Ralf Küppers; Riccardo Dalla-Favera

    2001-01-01

    Reciprocal chromosomal translocations involving the immunoglobulin (Ig) loci are a hallmark of most mature B cell lymphomas and usually result in dysregulated expression of oncogenes brought under the control of the Ig enhancers. Although the precise mechanisms involved in the development of these translocations remains essentially unknown, a clear relationship has been established with the mechanisms that lead to Ig

  13. Translocation of Canada Geese branta canadensis in great Britain

    Microsoft Academic Search

    J. S. Kirby; W. G. Haines; G. E. Austin

    1999-01-01

    In Britain, Canada Geese Branta canadensis have been translocated into new areas and\\/or areas of low abundance, principally in order to solve problems of local damage to crops or amenity grasslands and to provide new sport?shooting opportunities for wildfowling clubs. This paper, based on a compilation of the available translocation records, provides the most definitive record of the extent of

  14. To translocate, or not: that is the problem

    PubMed Central

    Lencer, Wayne I.; Tweten, Rodney K.

    2011-01-01

    Summary The botulinum toxins (BoNTs) enter the cytosol of host cells by translocation across the limiting membrane of acidic endosomes. In this issue, Sun et. al (2011) show that BoNT binding to one of its cell surface receptors renders it susceptible to pH-dependent conformational changes required for translocation and cellular toxicity. PMID:21925105

  15. Cytogenetic observations on a Robertsonian translocation in Saanen goats (1)

    E-print Network

    Boyer, Edmond

    Cytogenetic observations on a Robertsonian translocation in Saanen goats (1) I. BURGUETE D. DI type was detected in a herd of 15 goats of the Saanen breed, reared on a farm located in southern Italy-armed chromosome. Key words : Robertsonian translocation, goat, chromosomes. Résumé Etude cytogénétique d

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

    PubMed Central

    Tincati, Camilla; Silvestri, Guido

    2013-01-01

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

  17. Translocation events in a single-walled carbon nanotube

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

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

  18. The layer impact of DNA translocation through graphene nanopores

    E-print Network

    Wenping Lv; Maodu Chen; Renan Wu

    2012-10-24

    Graphene nanopore based sensor devices are exhibiting the great potential for the detection of DNA. To understand the fundamental aspects of DNA translocating through a graphene nanopore, in this work, molecular dynamics (MD) simulations and potential of mean force (PMF) calculations were carried out to investigate the layer impact of small graphene nanopore (2 nm-3 nm) to DNA translocation. It was observed that the ionic conductance was sensitive to graphene layer of open-nanopores, the probability for DNA translocation through graphene nanopore was related with the thickness of graphene nanopores. MD simulations showed that DNA translocation time was most sensitive to the thickness of graphene nanopore for a 2.4 nm aperture, and the observed free energy barrier of PMFs and the profile change revealed the increased retardation of DNA translocation through bilayer graphene nanopore as compared to monolayer graphene nanopore.

  19. 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.

  20. Strandwise translocation of a DNA glycosylase on undamaged DNA

    SciTech Connect

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

    2012-05-14

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

  1. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations.

    PubMed

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S; Knudsen, Helle; Lauritzen, Anne F; Nielsen, Signe L; Klausen, Tobias W; Nørgaard, Peter

    2014-01-01

    In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 double-hit (DH) translocations have been associated with inferior survival. We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene (IG-MYC), as opposed to a non-immunoglobulin partner gene (nonIG-MYC). In a prospective, unselected cohort of 237 LBCL patients MYC and BCL2 translocations were identified by fluorescent in situ hybridisation (FISH) with split probes. MYC translocation partner gene was identified by IGH/MYC fusion probes and/or kappa/lambda split probes. Clinical data were collected from patient files. MYC translocation was identified in 28/225 patients. IG-MYC translocation partner gene was identified in 12/24 patients. DH translocation was identified in 23/228 patients. IG-MYC translocation partner gene was identified in 9/19 DH patients. Neither MYC-nor DH translocation showed correlation with survival. However, MYC translocation with IG-MYC translocation partner gene was associated with worse OS compared with both MYC translocation with nonIG-MYC translocation partner gene (P = 0.02) as well as absence of MYC translocation (P = 0.03). In patients with DH a similar, however, stronger correlation was seen (P = 0.003 and P = 0.0004 respectively). MYC - or DH translocation with nonIG-MYC translocation partner gene was not associated with worse overall survival (P = 0.2 and P = 0.3 respectively). Most patients received Rituximab (86%) and CHOP/CHOP-like chemotherapy regimes (81%). We suggest that prognostic stratification of LBCL patients by MYC and/or DH translocations should include identification of MYC translocation partner gene because approximately half of the cases harbour nonIG-MYC translocation partner genes with no or minor influence on survival. PMID:24118498

  2. Crystal structure of the Yersinia enterocolitica type III secretion chaperone SycD in complex with a peptide of the minor translocator YopD

    PubMed Central

    2012-01-01

    Background Type III secretion systems are used by Gram-negative bacteria as “macromolecular syringes” to inject effector proteins into eukaryotic cells. Two hydrophobic proteins called translocators form the necessary pore in the host cell membrane. Both translocators depend on binding to a single chaperone in the bacterial cytoplasm to ensure their stability and efficient transport through the secretion needle. It was suggested that the conserved chaperones bind the more divergent translocators via a hexapeptide motif that is found in both translocators and conserved between species. Results We crystallized a synthetic decapeptide from the Yersinia enterocolitica minor type III secretion translocator YopD bound to its cognate chaperone SycD and determined the complex structure at 2.5?Å resolution. The structure of peptide-bound SycD is almost identical to that of apo SycD with an all helical fold consisting of three tetratricopeptide repeats (TPRs) and an additional C-terminal helix. Peptide-bound SycD formed a kinked head-to-head dimer that had previously been observed for the apo form of SycD. The homodimer interface comprises both helices of the first tetratricopeptide repeat. The YopD peptide bound in extended conformation into a mainly hydrophobic groove on the concave side of SycD. TPRs 1 and 2 of SycD form three hydrophobic pockets that accommodated the conserved hydrophobic residues at position 1, 3 and 6 of the translocator hexapeptide sequence. Two tyrosines that are highly conserved among translocator chaperones contribute to the hydrophobic patches but also form hydrogen bonds to the peptide backbone. Conclusions The interaction between SycD and YopD is very similar to the binding of the Pseudomonas minor translocator PopD to its chaperone PcrH and the Shigella major translocator IpaB to its chaperone IpgC. This confirms the prediction made by Kolbe and co-workers that a hexapeptide with hydrophobic residues at three positions is a conserved chaperone binding motif. Because the hydrophobic groove on the concave side of translocator chaperones is involved in binding of the major and the minor translocator, simultaneous binding of both translocators to a single type III secretion class II chaperone appears unlikely. PMID:22708907

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

    PubMed Central

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

    2011-01-01

    We studied a man with distal hypospadias, partial anomalous pulmonary venous return, mild limb-length inequality and a balanced translocation involving chromosomes 9 and 13. To gain insight into the etiology of his birth defects, we mapped the translocation breakpoints by high-resolution comparative genomic hybridization (CGH), using chromosome 9- and 13-specific tiling arrays to analyze genetic material from a spontaneously aborted fetus with unbalanced segregation of the translocation. The chromosome 13 breakpoint was ?400?kb away from the nearest gene, but the chromosome 9 breakpoint fell within an intron of Basonuclin 2 (BNC2), a gene that encodes an evolutionarily conserved nuclear zinc-finger protein. The BNC2/Bnc2 gene is abundantly expressed in developing mouse and human periurethral tissues. In all, 6 of 48 unrelated subjects with distal hypospadias had nine novel nonsynonymous substitutions in BNC2, five of which were computationally predicted to be deleterious. In comparison, two of 23 controls with normal penile urethra morphology, each had a novel nonsynonymous substitution in BNC2, one of which was predicted to be deleterious. Bnc2?/? mice of both sexes displayed a high frequency of distal urethral defects; heterozygotes showed similar defects with reduced penetrance. The association of BNC2 disruption with distal urethral defects and the gene's expression pattern indicate that it functions in urethral development. PMID:21368915

  4. Microwave Background, Backgrounds Hierarchy - Polyphony of Universe

    E-print Network

    A. M. Chechelnitsky

    2001-05-18

    We discuss the structure, physical nature, dynamic genesis of clearly detected diffuse backgrounds (radiations) in the Universe. From the point of view of Wave Universe concept it is shown, that observed Backgrounds Hierarchy (Polyphony of Universe) is close connected and causely determined by the sound velocity Hierarchy of the physical medium, cosmic (polycomponent) plasma. The well-known Microwave Background (Cosmic Background Radiation - CBR) corresponds to the F[3] Background, that is characterized by the calculated sound velocity C*[3]=11.483 km/s, by the calculated temperature T*[3]=2.9 grad.K and by wavelength of the radiation intensity maximum lambda*[3]=1 mm.

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

    PubMed Central

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

    2014-01-01

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

  6. 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

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

    PubMed Central

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

    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

  8. Effects of calcium on rhizotoxicity and the accumulation and translocation of copper by grapevines.

    PubMed

    Chen, Pei-Yi; Lee, Yung-I; Chen, Bo-Ching; Juang, Kai-Wei

    2013-12-01

    We assessed the effects of background concentrations of calcium (Ca) in solution on rhizotoxicity of copper (Cu) in and the accumulation and translocation of Cu by the grapevine, Vitis vinifera L. var. Kyoho. Grapevine cuttings in a hydroponic system were exposed to Cu-spiked solutions (0, 1, 2.5, 5, 10, and 25 ?M) with two Ca backgrounds (0.5 and 5 mM) for 15 days. We found that when Cu exposure exceeded 5 ?M, no new white roots were generated from the cuttings. When exposed to a Cu concentration of 25 ?M, the lateral roots were sparse, appeared dark and exhibited malformed terminal swellings. The morphological phenomena of root response to an increase in Cu levels were relatively pronounced at a background concentration of 5 mM Ca; epidermal cell walls thickened, cortical cells remained intact and root terminal swelling was enhanced with Cu exposure. A 5 mM Ca background concentration enhanced the reduction in relative root elongation, but alleviated the reduction in relative root dry weight with increased Cu exposure. Moreover, there was a prominent increase in root Cu concentrations with increased Cu exposure, but the increases in leaf Cu concentrations were much less. The Cu profile of Cu exposure in a 5 mM Ca background concentration appeared higher in root, but lower in leaf than the Cu profile in a 0.5 mM Ca background; therefore, increase of Ca background concentrations would enhance Cu to be accumulated by root, but not translocated into the leaf. PMID:24211513

  9. Robertsonian translocations in wheat arise by centric misdivision of univalents at anaphase I and rejoining of broken centromeres during interkinesis of meiosis II.

    PubMed

    Friebe, B; Zhang, P; Linc, G; Gill, B S

    2005-01-01

    The mechanism of origin of Robertsonian translocations was investigated in plants monosomic for chromosome 1A of wheat and 1H(t) of Elymus trachycaulus by GISH. Chromosomes 1A and 1H(t) stayed univalent in all metaphase I cells analyzed, suggesting that Robertsonian translocations do not originate from meiotic recombination in centromeric regions with shared DNA sequence homology. At ana-/telophase I, the 1H(t) and 1A univalents underwent either chromosome or chromatid segregation and misdivided in 6-7% of the pollen mother cells. None of the ana-/telophases I analyzed had Robertsonian translocations, which were only observed in 2% of the "half tetrads" at ana-/telophase II. The frequency of Robertsonian translocations observed at ana-/telophase II corresponds well with the number of Robertsonian translocations (1-4%) detected in progenies derived from plants monosomic for group-1 chromosomes of wheat (1A, 1B, and 1D) and 1H(t) of E. trachycaulus. Our data suggest that Robertsonian translocations arise from centric misdivision of univalents at ana-/telophase I, followed by segregation of the derived telocentric chromosomes to the same nucleus, and fusion of the broken ends during the ensuing interkinesis. PMID:15753589

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  11. 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.

  12. Polymer Translocation Dynamics in the Quasi-Static Limit

    E-print Network

    James M. Polson; Anthony C. M. McCaffrey

    2013-03-16

    Monte Carlo (MC) simulations are used to study the dynamics of polymer translocation through a nanopore in the limit where the translocation rate is sufficiently slow that the polymer maintains a state of conformational quasi-equilibrium. The system is modeled as a flexible hard-sphere chain that translocates through a cylindrical hole in a hard flat wall. In some calculations, the nanopore is connected at one end to a spherical cavity. Translocation times are measured directly using MC dynamics simulations. For sufficiently narrow pores, translocation is sufficiently slow that the mean translocation time scales with polymer length N according to \\propto (N-N_p)^2, where N_p is the average number of monomers in the nanopore; this scaling is an indication of a quasi-static regime in which polymer-nanopore friction dominates. We use a multiple-histogram method to calculate the variation of the free energy with Q, a coordinate used to quantify the degree of translocation. The free energy functions are used with the Fokker-Planck formalism to calculate translocation time distributions in the quasi-static regime. These calculations also require a friction coefficient, characterized by a quantity N_{eff}, the effective number of monomers whose dynamics are affected by the confinement of the nanopore. This was determined by fixing the mean of the theoretical distribution to that of the distribution obtained from MC dynamics simulations. The theoretical distributions are in excellent quantitative agreement with the distributions obtained directly by the MC dynamics simulations for physically meaningful values of N_{eff}. The free energy functions for narrow-pore systems exhibit oscillations with an amplitude that is sensitive to the nanopore length. Generally, larger oscillation amplitudes correspond to longer translocation times.

  13. 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.

  14. Dialysis dose and frequency

    Microsoft Academic Search

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

    2004-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. Cosmic microwave background theory.

    PubMed

    Bond, J R

    1998-01-01

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

  17. Effect of the cGMP pathway on AQP2 expression and translocation: potential implications for nephrogenic diabetes insipidus

    Microsoft Academic Search

    M. Boone; M. L. A. Kortenoeven; J. H. Robben; P. M. T. Deen

    2010-01-01

    BACKGROUND: Arginine vasopressin (AVP) binding to the V2 receptor (V2R) in renal collecting duct principal cells induces a cAMP signalling cascade resulting in the activation of protein kinase A (PKA), translocation of aquaporin-2 (AQP2) to the apical membrane and an increase in AQP2 expression. Consequently, concentration of urine is initiated. X-linked nephrogenic diabetes insipidus (NDI), characterized by the inability to

  18. Alpha-Lipoic Acid Attenuates Cisplatin-Induced Tubulointerstitial Injuries through Inhibition of Mitochondrial Bax Translocation in Rats

    Microsoft Academic Search

    Young Mo Lee; So Yon Bae; Nam Hee Won; Heui Jung Pyo; Young Joo Kwon

    2009-01-01

    Background: Renal tubule cell apoptosis plays a pivotal role in cisplatin-induced nephrotoxicity. ?-Lipoic acid (LA), a thiol antioxidant, is well known to be cytoprotective in various cell death models through its involvement in the death receptor apoptosis pathway. However, we hypothesized that LA would attenuate cisplatin-induced nephrotoxicity through inhibition of mitochondrial bax translocation in rats. Methods and Materials: Sprague-Dawley rats

  19. 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.

  20. Multiscale model of platelet translocation and collision

    PubMed Central

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

    2012-01-01

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

  1. Mechanical Design of Translocating Motor Proteins

    PubMed Central

    Lang, Matthew J.

    2013-01-01

    Translocating motors generate force and move along a biofilament track to achieve diverse functions including gene transcription, translation, intracellular cargo transport, protein degradation, and muscle contraction. Advances in single molecule manipulation experiments, structural biology, and computational analysis are making it possible to consider common mechanical design principles of these diverse families of motors. Here, we propose a mechanical parts list that include track, energy conversion machinery, and moving parts. Energy is supplied not just by burning of a fuel molecule, but there are other sources or sinks of free energy, by binding and release of a fuel or products, or similarly between the motor and the track. Dynamic conformational changes of the motor domain can be regarded as controlling the flow of free energy to and from the surrounding heat reservoir. Multiple motor domains are organized in distinct ways to achieve motility under imposed physical constraints. Transcending amino acid sequence and structure, physically and functionally similar mechanical parts may have evolved as nature’s design strategy for these molecular engines. PMID:19452133

  2. Control of protein function through optochemical translocation.

    PubMed

    Engelke, Hanna; Chou, Chungjung; Uprety, Rajendra; Jess, Phillip; Deiters, Alexander

    2014-10-17

    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 applications-light-triggered transcription and light-triggered protease cleavage-both 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

  3. Energy-dependent intracellular translocation of proparathormone

    PubMed Central

    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

  4. 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 applications—light-triggered transcription and light-triggered protease cleavage—both 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

  5. Polymer translocation through a long nanopore Elena Slonkina

    E-print Network

    is also technologi- cally important in food and medicine production, in oil re- covery and separation.1063/1.1560932 I. INTRODUCTION Translocation of polymers across a nanopore plays a critical role in numerous

  6. Sequence dependence of DNA translocation through a nanopore

    E-print Network

    Kaifu Luo; Tapio Ala-Nissila; See-Chen Ying; Aniket Bhattacharya

    2007-12-01

    We investigate the dynamics of DNA translocation through a nanopore using 2D Langevin dynamics simulations, focusing on the dependence of the translocation dynamics on the details of DNA sequences. The DNA molecules studied in this work are built from two types of bases $A$ and $C$, which has been shown previously to have different interactions with the pore. We study DNA with repeating blocks $A_nC_n$ for various values of $n$, and find that the translocation time depends strongly on the {\\em block length} $2n$ as well as on the {\\em orientation} of which base entering the pore first. Thus, we demonstrate that the measurement of translocation dynamics of DNA through nanopore can yield detailed information about its structure. We have also found that the periodicity of the block sequences are contained in the periodicity of the residence time of the individual nucleotides inside the pore.

  7. Genic Heterozygosity and Variation in Permanent Translocation Heterozygotes of the OENOTHERA BIENNIS Complex

    PubMed Central

    Levy, Morris; Levin, Donald A.

    1975-01-01

    Genic heterozygosity and variation were studied in the permanent translocation heterozygotes Oenothera biennis I, Oe. biennis II, Oe. biennis III, Oe. strigosa, Oe. parviflora I, Oe. parviflora II, and in the related bivalent formers Oe. argillicola and Oe. hookeri. From variation at 20 enzyme loci, we find that translocation heterozygosity for the entire chromosome complex is accompanied by only moderate levels of genic heterozygosity: 2.8% in Oe. strigosa, 9.5% in Oe. biennis and 14.9% in Oe. parviflora. Inbred garden strains of Oe. argillicola exhibited 8% heterozygosity; neither garden nor wild strains of Oe. hookeri displayed heterozygosity and only a single allozyme genotype was found. The mean number of alleles per locus is only 1.30 in Oe. strigosa, 1.40 in Oe. biennis, and 1.55 in Oe. parviflora, compared to 1.40 in Oe. argillicola. Clearly, the ability to accumulate and/or retain heterozygosity and variability has not been accompanied by extraordinary levels of either. Clinal variation is evident at some loci in each ring-former. A given translocation complex may vary geographically in its allozymic constitution. From gene frequencies, Oe. biennis I, II, and III, Oe. strigosa and Oe. hookeri are judged to be very closely related, whereas Oe. argillicola seems quite remote; Oe. parviflora is intermediate to the two phylads. Gene frequencies also suggest that Oe. argillicola diverged from the Euoenothera progenitor about 1,000,000 years ago, whereas most of the remaining evolution in the complex has occurred within the last 150,000 years. PMID:17248680

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

    USGS Publications Warehouse

    Troy, Ronald J.; Coates, Peter S.; Connelly, John W.; Gillette, Gifford; Delehanty1, 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

  9. Controlled translocation of DNA segments through nanoelectrode gaps

    SciTech Connect

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

    2008-01-01

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

  10. 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

  11. Millisecond dynamics of RNA polymerase II translocation at atomic resolution.

    PubMed

    Silva, Daniel-Adriano; Weiss, Dahlia R; Pardo Avila, Fátima; Da, Lin-Tai; Levitt, Michael; Wang, Dong; Huang, Xuhui

    2014-05-27

    Transcription is a central step in gene expression, in which the DNA template is processively read by RNA polymerase II (Pol II), synthesizing a complementary messenger RNA transcript. At each cycle, Pol II moves exactly one register along the DNA, a process known as translocation. Although X-ray crystal structures have greatly enhanced our understanding of the transcription process, the underlying molecular mechanisms of translocation remain unclear. Here we use sophisticated simulation techniques to observe Pol II translocation on a millisecond timescale and at atomistic resolution. We observe multiple cycles of forward and backward translocation and identify two previously unidentified intermediate states. We show that the bridge helix (BH) plays a key role accelerating the translocation of both the RNA:DNA hybrid and transition nucleotide by directly interacting with them. The conserved BH residues, Thr831 and Tyr836, mediate these interactions. To date, this study delivers the most detailed picture of the mechanism of Pol II translocation at atomic level. PMID:24753580

  12. Millisecond dynamics of RNA polymerase II translocation at atomic resolution

    PubMed Central

    Silva, Daniel-Adriano; Weiss, Dahlia R.; Pardo Avila, Fátima; Da, Lin-Tai; Levitt, Michael; Wang, Dong; Huang, Xuhui

    2014-01-01

    Transcription is a central step in gene expression, in which the DNA template is processively read by RNA polymerase II (Pol II), synthesizing a complementary messenger RNA transcript. At each cycle, Pol II moves exactly one register along the DNA, a process known as translocation. Although X-ray crystal structures have greatly enhanced our understanding of the transcription process, the underlying molecular mechanisms of translocation remain unclear. Here we use sophisticated simulation techniques to observe Pol II translocation on a millisecond timescale and at atomistic resolution. We observe multiple cycles of forward and backward translocation and identify two previously unidentified intermediate states. We show that the bridge helix (BH) plays a key role accelerating the translocation of both the RNA:DNA hybrid and transition nucleotide by directly interacting with them. The conserved BH residues, Thr831 and Tyr836, mediate these interactions. To date, this study delivers the most detailed picture of the mechanism of Pol II translocation at atomic level. PMID:24753580

  13. 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

  14. 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.

  15. 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.

  16. Effects of rifaximin on bacterial translocation in thioacetamide-induced liver injury in rats.

    PubMed

    Harputluoglu, Murat M M; Demirel, Ulvi; Gul, Mehmet; Temel, Ismail; Gursoy, Sule; Selcuk, Engin Burak; Aladag, Murat; Bilgic, Yilmaz; Gunduz, Ercan; Seckin, Yuksel

    2012-08-01

    Intestinal bacterial overgrowth (IBO) and increased mucosal permeability are suggested to increase bacterial translocation (BT) in liver injury. Rifaximin (RIF) is a minimally absorbed oral antimicrobial agent that restores gut microflora imbalance. The aim of the present study was to investigate the effects of RIF on BT frequency in thioacetamide (TAA)-induced liver injury. Group 1 was the control. In group 2 (TAA), rats received TAA daily for 3 days. In group 3 (TAA + RIF), RIF was commenced on the same day as the first dose of TAA. In group 4 (RIF), rats received only RIF. Ileal aspirate Escherichia coli counts were significantly lower in the TAA + RIF group than in TAA group. There was no difference in BT frequency between the TAA and TAA + RIF groups. Our results suggest that factors such as intestinal barrier dysfunction and impaired host immune shield, apart from IBO, play an important role in BT in this model. PMID:22527146

  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. Fast and automatic processing of multi-level events in nanopore translocation experiments

    NASA Astrophysics Data System (ADS)

    Raillon, C.; Granjon, P.; Graf, M.; Steinbock, L. J.; Radenovic, A.

    2012-07-01

    We have developed a method to analyze in detail, translocation events providing a novel and flexible tool for data analysis of nanopore experiments. Our program, called OpenNanopore, is based on the cumulative sums algorithm (CUSUM algorithm). This algorithm is an abrupt change detection algorithm that provides fitting of current blockages, allowing the user to easily identify the different levels in each event. Our method detects events using adaptive thresholds that adapt to low-frequency variations in the baseline. After event identification, our method uses the CUSUM algorithm to fit the levels inside every event and automatically extracts their time and amplitude information. This facilitates the statistical analysis of an event population with a given number of levels. The obtained information improves the interpretation of interactions between the molecule and nanopore. Since our program does not require any prior information about the analyzed molecules, novel molecule-nanopore interactions can be characterized. In addition our program is very fast and stable. With the progress in fabrication and control of the translocation speed, in the near future, our program could be useful in identification of the different bases of DNA.We have developed a method to analyze in detail, translocation events providing a novel and flexible tool for data analysis of nanopore experiments. Our program, called OpenNanopore, is based on the cumulative sums algorithm (CUSUM algorithm). This algorithm is an abrupt change detection algorithm that provides fitting of current blockages, allowing the user to easily identify the different levels in each event. Our method detects events using adaptive thresholds that adapt to low-frequency variations in the baseline. After event identification, our method uses the CUSUM algorithm to fit the levels inside every event and automatically extracts their time and amplitude information. This facilitates the statistical analysis of an event population with a given number of levels. The obtained information improves the interpretation of interactions between the molecule and nanopore. Since our program does not require any prior information about the analyzed molecules, novel molecule-nanopore interactions can be characterized. In addition our program is very fast and stable. With the progress in fabrication and control of the translocation speed, in the near future, our program could be useful in identification of the different bases of DNA. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30951c

  19. 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

  20. [ISPpy1, a novel mobile element of the ancient Psychrobacter maritimus permafrost strain: translocations in Escherichia coli K-12 cells and formation of composite transposons].

    PubMed

    Petrova, M A; Gorlenko, Zh M; Scherbatova, N A; Mindlin, S Z

    2012-03-01

    It was shown that IS element ISPpyl isolated earlier in the permafrost strain Psychrobacter maritimus MR29-12 has a high level of functional activity in cells of the heterologous host Escherichia coli K-12. ISPpyl can be translocated in E. coli cells by itself and mobilize adjacent genes and can also form composite transposons flanked by two copies of this element. Apart from translocations between different plasmids, the composite ISPpyl-containing transposon Tn5080a is capable of translocation from the plasmid into the E. coli chromosome with high frequency and from the chromosome into the plasmid. Among products of Tn5080a transposition into plasmid R388, simple insertions were predominantly formed together with cointegrates. Upon mobilization of adjacent genes with the use of one ISPpyl copy, only cointegrates arise. PMID:22679779

  1. Background sources at PEP

    SciTech Connect

    Lynch, H.; Schwitters, R.F.; Toner, W.T.

    1988-01-01

    Important sources of background for PEP experiments are studied. Background particles originate from high-energy electrons and positrons which have been lost from stable orbits, ..gamma..-rays emitted by the primary beams through bremsstrahlung in the residual gas, and synchrotron radiation x-rays. The effect of these processes on the beam lifetime are calculated and estimates of background rates at the interaction region are given. Recommendations for the PEP design, aimed at minimizing background are presented. 7 figs., 4 tabs.

  2. Increased transperitoneal bacterial translocation in laparoscopic surgery

    Microsoft Academic Search

    M. C. Horattas; N. Haller; D. Ricchiutti

    2003-01-01

    Background: The indications for laparoscopic surgery have expanded to include diseases possibly associated with peritonitis such as appendicitis, perforated peptic ulcers, and diverticulitis. The safety of carbon dioxide (CO 2) pneumoperitoneum in the presence of peritonitis has not been proved. Our previous investigations demonstrated increased bacteremia associated with CO 2 insufflation. In effort to clarify the relative effects of intraabdominal

  3. Inhibition of endotoxin-induced bacterial translocation in mice.

    PubMed Central

    Deitch, E A; Ma, L; Ma, W J; Grisham, M B; Granger, D N; Specian, R D; Berg, R D

    1989-01-01

    The primary functions of the gut are to absorb nutrients and exclude bacteria and their products. However, under certain circumstances the gut may lose its barrier function and serve as a reservoir for systemic microbial infections. These experiments were performed to determine the mechanisms whereby endotoxin causes bacteria to escape (translocate) from the gut. Bacteria translocated from the gut to the mesenteric lymph nodes of mice challenged with nonlethal doses of Escherichia coli 026:B6 or E. coli 0111:B4 endotoxin. Physical disruption of the gut mucosal barrier appears to be the primary mechanism whereby endotoxin promotes bacterial translocation. Mucosal injury and endotoxin-induced bacterial translocation were reduced by inhibition (allopurinol) or inactivation (tung-sten diet) of xanthine oxidase activity (P less than 0.01), but were not affected by the platelet-activation factor antagonists, SRI 63-441 or BN 52021. Because the inhibition or inactivation of xanthine oxidase activity reduced both the extent of mucosal injury and endotoxin-induced bacterial translocation, the effect of endotoxin on the gut appears to be mediated, at least to some degree, by xanthine oxidase-generated, oxygen-free radicals. Images PMID:2661590

  4. Translocation and Endocytosis for Cell-penetrating Peptide Internalization

    PubMed Central

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

    2009-01-01

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

  5. Nonabsorbable antibiotics reduce bacterial and endotoxin translocation in hepatectomised rats.

    PubMed

    Kakkos, S K; Kirkilesis, J; Scopa, C D; Arvaniti, A; Alexandrides, T; Vagianos, C E

    1997-01-01

    There is increasing evidence that septic complications, occurring after major hepatectomies, may be caused by gram negative bacteria, translocating from the gut. We investigated in rats, the effect of extended hepatectomy on the structure and morphology of the intestinal mucosa as well as on the translocation of intestinal bacteria and endotoxins. We also examined the effect of nonabsorbable antibiotics on reducing the intestinal flora and consequently the phenomenon of translocation by administering neomycin sulphate and cefazoline. Hepatectomy was found to increase translocation, while administration of nonabsorbable antibiotics decreased it significantly. In addition, hepatectomy increased the aerobic cecal bacterial population, which normalised in the group receiving antibiotics. Among the histological parameters evaluated, villus height demonstrated a significant reduction after hepatectomy, while the number of villi per cm and the number of mitoses per crypt, remained unchanged. Our results indicate that administration of nonabsorbable antibiotics presents a positive effect on bacterial and endotoxin translocation after extended hepatectomy, and this may be related to reduction of colonic bacterial load as an intraluminal effect of antibiotics. PMID:9298382

  6. Bacterial translocation across ePTFE vascular graft surfaces

    PubMed Central

    Narasimhan, Supriya; Aslam, Saima; Lin, Peter H.; Bechara, Carlos F.; Mansouri, Mohammad D.; Darouiche, Rabih O.

    2013-01-01

    Summary Objectives Vascular graft infections arise from bacterial colonization of either the external or internal graft surfaces. We assessed whether methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli could translocate through pores of ePTFE grafts. Methods To assess translocation from the internal to the external surface, we placed 105 cfu of bacterial suspension inside ePTFE graft segments and suspended them in sterile broth for 72 h. To assess translocation from the external to the internal surface, we placed sterile broth inside ePTFE segments, and incubated them for 72 h in a bacterial suspension (105 cfu/mL). At 72 h, in addition to culturing the sterile broth and bacterial suspensions, the external and internal surfaces were first qualitatively cultured separately and then quantitatively cultured by sonication. Results At 72 h, the sterile broth remained sterile. The bacterial suspensions yielded 107–109 cfu/mL. Graft cultures indicated that colonization of one surface with either organism did not result in bacterial translocation to the other surface. Quantitative bacterial counts of the external vs. internal surfaces were significantly different (p < 0.01). Conclusions MRSA and E. coli do not translocate across ePTFE graft surfaces. These in-vitro findings help elucidate the pathogenesis of graft infections and prompt conduction of validation studies in-vivo. PMID:20362612

  7. Botulinum Neurotoxin Devoid of Receptor Binding Domain Translocates Active Protease

    PubMed Central

    Fischer, Audrey; Mushrush, Darren J.; Lacy, D. Borden; Montal, Mauricio

    2008-01-01

    Clostridium botulinum neurotoxin (BoNT) causes flaccid paralysis by disabling synaptic exocytosis. Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes, leading to the formation of a protein-conducting channel. The ?50 kDa light chain (LC) protease is translocated into the cytosol by the ?100 kDa heavy chain (HC), which consists of two modules: the N-terminal translocation domain (TD) and the C-terminal Receptor Binding Domain (RBD). Here we exploited the BoNT modular design to identify the minimal requirements for channel activity and LC translocation in neurons. Using the combined detection of substrate proteolysis and single-channel currents, we showed that a di-modular protein consisting only of LC and TD was sufficient to translocate active protease into the cytosol of target cells. The RBD is dispensable for cell entry, channel activity, or LC translocation; however, it determined a pH threshold for channel formation. These findings indicate that, in addition to its individual functions, each module acts as a chaperone for the others, working in concert to achieve productive intoxication. PMID:19096517

  8. Botulinum neurotoxin devoid of receptor binding domain translocates active protease.

    PubMed

    Fischer, Audrey; Mushrush, Darren J; Lacy, D Borden; Montal, Mauricio

    2008-12-01

    Clostridium botulinum neurotoxin (BoNT) causes flaccid paralysis by disabling synaptic exocytosis. Intoxication requires the tri-modular protein to undergo conformational changes in response to pH and redox gradients across endosomes, leading to the formation of a protein-conducting channel. The approximately 50 kDa light chain (LC) protease is translocated into the cytosol by the approximately 100 kDa heavy chain (HC), which consists of two modules: the N-terminal translocation domain (TD) and the C-terminal Receptor Binding Domain (RBD). Here we exploited the BoNT modular design to identify the minimal requirements for channel activity and LC translocation in neurons. Using the combined detection of substrate proteolysis and single-channel currents, we showed that a di-modular protein consisting only of LC and TD was sufficient to translocate active protease into the cytosol of target cells. The RBD is dispensable for cell entry, channel activity, or LC translocation; however, it determined a pH threshold for channel formation. These findings indicate that, in addition to its individual functions, each module acts as a chaperone for the others, working in concert to achieve productive intoxication. PMID:19096517

  9. A Somatic Origin of Homologous Robertsonian Translocations and Isochromosomes

    PubMed Central

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

    1994-01-01

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

  10. Some Factors Regulating Auxin Translocation in Intact Bean Seedlings 1

    PubMed Central

    Long, John; Basler, Eddie

    1973-01-01

    Several factors which influence the translocation patterns of stem-injected indoleacetic acid, 2,4-dichlorophenoxyacetic acid, and 2,4,5-trichlorophenoxyacetic acid in bean seedlings (Phaseolus vulgaris L. cv. Stringless Greenpod) were characterized. The acropetal translocation of auxin from the site of injection is markedly sensitive to concentration in the range of 1.0 to 5.0 micrograms per plant. The antiauxin p-chlorophenoxyisobutyric acid enhanced translocation of 2,4,5-trichlorophenoxyacetic acid to the growing shoots and primary leaves. Translocation to the roots was unaffected by p-chlorophenoxyisobutyric acid while leaching of 2,4,5-trichlorophenoxyacetic acid into the nutrient solution was enhanced slightly. Steam girdling experiments revealed that translocation to the primary leaves was in the xylem. The protein synthesis inhibitor, cycloheximide, inhibited accumulation of 2,4,5-trichlorophenoxyacetic acid in young shoots, epicotyls, and roots and enhanced accumulation in the primary leaves. The relative exchangeability of auxin between xylem and phloem is discussed in terms of regulation of auxin movements in intact bean seedlings. Images PMID:16658273

  11. 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.

  12. Shielding and background reduction

    Microsoft Academic Search

    R. Núñez-Lagos; A. Virto

    1996-01-01

    The background spectrum in a Low Background intrinsic germanium detector was analysed. Different possible sources of background and the influence of the materials used as well as the thickness of shielding was studied. Lead, copper, nylon, delrin and teflon of different thicknessewere used. Too much shielding material could induce some gamma rays from neutron production in the shielding due to

  13. A Thermal Graviton Background from Extra Dimensions

    E-print Network

    E. R. Siegel; J. N. Fry

    2005-04-05

    Inflationary cosmology predicts a low-amplitude graviton background across a wide range of frequencies. This Letter shows that if one or more extra dimensions exist, the graviton background may have a thermal spectrum instead, dependent on the fundamental scale of the extra dimensions. The energy density is shown to be significant enough that it can affect nucleosynthesis in a substantial way. The possibility of direct detection of a thermal graviton background using the 21-cm hydrogen line is discussed. Alternative explanations for the creation of a thermal graviton background are also examined.

  14. The SWI/SNF protein ATRX co-regulates pseudoautosomal genes that have translocated to autosomes in the mouse genome

    PubMed Central

    Levy, Michael A; Fernandes, Andrew D; Tremblay, Deanna C; Seah, Claudia; Bérubé, Nathalie G

    2008-01-01

    Background Pseudoautosomal regions (PAR1 and PAR2) in eutherians retain homologous regions between the X and Y chromosomes that play a critical role in the obligatory X-Y crossover during male meiosis. Genes that reside in the PAR1 are exceptional in that they are rich in repetitive sequences and undergo a very high rate of recombination. Remarkably, murine PAR1 homologs have translocated to various autosomes, reflecting the complex recombination history during the evolution of the mammalian X chromosome. Results We now report that the SNF2-type chromatin remodeling protein ATRX controls the expression of eutherian ancestral PAR1 genes that have translocated to autosomes in the mouse. In addition, we have identified two potentially novel mouse PAR1 orthologs. Conclusion We propose that the ancestral PAR1 genes share a common epigenetic environment that allows ATRX to control their expression. PMID:18842153

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

    PubMed Central

    2014-01-01

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

  16. A balanced translocation truncates Neurotrimin in a family with intracranial and thoracic aortic aneurysm

    PubMed Central

    Luukkonen, Tiia; Pöyhönen, Minna; Palotie, Aarno; Ellonen, Pekka; Lagström, Sonja; Lee, Joseph H; Terwilliger, Joseph D; Salonen, Riitta; Varilo, Teppo

    2014-01-01

    Background Balanced chromosomal rearrangements occasionally have strong phenotypic effects, which may be useful in understanding pathobiology. However, conventional strategies for characterizing breakpoints are laborious and inaccurate. We present here a proband with a thoracic aortic aneurysm and a balanced translocation t(10;11)(q23.2;q24.2). Our purpose was to sequence the chromosomal breaks in this family to reveal a novel candidate gene for aneurysm. Methods and results Intracranial and thoracic aortic aneurysms appear to run in the family in an autosomal dominant manner: After exploring the family history, we observed that the proband’s two siblings both died from cerebral hemorrhage, and the proband’s parent and parent’s sibling died from aortic rupture. After application of a genome-wide paired-end DNA sequencing method for breakpoint mapping, we demonstrate that this translocation breaks intron 1 of a splicing isoform of Neurotrimin (NTM) at 11q25 in a previously implicated candidate region for intracranial (IAs) and aortic aneurysms (AAs) (OMIM 612161). Conclusions Our results demonstrate the feasibility of genome-wide paired-end sequencing for the characterization of balanced rearrangements and identification of candidate genes in patients with potentially disease-associated chromosome rearrangements. The family samples were gathered as a part of our recently launched National Registry of Reciprocal Balanced Translocations and Inversions in Finland (n=2575), and we believe that such a registry will be a powerful resource for the localization of chromosomal aberrations, which can bring insight into the etiology of related phenotypes. PMID:23054244

  17. 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

  18. Eld's deer translocated to human-inhabited areas become nocturnal.

    PubMed

    Pan, Duo; Teng, Liwei; Cui, Fangjie; Zeng, Zhigao; Bravery, Benjamin D; Zhang, Qiong; Song, Yanling

    2011-02-01

    As human populations expand and nonhuman animals decline, understanding the interactions between people and wildlife is essential. For endangered species, appreciating the effect of human disturbance can be important for their conservation. However, a human disturbance angle is often absent from ecological research, despite growing evidence of the negative impact of nonfatal human interference. Here, we monitored Hainan Eld's deer living within a reserve and translocated animals living amongst villagers. We show that translocated deer deviated from a crepuscular activity pattern and became increas-. ingly nocturnal, and most active when villagers were not. It appears that translocated deer adapted over time to human disturbance and this pattern is similar to that of other species during periods of hunting. People do not pose an actual threat to Eld's deer, but their presence triggered a response akin to predator avoidance and may be interfering with broader aspects of their biology and conservation. PMID:21404824

  19. Uptake and translocation of hexachlorobenzene: Oilpumpkin and sunflower

    SciTech Connect

    NONE

    1993-10-01

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

  20. A nanopore-nanofiber mesh biosensor to control DNA translocation

    PubMed Central

    Squires, Allison; Hersey, Joseph S.; Grinstaff, Mark W.; Meller, Amit

    2014-01-01

    Solid-state nanopores show promise as single-molecule sensors for biomedical applications, but to increase their resolution and efficiency analyte molecules must remain longer in the nanopore sensing volume. Here we demonstrate a novel, facile, and customizable nanopore sensor modification that reduces double stranded DNA translocation velocity by two orders of magnitude or more via interactions outside the nanopore. This is achieved by electrospinning a copolymer nanofiber mesh (NFM) directly onto a solid-state nanopore (NP) chip. The effect of NFMs on dsDNA translocation through a nanopore is highlighted using a set of NFMs of varying mesh composition that reduce translocation speed relative to a bare pore from 1× to >100×. A representative NFM from this set is effective on DNA as long as 20 kbp, improves nanopore resolution, and allows discrimination among different DNA lengths. PMID:24143914

  1. A nanopore-nanofiber mesh biosensor to control DNA translocation.

    PubMed

    Squires, Allison H; Hersey, Joseph S; Grinstaff, Mark W; Meller, Amit

    2013-11-01

    Solid-state nanopores show promise as single-molecule sensors for biomedical applications, but to increase their resolution and efficiency, analyte molecules must remain longer in the nanopore sensing volume. Here we demonstrate a novel, facile, and customizable nanopore sensor modification that reduces the double-stranded DNA translocation velocity by 2 orders of magnitude or more via interactions outside the nanopore. This is achieved by electrospinning a copolymer nanofiber mesh (NFM) directly onto a solid-state nanopore (NP) chip. The effect of NFMs on dsDNA translocation through an NP is highlighted using a set of NFMs of varying mesh composition that reduce the translocation speed relative to a bare pore from 1- to >100-fold. A representative NFM from this set is effective on DNA as long as 20 kbp, improves the nanopore resolution, and allows discrimination among different DNA lengths. PMID:24143914

  2. Crystallographic snapshot of cellulose synthesis and membrane translocation.

    PubMed

    Morgan, Jacob L W; Strumillo, Joanna; Zimmer, Jochen

    2013-01-10

    Cellulose, the most abundant biological macromolecule, is an extracellular, linear polymer of glucose molecules. It represents an essential component of plant cell walls but is also found in algae and bacteria. In bacteria, cellulose production frequently correlates with the formation of biofilms, a sessile, multicellular growth form. Cellulose synthesis and transport across the inner bacterial membrane is mediated by a complex of the membrane-integrated catalytic BcsA subunit and the membrane-anchored, periplasmic BcsB protein. Here we present the crystal structure of a complex of BcsA and BcsB from Rhodobacter sphaeroides containing a translocating polysaccharide. The structure of the BcsA-BcsB translocation intermediate reveals the architecture of the cellulose synthase, demonstrates how BcsA forms a cellulose-conducting channel, and suggests a model for the coupling of cellulose synthesis and translocation in which the nascent polysaccharide is extended by one glucose molecule at a time. PMID:23222542

  3. Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints.

    PubMed

    Raghavan, S C; Kirsch, I R; Lieber, M R

    2001-08-01

    Chromosomal translocations and deletions are among the major events that initiate neoplasia. For lymphoid chromosomal translocations, misrecognition by the RAG (recombination activating gene) complex of V(D)J recombination is one contributing factor that has long been proposed. The chromosomal translocations involving LMO2 (t(11;14)(p13;q11)), Ttg-1 (t(11;14)(p15;q11)), and Hox11 (t(10;14)(q24;q11)) are among the clearest examples in which it appears that a D or J segment has synapsed with an adventitious heptamer/nonamer at a gene outside of one of the antigen receptor loci. The interstitial deletion at 1p32 involving SIL (SCL-interrupting locus)/SCL (stem cell leukemia) is a case involving two non-V(D)J sites that have been suggested to be V(D)J recombination mistakes. Here we have used our human extrachromosomal substrate assay to formally test the hypothesis that these regions are V(D)J recombination misrecognition sites and, more importantly, to quantify their efficiency as V(D)J recombination targets within the cell. We find that the LMO2 fragile site functions as a 12-signal at an efficiency that is only 27-fold lower than that of a consensus 12-signal. The Ttg-1 site functions as a 23-signal at an efficiency 530-fold lower than that of a consensus 23-signal. Hox11 failed to undergo recombination as a 12- or 23-signal and was at least 20,000-fold less efficient than consensus signals. SIL has been predicted to function as a 12-signal and SCL as a 23-signal. However, we find that SIL actually functions as a 23-signal. These results provide a formal demonstration that certain chromosomal fragile sites can serve as RAG complex targets, and they determine whether these sites function as 12- versus 23-signals. These results quantify one of the three major factors that determine the frequency of these translocations in T-cell acute lymphocytic leukemia. PMID:11390401

  4. Cosmological String Backgrounds

    E-print Network

    Dieter Luest

    1993-03-31

    Talk given at the ``4th Hellenic School on Elementary Particle Physics", Corfu, 2-20 September 1992: The propagation of strings in cosmological space-time backgrounds is reviewed. We show the relation of a special class of cosmological backgrounds to exact conformal field theory. Particular emphasis is put on the singularity structure of the cosmological space-time and on the discrete duality symmetries of the string background.

  5. 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)

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

    PubMed Central

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

    2013-01-01

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

  7. Tic62: a protein family from metabolism to protein translocation

    PubMed Central

    Balsera, Mónica; Stengel, Anna; Soll, Jürgen; Bölter, Bettina

    2007-01-01

    Background The function and structure of protein translocons at the outer and inner envelope membrane of chloroplasts (Toc and Tic complexes, respectively) are a subject of intensive research. One of the proteins that have been ascribed to the Tic complex is Tic62. This protein was proposed as a redox sensor protein and may possibly act as a regulator during the translocation process. Tic62 is a bimodular protein that comprises an N-terminal module, responsible for binding to pyridine nucleotides, and a C-terminal module which serves as a docking site for ferredoxin-NAD(P)-oxido-reductase (FNR). This work focuses on evolutionary analysis of the Tic62-NAD(P)-related protein family, derived from the comparison of all available sequences, and discusses the structure of Tic62. Results Whereas the N-terminal module of Tic62 is highly conserved among all oxyphototrophs, the C-terminal region (FNR-binding module) is only found in vascular plants. Phylogenetic analyses classify four Tic62-NAD(P)-related protein subfamilies in land plants, closely related to members from cyanobacteria and green sulphur bacteria. Although most of the Tic62-NAD(P)-related eukaryotic proteins are localized in the chloroplast, one subgroup consists of proteins without a predicted transit peptide. The N-terminal module of Tic62 contains the structurally conserved Rossman fold and probably belongs to the extended family of short-chain dehydrogenases-reductases. Key residues involved in NADP-binding and residues that may attach the protein to the inner envelope membrane of chloroplasts or to the Tic complex are proposed. Conclusion The Tic62-NAD(P)-related proteins are of ancient origin since they are not only found in cyanobacteria but also in green sulphur bacteria. The FNR-binding module at the C-terminal region of the Tic62 proteins is probably a recent acquisition in vascular plants, with no sequence similarity to any other known motifs. The presence of the FNR-binding domain in vascular plants might be essential for the function of the protein as a Tic component and/or for its regulation. PMID:17374152

  8. What happens to translocated game birds that `disappear'? M. J. Dickens1

    E-print Network

    Reed, Michael

    -translocation. In this study, we used chukar Alectoris chukar as a surrogate for translocated game birds in order to conduct; movement; homing; chukar. Correspondence Molly Dickens, Department of Biology, Tufts University, 163

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

    E-print Network

    Ten Brink, Craig Eric

    1996-01-01

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

  10. ASSESSMENT OF A WESTERN CANADA GOOSE TRANSLOCATION: LANDSCAPE USE, MOVEMENT

    E-print Network

    Black, Jeff

    , AND POPULATION VIABILITY KENNETH M. GRIGGS,1 Waterfowl Ecology Research Group, Department of Wildlife, Humboldt State University, Arcata, CA 95521, USA JEFFREY M. BLACK, Waterfowl Ecology Research Group, Department and Temple 1995, Wolf et al. 1996). However, the practice of translocation of wild animals

  11. Oncogene Translocations and Non-Hodgkin Lymphoma (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

  12. Gene flow and endangered species translocations: a topic revisited

    Microsoft Academic Search

    Andrew Storfer

    1999-01-01

    Understanding the evolutionary role of gene flow is pivotal to the conservation of endangered populations. Gene flow can be enhanced through population translocations that are conducted to maintain genetic variation and combat the negative consequences of inbreeding depression (two of the major concerns in the conservation of subdivided or isolated populations). While researchers have given extensive consideration to the idea

  13. Translocation-Deletions Distance Formula for Sorting Genomes

    Microsoft Academic Search

    Fanchang Hao; Junfeng Luan; Daming Zhu

    2009-01-01

    Given two signed multi-chromosomal genomes Pi and Gamma, where gene set of Gamma is the proper subset of that of Pi, the problem of sorting by translocation-deletions, which is abbrebiated as STD, is to find the shortest sequence transforming Pi to Gamma via the two operations mentioned above only. A lower bound of the distance from Pi to Gamma and

  14. Scaling Exponents for Polymer Translocation through a Nanopore

    NASA Astrophysics Data System (ADS)

    Luo, Kaifu; Ala-Nissila, Tapio; Pomorski, Pawel; Karttunen, Mikko; Ying, See-Chen; Bhattacharya, Aniket

    2008-03-01

    We present results of extensive computer simulations and scaling theory for computing the relevant scaling exponents associated with polymer translocation through a nanopore [1]. We present results for the scaling of the average translocation time and the fluctuation in the reaction coordinate for the case of spontaneous and field-driven translocation in 2D and 3D. The models used include: (i) the fluctuating bond model with single-segment Monte Carlo moves, (ii) Langevin dynamics, and (iii) GROMACS MD simulations using the bead-spring model for flexible polymers without an explicit solvent. We contrast our results to the recently presented alternate theories for polymer translocation [2,3]. ootnotetextsize 1. K. Luo et al., J. Chem. Phys. 124, 034714 (2006); 124, 114704 (2006); 126, 145101 (2007); Phys. Rev. Lett. 99, 148102 (2007); I. Huopaniemi et al., J. Chem. Phys. 125, 124901 (2006); Phys. Rev. E 75, 061912 (2007); K. Luo et al., e-print arXiv:0709.4615.2. J. K. Wolterink et al., Phys. Rev. Lett. 96, 208301 (2006); D. Panja et al., J. Phys.: Condens. Matter 19, 432202 (2007).3. J. L. A. Dubbeldam et al., Europhys. Lett. 79, 18002 (2007); Phys. Rev. E 76, 010801 (2007).

  15. 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.

  16. Tools and Technology Post-Release Acclimation of Translocated

    E-print Network

    Beck, Jeffrey L.

    , Department 3354, 1000 E University Avenue, Laramie, WY 82071, USA JEFFREY L. BECK, Department of Ecosystem. Because acclimation periods after translocation releases are associated with increased mortality risk, managers should consider supplemental releases to minimize acclimation periods. Ã? 2014 The Wildlife Society

  17. Protein translocation into and across the chloroplastic envelope membranes

    Microsoft Academic Search

    J. Soll; R. Tien

    1998-01-01

    Post-translational protein import into chloroplasts follows a common route characterised by the need for nucleoside-triphosphates at various steps and two distinct protein import machineries at the outer and inner envelope membrane, respectively. Several subunits of these complexes have been elucidated. In contrast, protein translocation into the chloroplastic outer envelope uses distinct and various but poorly characterised insertion pathways. A topological

  18. Cholesterol Translocation in a Phospholipid Membrane Amit Choubey,

    E-print Network

    Southern California, University of

    Cholesterol Translocation in a Phospholipid Membrane Amit Choubey, Rajiv K. Kalia,§ * Noah of Southern California, Los Angeles, California ABSTRACT Cholesterol (CHOL) molecules play a key role), this is not the case for cholesterol (CHOL). Although the transport rate of CHOL has been elusive from an experimental

  19. Nuclear translocation of immulectin-3 stimulates hemocyte proliferation

    PubMed Central

    Ling, Erjun; Ao, Jingqun; Yu, Xiao-Qiang

    2015-01-01

    Immulectin-3 (IML-3) is a C-type lectin from the tobacco hornworm Manduca sexta that contains a motif (NWGV) similar to the BH1 motif (NWGR) of the mammalian galectin-3. IML-3 is synthesized in fat body and secreted into hemolymph, but can be translocated into hemocytes. In this study, we showed that IML-3 was predominantly localized to the nucleus of hemocytes and some metaphase, anaphase and telophase hemocytes from M. sexta larvae injected with bacterial lipopolysaccharide (LPS). IML-3 was detected in the membrane and soluble extracts of hemocytes, suggesting that it may be translocated into hemocytes via receptor-mediated endocytosis. To investigate the role of IML-3 translocation to the nucleus, we expressed recombinant wild-type IML-3 and a deletion mutant ?IML-3 that has the NWGV motif deleted in Drosophila S2 cells. We found that recombinant wild-type IML-3, but not ?IML-3, was localized to the nucleus of some S2 cells and also detected in the nuclear extract. Expression of recombinant wild-type IML-3, but not ?IML-3 or GFP, increased the number of proliferating S2 cells. Our results suggest that nuclear translocation of IML-3 may stimulate hemocyte proliferation. PMID:18282603

  20. Polymer translocation into and out of an ellipsoidal cavity

    E-print Network

    James M. Polson

    2015-02-19

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

  1. 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

  2. Mitochondrial translocation of Nur77 mediates cardiomyocyte apoptosis

    PubMed Central

    Cheng, Zhaokang; Völkers, Mirko; Din, Shabana; Avitabile, Daniele; Khan, Mohsin; Gude, Natalie; Mohsin, Sadia; Bo, Tao; Truffa, Silvia; Alvarez, Roberto; Mason, Matt; Fischer, Kimberlee M.; Konstandin, Mathias H.; Zhang, Xiao-kun; Heller Brown, Joan; Sussman, Mark A.

    2011-01-01

    Aims The cascade of events leading to compromised mitochondrial integrity in response to stress is mediated by various combinatorial interactions of pro- and anti-apoptotic molecules. Nur77, an immediate early gene that encodes a nuclear orphan receptor, translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis in cancer cells in response to various pro-apoptotic treatments. However, the role of Nur77 in the cardiac setting is still unclear. The objective of this study is to determine the physiological relevance and pathophysiological importance of Nur77 in cardiomyocytes. Methods and results Myocardial Nur77 is upregulated following cardiomyopathic injury and, while expressed in the postnatal myocardium, declines in level within weeks after birth. Nur77 is localized predominantly in cardiomyocyte nuclei under normal conditions where it is not apoptotic, but translocates to mitochondria in response to oxidative stress both in vitro and in vivo. Mitochondrial localization of Nur77 induces cytochrome c release and typical morphological features of apoptosis, including chromatin condensation and DNA fragmentation. Knockdown of Nur77 rescued hydrogen peroxide-induced cardiomyocyte apoptosis. Conclusion Translocation of Nur77 from the nucleus to the mitochondria in cardiomyocytes results in the loss of mitochondrial integrity and subsequent apoptosis in response to ischaemia/reperfusion injury. Our findings identify Nur77 as a novel mediator of cardiomyocyte apoptosis and warrants further investigation of mitochondrial Nur77 translocation as a mechanism to control cell death in the treatment of ischaemic heart diseases. PMID:21228009

  3. 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...

  4. Chaperone-assisted translocation of a polymer through a nanopore

    E-print Network

    Wancheng Yu; Kaifu Luo

    2011-08-02

    Using Langevin dynamics simulations, we investigate the dynamics of chaperone-assisted translocation of a flexible polymer through a nanopore. We find that increasing the binding energy $\\epsilon$ between the chaperone and the chain and the chaperone concentration $N_c$ can greatly improve the translocation probability. Particularly, with increasing the chaperone concentration a maximum translocation probability is observed for weak binding. For a fixed chaperone concentration, the histogram of translocation time $\\tau$ has a transition from long-tailed distribution to Gaussian distribution with increasing $\\epsilon$. $\\tau$ rapidly decreases and then almost saturates with increasing binding energy for short chain, however, it has a minimum for longer chains at lower chaperone concentration. We also show that $\\tau$ has a minimum as a function of the chaperone concentration. For different $\\epsilon$, a nonuniversal dependence of $\\tau$ on the chain length $N$ is also observed. These results can be interpreted by characteristic entropic effects for flexible polymers induced by either crowding effect from high chaperone concentration or the intersegmental binding for the high binding energy.

  5. The Transposase Domain Protein Metnase/SETMAR Suppresses Chromosomal Translocations

    PubMed Central

    Wray, Justin; Williamson, Elizabeth A.; Chester, Sean; Farrington, Jacqueline; Sterk, Rosa; Weinstock, David M.; Jasin, Maria; Lee, Suk-Hee; Nickoloff, Jac A.; Hromas, Robert

    2010-01-01

    Chromosomal translocations are common in leukemia, but little is known about their mechanism. Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. Transposases were thought to be extinct in primates because they would mediate deleterious DNA movement. In primates, Metnase interacts with DNA Ligase IV (Lig IV), and promotes non-homologous end joining (NHEJ) DNA repair. We show here that the primate-specific protein Metnase can also enhance NHEJ in murine cells, and can also interact with murine Lig IV, indicating that it integrated into the pre-existing NHEJ pathway after its development in primates. Significantly, expressing Metnase in murine cells significantly reduces chromosomal translocations. We propose that the fusion of the histone methylase SET domain and the transposase domain in the anthropoid lineage to form primate Metnase promotes accurate intra-chromosomal NHEJ, and thereby suppresses inter-chromosomal translocations. Thus, Metnase may have been selected for because it has a function opposing transposases, and may thus play a key role in suppressing translocations that underlie oncogenicity. PMID:20620605

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

    E-print Network

    Meller, Amit

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

  7. Yeast Pol4 Promotes Tel1-Regulated Chromosomal Translocations

    PubMed Central

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

    2013-01-01

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

  8. AMP kinase activation and glut4 translocation in isolated cardiomyocytes.

    PubMed

    Webster, I; Friedrich, S O; Lochner, A; Huisamen, B

    2010-01-01

    Activation of AMP-activated protein kinase (AMPK) results in glucose transporter 4 (GLUT4) translocation from the cytosol to the cell membrane, and glucose uptake in the skeletal muscles. This increased activation of AMPK can be stimulated by a pharmacological agent, AICAR (5' -aminoimidazole-4-carboxamide ribonucleoside), which is converted intracellularly into ZMP (5' -aminoimidazole-4-carboxamideribonucleosidephosphate), an AMP analogue. We utilised AICAR and ZMP to study GLUT4 translocation and glucose uptake in isolated cardiomyocytes. Adult ventricular cardiomyocytes were treated with AICAR or ZMP, and glucose uptake was measured via [3H] -2-deoxyglucose accumulation. PKB/Akt, AMPK and acetyl-CoA-carboxylase phosphorylation and GLUT4 translocation were detected by Western blotting or flow cytometry. AICAR and ZMP promoted AMPK phosphorylation. Neither drug increased glucose uptake but on the contrary, inhibited basal glucose uptake, although GLUT4 translocation from the cytosol to the membrane occurred. Using flow cytometry to detect the exofacial loop of the GLUT4 protein, we showed ineffective insertion in the membrane under these conditions. Supplementing with nitric oxide improved insertion in the membrane but not glucose uptake. We concluded that activation of AMPK via AICAR or ZMP was not sufficient to induce GLUT4-mediated glucose uptake in isolated cardiomyocytes. Nitric oxide plays a role in proper insertion of the protein in the membrane but not in glucose uptake. PMID:20532430

  9. DNA translocation through low-noise glass nanopores.

    PubMed

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

    2013-12-23

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

  10. The Cosmic Microwave Background

    E-print Network

    Arthur Kosowsky

    2001-02-23

    This set of lectures provides an overview of the basic theory and phenomenology of the cosmic microwave background. Topics include a brief historical review; the physics of temperature and polarization fluctuations; acoustic oscillations of the primordial plasma; the space of inflationary cosmological models; current and potential constraints on these models from the microwave background; and constraints on inflation.

  11. Acidification induces Bax translocation to the mitochondria and promotes ultraviolet light-induced apoptosis

    Microsoft Academic Search

    Lin Yang; Yongyu Mei; Qifeng Xie; Xiaoyan Han; Fucheng Zhang; Lin Gu; Yufeng Zhang; Youming Chen; Gang Li; Zhiliang Gao

    2008-01-01

    It has been suggested that Bax translocation to the mitochondria is related to apoptosis, and that cytosol acidification contributes\\u000a to apoptosis events. However, the mechanisms remain obscure. We investigated the effect of acidification on Bax translocation\\u000a and on ultraviolet (UV) light-induced apoptosis. The Bax translocation assay in vitro showed that Bax translocated to the mitochondria at pH 6.5, whereas no

  12. Replication pattern of the X chromosomes in three X\\/autosomal translocations

    Microsoft Academic Search

    A. Hagemeijer; J. Hoovers; E. M. E. Smit; D. Bootsma

    1977-01-01

    Three X\\/autosomal translocations, two familial and one de novo, were analyzed. Late-replicating chromosomes and chromosome regions were studied with R-banding techniques after BrdU incorporation. The first translocation, t(X;4)(q21;ql3), was a de novo translocation, found in a woman with amenorrhea. The structurally normal X was late replicating in all cells. The second translocation, t(X;6)(p21;q26), was found in an unbalanced form, 46,

  13. Correlators in nontrivial backgrounds

    SciTech Connect

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

    2009-01-15

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

  14. 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

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

    Microsoft Academic Search

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

    1985-01-01

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

  16. Optimal adaptive management for the translocation of a threatened species.

    PubMed

    Rout, Tracy M; Hauser, Cindy E; Possingham, Hugh P

    2009-03-01

    Active adaptive management (AAM) is an approach to wildlife management that acknowledges our imperfect understanding of natural systems and allows for some resolution of our uncertainty. Such learning may be characterized by risky strategies in the short term. Experimentation is only considered acceptable if it is expected to be repaid by increased returns in the long term, generated by an improved understanding of the system. By setting AAM problems within a decision theory framework, we can find this optimal balance between achieving our objectives in the short term and learning for the long term. We apply this approach to managing the translocation of the bridled nailtail wallaby (Onychogalea fraenata), an endangered species from Queensland, Australia. Our task is to allocate captive-bred animals, between two sites or populations to maximize abundance at the end of the translocation project. One population, at the original site of occupancy, has a known growth rate. A population potentially could be established at a second site of suitable habitat, but we can only learn the growth rate of this new population by monitoring translocated animals. We use a mathematical programming technique called stochastic dynamic programming, which determines optimal management decisions for every possible management trajectory. We find optimal strategies under active and passive adaptive management, which enables us to examine the balance between learning and managing directly. Learning is more often optimal when we have less prior information about the uncertain population growth rate at the new site, when the growth rate at the original site is low, and when there is substantial time remaining in the translocation project. Few studies outside the area of optimal harvesting have framed AAM within a decision theory context. This is the first application to threatened species translocation. PMID:19323207

  17. RNase A Does Not Translocate the Alpha-Hemolysin Pore

    PubMed Central

    Krasniqi, Besnik; Lee, Jeremy S.

    2014-01-01

    The application of nanopore sensing utilizing the ?-hemolysin pore to probe proteins at single-molecule resolution has expanded rapidly. In some studies protein translocation through the ?-hemolysin has been reported. However, there is no direct evidence, as yet, that proteins can translocate the ?-hemolysin pore. The biggest challenge to obtaining direct evidence is the lack of a highly sensitive assay to detect very low numbers of protein molecules. Furthermore, if an activity based assay is applied then the proteins translocating by unfolding should refold back to an active confirmation for the assay technique to work. To overcome these challenges we selected a model enzyme, ribonuclease A, that readily refolds to an active conformation even after unfolding it with denaturants. In addition we have developed a highly sensitive reverse transcription polymerase chain reaction based activity assay for ribonuclease A. Initially, ribonuclease A, a protein with a positive net charge and dimensions larger than the smallest diameter of the pore, was subjected to nanopore analysis under different experimental conditions. Surprisingly, although the protein was added to the cis chamber (grounded) and a positive potential was applied, the interaction of ribonuclease A with ?-hemolysin pore induced small and large blockade events in the presence and the absence of a reducing and/or denaturing agent. Upon measuring the zeta potential, it was found that the protein undergoes a charge reversal under the experimental conditions used for nanopore sensing. From the investigation of the effect of voltage on the interaction of ribonuclease A with the ?-hemolysin pore, it was impossible to conclude if the events observed were translocations. However, upon testing for ribonuclease A activity on the trans chamber it was found that ribonuclease A does not translocate the ?-hemolysin pore. PMID:24505349

  18. Background stratospheric aerosol layer

    SciTech Connect

    Hofmann, D.J.; Rosen, J.M.

    1981-01-01

    Balloonborne aerosol particle counter measurements are used in studying the stratospheric sulfate layer at Laramie, Wyoming, during 1978 and 1979, a 2-year volcanically quiescent period in which the layer appears to have been in a near equilibrium background state. Subtracting the background aerosol concentration from data obtained during an earlier volcanically active period indicates that the actual decay rate of volcanic aerosol is over 30% faster than one would obtain without this correction. At background, the aerosol size distribution is found to remain remarkably constant between the tropopause and an altitude of approx.25 km, with a sudden transition to a distribution dominated by smaller particles above this altitude. The observations, in some respects, compare favorably with equilibrium one-dimensional stratospheric aerosol models and thus to some extent support the concept of relatively inert tropospheric sulfurous gases, such as carbonyl sulfide and carbon disulfide, as the main background stratospheric aerosol sulfur source. Models which incorporate sulfur chemistry are apparently not able to predict the observed variation of particle size with altitude. The 2-year background period is not long enough in itself to establish long-term trends. The eruption of Mt. St. Helens in May 1980 has considerably disrupted the background stratospheric aerosol which will probably not recover for several years. A comparison of the 1978--79 observations with Junge's original measurements made some 20 years earlier, also during a period void of volcanic perturbations, does not preclude a long-term increase in the background stratospheric aerosol level.

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Chieffo, C.; Barnoski, B.L.; Emanuel, B.S. [Children`s Hospital of Philadelphia, PA (United States)] [and others

    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.

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

    PubMed Central

    2013-01-01

    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. PMID:23676116

  2. 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.

  3. The Cosmic Background Radiation

    E-print Network

    George Smoot; Douglas Scott

    1997-11-08

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

  4. Building Background Knowledge

    NSDL National Science Digital Library

    Donna Ross

    2010-01-01

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

  5. Introduction Biological Background

    E-print Network

    Mahaffy, Joseph M.

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

  6. Introduction 1 Background 1

    E-print Network

    squirrel (Sciurus carolinensis). The grey squirrel was introduced to Britain in the late 19 th century populations in Northern Ireland. Background The red squirrel (Sciurus vulgaris) was once ubiquitous

  7. The GLAST Background Model

    SciTech Connect

    Ormes, J. F. [University of Denver (United States); Atwood, W. [University of California at Santa Cruz (United States); Burnett, T. [University of Washington (United States); Grove, E. [Naval Research Laboratory (United States); Longo, F. [Instituto Nazionale di Fisica Nucleare (INFN)-Pisa (Italy); McEnery, J.; Ritz, S. [NASA Goddard Space Flight Center (United States); Mizuno, T. [Hiroshima University (Japan)

    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.

  8. The GLAST Background Model

    SciTech Connect

    Ormes, J.F.; /Denver U.; Atwood, W.; /UC, Santa Cruz; Burnett, T.; /Washington U., Seattle; Grove, E.; /Naval Research Lab, Wash., D.C.; Longo, F.; /INFN, Pisa; McEnery, J.; /NASA, Goddard; Mizuno, T.; /Hiroshima U.; 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.

  9. The Cosmic Microwave Background

    E-print Network

    Joseph Silk

    2002-12-12

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

  10. Arbitrary background picture segmentation

    Microsoft Academic Search

    S. Itzikowitz; S. Sheraizin

    2002-01-01

    In this paper, we present a new method for real time arbitrary background picture segmentation. We consider the following picture conditions: color picture, noisy picture, scene light changes, and still image arbitrary background. They are typical for many applications, e.g. for video security system, videophone, videoconference, V-commerce, etc. A set-theoretic approach has been used for picture model creation, adaptive picture

  11. Measurement of Cosmic Microwave Background Radiation

    Microsoft Academic Search

    ARNO A. PENZIAS

    1968-01-01

    The techniques associated with the measurement of antenna temperature at microwave frequencies are discussed. A number of experiments designed to measure cosmic microwave background radiation are described and their results compared. These results give a very good fit to a 3°K black body curve between 1.4 and 35 GHz.

  12. On tune deafness (dysmelodia): frequency, development, genetics and musical background.

    PubMed

    Kalmus, H; Fry, D B

    1980-05-01

    With the aid of the Distorted Tunes Test a group of British adults could be established whose melodic aptitude was below a certain level and whom we called tune deaf. They are only a fraction of those popularly called tone deaf. The Distorted Tunes Test is only slightly correlated with pitch discrimination, short term tonal memory or number memory. In children ability to pass the Distorted Tunes Test develops at greatly varying speeds and to a varying degree, reaching stability in adolescence. Tune deafness has a familial distribution and segregates in a way suggesting an autosomal dominant trait with imperfect penetrance. Some degree of positive assortative mating has been established. Some people, unfamiliar with the British melodies which form the basis of the test, pass it. This indicates the existence of a partly innate and partly acquired competence to judge what is acceptable and what is not, within the tradition of Western popular or classical music. This seems to indicate the existence of some deep structure of tonality, comparable with Chomsky's deep language structure. Asians who have not been much exposed to this kind of music find the task very difficult. PMID:7396411

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

    PubMed

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

    2015-05-01

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

  14. Chromosomal translocations in human cells are generated by canonical nonhomologous end-joining

    PubMed Central

    Ghezraoui, Hind; Piganeau, Marion; Renouf, Benjamin; Renaud, Jean-Baptiste; Sallmyr, Annahita; Ruis, Brian; Oh, Sehyun; Tomkinson, Alan; Hendrickson, Eric A.; Giovannangeli, Carine; Jasin, Maria; Brunet, Erika

    2015-01-01

    Summary Breakpoint junctions of the chromosomal translocations that occur in human cancers display hallmarks of nonhomologous end-joining (NHEJ). In mouse cells, translocations are suppressed by canonical NHEJ (c-NHEJ) components, which include DNA ligase IV (LIG4), and instead arise from alternative NHEJ (alt-NHEJ). Here we used designer nucleases (ZFNs, TALENs, and CRISPR/Cas9) to introduce DSBs on two chromosomes to study translocation joining mechanisms in human cells. Remarkably, translocations were altered in cells deficient for LIG4 or its interacting protein XRCC4. Translocation junctions had significantly longer deletions and more microhomology, indicative of alt-NHEJ. Thus, unlike mouse cells, translocations in human cells are generated by c-NHEJ. Human cancer translocations induced by paired Cas9 nicks also showed a dependence on c-NHEJ, despite having distinct joining characteristics. These results demonstrate an unexpected and striking species-specific difference for common genomic rearrangements associated with tumorigenesis. PMID:25201414

  15. EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced mitochondrial translocalization: A potential mechanism of EGFR-driven antagonism of apoptosis

    Microsoft Academic Search

    Xinyu Cao; Hu Zhu; Francis Ali-Osman; Hui-Wen Lo

    2011-01-01

    Background  Epidermal growth factor receptor (EGFR) plays an essential role in normal development, tumorigenesis and malignant biology\\u000a of human cancers, and is known to undergo intracellular trafficking to subcellular organelles. Although several studies have\\u000a shown that EGFR translocates into the mitochondria in cancer cells, it remains unclear whether mitochondrially localized EGFR\\u000a has an impact on the cells and whether EGFRvIII, a

  16. Post-translational translocation into the endoplasmic reticulum.

    PubMed

    Johnson, Nicholas; Powis, Katie; High, Stephen

    2013-11-01

    Proteins destined for the endomembrane system of eukaryotic cells are typically translocated into or across the membrane of the endoplasmic reticulum and this process is normally closely coupled to protein synthesis. However, it is becoming increasingly apparent that a significant proportion of proteins are targeted to and inserted into the ER membrane post-translationally, that is after their synthesis is complete. These proteins must be efficiently captured and delivered to the target membrane, and indeed a failure to do so may even disrupt proteostasis resulting in cellular dysfunction and disease. In this review, we discuss the mechanisms by which various protein precursors can be targeted to the ER and either inserted into or translocated across the membrane post-translationally. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum. PMID:23266354

  17. 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.

  18. Cosmic Microwave Background Polarization

    E-print Network

    Arthur Kosowsky

    1995-02-03

    Polarization of the cosmic microwave background, though not yet detected, provides a source of information about cosmological parameters complementary to temperature fluctuations. This paper provides a complete theoretical treatment of polarization fluctuations. After a discussion of the physics of polarization, the Boltzmann equation governing the evolution of the photon density matrix is derived from quantum theory and applied to microwave background fluctuations, resulting in a complete set of transport equations for the Stokes parameters from both scalar and tensor metric perturbations. This approach is equivalent at lowest order in scattering kinematics to classical radiative transfer, and provides a general framework for treating the cosmological evolution of density matrices. The metric perturbations are treated in the physically appealing longitudinal gauge. Expressions for various temperature and polarization correlation functions are derived. Detection prospects and theoretical utility of microwave background polarization are briefly discussed.

  19. X-Autosome translocations: Cytogenetic characteristics and their consequences

    Microsoft Academic Search

    M. G. Mattei; J. F. Mattei; S. Ayme; F. Giraud

    1982-01-01

    To define the principal characteristics of X-autosome translocations, the authors present a study of 105 cases, five of which are personal observations. The autosomal pairs 15, 21, and 22 are affected by t(X-Aut) more often than would be expected. The distribution of breakpoints on the X chromosome does not differ significantly from the expected distribution. The analysis of different patterns

  20. Phosphatidylserine translocation in human spermatozoa from impaired spermatogenesis

    Microsoft Academic Search

    C Almeida; M Sousa; A Barros

    2009-01-01

    The aim of the present study was to evaluate phosphatidylserine translocation in specific patient groups and compare the rates of apoptosis between ejaculated and testicular spermatozoa. Fifty-six patients undergoing infertility treatments were included in the present study. Semen samples (n=37) were obtained from cases with normozoospermia (n=9) and abnormal semen parameters (n=28). Testicular biopsy was performed in 19 patients, eight

  1. A Mouse Translocation Suppressing Sex-Linked Variegation

    Microsoft Academic Search

    Mary F. Lyon; A. G. Searle; C. E. Ford; S. Ohno

    1964-01-01

    Female mice heterozygous for the sex-linked gene tabby (To) normally show a striped or variegated coat pattern resulting from random inactivation of one or other X-chromosome. In a stock descended from an irradiated female this variegation did not occur and heterozygotes for tabby looked wild-type. This led to the hypothesis that the wild-type allele of Ta had been translocated to

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

    SciTech Connect

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

    1994-04-15

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

  3. Assessing losses of genetic diversity due to translocation: long-term case histories in Merriam's turkey ( Meleagris gallopavo merriami )

    Microsoft Academic Search

    Karen E. Mock; E. K. Latch; O. E. Rhodes Jr

    2004-01-01

    Translocation is a widely used tool in wildlife management, but populations established as a result of translocations may be subject to a range of genetic problems, including loss of genetic diversity and founder effects. The genetic impact of single translocation events can be difficult to assess because of complex management histories in translocated or source populations. Here we use molecular

  4. Matching Background Color

    NSDL National Science Digital Library

    David Ipsen

    2008-04-01

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

  5. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1991-01-01

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

  6. 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.

  7. Cosmic Microwave Background

    NSDL National Science Digital Library

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

  8. Intracellular translocation of histone deacetylase 5 regulates neuronal cell apoptosis.

    PubMed

    Wei, Jia-Yi; Lu, Qiu-Nan; Li, Wan-Ming; He, Wei

    2015-04-16

    Histone deacetylase 5 (HDAC5) undergoes signal-dependent shuttling between the nucleus and cytoplasm, which is regulated in part by calcium/calmodulin-dependent kinase (CaMK)-mediated phosphorylation. Here, we report that HDAC5 regulates the survival of cortical neurons in pathological conditions. HDAC5 was evenly localized to the nucleus and cytoplasm in cultured cortical neurons. However, in response to 50?M NMDA conditions that induced neuronal cell apoptosis, nuclear-distributed HDAC5 was rapidly phosphorylated and translocated into cytoplasm of the cultured cortical neurons. Treatment with a CaMKII inhibitor KN93 suppressed HDAC5 phosphorylation and nuclear translocation induced by NMDA, whereas constitutively active CaMKII? (T286D) stimulated HDAC5 nuclear export. Importantly, we showed that ectopic expression of nuclear-localized HDAC5 in cortical neurons suppressed NMDA-induced apoptosis. Finally, inactivation of HDAC5 by treatment with the class II-specific HDAC inhibitor trichostatin A (TSA) promoted NMDA-induced neuronal cell apoptosis. Altogether, these data identify HDAC5 and its intracellular translocation as key effectors of multiple pathways that regulate neuronal cell apoptosis. PMID:25661252

  9. 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

  10. 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

  11. Controlling polymer translocation and ion transport via charge correlations

    E-print Network

    Sahin Buyukdagli; Tapio Ala-Nissila

    2014-10-10

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

  12. Growth factor deprivation induces cytosolic translocation of SIRT1

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  13. 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.

  14. Compositions and methods for detecting gene rearrangements and translocations

    DOEpatents

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

    2000-01-01

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

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

    PubMed

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

    2010-10-01

    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

  16. Mechanism of Inhibition of Translocation by Localized Chilling 1

    PubMed Central

    Giaquinta, R. T.; Geiger, D. R.

    1973-01-01

    Arrhenius plots of translocation velocity as a function of petiole temperature show a marked increase in temperature dependence below 10 C in bean (a chilling-sensitive species) but not in sugar beet (chilling-resistant). The increased temperature dependence below 10 C was not observed for cytoplasmic streaming or oxygen uptake in bean. Bean petioles were served to release pressure in order to determine whether sieve tubes are obstructed in cold-treated petioles. The resulting pressure release caused serious displacement of the crystalline protein bodies in the sieve tubes of petioles at 25 C, but in those locally cooled to 0 C for 30 minutes little displacement occurred, indicating obstruction in the latter. An ultrastructural study of sieve tubes in tissue frozen rapidly in situ and dehydrated by freeze substitution revealed that treatment at 0 C for 30 minutes caused structural alteration and displacement of the cytoplasmic material lining the sieve tube wall resulting in occlusion of sieve plates. The sieve plates of the control petioles at 25 C were generally clear of obstructions. The results indicate that inhibition of translocation by chilling in chilling-sensitive plants results from physical blockage of sieve plates rather than from direct inhibition of a metabolic process which drives translocation. Images PMID:16658332

  17. Coliphage HK022 Nun protein inhibits RNA polymerase translocation.

    PubMed

    Vitiello, Christal L; Kireeva, Maria L; Lubkowska, Lucyna; Kashlev, Mikhail; Gottesman, Max

    2014-06-10

    The Nun protein of coliphage HK022 arrests RNA polymerase (RNAP) in vivo and in vitro at pause sites distal to phage ? N-Utilization (nut) site RNA sequences. We tested the activity of Nun on ternary elongation complexes (TECs) assembled with templates lacking the ? nut sequence. We report that Nun stabilizes both translocation states of RNAP by restricting lateral movement of TEC along the DNA register. When Nun stabilized TEC in a pretranslocated register, immediately after NMP incorporation, it prevented binding of the next NTP and stimulated pyrophosphorolysis of the nascent transcript. In contrast, stabilization of TEC by Nun in a posttranslocated register allowed NTP binding and nucleotidyl transfer but inhibited pyrophosphorolysis and the next round of forward translocation. Nun binding to and action on the TEC requires a 9-bp RNA-DNA hybrid. We observed a Nun-dependent toe print upstream to the TEC. In addition, mutations in the RNAP ?' subunit near the upstream end of the transcription bubble suppress Nun binding and arrest. These results suggest that Nun interacts with RNAP near the 5' edge of the RNA-DNA hybrid. By stabilizing translocation states through restriction of TEC lateral mobility, Nun represents a novel class of transcription arrest factors. PMID:24853501

  18. Twin-arginine-dependent translocation of folded proteins

    PubMed Central

    Fröbel, Julia; Rose, Patrick; Müller, Matthias

    2012-01-01

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

  19. 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).

  20. The detection of microbial DNA in the blood: a sensitive method for diagnosing bacteremia and/or bacterial translocation in surgical patients.

    PubMed Central

    Kane, T D; Alexander, J W; Johannigman, J A

    1998-01-01

    OBJECTIVE: The purpose was to determine the sensitivity of detecting microbial DNA in the blood of surgical patients as a measure for diagnosing systemic infection and/or translocation from the gut. SUMMARY BACKGROUND DATA: Microbial infections and translocation of intestinal bacteria are thought to contribute to multiple system organ failure, but bacterial cultures are often negative in patients with this complication. METHODS: DNA was extracted from the blood of 40 surgical patients and 20 healthy controls. Polymerase chain reaction (PCR) techniques were used to amplify genes from Escherichia coli, Bacteroides fragilis, and a region of 16S ribosomal RNA found in many gram-positive and -negative bacteria. RESULTS: Bacterial DNA genes were not detected in healthy volunteers but were found in all patients with positive blood cultures. All eight transplant patients receiving OKT3 therapy had microbial DNA in their blood, possibly indicating translocation from the gut. Sixty-four percent of critically ill patients had microbial DNA detected in their blood, but only 3 (14%) had positive blood cultures. CONCLUSIONS: The PCR method is more sensitive than blood cultures for detecting bacterial components in the blood of critically ill surgical patients and may detect microbial translocation from the intestine. Images Figure 1. Figure 2. Figure 3. PMID:9445103

  1. Impact of Protein-Protein Interactions on Global Intermolecular Translocation Rates of the Transcription Factors Sox2 and Oct1 Between DNA Cognate Sites Analyzed by z-Exchange

    E-print Network

    Clore, G. Marius

    of the Transcription Factors Sox2 and Oct1 Between DNA Cognate Sites Analyzed by z-Exchange NMR Spectroscopy Yuki of Sox2/Oct1 interaction on intermolecular translocation 1 Address correspondence to: G. Marius Clore and intersegment transfer / z-exchange spectroscopy Background: Sox2 and Oct1 interact on a variety of promoters

  2. Cosmic background radiation

    Microsoft Academic Search

    George Smoot; Douglas Scott

    2000-01-01

    We summarise the current status of cosmic microwave background spectrum and\\u000aanisotropy measurements, and their theoretical interpretation. This is the\\u000aupdate of the mini-review for the 1997 web-version of the Review of Particle\\u000aProperties.

  3. Local microwave background radiation

    E-print Network

    Domingos Soares

    2014-11-13

    An inquiry on a possible local origin for the Microwave Background Radiation is made. Thermal MBR photons are contained in a system called {\\it magnetic bottle} which is due to Earth magnetic field and solar wind particles, mostly electrons. Observational tests are anticipated.

  4. PANDEMIC INFLUENZA background briefing

    E-print Network

    Rambaut, Andrew

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

  5. EBSD Images Theoretical Background

    E-print Network

    Candea, George

    function during a welding procedure. Consistent grain growth curves were obtained with this techniqueMotivation EBSD Images Theoretical Background Defects in the Weld Grain Growth Low Speed Welding High Speed Welding Conclusion Heat-Affected Zone Observations Welding Experiments The low density

  6. Microsoft External Research Backgrounder

    E-print Network

    Narasayya, Vivek

    Microsoft External Research Backgrounder has been a part of a number of highly successful, cutting-edge collaborative projects over the years. In fact, in fiscal year 2008, Microsoft External Research supported External Research supports long-term initiatives to enhance teaching and learning through the creative use

  7. David Smith Academic background

    E-print Network

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

  8. Cosmic Microwave Background Anisotropies

    Microsoft Academic Search

    Wayne Hu; Scott Dodelson

    2002-01-01

    Cosmic microwave background (CMB) temperature anisotropies have and will continue to revolutionize our understanding of cosmology. The recent discovery of the previously predicted acoustic peaks in the power spectrum has established a working cosmological model: a critical density universe consisting of mainly dark matter and dark energy, which formed its structure through gravitational instability from quantum fluctuations during an inflationary

  9. Radioactive Decay 1. Background

    E-print Network

    Elster, Charlotte

    Radioactive Decay 1. Background It is well known that many nuclei are unstable and are transformed into other nuclear species by means of either alpha decay or beta decay. The rate at which those radioactive on the number N of radioactive nuclei in the sample and also on the probability for each nucleus to decay

  10. Reduced genetic diversity and significant genetic differentiation after translocation: Comparison of the remnant and translocated populations of bridled nailtail wallabies ( Onychogalea fraenata )

    Microsoft Academic Search

    Dominique P. Sigg

    2006-01-01

    Loss of genetic diversity and increased population differentiation from source populations are common problems associated with translocation programmes established from captive-bred stock or a small number of founders. The bridled nailtail wallaby is one of the most endangered macropods in Australia, having been reduced to a single remnant population in the last 100 years. A translocated population of bridled nailtail wallabies

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

    SciTech Connect

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

    1994-09-01

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

  12. 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

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

    PubMed Central

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

    2012-01-01

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

  14. The Anisotropy of the Microwave Background to l = 3500: Mosaic Observations with the Cosmic Background Imager

    Microsoft Academic Search

    T. J. Pearson; B. S. Mason; A. C. S. Readhead; M. C. Shepherd; J. L. Sievers; P. S. Udomprasert; J. K. Cartwright; A. J. Farmer; S. Padin; S. T. Myers; J. R. Bond; C. R. Contaldi; U.-L. Pen; S. Prunet; D. Pogosyan; J. E. Carlstrom; J. Kovac; E. M. Leitch; C. Pryke; N. W. Halverson; W. L. Holzapfel; P. Altamirano; L. Bronfman; S. Casassus; J. May; M. Joy

    2003-01-01

    Using the Cosmic Background Imager (CBI), a 13-element interferometer array operating in the 26-36 GHz frequency band, we have observed 40 deg2 of sky in three pairs of fields, each ~145'×165', using overlapping pointings (mosaicking). We present images and power spectra of the cosmic microwave background radiation in these mosaic fields. We remove ground radiation and other low-level contaminating signals

  15. Wandering in the Background: A Cosmic Microwave Background Explorer

    E-print Network

    Hu, Wayne

    Wandering in the Background: A Cosmic Microwave Background Explorer by Wayne T. Hu B.A. (Princeton Spinrad 1995 #12;1 Wandering in the Background: A Cosmic Microwave Background Explorer by Wayne T. Hu and geometry. Stressing model independent results, we show how the microwave background can be used to extract

  16. Gravitational wave background from binary systems

    SciTech Connect

    Rosado, Pablo A. [Albert Einstein Institute, Max Planck Institute for Gravitational Physics, 30167 Hannover (Germany)

    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.

  17. HMGB1 neutralization is associated with bacterial translocation during acetaminophen hepatotoxicity

    PubMed Central

    2014-01-01

    Background Acetaminophen (APAP) hepatotoxicity is associated with a high rate of gram-negative enteric bacterial infection; however, the underlying mechanism is still unknown. APAP overdose induces massive hepatocyte necrosis, necrotic tissue releases high mobility group B1 (HMGB1) and exogenous HMGB1 is able to induce gut bacterial translocation (BT) in normal mice; therefore, it is possible that HMGB1 mediates gut BT in APAP hepatotoxicity. This study aims to test this hypothesis by using anti-HMGB1 neutralizing antibody to treat APAP overdose for 24-48 hours. Methods Male C57BL/6 mice were intraperitoneally (i.p.) injected with a single dose of APAP (350 mg/kg dissolved in 1 mL sterile saline). 2 hrs after APAP injection, the APAP challenged mice were randomized to receive treatment with either anti-HMGB1 antibody (400 ?g per dose) or non-immune (sham) IgG every 24 h for a total of 2 doses. Results 24 and 48 hrs after APAP challenge, anti-HMGB1 treatment instead of sham IgG therapy significantly decreased serum HMGB1 concentrations and reduced BT by 85%; serum HMGB1 levels were positively correlated with the amount of BT; anti-HMGB1 therapy decreased hepatic BT at 48 h, which was associated with better recovered liver structure and better restored hepatic immune system that was shown by enhanced hepatic mRNA expression of TNF-?, IL-6 and extensive proliferation of inflammatory and reticuloendothelial cells; however, anti-HMGB1 treatment did not decrease gut mucosal permeability as compared to the sham IgG therapy at either 24 or 48 hrs. Conclusion HMGB1 neutralization is associated with bacterial translocation during APAP hepatotoxicity. PMID:24708589

  18. Choroideremia in a woman with ectodermal dysplasia and complex translocations involving chromosomes X, 1, and 3

    PubMed Central

    Mukkamala, Krishna; Gentile, Ronald C.; Willner, Judith; Tsang, Stephen

    2011-01-01

    Background Choroideremia is an X-linked recessive disorder characterized by vision loss with progressive atrophy of the retinal photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris. Ectodermal dysplasia is a heterogeneous group of disorders characterized by a deficiency of two or more ectodermal derivatives. We report on the phenotypic and genetic characteristics of a 29-year-old woman with both choroideremia and ectodermal dysplasia. Materials and Methods Observational case report with physical and ophthalmic examination, fluorescein angiography (FA), visual field testing, electroretinography, and cytogenetic analysis. This study adhered to the tenets of the Declaration of Helsinki and The New York Eye and Ear Infirmary Institutional Review Board guidelines. Results Physical and ocular examination revealed hypotrichosis, hypohidrosis, full dentures, meibomian gland hypoplasia, and a decrease in corneal tear film. Visual acuity was hand motions in the right eye and 20/50 in the left eye. Fundus examination and fluorescein angiography were consistent with advanced choroideremia and revealed diffuse bilateral RPE and chorioretinal atrophy with sparing of the fovea. Visual field testing had less than 10-degree central islands in both eyes. Scotopic electroretinogram (ERG) was flat with a small flicker response. Cytogenetic analysis showed a complex translocation involving chromosomes X, 1, and 3: 46,X,t(X;1;3)(q13;q24;q21),inv(9)(p11q13). Selective inactivation of the normal X chromosome was present in blood and skin. Chromosomal analyses of the proband's family (mother and two brothers) were normal. Conclusion An X-autosome chromosomal translocation combined with non-random inactivation of the normal X-chromosome in a woman resulted in the phenotypic findings of choroideremia and ectodermal dysplasia. PMID:21067479

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

    PubMed Central

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

    2006-01-01

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

  20. Stabilization of Dicentric Translocations through Secondary Rearrangements Mediated by Multiple Mechanisms in S. cerevisiae

    PubMed Central

    Pennaneach, Vincent; Kolodner, Richard D.

    2009-01-01

    Background The gross chromosomal rearrangements (GCRs) observed in S. cerevisiae mutants with increased rates of accumulating GCRs include predicted dicentric GCRs such as translocations, chromosome fusions and isoduplications. These GCRs resemble the genome rearrangements found as mutations underlying inherited diseases as well as in the karyotypes of many cancers exhibiting ongoing genome instability Methodology/Principal Findings The structures of predicted dicentric GCRs were analyzed using multiple strategies including array-comparative genomic hybridization, pulse field gel electrophoresis, PCR amplification of predicted breakpoints and sequencing. The dicentric GCRs were found to be unstable and to have undergone secondary rearrangements to produce stable monocentric GCRs. The types of secondary rearrangements observed included: non-homologous end joining (NHEJ)-dependent intramolecular deletion of centromeres; chromosome breakage followed by NHEJ-mediated circularization or broken-end fusion to another chromosome telomere; and homologous recombination (HR)-dependent non-reciprocal translocations apparently mediated by break-induced replication. A number of these GCRs appeared to have undergone multiple bridge-fusion-breakage cycles. We also observed examples of chromosomes with extensive ongoing end decay in mec1 tlc1 mutants, suggesting that Mec1 protects chromosome ends from degradation and contributes to telomere maintenance by HR. Conclusions/Significance HR between repeated sequences resulting in secondary rearrangements was the most prevalent pathway for resolution of dicentric GCRs regardless of the structure of the initial dicentric GCR, although at least three other resolution mechanisms were observed. The resolution of dicentric GCRs to stable rearranged chromosomes could in part account for the complex karyotypes seen in some cancers. PMID:19636429

  1. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1989-01-01

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

  2. Giants On Deformed Backgrounds

    E-print Network

    Marco Pirrone

    2006-12-07

    We study giant graviton probes in the framework of the three--parameter deformation of the AdS_5 x S^5 background. We examine both the case when the brane expands in the deformed part of the geometry and the case when it blows up into AdS. Performing a detailed analysis of small fluctuations around the giants, the configurations turn out to be stable. Our results hold even for the supersymmetric Lunin-Maldacena deformation.

  3. 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.

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

    SciTech Connect

    Truong Le Xuan Nguyen [Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Choi, Joung Woo [Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Lee, Sang Bae [Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Ye, Keqiang [Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322 (United States); Woo, Soo-Dong [Department of Plant Medicine, College of Agriculture, Life and Environment Sciences, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Lee, Kyung-Hoon [Department of Anatomy, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of); Ahn, Jee-Yin [Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746 (Korea, Republic of)]. 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.

  5. Reverse DNA translocation through a solid-state nanopore by magnetic tweezers

    PubMed Central

    Peng, Hongbo; Ling, Xinsheng Sean

    2009-01-01

    Voltage-driven DNA translocation through nanopores has attracted wide interest for many potential applications in molecular biology and biotechnology. However, it is intrinsically difficult to control the DNA motion in standard DNA translocation processes in which a strong electric field is required in drawing DNA into the pore, but it also leads to uncontrollable fast DNA translocation. Here we explore a new type of DNA translocation. We dub it ‘reverse DNA translocation’, in which the DNA is pulled through a nanopore mechanically by a magnetic bead, driven by a magnetic-field gradient. This technique is compatible with simultaneous ionic current measurements and is suitable for multiple nanopores, paving the way for large scale applications. We report the first experiment of reverse DNA translocation through a solid-state nanopore using magnetic tweezers. PMID:19420602

  6. 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.

  7. Cosmology and the Cosmic Background Explorer (COBE)

    NASA Technical Reports Server (NTRS)

    Boggess, Nancy W.

    1989-01-01

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

  8. Internal and External Radioactive Backgrounds

    E-print Network

    Chapter 3 Internal and External Radioactive Backgrounds New physics is often discovered by pushing;Chapter 3: Internal and External Radioactive Backgrounds 104 the rate of background. High-energy neutrino to find suitable construction materials. 3.1 External Backgrounds External backgrounds are those in which

  9. Highly sensitive measurement of single DNA translocation through an ultraviolet light spot on silicon nanopore

    NASA Astrophysics Data System (ADS)

    Yamazaki, Hirohito; Kimura, Shinji; Tsukahara, Mutsumi; Ito, Shintaro; Esashika, Keiko; Saiki, Toshiharu

    2014-02-01

    Nanopore-based sensing is an attractive candidate for developing single-molecule DNA sequencing technology. Recently, optical detection with a parallel nanopore array has been demonstrated. Although this method is a promising approach to develop high thorough-put measurement, the approach requires observation at low-background condition. In this paper, we propose a new optical method for nanopore DNA sequencing with high resolution and a high signal-tonoise ratio. We use ultraviolet light for the excitation of a fluorescent probe and a nanopore in a silicon membrane. Because silicon has a large refractive index and an extinction coefficient at ultraviolet wavelengths, light transmission thorough the membrane is negligible. This contributes to low background measurement of fluorescence from fluorophore-labeled DNA strands. In addition, the z-polarization component of the electric field is attributed to generating a large electric field gradient at the nanopore exit due to its boundary condition at the silicon surface. Our numerical electromagnetic simulation revealed that the z-component electric field was dominant compared to the xcomponent electric filed. The intensity of the electric field increased steeply in 2 nm, when ultraviolet light of 375nm wavelength was focused on a 10nm-thick silicon membrane with a 7 nm-diameter nanopore. This steeply increasing electric field can be sufficient resolution for the sequencing of designed DNA polymer. Finally, our experimental results demonstrated optical detection of single DNA translocation events with a high signal-to-noise ratio under applied voltage.

  10. Uptake and translocation of paclobutrazol by shoots of M.26 apple rootstock

    Microsoft Academic Search

    P. J. Richardson; J. D. Quinlan

    1986-01-01

    When 14C-paclobutrazol, a gibberellin synthesis inhibitor, was applied to different parts of actively-growing M.26 apple rootstock shoots it was translocated acropetally when applied to the young stem and, to a lesser extent, from the youngest unrolled leaf. Paclobutrazol was not translocated out of leaf laminae, shoot tips or from one-year-old wood but translocation occurred out of a treated petiole into

  11. Hyperthermia increases gamma-ray and fission neutron-induced translocations in Drosophila

    SciTech Connect

    Mittler, S.

    1984-01-01

    Hyperthermia has been reported in Drosophila melanogaster to increase radiation-induced chromosome rearrangements, chromosome loss, recessive and dominant lethals. To determine whether hyperthermia would also affect high linear energy transfer (LET)-induced genetic damage such as translocations, which involve breakage and reunion of chromosomes, a genetic system was employed not only allowing detection of ordinary 2;3 translocations, but also permitting a more accurate measure of Y-autosome translocations.

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

    PubMed

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

    2015-01-01

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

  13. Mitochondrial function in Antarctic nototheniids with ND6 translocation.

    PubMed

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

    2012-01-01

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

  14. Mitochondrial Function in Antarctic Nototheniids with ND6 Translocation

    PubMed Central

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

    2012-01-01

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

  15. Biopersistence and Brain Translocation of Aluminum Adjuvants of Vaccines

    PubMed Central

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

    2015-01-01

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

  16. Alterations in rat intestinal transit by morphine promote bacterial translocation.

    PubMed

    Runkel, N S; Moody, F G; Smith, G S; Rodriguez, L F; Chen, Y; Larocco, M T; Miller, T A

    1993-08-01

    Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N = 8) or morphine sulfate (20 mg/kg; N = 8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8 +/- 8.2% vs. 55.8 +/- 4.0%; P < 0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8344112

  17. 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

  18. 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.

  19. Carbon Dioxide Concentration at Night Affects Translocation from Soybean Leaves

    PubMed Central

    BUNCE, JAMES A.

    2002-01-01

    Studies have indicated that the concentration of carbon dioxide [CO2] during the dark period may influence plant dry matter accumulation. It is often suggested that these effects on growth result from effects of [CO2] on rates of respiration, but responses of respiration to [CO2] remain controversial, and connections between changes in respiration rate and altered growth rate have not always been clear. The present experiments tested whether translocation, a major consumer of energy from respiration in exporting leaves, was sensitive to [CO2]. Nineteen?day?old soybean plants grown initially at a constant [CO2] of 350 µmol mol–1 were exposed to three consecutive nights with a [CO2] of 220–1400 µmol mol–1, with a daytime [CO2] of 350 µmol mol–1. Change in dry mass of the individual second, third and fourth trifoliate leaves over the 3?d period was determined, along with rates of respiration and photosynthesis of second leaves, measured by net CO2 exchange. Translocation was determined from mass balance for second leaves. Additional experiments were conducted where the [CO2] around individual leaves was controlled separately from that of the rest of the plant. Results indicated that low [CO2] at night increased both respiration and translocation and elevated [CO2] decreased both processes, to similar relative extents. The effect of [CO2] during the dark on the change in leaf mass over 3 d was largest in second leaves, where the change in mass was about 50 % greater at 1400 µmol mol–1 CO2 than at 220 µmol mol–1 CO2. The response of translocation to [CO2] was localized in individual leaves. Results indicated that effects of [CO2] on net carbon dioxide exchange rate in the dark either caused or reflected a change in a physiologically important process which is known to depend on energy supplied by respiration. Thus, it is unlikely that the observed effects of [CO2] on respiration were artefacts of the measurement process in this case. PMID:12234152

  20. 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.

  1. Chemical catalysis by the translocator protein (18 kDa).

    PubMed

    Ginter, Christopher; Kiburu, Irene; Boudker, Olga

    2013-05-28

    Translocator proteins (18 kDa) (TSPOs) are conserved integral membrane proteins. In both eukaryotes and prokaryotes, TSPOs interact with porphyrins, precursors of heme, and photosynthetic pigments. Here we demonstrate that bacterial TSPOs catalyze rapid porphyrin degradation in a light- and oxygen-dependent manner. The reaction is inhibited by a synthetic TSPO ligand PK11195 and by mutations of conserved residues, which affect either porphyrin binding or catalytic activity. We hypothesize that TSPOs are ancient enzymes mediating porphyrin catabolism with the consumption of reactive oxygen species. PMID:23651039

  2. Steric Modulation of Ionic Currents in DNA Translocation Through Nanopores

    NASA Astrophysics Data System (ADS)

    Mazzone, Valerio; Melchionna, Simone; Marconi, Umberto Marini Bettolo

    2015-03-01

    Ionic currents accompanying DNA translocation strongly depend on molarity of the electrolyte solution and the shape and surface charge of the nanopore. By means of the Poisson-Nernst-Planck equations it is shown how conductance is modulated by the presence of the DNA intruder and as a result of competing electrostatic and confinement factors. The theoretical results reproduce quantitatively the experimental ones and are summarized in a conductance diagram that allows distinguishing the region of reduced conductivity from the region of enhanced conductivity as a function of molarity and the pore dimension.

  3. Sperm chromosome complements from two human reciprocal translocation heterozygotes

    Microsoft Academic Search

    Elizabeth L. Spriggs; Renee H. Martin; Maj Hulten

    1992-01-01

    Summary  Using the hamster oocyte\\/human sperm fusion technique, we studied sperm chromosome complements in two male reciprocal translocation heterozygotes, 46,XY,t(11;17)(p11.2;q12.3) and 46,XY,t(1;11) (p36.3;q13.1). For the t(11;17) carrier, 202 sperm chromosome complements were obtained, but 18 karyotypes were not included in the segregation data because of multiple breaks and rearrangements. The alternate and adjacent I types, adjacent II, and 31 segregations accounted

  4. Gaussianity of LISA's confusion backgrounds

    SciTech Connect

    Racine, Etienne [Department of Physics, Mathematics and Astronomy, California Institute of Technology, Pasadena, California 91125 (United States); Cutler, Curt [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91109 (United States)

    2007-12-15

    Data analysis for the proposed Laser Interferometer Space Antenna (LISA) will be complicated by the huge number of sources in the LISA band. In the frequency band {approx}10{sup -4}-2x10{sup -3} Hz, galactic white dwarf binaries (GWDBs) are sufficiently dense in frequency space that it will be impossible to resolve most of them, and ''confusion noise'' from the unresolved Galactic binaries will dominate over instrumental noise in determining LISA's sensitivity to other sources in that band. Confusion noise from unresolved extreme-mass-ratio inspirals (EMRIs) could also contribute significantly to LISA's total noise curve. To date, estimates of the effect of LISA's confusion noise on matched-filter searches and their detection thresholds have generally approximated the noise as Gaussian, based on the central limit theorem. However in matched-filter searches, the appropriate detection threshold for a given class of signals may be located rather far out on the tail of the signal-to-noise probability distribution, where a priori it is unclear whether the Gaussian approximation is reliable. Using the Edgeworth expansion and the theory of large deviations, we investigate the probability distribution of the usual matched-filter detection statistic, far out on the tail of the distribution. We apply these tools to four somewhat idealized versions of LISA data searches: searches for EMRI signals buried in GWDB confusion noise, and searches for massive black hole binary signals buried in (i) GWDB noise, (ii) EMRI noise, and (iii) a sum of EMRI noise and Gaussian noise. Assuming reasonable short-distance cutoffs in the populations of confusion sources (since the very closest and hence strongest sources will be individually resolvable), modifications to the appropriate detection threshold, due to the non-Gaussianity of the confusion noise, turn out to be quite small for realistic cases. The smallness of the correction is partly due to the fact that these three types of sources evolve on quite different time scales, so no single background source closely resembles any search template. We also briefly discuss other types of LISA searches where the non-Gaussianity of LISA's confusion backgrounds could perhaps have a much greater impact on search reliability and efficacy.

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

    E-print Network

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

    2014-08-20

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

  6. 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.

  7. 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 ?-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

  8. 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.

  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 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

  10. A G-protein subunit translocation embedded network motif underlies GPCR regulation of calcium oscillations.

    PubMed

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

    2014-07-01

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  12. Cosmic microwave?background?theory

    PubMed Central

    Bond, J. Richard

    1998-01-01

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

  13. Stochastic background from inspiralling double neutron stars

    E-print Network

    Tania Regimbau

    2006-12-30

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

  14. 23. Cosmic microwave background 1 23. COSMIC MICROWAVE BACKGROUND

    E-print Network

    23. Cosmic microwave background 1 23. COSMIC MICROWAVE BACKGROUND Revised August 2009 by D. Scott from beyond our Galaxy is dominated by the Cosmic Microwave Background (CMB), discovered in 1965 [1;2 23. Cosmic microwave background 23.2.1. The Monopole : The CMB has a mean temperature of T = 2

  15. 25. Cosmic microwave background 1 25. COSMIC MICROWAVE BACKGROUND

    E-print Network

    25. Cosmic microwave background 1 25. COSMIC MICROWAVE BACKGROUND Revised August 2011 by D. Scott from beyond our Galaxy is dominated by the cosmic microwave background (CMB), discovered in 1965 [1://pdg.lbl.gov) June 18, 2012 16:19 #12;2 25. Cosmic microwave background 25.2.1. The Monopole : The CMB has a mean

  16. 23. Cosmic microwave background 1 23. COSMIC MICROWAVE BACKGROUND

    E-print Network

    23. Cosmic microwave background 1 23. COSMIC MICROWAVE BACKGROUND Revised August 2011 by D. Scott from beyond our Galaxy is dominated by the cosmic microwave background (CMB), discovered in 1965 [1 update for the 2012 edition (pdg.lbl.gov) February 16, 2012 14:07 #12;2 23. Cosmic microwave background

  17. Discovery of the Microwave Background Cosmic microwave background radiation

    E-print Network

    Barnes, Joshua Edward

    Discovery of the Microwave Background Cosmic microwave background radiation Signals from the early universe, or pigeon droppings? #12;Microwave Background Radiation The spectrum is a near- perfect match energy reaching us from all directions. #12;Origin of the Microwave Background Back at z > 0, microwave

  18. Novel class of potential therapeutics that target ricin retrograde translocation.

    PubMed

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

    2014-01-01

    Ricin toxin, an A-B toxin from Ricinus communis, induces cell death through the inhibition of protein synthesis. The toxin binds to the cell surface via its B chain (RTB) followed by its retrograde trafficking through intracellular compartments to the ER where the A chain (RTA) is transported across the membrane and into the cytosol. Ricin A chain is transported across the ER membrane utilizing cellular proteins involved in the disposal of aberrant ER proteins by a process referred to as retrograde translocation. Given the current lack of therapeutics against ricin intoxication, we developed a high-content screen using an enzymatically attenuated RTA chimera engineered with a carboxy-terminal enhanced green fluorescent protein (RTA(E177Q)egfp) to identify compounds that target RTA retrograde translocation. Stabilizing RTA(E177Q)egfp through the inclusion of proteasome inhibitor produced fluorescent peri-nuclear granules. Quantitative analysis of the fluorescent granules provided the basis to discover compounds from a small chemical library (2080 compounds) with known bioactive properties. Strikingly, the screen found compounds that stabilized RTA molecules within the cell and several compounds limited the ability of wild type RTA to suppress protein synthesis. Collectively, a robust high-content screen was developed to discover novel compounds that stabilize intracellular ricin and limit ricin intoxication. PMID:24366208

  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. Novel Class of Potential Therapeutics that Target Ricin Retrograde Translocation

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Meier, R; Alessi, D R; Cron, P; Andjelkovi?, 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

  2. Molecular determinants of nucleolar translocation of RNA helicase A

    SciTech Connect

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

    2007-10-15

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

  3. 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.

  4. Translocation of structural P proteins in the phloem.

    PubMed Central

    Golecki, B; Schulz, A; Thompson, G A

    1999-01-01

    Phloem-specific proteins (P proteins) are particularly useful markers to investigate long-distance trafficking of macromolecules in plants. In this study, genus-specific molecular probes were used in combination with intergeneric grafts to reveal the presence of a pool of translocatable P protein subunits. Immunoblot analyses demonstrated that Cucurbita spp P proteins PP1 and PP2 are translocated from Cucurbita maxima stocks and accumulate in Cucumis sativus scions. Cucurbita maxima or Cucurbita ficifolia PP1 and PP2 mRNAs were not detected in Cucumis sativus scions by either RNA gel blot analysis or reverse transcription-polymerase chain reaction, indicating that the proteins, rather than transcripts, are translocated. Tissue prints of the Cucumis sativus scion, using antibodies raised against Cucurbita maxima PP1 or PP2, detected both proteins in the fascicular phloem of the stem at points distal to the graft union and in the petiole of a developing leaf, suggesting that the proteins move within the assimilate stream toward sink tissues. Cucurbita maxima PP1 was immunolocalized by light microscopy in sieve elements of the extrafascicular phloem of Cucumis sativus scions, whereas Cucurbita maxima PP2 was detected in both sieve elements and companion cells. PMID:9878637

  5. Mitochondrial translocation of ?-synuclein is promoted by intracellular acidification

    PubMed Central

    Cole, Nelson B.; DiEuliis, Diane; Leo, Paul; Mitchell, Drake C.; Nussbaum, Robert L.

    2008-01-01

    Mitochondrial dysfunction plays a central role in the selective vulnerability of dopaminergic neurons in Parkinson’s disease (PD) and is influenced by both environmental and genetic factors. Expression of the PD protein ?-synuclein or its familial mutants often sensitizes neurons to oxidative stress and to damage by mitochondrial toxins. This effect is thought to be indirect, since little evidence physically linking ?-synuclein to mitochondria has been reported. Here, we show that the distribution of ?-synuclein within neuronal and non-neuronal cells is dependent on intracellular pH. Cytosolic acidification induces translocation of ?-synuclein from the cytosol onto the surface of mitochondria. Translocation occurs rapidly under artificially-induced low pH conditions and as a result of pH changes during oxidative or metabolic stress. Binding is likely facilitated by low pH-induced exposure of the mitochondria-specific lipid cardiolipin. These results imply a direct role for ?-synuclein in mitochondrial physiology, especially under pathological conditions, and in principle, link ?-synuclein to other PD genes in regulating mitochondrial homeostasis. PMID:18440504

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

    PubMed

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

    1999-07-01

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

  7. Antibody evidence for different conformational states of ADP, ATP translocator protein isolated from mitochondria.

    PubMed Central

    Buchanan, B B; Eiermann, W; Riccio, P; Aquila, H; Klingenberg, M

    1976-01-01

    Consistent with the previously proposed reorientation mechanism for the ADP,ATP translocator protein of mitochondria, evidence has now been obtained for the existence of two distinct conformational states of the isolated translocator protein. Previous studies indicated that when the mitochondrial translocator protein is in the c-state(i.e., when its binding site faces the cytosol side) the protein binds primarily the ligand carboxyatractylate (CAT), and when the translocator protein is in the m-state(i.e., when its binding site faces the mitochondrial matrix) the translocator protein binds primarily bongkrekate. Direct evidence for this formulation has now come from the application of antibodies to the isolated translocator protein-ligand complex. Two antibodies were produced against the ADP,ATP translocator protein isolated from beef heart mitochondria. One antibody, which was produced against the protein isolated as the CAT-binding protein complex, was found to be highly specific for that complex and did not react with the protein in the conformation state conferred by the bongkrekate ligand. This antibody did not cover the CAT-binding site, as evidenced by the exchange of unlabeled CAT with [35S]CAT bound to the translocator protein. However, the same antibody inhibited a transition of the protein from the c-state to the m-state, as evidenced by an inhibition of the displacement of[35S]CAT by bongkrekate (added jointly with ADP). It appears, therefore, that the antibody immobilized the translocator protein in the c-state. The second antibody produced against the (somewhat less pure) ADP,ATP translocator protein, isolated as the bongkrekate-binding protein complex, did not react with the CAT-binding protein. Thus, the second antibody appeared to be specific for the translocator protein in the m-state. Neither antibody inhibited mitochondrial ADP,ATP transport. PMID:1065877

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

    PubMed Central

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

    2005-01-01

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

  9. The Cosmic Background Radiation

    E-print Network

    G. F. Smoot; D. Scott

    1996-03-28

    We review the current status of experimental data for spectral distortions and angular anisotropies of the cosmic microwave background, as well as discussing the relevant physical processes. This is one of a number of new articles in astrophysics and cosmology which will appear in the 1996 Review of Particle Properties (Phys. Rev. D. in press). Other relevant reviews include: "Big-Bang Cosmology" by K.A. Olive; "Big-Bang Nucleosynthesis" by K.A. Olive & D.N. Schramm; "The Hubble Constant" by C.J. Hogan; "Dark Matter" by M. Srednicki; "Cosmic Rays" by T.K. Gaisser & T. Stanev; "Solar Neutrinos" by K. Nakamura. Additional information is also available, such as astrophysical and cosmological constraints on particles such as axions and neutrinos, as well as tables of physical constants and astrophysical constants. These articles are part of a new initiative to widen the scope of the RPP by providing a regular review of some important topics and parameters in astrophysics.

  10. 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.

  11. Differential Effect of Ischemic and Pharmacological Preconditioning on PKC Isoform Translocation in Adult Rat Cardiac Myocytes

    Microsoft Academic Search

    Vasiliki Tsouka; Thomais Markou; Antigone Lazou

    2002-01-01

    The role of PKC isoforms in the protection of ischemic preconditioning remains controversial. The aim of the present study was to compare PKC translocation in ischemic and pharmacological preconditioning and to test the hypothesis that induction of the preconditioned state results in a sustained translocation of PKC during the following ischemic period. Isolated rat cardiac myocytes were subjected to established

  12. Sec and Tat-Dependent Translocation of  -Lactamases across the Escherichia coli Inner Membrane

    Microsoft Academic Search

    N. Pradel; J. Delmas; L. F. Wu; C. L. Santini; R. Bonnet

    2009-01-01

    -Lactamases represent the major resistance mechanism of gram-negative bacteria against -lactam anti- biotics. The amino acid sequences of these proteins vary widely, but all are located in the periplasm of bacteria. In this study, we investigated the translocation mechanism of representative -lactamases in an Escherichia coli model. N-terminal signal sequence analyses, antibiotic activity assay, and direct measurement of translocation of

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

    Microsoft Academic Search

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

    2001-01-01

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

  14. Preprotein translocation across the endoplasmic reticulum membrane in milieus crowded by proteins

    NASA Astrophysics Data System (ADS)

    Vélez, José. Antonio; Guzmán, Orlando; Navarro, Fernando

    2012-02-01

    Translocation of preproteins chains between the cytoplasm and the endoplasmic reticulum lumen takes place in a milieu crowded primarily by proteins. We compute translocation and retrotranslocation times for chains of different length in a milieu crowded by spherical agents at volume fractions equivalent to that found in cells. These numerical times obtained from a diffusion-equation model subject to a potential given by the free energy of one chain, indicate that crowding increases the translocation time by up to five times compared to those in dilute conditions for average-size chains and by up to a thousand times for long chains. Retrotranslocation times become smaller than translocation ones, in approximately 75%. Translocation rates obtained in this work are similar to those found in a theoretical model for Brownian-ratchet translocation and coincide with in vitro experimental results (1-8 aminoacid/s) only in the limit of very long chains; for shorter chains, translocation rates are much faster. Our prediction that for long chains translocation rates would be significantly slowed by crowding can be tested experimentally using vesicles. Discrepancy of time-scales with experiments for short chains indicates that other factors beside crowding must be included in our model.

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

    Microsoft Academic Search

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

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

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

    E-print Network

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

  17. Non-reciprocal chromosomal bridge-induced translocation (BIT) by targeted DNA integration in yeast

    Microsoft Academic Search

    Valentina Tosato; Sanjeev K. Waghmare; Carlo V. Bruschi

    2005-01-01

    Several experimental in vivo systems exist that generate reciprocal translocations between engineered chromosomal loci of yeast or Drosophila, but not without previous genome modifications. Here we report the successful induction of chromosome translocations in unmodified yeast cells via targeted DNA integration of the KANR selectable marker flanked by sequences homologous to two chromosomal loci randomly chosen on the genome. Using

  18. Motion\\/Emotion: Picturing Translocal Landscapes in the Nurturing Ecologies Research Project

    Microsoft Academic Search

    2008-01-01

    In the Nurturing Ecologies research project the aim is to consider the emotional value of the Lake District landscape to mobile, translocal communities living in Lancashire and Cumbria. The research attempts to capture in the visual form of a set of paintings, the sensory responses to the English Lake District that these translocal communities have. The Lake District is a

  19. UPTAKE, TRANSLOCATION, AND METABOLISM OF SULFENTRAZONE AND SULFENTRAZONE PLUS CLOMAZONE IN FLUE-CURED TOBACCO TRANSPLANTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research was conducted to evaluate root uptake, translocation, and metabolism of 14C-sulfentrazone alone or in a mixture with clomazone in solution in flue-cured tobacco transplants. Uptake and translocation of sulfentrazone was rapid and was not affected by the addition of clomazone. Fifty-nine p...

  20. 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...

  1. Cytologically Integrated Physical Restriction Fragment Length Polymorphism Maps for the Barley Genome Based on Translocation Breakpoints

    Microsoft Academic Search

    Gottfried Kunzel; Larissa Korzun; Armin Meister

    We have developed a new technique for the physical mapping of barley chromosomes using microdis- sected translocation chromosomes for PCR with sequence-tagged site primers derived from .300 geneti- cally mapped RFLP probes. The positions of 240 translocation breakpoints were integrated as physical landmarks into linkage maps of the seven barley chromosomes. This strategy proved to be highly efficient in relating

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

    E-print Network

    the localization of proteins transported through this pH pathway in isolated chloro- plasts. The Hcf106 gene is a component, is found in both bacteria and plants. Protein translocation across lipid bilayers is accomplishedSec-Independent Protein Translocation by the Maize Hcf106 Protein A. Mark Settles, Ann Yonetani

  3. 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...

  4. DNA translocation across protein channels: How does a polymer worm through a hole?

    Microsoft Academic Search

    M. Muthukumar

    2001-01-01

    Free energy barriers control the translocation of polymers through narrow channels. Based on an analogy with the classical nucleation and growth process, we have calculated the translocation time and its dependencies on the length, stiffness, and sequence of the polymer, solution conditions, and the strength of the driving electrochemical potential gradient. Our predictions will be compared with experimental results and

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

    SciTech Connect

    Wiley, J.E.; Stout, C.; Palmer, S.M. [East Carolina Univ. School of Medicine, Greenville, NC (United States)] [and others

    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.

  6. A new reciprocal translocation involving chromosomes 1/14 C. TAROCCO Fabrizia FRANCHI G. CROCI

    E-print Network

    Paris-Sud XI, Université de

    Note A new reciprocal translocation involving chromosomes 1/14 in a boar C. TAROCCO Fabrizia and carrier of a reciprocal balanced translocation involving chromosomes 1 and 14 is presented. High resolution chromosomes are analyzed and the break-points of the rearrangement are compared to those

  7. 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

  8. Recombinase, chromosomal translocations and lymphoid neoplasia: Targeting mistakes and repair failures

    Microsoft Academic Search

    Rodrig Marculescu; Katrina Vanura; Bertrand Montpellier; Sandrine Roulland; Trang Le; Jean-Marc Navarro; Ulrich Jäger; Fraser McBlane; Bertrand Nadel

    2006-01-01

    A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory element. Due to the unique feature of lymphoid cells to somatically rearrange and mutate receptor

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

    Microsoft Academic Search

    David Bain

    2006-01-01

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

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

    E-print Network

    Paris-Sud XI, Université de

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

  11. Translocations of the little spotted kiwi (Apteryx owenii) between offshore islands of New Zealand

    Microsoft Academic Search

    J. N. Jolly; R. M. Colbourne

    1991-01-01

    The little spotted kiwi (Apteryx owenii) is probably extinct on both main islands of New Zealand. Its only known surviving population is on Kapiti Island (1,970 ha). Translocations to other offshore islands are seen as essential to the survival of the species. In this paper we discuss the criteria for assessment of islands for translocations, and the early results of

  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 br

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

    PubMed Central

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

    2014-01-01

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

  14. Crystal structure of Mycobacterium tuberculosis SecA, a preprotein translocating ATPase

    PubMed Central

    Sharma, Vivek; Arockiasamy, Arulandu; Ronning, Donald R.; Savva, Christos G.; Holzenburg, Andreas; Braunstein, Miriam; Jacobs, William R.; Sacchettini, James C.

    2003-01-01

    In bacteria, the majority of exported proteins are translocated by the Sec system, which recognizes the signal sequence of a preprotein and uses ATP and the proton motive force to mediate protein translocation across the cytoplasmic membrane. SecA is an essential protein component of this system, containing the molecular motor that facilitates translocation. Here we report the three-dimensional structure of the SecA protein of Mycobacterium tuberculosis. Each subunit of the homodimer contains a “motor” domain and a translocation domain. The structure predicts that SecA can interact with the SecYEG pore and function as a molecular ratchet that uses ATP hydrolysis for physical movement of the preprotein. Knowledge of this structure provides a framework for further elucidation of the translocation process. PMID:12606717

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

    PubMed Central

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

    2011-01-01

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

  16. The Lateral Gate of SecYEG Opens during Protein Translocation*

    PubMed Central

    du Plessis, David J. F.; Berrelkamp, Greetje; Nouwen, Nico; Driessen, Arnold J. M.

    2009-01-01

    The SecYEG translocon of Escherichia coli mediates the translocation of preproteins across the cytoplasmic membrane. Here, we have examined the role of the proposed lateral gate of the translocon in translocation. A dual cysteine cross-linking approach allowed the introduction of cross-linker arms of various lengths between adjoining aminoacyl positions of transmembrane segments 2b and 7 of the lateral gate. Oxidation and short spacer linkers that fix the gate in the closed state abolished preprotein translocation, whereas long spacer linkers support translocation. The cross-linking data further suggests that SecYEG lateral gate opening and activation of the SecA ATPase are coupled processes. It is concluded that lateral gate opening is a critical step during SecA-dependent protein translocation. PMID:19366685

  17. Driven translocation of a polymer: role of pore friction and crowding

    E-print Network

    Johan L. A. Dubbeldam; V. G. Rostiashvili; T. A. Vilgis

    2014-10-03

    Force-driven translocation of a macromolecule through a nanopore is investigated by taking into account the monomer-pore friction as well as the "crowding" of monomers on the {\\it trans} - side of the membrane which counterbalance the driving force acting in the pore. The set of governing differential-algebraic equations for the translocation dynamics is derived and solved numerically. The analysis of this solution shows that the crowding of monomers on the trans side hardly affects the dynamics, but the monomer-pore friction can substantially slow down the translocation process. Moreover, the translocation exponent $\\alpha$ in the translocation time - vs. - chain length scaling law, $\\tau \\propto N^{\\alpha}$, becomes smaller when monomer-pore friction coefficient increases. This is most noticeable for relatively strong forces. Our findings may explain the variety of $\\alpha$ values which were found in experiments and computer simulations.

  18. 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.

  19. Chromosomal translocations in lymphoid neoplasia: a reappraisal of the recombinase model.

    PubMed

    Tycko, B; Sklar, J

    1990-01-01

    Chromosomal translocations are common in tumors and are considered to represent one of the major classes of genetic alterations productive of the malignant phenotype. Although the molecular mechanisms leading to translocations are unknown, structural analysis of translocations in tumors derived from lymphocytes and their precursors has suggested the involvement of the lymphocyte recombinase, a normal cellular enzyme (or enzyme complex) that is essential for antigen receptor gene rearrangement. Recent observations of frequent recombinase-mediated interchromosomal exchanges between separate antigen receptor genes in normal lymphocyte precursors have provided clear examples of the ability of the recombinase to catalyze chromosomal translocation events, some of which may actually contribute to increased diversity of antigen receptor proteins. These findings have established that, even in the normal setting, the recombinase is not constrained to act only on gene segments linked in cis, but can also function in trans. Certain tumor-associated chromosomal translocations can be explained as subversions of this enzymatic capability. PMID:2201335

  20. 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.

  1. The effect of sampling time on radiation-induced translocation yield in spermatogonial stem cells of male mice, differing in chromosomal constitution and sexual activity.

    PubMed

    Wessels-Kaalen, M C; Bakker, R; de Boer, P

    1990-11-01

    We have investigated the frequency of reciprocal translocations in the first differentiating spermatogonia entering the first meiotic division after 2 x 2.5 Gy X-rays, given 24 h apart, as well as the development of this parameter in later stem-cell generations by studying multivalent configurations at the first meiotic division. Diakinesis-metaphase I cells were found for the first time between 30 and 40 days after irradiation. Subsequently, meiotic stages were sampled at 120, 180 and 280 days post irradiation. From day 40 post irradiation on, half of the males were allowed to impregnate females which enabled us to estimate the length of the post-irradiation sterile period, the development of litter size and the possible effect of sexual activity on the development of reciprocal translocation-containing stem cells. Half of the males were karyologically normal, the other half were homozygous for a reciprocal translocation (T/T) that affects testis weight and about halves sperm production. Irrespective of male karyotype, the first meiocytes had an induced translocation frequency of 9.00 +/- 2.56% (n = 8 males), followed by frequencies of 20.70 +/- 4.87% (n = 15) at 180 days and 20.20 +/- 4.30% (n = 20) at 280 days (males with and without mating behavior showing no difference). At 120 days post irradiation, +/+ males had a frequency of 14.59 +/- 2.97% irrespective of sexual activity. T/T males (120 days post irradiation) that had mated showed a frequency of 18.63 +/- 0.85% (n = 4) compared with 13.64 +/- 2.36% (n = 7) for those that had not. The observed rise of multivalent-carrying spermatocytes in time was highly significant. Notwithstanding the differences in testis weight and epididymal sperm count between the karyotypes, fertile matings occurred on average 72 days after irradiation, though with relatively wide margins. For the T/T karyotype, the first litter was statistically smaller than the subsequent litters. At 78 days post irradiation, testis weights were back in the subnormal range for both karyotypes and hardly improved in time. Restoration of fertility thus coincided with the period just prior to the return to subnormal testis weights. The first diakinesis-metaphase I cells precede those that are numerous enough to accomplish 'return to fertility' by about 2 weeks. Thus differentiation of stem-cell spermatogonia already follows a few days after irradiation. A pattern of spermatogonial cell divisions compatible with 'return to fertility' is only established some 2 weeks later. PMID:2233835

  2. A Spatial and Temporal Frequency Based Figure-Ground Processor

    NASA Astrophysics Data System (ADS)

    Weisstein, Namoi; Wong, Eva

    1990-03-01

    Recent findings in visual psychophysics have shown that figure-ground perception can be specified by the spatial and temporal response characteristics of the visual system. Higher spatial frequency regions of the visual field are perceived as figure and lower spatial frequency regions are perceived as background/ (Klymenko and Weisstein, 1986, Wong and Weisstein, 1989). Higher temporal frequency regions are seen as background and lower temporal frequency regions are seen as figure (Wong and Weisstein, 1987, Klymenko, Weisstein, Topolski, and Hsieh, 1988). Thus, high spatial and low temporal frequencies appear to be associated with figure and low spatial and high temporal frequencies appear to be associated with background.

  3. Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene.

    PubMed

    Scheel, Julia; Hussong, Ragna; Schrenk, Dieter; Schmitz, Hans-Joachim

    2002-01-01

    The aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in vertebrate transcriptional regulation as the common subunit of transcriptionally active complexes like the aryl hydrocarbon receptor (AHR)/ARNT heterodimer and hypoxia-inducible factor 1, mediating cellular responses to certain xenobiotics and to hypoxia, respectively. A cohort of healthy Caucasian volunteers was screened for genetic variations of ARNT. Six polymorphic sites could be identified, a variation in a G-stretch upstream of the ATG translation start site, a frequent silent mutation (G567C), two polymorphic sites in intron 9, and two single nucleotide substitutions leading to amino acid exchanges, G1531A (D511N) and T1551G (D517E). The frequencies were 0.005 for the Asn-coding allele and for the Glu-coding allele, respectively, with no linkage between these two mutations. Although no significant correlation with activities of CYP1A2, which is under regulatory control of the AHR/ARNT transcription complex, could be established, metabolic or pathological phenotypes may be associated with these variations. PMID:12032587

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

    PubMed

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

    2015-05-01

    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 BRAF 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

  5. Heterologous protein production using the twin arginine translocation pathway

    DOEpatents

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

    2008-11-04

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

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

    PubMed Central

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

    2015-01-01

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

  7. Activation Induced Deaminase in Antibody Diversification and Chromosome Translocation

    PubMed Central

    Gazumyan, Anna; Bothmer, Anne; Klein, Isaac A.; Nussenzweig, Michel C; McBride, Kevin M.

    2015-01-01

    DNA damage, rearrangement and mutation of the human genome are the basis of carcinogenesis and thought to be avoided at all costs. An exception is the adaptive immune system where lymphocytes utilize programmed DNA damage to effect antigen receptor diversification. Both B and T lymphocytes diversify their antigen receptors through RAG1/2 mediated recombination, but B cells undergo two additional processes – somatic hypermutation (SHM) and class switch recombination (CSR), both initiated by Activation Induced Deaminase (AID). AID deaminates cytidines in DNA resulting in U:G mismatches that are processed into point mutations in SHM or double strand breaks in CSR. Although AID activity is focused at Immunoglobulin (Ig) gene loci, it also targets a wide array of non-Ig genes including oncogenes associated with lymphomas. Here we review the molecular basis of AID regulation, targeting, and initiation of CSR and SHM, as well as AID's role in generating chromosome translocations that contribute to lymphomagenesis. PMID:22429855

  8. Minireview: Translocator Protein (TSPO) and Steroidogenesis: A Reappraisal.

    PubMed

    Selvaraj, Vimal; Stocco, Douglas M; Tu, Lan N

    2015-04-01

    The 18-kDa translocator protein (TSPO), also known as the peripheral benzodiazepine receptor, is a transmembrane protein in the outer mitochondrial membrane. TSPO has long been described as being indispensable for mitochondrial cholesterol import that is essential for steroid hormone production. In contrast to this initial proposition, recent experiments reexamining TSPO function have demonstrated that it is not involved in steroidogenesis. This fundamental change has forced a reexamination of the functional interpretations made for TSPO that broadly impacts both basic and clinical research across multiple fields. In this minireview, we recapitulate the key studies from 25 years of TSPO research and concurrently examine their limitations that perhaps led towards the incorrect association of TSPO and steroid hormone production. Although this shift in understanding raises new questions regarding the molecular function of TSPO, these recent developments are poised to have a significant positive impact for research progress in steroid endocrinology. PMID:25730708

  9. Structural framework for DNA translocation via the viral portal protein

    PubMed Central

    Lebedev, Andrey A; Krause, Margret H; Isidro, Anabela L; Vagin, Alexei A; Orlova, Elena V; Turner, Joanne; Dodson, Eleanor J; Tavares, Paulo; Antson, Alfred A

    2007-01-01

    Tailed bacteriophages and herpesviruses load their capsids with DNA through a tunnel formed by the portal protein assembly. Here we describe the X-ray structure of the bacteriophage SPP1 portal protein in its isolated 13-subunit form and the pseudoatomic structure of a 12-subunit assembly. The first defines the DNA-interacting segments (tunnel loops) that pack tightly against each other forming the most constricted part of the tunnel; the second shows that the functional dodecameric state must induce variability in the loop positions. Structural observations together with geometrical constraints dictate that in the portal–DNA complex, the loops form an undulating belt that fits and tightly embraces the helical DNA, suggesting that DNA translocation is accompanied by a ‘mexican wave' of positional and conformational changes propagating sequentially along this belt. PMID:17363899

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

    PubMed Central

    Aljabry, Mansour

    2015-01-01

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

  11. START Background Report START, September 2013 1 BACKGROUND REPORT

    E-print Network

    Hill, Wendell T.

    START Background Report © START, September 2013 1 BACKGROUND REPORT Al-Shabaab Attack on Westgate evening, Sept. 24. Media sources report that Somali militant organization al-Shabaab has claimed deaths as of Sept. 25. START has developed this background report highlighting attacks attributed to al-Shabaab

  12. DNA translocation through an array of kinked nanopores

    NASA Astrophysics Data System (ADS)

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

    2010-08-01

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

  13. DNA translocation through an array of kinked nanopores

    NASA Astrophysics Data System (ADS)

    Chen, Zhu

    Synthetic solid-state nanopores are being intensively investigated as single-molecule sensors for detection and characterization of DNA, RNA, and proteins. This field has been inspired by the exquisite selectivity and flux demonstrated by natural biological channels and the dream of emulating these behaviors in more robust synthetic materials that are more readily integrated into practical devices. To date, the guided etching of polymer films, focused ion beam sculpting, and electron-beam lithography and tuning of silicon nitride membranes have emerged as three promising approaches to define synthetic solid-state pores with sub-nanometer resolution. These procedures have in common the formation of nominally cylindrical or conical pores aligned normal to the membrane surface. Here we report the formation of 'kinked' silica nanopores, using evaporation induced self-assembly, and their further tuning and chemical derivatization using atomic layer deposition. Compared to 'straight-through' proteinaceous nanopores of comparable dimensions, kinked nanopores exhibit a factor of up to 5x reduction in translocation velocity, which has been identified as one of the critical issues in DNA sequencing. Additionally we demonstrate an efficient two-step approach to create a nanopore array exhibiting nearly perfect selectivity for ssDNA over dsDNA. We show that a coarse-grained drift-diffusion theory with a sawtooth like potential can reasonably describe the velocity and translocation time of DNA through the pore. By control of pore size, length, and shape, we capture the major functional behaviors of protein pores in our solid-state nanopore system.

  14. 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

  15. Translocation of Cell Penetrating Peptide Engrafted Nanoparticles Across Skin Layers

    PubMed Central

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

    2010-01-01

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

  16. 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 (UNM); (Sandia); (UIUC); (Purdue)

    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.

  17. Induction of Hexose-Phosphate Translocator Activity in Spinach Chloroplasts.

    PubMed Central

    Quick, W. P.; Scheibe, R.; Neuhaus, H. E.

    1995-01-01

    Many environmental and experimental conditions lead to accumulation of carbohydrates in photosynthetic tissues. This situation is typically associated with major changes in the mRNA and protein complement of the cell, including metabolic repression of photosynthetic gene expression, which can be induced by feeding carbohydrates directly to leaves. In this study we examined the carbohydrate transport properties of chloroplasts isolated from spinach (Spinacia oleracea L.) leaves fed with glucose for several days. These chloroplasts contain large quantities of starch, can perform photosynthetic 3-phosphoglycerate reduction, and surprisingly also have the ability to perform starch synthesis from exogenous glucose-6-phosphate (Glc-6-P) both in the light and in darkness, similarly to heterotrophic plastids. Glucose-1-phosphate does not act as an exogenous precursor for starch synthesis. Light, ATP, and 3-phosphoglyceric acid stimulate Glc-6-P-dependent starch synthesis. Short-term uptake experiments indicate that a novel Glc-6-P-translocator capacity is present in the envelope membrane, exhibiting an apparent Km of 0.54 mM and a Vmax of 2.9 [mu]mol Glc-6-P mg-1 chlorophyll h-1. Similar results were obtained with chloroplasts isolated from glucose-fed potato leaves and from water-stressed spinach leaves. The generally held view that sugar phosphates transported by chloroplasts are confined to triose phosphates is not supported by these results. A physiological role for a Glc-6-P translocator in green plastids is presented with reference to the source/sink function of the leaf. PMID:12228584

  18. Cosmic microwave background images

    NASA Astrophysics Data System (ADS)

    Herranz, D.; Vielva, P.

    2010-01-01

    Cosmology concerns itself with the fundamental questions about the formation, structure, and evolution of the Universe as a whole. Cosmic microwave background (CMB) radiation is one of the foremost pillars of physical cosmology. Joint analyses of CMB and other astronomical observations are able to determine with ever increasing precision the value of the fundamental cosmological parameters and to provide us with valuable insight about the dynamics of the Universe in evolution. The CMB radiation is a relic of the hot and dense first moments of the Universe: a extraordinarily homogeneous and isotropic blackbody radiation, which shows small temperature anisotropies that are the key for understanding the conditions of the primitive Universe, testing cosmological models and probing fundamental physics at the very dawn of time. CMB observations are obtained by imaging of the sky at microwave wavelengths. However, the CMB signal is mixed with other astrophysical signals of both Galactic and extragalactic origin. To properly exploit the cosmological information contained in CMB images, they must be cleansed of these other astrophysical emissions first. Blind source separation (BSS) has been a very active field in the last few years. Conversely, the term "compact sources" is often used in the CMB literature referring to spatially bounded, small features in the images, such as galaxies and galaxy clusters. Compact sources and diffuse sources are usually treated separately in CMB image processing. We devote this tutorial to the case of compact sources. Many of the compact source-detection techniques that are widespread inmost fields of astronomy are not easily applicable to CMB images. In this tutorial, we present an overview of the fundamentals of compact object detection theory keeping in mind at every moment these particularities. Throughout the article, we briefly consider Bayesian object detection, model selection, optimal linear filtering, nonlinear filtering, and multif- requency detection of compact sources in CMB images. This article's goal is to present a tutorial on the detection, parameter estimation and statistical analysis of compact sources (far galaxies, galaxy clusters, and Galactic dense emission regions) in CMB observations.

  19. 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.

  20. 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.

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

    E-print Network

    California at Berkeley, University of

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

  2. The effect of translocation and temporary captivity on wildlife rehabilitation success: An experimental study using European hedgehogs ( Erinaceus europaeus)

    Microsoft Academic Search

    Susie E. Molony; Claire V. Dowding; Philip J. Baker; Innes C. Cuthill; Stephen Harris

    2006-01-01

    Translocation is frequently used to return rehabilitated animals to the wild, and is an important tool for the population management of endangered species. Whilst experimental field manipulations are important in determining optimal rehabilitation and translocation strategies, they are rarely implemented in practice. We used an experimental approach to examine the effects of translocation on post-release survival and behaviour, and the

  3. Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms

    Microsoft Academic Search

    Hesed M. Padilla-Nash; Kerstin Heselmeyer-Haddad; Danny Wangsa; Hongen Zhang; B. Michael Ghadimi; Merryn Macville; Meena Augustus; Eva Hilgenfeld; Thomas Ried

    2001-01-01

    Jumping translocations (JTs) and segmental jumping translocations (SJTs) are unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to multiple recipient chromosomes. In leukemia, where JTs have been predominantly observed, the donor segment (usually 1q) preferentially fuses to the telomere regions of recipient chromosomes. In this study, spectral karyotyping (SKY) and FISH analysis revealed 188 JTs

  4. The Role of LMO2 in Development and in T Cell Leukemia After Chromosomal Translocation or Retroviral Insertion

    Microsoft Academic Search

    Chang-Hoon Nam; Terence H. Rabbitts

    2006-01-01

    Chromosomal translocations are primary events in the development of leukemias, representing at least one genetic feature of the putative cancer stem cell. Studies of genes influenced by chromosomal translocations have yielded a vast amount of information about how cancer is initiated and maintained. In particular, acute leukemias have demonstrated that chromosomal translocations often involve transcription regulators that function by interacting

  5. StreptomycesThe twin-arginine translocation pathway is a major route of protein export in Pohlschrder, and Tracy Palmer

    E-print Network

    Palmer, Tracy

    coelicolor StreptomycesThe twin-arginine translocation pathway is a major route of protein export.pnas.org/misc/reprints.shtml To order reprints, see: Notes: #12;The twin-arginine translocation pathway is a major route of protein, and approved September 27, 2006 (received for review August 15, 2006) The twin-arginine translocation (Tat

  6. Chromatin structure analysis of spermatozoa from reciprocal chromosome translocation (RCT) carriers with known meiotic segregation patterns.

    PubMed

    Olszewska, Marta; Fraczek, Monika; Huleyuk, Nataliya; Czernikiewicz, Anna; Wiland, Ewa; Boksa, Magdalena; Zastavna, Danuta; Panasiuk, Barbara; Midro, Alina T; Kurpisz, Maciej

    2013-09-01

    The presence of reciprocal chromosome translocations (RCTs), as well as sperm chromatin disturbances, is known to exert negative influence on male fertility. The aim of this study was to identify an association between chromosome structural rearrangements in male RCT carriers and sperm seminological parameters (concentration, motility, morphology), chromatin status (fragmentation and maturity), meiotic segregation pattern and observed chromosomal hyperhaploidy. Sperm samples originated from ten male RCT carriers with reproductive failure/success. TUNEL assay (DNA fragmentation) and chromomycin A3 (CMA3)/aniline blue (AB) staining (chromatin maturity) were used to analyze sperm chromatin status while fluorescent in situ hybridization (FISH) was applied to observe meiotic segregation patterns and hyperhaploidy in spermatozoa. We found that the mean level of sperm DNA fragmentation in the RCT carrier group (18.0 ± 11.9%) was significantly higher (p=0.0006) than the mean of the control group (7.5 ± 4.3%). There was no correlation observed between sperm DNA fragmentation levels (5.6-38.0%) and the frequency of genetically normal/balanced gametes (34.3-62.4%), sperm seminological quality or revealed reproductive failure. In contrast, a correlation between the frequencies of genetically normal/balanced spermatozoa and of gametes with mature chromatin was observed (CMA3: R=0.4524, p=0.2604; AB: R=0.5238, p=0.1827). A statistically significant increase in the hyperhaploidy level of selected chromosomes in all analyzed RCT carriers was documented but was not correlated to sperm seminology or fertility status. Further evaluation and additional assays toward sperm chromatin quality assessment in RCT carriers is suggested to explain the complexity of genomic structural rearrangements and its possible relevance to reproductive success or failure. PMID:24011192

  7. Analysis of the plastidic phosphate translocator gene family in Arabidopsis and identification of new phosphate translocator-homologous transporters, classified by their putative substrate-binding site.

    PubMed

    Knappe, Silke; Flügge, Ulf-Ingo; Fischer, Karsten

    2003-03-01

    Analysis of the Arabidopsis genome revealed the complete set of plastidic phosphate translocator (pPT) genes. The Arabidopsis genome contains 16 pPT genes: single copies of genes coding for the triose phosphate/phosphate translocator and the xylulose phosphate/phosphate translocator, and two genes coding for each the phosphoenolpyruvate/phosphate translocator and the glucose-6-phosphate/phosphate translocator. A relatively high number of truncated phosphoenolpyruvate/phosphate translocator genes (six) and glucose-6-phosphate/phosphate translocator genes (four) could be detected with almost conserved intron/exon structures as compared with the functional genes. In addition, a variety of PT-homologous (PTh) genes could be identified in Arabidopsis and other organisms. They all belong to the drug/metabolite transporter superfamily showing significant similarities to nucleotide sugar transporters (NSTs). The pPT, PTh, and NST proteins all possess six to eight transmembrane helices. According to the analysis of conserved motifs in these proteins, the PTh proteins can be divided into (a) the lysine (Lys)/arginine group comprising only non-plant proteins, (b) the Lys-valine/alanine/glycine group of Arabidopsis proteins, (c) the Lys/asparagine group of Arabidopsis proteins, and (d) the Lys/threonine group of plant and non-plant proteins. None of these proteins have been characterized so far. The analysis of the putative substrate-binding sites of the pPT, PTh, and NST proteins led to the suggestion that all these proteins share common substrate-binding sites on either side of the membrane each of which contain a conserved Lys residue. PMID:12644669

  8. REPORT NO. 5 background material

    E-print Network

    REPORT NO. 5 background material for the development of radiation protection standards July 1964 Staff Report of the FEDERAL RADIATION COUNCIL #12;REPORT NO. 5 background material for the development INTRODUCTION This report contains background material used in the development of guidance for Federal agencies

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

    SciTech Connect

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

    1994-09-01

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

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

    SciTech Connect

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

    1989-11-01

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

  11. Mineralocorticoid and glucocorticoid receptor mRNA expression in the brain of translocated chukar (Alectoris chukar).

    PubMed

    Dickens, Molly J; Meddle, Simone L; Michael Romero, L

    2011-02-01

    Although translocation is an important conservation tool in the effort to create self-sustaining wild populations of threatened species, avian translocations have a high failure rate and causes for failure are poorly understood. While "stress" is considered to play a major role in translocation failure, the physiological changes associated with chronic stress resulting from translocation have been investigated only recently. Translocation results in chronic stress-induced alterations of stress response physiology in the chukar (Alectoris chukar) and in the present study we tested the hypothesis that changes in the hypothalamic-pituitary-adrenal axis (HPA) are correlated with changes in the brain, specifically at the level of the glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) in the hippocampus and hypothalamus. Our previous research has shown that there are apparent changes in GR and MR expression in the brain of experimentally chronically stressed European starlings (Sturnus vulgaris). In the present study however, translocation had no major detectable effect on levels of GR or MR mRNA expression in the hippocampus or hypothalamus of wild chukar suggesting that the observed dysregulation of the HPA axis by translocation may not be a result of such upstream changes. PMID:21118689

  12. First passage time distribution of chaperone driven polymer translocation through a nanopore: Homopolymer and heteropolymer cases

    NASA Astrophysics Data System (ADS)

    Abdolvahab, Rouhollah Haji; Metzler, Ralf; Ejtehadi, Mohammad Reza

    2011-12-01

    Combining the advection-diffusion equation approach with Monte Carlo simulations we study chaperone driven polymer translocation of a stiff polymer through a nanopore. We demonstrate that the probability density function of first passage times across the pore depends solely on the Péclet number, a dimensionless parameter comparing drift strength and diffusivity. Moreover it is shown that the characteristic exponent in the power-law dependence of the translocation time on the chain length, a function of the chaperone-polymer binding energy, the chaperone concentration, and the chain length, is also effectively determined by the Péclet number. We investigate the effect of the chaperone size on the translocation process. In particular, for large chaperone size, the translocation progress and the mean waiting time as function of the reaction coordinate exhibit pronounced sawtooth-shapes. The effects of a heterogeneous polymer sequence on the translocation dynamics is studied in terms of the translocation velocity, the probability distribution for the translocation progress, and the monomer waiting times.

  13. Translocation of a Polymer through a Nanopore across a Viscosity Gradient

    E-print Network

    Hendrick W. de Haan; Gary W. Slater

    2012-09-14

    The translocation of a polymer through a pore in a membrane separating fluids of different viscosities is studied via several computational approaches. Starting with the polymer halfway, we find that as a viscosity difference across the pore is introduced, translocation will predominately occur towards one side of the membrane. These results suggest an intrinsic pumping mechanism for translocation across cell walls which could arise whenever the fluid across the membrane is inhomogeneous. Somewhat surprisingly, the sign of the preferred direction of translocation is found to be strongly dependent on the simulation algorithm: for Langevin Dynamics (LD) simulations, a bias towards the low viscosity side is found while for Brownian Dynamics (BD), a bias towards the high viscosity is found. Examining the translocation dynamics in detail across a wide range of viscosity gradients and developing a simple force model to estimate the magnitude of the bias, the LD results are demonstrated to be more physically realistic. The LD results are also compared to those generated from a simple, one dimensional random walk model of translocation to investigate the role of the internal degrees of freedom of the polymer and the entropic barrier. To conclude, the scaling of the results across different polymer lengths demonstrates the saturation of the preferential direction with polymer length and the non-trivial location of the maximum in the exponent corresponding to the scaling of the translocation time with polymer length.

  14. Robertsonian Translocation t (21; 21) in a Female Born to Normal Parents: A Case Report

    PubMed Central

    Sarma, Mukul; Nirmolia, Tulika; Shankarishan, Priyanka

    2015-01-01

    Downs syndrome (DS) occurs due to an extra copy of chromosome 21. About 3% of cases of Downs syndrome occur due to Robertsonian translocation, most commonly t (14; 21), other types of translocations are very rare cause of the syndrome. A 10-year-old patient with mental retardation was admitted following road traffic accident. Patient had flabby muscles, had delayed mile stones, stunted growth for the age, slanting of eyes, flat nasal bridge, and ineligible speech. On cytogenetic analysis the patient had karyotype showing one normal chromosome 21 and one Robertsonian translocation t (21; 21). Parents and siblings of the patient were phenotypically normal. Robertsonian translocation t (21; 21), can occur by transmission from carrier parent, due to ovarian mosaicism for Robertsonian translocation or may appear de novo. In the present case as the parents had normal karyotype and siblings were phenotypically normal, Robertsonian translocation probably have arisen de novo. The present case was a case of Downs syndrome with Robertsonian translocation t (21;21) probably arising de novo. PMID:25738006

  15. Single molecule detection of intermediates during botulinum neurotoxin translocation across membranes

    PubMed Central

    Fischer, Audrey; Montal, Mauricio

    2007-01-01

    The dynamics of Clostridium botulinum neurotoxins (BoNTs) protein-translocation across membranes was investigated by using a single molecule assay with millisecond resolution on excised patches of neuronal cells. Translocation of BoNT/A light chain (LC) by heavy chain (HC) was observed in real time as an increase of channel conductance: the HC channel is occluded by the LC during transit, then unoccluded after completion of translocation and release of LC-cargo. We identified an entirely unknown succession of intermediate conductance stages during LC translocation. For the single-chain BoNT/E, by contrast to the di-chain BoNT/A, we demonstrate that productive translocation requires proteolysis of the LC cargo from the HC chaperone. We propose a model for the set of protein–protein interactions between translocase and cargo at each step of translocation that supports the notion of an interdependent, tight interplay between the HC chaperone and the LC cargo preventing LC aggregation and dictating the outcome of translocation: productive passage of cargo or abortive channel occlusion by cargo. PMID:17563359

  16. Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel.

    PubMed

    Montal, Mauricio

    2009-10-01

    Clostridial botulinum neurotoxins (BoNTs) inhibit synaptic exocytosis; intoxication requires the di-chain protein to undergo conformational changes in response to pH and redox gradients across the endosomal membrane with consequent formation of a protein-conducting channel by the heavy chain (HC) that translocates the light chain (LC) protease into the cytosol, colocalizing it with the substrate SNARE proteins. We investigate the dynamics of protein translocation across membranes using a sensitive single-molecule assay to track translocation events with millisecond resolution on lipid bilayers and on membrane patches of Neuro 2A cells. Translocation of BoNT/A LC by the HC is observed in real time as changes of channel conductance: the channel is occluded by the light chain during transit, and open after completion of translocation and release of cargo, acting intriguingly similar to the protein-conducting/translocating channels of the endoplasmic reticulum, mitochondria, and chloroplasts. Our findings support the notion of an interdependent, tight interplay between the HC transmembrane chaperone and the LC cargo that prevents LC aggregation and dictates the productive passage of cargo through the channel and completion of translocation. The protein-conducting channel of BoNT, a key element in the process of neurotoxicity, emerges therefore as a target for antidote discovery - a novel paradigm of paramount significance to health science and biodefense. PMID:19111565

  17. Translocation of Botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel

    PubMed Central

    Montal, Mauricio

    2009-01-01

    Clostridial botulinum neurotoxins (BoNTs) inhibit synaptic exocytosis; intoxication requires the di-chain protein to undergo conformational changes in response to pH and redox gradients across the endosomal membrane with consequent formation of a protein-conducting channel by the heavy chain (HC) that translocates the light chain (LC) protease into the cytosol, colocalizing it with the substrate SNARE proteins. We investigate the dynamics of protein-translocation across membranes using a sensitive single molecule assay to track translocation events with millisecond resolution on lipid bilayers and on membrane patches of Neuro 2A cells. Translocation of BoNT/A LC by the HC is observed in real time as changes of channel conductance: the channel is occluded by the light chain during transit, and open after completion of translocation and release of cargo, acting intriguingly similar to the protein-conducting/translocating channels of the endoplasmic reticulum, mitochondria, and chloroplasts. Our findings support the notion of an interdependent, tight interplay between the HC transmembrane chaperone and the LC cargo that prevents LC aggregation and dictates the productive passage of cargo through the channel and completion of translocation. The protein-conducting channel of BoNT, a key element in the process of neurotoxicity, emerges therefore as a target for antidote discovery –a novel paradigm of paramount significance to health science and biodefense. PMID:19111565

  18. 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.

  19. Cancer translocations in human cells induced by zinc finger and TALE nucleases

    PubMed Central

    Piganeau, Marion; Ghezraoui, Hind; De Cian, Anne; Guittat, Lionel; Tomishima, Mark; Perrouault, Loic; René, Oliver; Katibah, George E.; Zhang, Lei; Holmes, Michael C.; Doyon, Yannick; Concordet, Jean-Paul; Giovannangeli, Carine; Jasin, Maria; Brunet, Erika

    2013-01-01

    Chromosomal translocations are signatures of numerous cancers and lead to expression of fusion genes that act as oncogenes. The wealth of genomic aberrations found in cancer, however, makes it challenging to assign a specific phenotypic change to a specific aberration. In this study, we set out to use genome editing with zinc finger (ZFN) and transcription activator-like effector (TALEN) nucleases to engineer, de novo, translocation-associated oncogenes at cognate endogenous loci in human cells. Using ZFNs and TALENs designed to cut precisely at relevant translocation breakpoints, we induced cancer-relevant t(11;22)(q24;q12) and t(2;5)(p23;q35) translocations found in Ewing sarcoma and anaplastic large cell lymphoma (ALCL), respectively. We recovered both translocations with high efficiency, resulting in the expression of the EWSR1–FLI1 and NPM1–ALK fusions. Breakpoint junctions recovered after ZFN cleavage in human embryonic stem (ES) cell–derived mesenchymal precursor cells fully recapitulated the genomic characteristics found in tumor cells from Ewing sarcoma patients. This approach with tailored nucleases demonstrates that expression of fusion genes found in cancer cells can be induced from the native promoter, allowing interrogation of both the underlying mechanisms and oncogenic consequences of tumor-related translocations in human cells. With an analogous strategy, the ALCL translocation was reverted in a patient cell line to restore the integrity of the two participating chromosomes, further expanding the repertoire of genomic rearrangements that can be engineered by tailored nucleases. PMID:23568838

  20. 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.

  1. Kinetics of Contraction-Induced GLUT4 Translocation in Skeletal Muscle Fibers From Living Mice

    PubMed Central

    Lauritzen, Hans P.M.M.; Galbo, Henrik; Toyoda, Taro; Goodyear, Laurie J.

    2010-01-01

    OBJECTIVE Exercise is an important strategy for the treatment of type 2 diabetes. This is due in part to an increase in glucose transport that occurs in the working skeletal muscles. Glucose transport is regulated by GLUT4 translocation in muscle, but the molecular machinery mediating this process is poorly understood. The purpose of this study was to 1) use a novel imaging system to elucidate the kinetics of contraction-induced GLUT4 translocation in skeletal muscle and 2) determine the function of AMP-activated protein kinase ?2 (AMPK?2) in this process. RESEARCH DESIGN AND METHODS Confocal imaging was used to visualize GLUT4-enhanced green fluorescent protein (EGFP) in transfected quadriceps muscle fibers in living mice subjected to contractions or the AMPK-activator AICAR. RESULTS Contraction increased GLUT4-EGFP translocation from intracellular vesicle depots to both the sarcolemma and t-tubules with similar kinetics, although translocation was greater with contractions elicited by higher voltage. Re-internalization of GLUT4 did not begin until 10 min after contractions ceased and was not complete until 130 min after contractions. AICAR increased GLUT4-EGFP translocation to both sarcolemma and t-tubules with similar kinetics. Ablation of AMPK?2 activity in AMPK?2 inactive transgenic mice did not change GLUT4-EGFP?s basal localization, contraction-stimulated intracellular GLUT4-EGFP vesicle depletion, translocation, or re-internalization, but diminished AICAR-induced translocation. CONCLUSIONS We have developed a novel imaging system to study contraction-stimulated GLUT4 translocation in living mice. Contractions increase GLUT4 translocation to the sarcolemma and t-tubules with similar kinetics and do not require AMPK?2 activity. PMID:20622170

  2. A voltage-gated pore for translocation of tRNA

    SciTech Connect

    Koley, Sandip; Adhya, Samit, E-mail: nilugrandson@gmail.com

    2013-09-13

    Highlights: •A tRNA translocating complex was assembled from purified proteins. •The complex translocates tRNA at a membrane potential of ?60 mV. •Translocation requires Cys and His residues in the Fe–S center of RIC6 subunit. -- Abstract: Very little is known about how nucleic acids are translocated across membranes. The multi-subunit RNA Import Complex (RIC) from mitochondria of the kinetoplastid protozoon Leishmania tropica induces translocation of tRNAs across artificial or natural membranes, but the nature of the translocation pore remains unknown. We show that subunits RIC6 and RIC9 assemble on the membrane in presence of subunit RIC4A to form complex R3. Atomic Force Microscopy of R3 revealed particles with an asymmetric surface groove of ?20 nm rim diameter and ?1 nm depth. R3 induced translocation of tRNA into liposomes when the pH of the medium was lowered to ?6 in the absence of ATP. R3-mediated tRNA translocation could also be induced at neutral pH by a K{sup +} diffusion potential with an optimum of 60–70 mV. Point mutations in the Cys{sub 2}–His{sub 2} Fe-binding motif of RIC6, which is homologous to the respiratory Complex III Fe–S protein, abrogated import induced by low pH but not by K{sup +} diffusion potential. These results indicate that the R3 complex forms a pore that is gated by a proton-generated membrane potential and that the Fe–S binding region of RIC6 has a role in proton translocation. The tRNA import complex of L. tropica thus contains a novel macromolecular channel distinct from the mitochondrial protein import pore that is apparently involved in tRNA import in some species.

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

    SciTech Connect

    Boghosian-Sell, L.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Comings, D.E. [City of Hope Medical Center, Duarte, CA (United States)

    1996-11-01

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

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

    E-print Network

    Salvatore Assenza; Paolo De Los Rios; Alessandro Barducci

    2014-11-25

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

  5. Muscle contraction increases carnitine uptake via translocation of OCTN2

    SciTech Connect

    Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan)] [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan)] [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)] [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan)] [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan)] [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)] [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  6. Characterization of human chromosomal material exchange with regard to the chromosome translocations using next-generation sequencing data.

    PubMed

    Xu, Chao; Zhang, Jigang; Wang, Yu-Ping; Deng, Hong-Wen; Li, Jian

    2014-01-01

    As an important subtype of structural variations, chromosomal translocation is associated with various diseases, especially cancers, by disrupting gene structures and functions. Traditional methods for identifying translocations are time consuming and have limited resolutions. Recently, a few studies have employed next-generation sequencing (NGS) technology for characterizing chromosomal translocations on human genome, obtaining high-throughput results with high resolutions. However, these studies are mainly focused on mechanism-specific or site-specific translocation mapping. In this study, we conducted a comprehensive genome-wide analysis on the characterization of human chromosomal material exchange with regard to the chromosome translocations. Using NGS data of 1,481 subjects from the 1000 Genomes Project, we identified 15,349,092 translocated DNA fragment pairs, ranging from 65 to 1,886 bp and with an average size of approximately 102 bp. On average, each individual genome carried about 10,364 pairs, covering approximately 0.069% of the genome. We identified 16 translocation hot regions, among which two regions did not contain repetitive fragments. Results of our study overlapped with a majority of previous results, containing approximately 79% of approximately 2,340 translocations characterized in three available translocation databases. In addition, our study identified five novel potential recurrent chromosomal material exchange regions with greater than 20% detection rates. Our results will be helpful for an accurate characterization of translocations in human genomes, and contribute as a resource for future studies of the roles of translocations in human disease etiology and mechanisms. PMID:25349267

  7. Light-Dependent Translocation of Arrestin in Rod Photoreceptors is Signaled Through a Phospholipase C Cascade and Requires ATP

    PubMed Central

    Orisme, Wilda; Li, Jian; Goldmann, Tobias; Bolch, Susan; Wolfrum, Uwe; Smith, W. Clay

    2009-01-01

    Partitioning of cellular components is a critical mechanism by which cells can regulate their activity. In rod photoreceptors, light induces a large-scale translocation of arrestin from the inner segments to the outer segments. The purpose of this project is to elucidate the signaling pathway necessary to initiate arrestin translocation to the outer segments and the mechanism for arrestin translocation. Mouse retinal organotypic cultures and eyes from transgenic Xenopus tadpoles expressing a fusion of GFP and rod arrestin were treated with both activators and inhibitors of proteins in the phosphoinositide pathway. Confocal microscopy was used to image the effects of the pharmacological agents on arrestin translocation in rod photoreceptors. Retinas were also depleted of ATP using potassium cyanide to assess the requirement for ATP in arrestin translocation. In this study, we demonstrate that components of the G-protein-linked phospholipase C (PLC) pathway play a role in initiating arrestin translocation. Our results show that arrestin translocation can be stimulated by activators of PLC and protein kinase C (PKC), and by cholera toxin in the absence of light. Arrestin translocation to the outer segments is significantly reduced by inhibitors of PLC and PKC. Importantly, we find that treatment with potassium cyanide inhibits arrestin translocation in response to light. Collectively, our results suggest that arrestin translocation is initiated by a G-protein-coupled cascade through PLC and PKC signaling. Furthermore, our results demonstrate that at least the initiation of arrestin translocation requires energy input. PMID:19887106

  8. START Background Report START, May 2014 1 BACKGROUND REPORT

    E-print Network

    Hill, Wendell T.

    START Background Report © START, May 2014 1 BACKGROUND REPORT Boko Haram Recent Attacks On Tuesday, April 15, 2014, the terrorist organization Boko Haram attacked a girls' school in Chibok, Borno state, in northern Nigeria, abducting between 250-300 young school girls. Boko Haram's leader, Abubakar Shekau

  9. MAR Background Report MAR Background Report: Indigenous Protest in Brazil

    E-print Network

    Milchberg, Howard

    MAR Background Report MAR Background Report: Indigenous Protest in Brazil Hundreds of indigenous people demonstrated at the National Congress in Brasilia, capital of Brazil, following the announcement in the 1990s in the midst of extensive protests in Brazil and around the world. On February 8, an indigenous

  10. Role of the macrophage in the translocation of intestinal bacteria.

    PubMed

    Wells, C L; Maddaus, M A; Simmons, R L

    1987-01-01

    To clarify the role of the macrophage in the translocation of intestinal bacteria, groups (n = 10) of Swiss Webster mice (Immunocompetent) and C3H/HeJ mice (macrophage defective) were given bacitracin/streptomycin in their drinking water to eliminate the majority of the intestinal microflora. These mice were then "monoassociated" with a streptomycin-resistant strain of Escherichia coli. Forty-eight hours later, E coli was present in all animals at a concentration of 10(11)/g of cecum. In four separate experiments, E coli was recovered from 100% of the mesenteric lymph nodes (MLNs) of the immunocompetent Swiss Webster mice and from 10%, 40%, 30%, and 50% of the MLNs of macrophage-defective C3H/HeJ mice. Swiss Webster mice were then similarly monoassociated by antibiotic decontamination followed by administration of antibiotic-resistant, fluorescein-labeled E coli in their drinking water; cohort groups of mice were given fluorescein-labeled latex beads (1 micron in diameter) in their drinking water. Two, four, and 11 days later, the MLNs were removed and single cell suspensions were analyzed in the fluorescence-activated cell sorter. The fluorescein label was detected exclusively in the macrophage (esterase-positive) population. These results support the hypothesis that intestinal macrophages may play a key role in the transport of intestinal particles (including bacteria) into extraintestinal sites. PMID:3541854

  11. Histone Deacetylase 3 Promotes RCAN1 Stability and Nuclear Translocation

    PubMed Central

    Han, Kyung Ah; Kang, Hye Seon; Lee, Jee Won; Yoo, Lang; Im, Eunju; Hong, Ahyoung; Lee, Yun Ju; Shin, Woo Hyun; Chung, Kwang Chul

    2014-01-01

    Regulator of calcineurin 1 (RCAN1; also referred as DSCR1 or MCIP1) is located in close proximity to a Down syndrome critical region of human chromosome 21. Although RCAN1 is an endogenous inhibitor of calcineurin signaling that controls lymphocyte activation, apoptosis, heart development, skeletal muscle differentiation, and cardiac function, it is not yet clear whether RCAN1 might be involved in other cellular activities. In this study, we explored the extra-functional roles of RCAN1 by searching for novel RCAN1-binding partners. Using a yeast two-hybrid assay, we found that RCAN1 (RCAN1-1S) interacts with histone deacetylase 3 (HDAC3) in mammalian cells. We also demonstrate that HDAC3 deacetylates RCAN1. In addition, HDAC3 increases RCAN1 protein stability by inhibiting its poly-ubiquitination. Furthermore, HDAC3 promotes RCAN1 nuclear translocation. These data suggest that HDAC3, a new binding regulator of RCAN1, affects the protein stability and intracellular localization of RCAN1. PMID:25144594

  12. Absorption and translocation of nitrogen in rhizomes of Leymus chinensis.

    PubMed

    Liu, Hongsheng; Liu, Huajie; Song, Youhong

    2011-03-15

    Leymus chinensis is a dominant species in the Inner Mongolia steppe, northern China. Plant growth in northern China grassland is often limited by low soil nitrogen availability. The objective of this study is to investigate whether rhizomes of Leymus chinensis are involved in the contribution of N uptake. The N concentration, (15)N concentration and (15)N proportion in roots, rhizomes and shoots after 48 h exposure of roots (L(root)) and rhizomes (L(rhizo)) separately and roots and rhizomes together (L(r+r)) to 0.1 mM (15)NH?(4)(15)NO(3) solution were measured using root-splitting equipment and stable isotope ((15)N) techniques, respectively. The N content and dry mass were not affected by the labeling treatment. In contrast, the (15)N concentration in shoots, rhizomes and roots was significantly increased by the labeling in rhizomes, indicating that the inorganic nitrogen was absorbed via rhizomes from the solution and can be transported to other tissues, with preference to shoots rather than roots. Meanwhile, the absolute N absorption and translocation among compartments were also calculated. The N absorption via rhizomes was much smaller than via roots; however, the uptake efficiency per surface unit via rhizomes was greater than via roots. The capacity and high efficiency to absorb N nutrient via rhizomes enable plants to use transient nutrient supplies in the top soil surface. PMID:21290454

  13. Role of Numb expression and nuclear translocation in endometrial cancer

    PubMed Central

    WANG, CHAO; CUI, TAO; FENG, WEIWEI; LI, HUASHUN; HU, LINA

    2015-01-01

    The cell fate determinant Numb orchestrates numerous cell physiological and pathological processes and previous evidence has indicated that Numb expression is associated with tumorigenesis. The present study investigated the potential role of Numb in endometrial cancer (EC). Numb expression was compared between the normal endometrium and EC tissue by immunohistochemistry, and the protein levels were assessed by western blotting and confocal microscopy in the human endometrial HEC-1B cancer cell line and normal epithelial cells. The intracellular localization of Numb in HEC-1B cells was examined by immunofluorescence. Numb was found to be expressed at higher levels in endometrial cancer compared with the normal endometrium. Although Numb localizes to the cytoplasm and plasma membrane in the normal epithelium, the present study found that Numb accumulated in the nucleus of HEC-1B cells. The present data reveals the upregulation of Numb expression in EC tissues and indicates that Numb plays a role in the occurrence of EC, which may be mediated by its translocation into the nucleus. The role of Numb in cancer development requires additional investigation. PMID:25788995

  14. Nuclear translocation of ?-catenin is essential for glioma cell survival.

    PubMed

    Shi, Zhendong; Qian, Xiaomin; Li, Lanquan; Zhang, Junxia; Zhu, Shanjun; Zhu, Jialin; Chen, Luyue; Zhang, Kailiang; Han, Lei; Yu, Shizhu; Pu, Peiyu; Jiang, Tao; Kang, Chunsheng

    2012-12-01

    Identification of molecular pathways that are essential for cancer cell survival is vital for understanding the underlying biology, as well as to design effective cancer therapeutics. ?-catenin, a multifunctional oncogenic protein, participates in cell development. Its multifaceted functions primarily lie to the subcellular distribution. The present study demonstrated that ?-catenin accumulated in the nucleus to a greater extent in high-grade gliomas compared with low-grade gliomas. In addition, nuclear localization correlated with a worse prognosis for patients, as determined by immunohistochemical analysis of 74 glioma samples. Nuclear expression of ?-catenin was down-regulated in LN229 and U87 glioma cells by a small molecule inhibitor of ?-catenin/TCF4 signaling, demonstrating strongly inhibited ?-catenin/TCF4 transcriptional activity and STAT3 luciferase activity, as well as decreased mRNA and protein levels of nuclear ?-catenin, TCF4, EGFR, AKT1, AKT2 and STAT3. Furthermore, repressed nuclear translocation of ?-catenin resulted in inhibition of proliferation and invasiveness, and also induced apoptosis of glioma cells. Similar results were also observed in vivo; intratumoral injection of such small molecule inhibitor downregulated expression of nuclear ?-catenin, TCF4, and components of the EGFR pathway, and also delayed tumor growth in nude mice harboring subcutaneous U87 xenografts. Results from the present study provided evidence that nuclear accumulation of ?-catenin participated in malignant progression of gliomas and implicated poor prognosis, highlighting it as a potential therapeutic target for gliomas. PMID:22415719

  15. A Translocated Bacterial Protein Protects Vascular Endothelial Cells from Apoptosis

    PubMed Central

    Schmid, Michael C; Scheidegger, Florine; Dehio, Michaela; Balmelle-Devaux, Nadège; Schulein, Ralf; Guye, Patrick; Chennakesava, Cuddapah S; Biedermann, Barbara; Dehio, Christoph

    2006-01-01

    The modulation of host cell apoptosis by bacterial pathogens is of critical importance for the outcome of the infection process. The capacity of Bartonella henselae and B. quintana to cause vascular tumor formation in immunocompromised patients is linked to the inhibition of vascular endothelial cell (EC) apoptosis. Here, we show that translocation of BepA, a type IV secretion (T4S) substrate, is necessary and sufficient to inhibit EC apoptosis. Ectopic expression in ECs allowed mapping of the anti-apoptotic activity of BepA to the Bep intracellular delivery domain, which, as part of the signal for T4S, is conserved in other T4S substrates. The anti-apoptotic activity appeared to be limited to BepA orthologs of B. henselae and B. quintana and correlated with (i) protein localization to the host cell plasma membrane, (ii) elevated levels of intracellular cyclic adenosine monophosphate (cAMP), and (iii) increased expression of cAMP-responsive genes. The pharmacological elevation of cAMP levels protected ECs from apoptosis, indicating that BepA mediates anti-apoptosis by heightening cAMP levels by a plasma membrane–associated mechanism. Finally, we demonstrate that BepA mediates protection of ECs against apoptosis triggered by cytotoxic T lymphocytes, suggesting a physiological context in which the anti-apoptotic activity of BepA contributes to tumor formation in the chronically infected vascular endothelium. PMID:17121462

  16. [Studies on the Robertsonian translocation of Microtus mandarinus].

    PubMed

    Qu, A; Gao, H; Feng, Z J; Zheng, Y I; Zhang, M; Telman, D; Zhu, B C

    2000-12-01

    The type of chromosome No. 1 and chromosome number from 53 individuals of Microtus mandarinus have been studied and compared in three sex types: XY, XX, XO. We found that the first pair of autosomes are very unstable, and there are three types: (1) M, M (With a double metacentric chromosome), (2) M, T, T, (With single metacentric chromosome). (3) T, T, T, T (Without metacentric chromosome). The chromosome number of the same sex individuals changes regularly with the type change of chromosome No. 1, that is, the increase of one chromosome in 2n number is always accompanied by the increase of two T and the decrease of one M, and vice versa. The synaptonemal complexes (SCs) of spermatocyte in pachytene nuclei from the males (2n = 51) were analysed by the electron microscopy. The SCs studies demonstrate that there are 23 fully paired autosomal bivalents, XY-bivalent and an autosomal trivalent. This trivalent is formed by one metacentric and two telocentric elements and characterized by the presence of two short side-arms. Meanwhile, all trivalents are in a cis configuration. The study of G-banding also demonstrates that the No. 1 autosome polymorphism is caused by Robertsonian translocation. Robertsonian fission is the main reason of the polymorphism of chromosome No. 1 and of variation of chromosome number in M. mandarinus. PMID:12549076

  17. Characterization of nuclear ferritin and mechanism of translocation

    PubMed Central

    2005-01-01

    Ferritin, normally considered a cytoplasmic iron-storage protein, is also found in cell nuclei. It is an established fact that H-ferritin is the major form of nuclear ferritin, but little is known about the roles of ferritin in nuclei or about the mechanisms that control its appearance within the nuclear volume. In the present study, we show that, for human SW1088 astrocytoma cells, the nuclear and cytoplasmic forms of H-ferritin are products of the same mRNA. Histochemical and biochemical evidence is presented showing that ferritin is distributed non-randomly within the nuclear volume and that it preferentially associates with heterochromatin. Both cytoplasmic and nuclear populations of H-ferritin contain mixtures of non- and O-glycosylated forms, but the nuclear population is enriched in O-glycosylated forms. Cells treated with alloxan, a potent inhibitor of O-glycosylation, contained significantly less nuclear ferritin compared with cells grown in control media. Alloxan inhibited the reappearance of H-ferritin in nuclei of cells released from conditions of iron depletion, but did not prevent its disappearance from nuclei of cells undergoing iron depletion. These results suggest that O-glycosylation accompanies the transfer of ferritin from the cytoplasm to the nucleus, but does not influence the reverse process. The picture that emerges is one in which ferritin translocation between the cytoplasm and the nucleus is post-translationally regulated and responds to environmental and nutritional cues. PMID:15675895

  18. Directed translocation of a flexible polymer through a cone-shaped channel

    E-print Network

    Narges Nikoofard; Hamidreza Khalilian; Hossein Fazli

    2012-11-13

    Entropy-driven directed translocation of a flexible polymer through a cone-shaped channel is studied theoretically and using computer simulation. For a given length of the channel, the effective force of entropic origin acting on the polymer is calculated as a function of the apex angle of the channel. It is found that the translocation time is a non-monotonic function of the apex angle. By increasing the apex angle from zero, the translocation time shows a minimum and then a maximum. Also, it is found that regardless of the value of the apex angle, the translocation time is a uniformly decreasing function of the channel length. The results of the theory and the simulation are in good qualitative agreement.

  19. Microbial translocation and T cell activation are not associated in chronic HIV-infected children.

    PubMed

    Madrid, Lola; Noguera-Julian, Antoni; Falcon-Neyra, Lola; Fortuny, Claudia; De Felipe, Beatriz; Torrebadell, Montserrat; Sanchez, Berta; Valls, Anna; López-Cortès, Luis; Benmarzouk-Hidalgo, Omar J; Neth, Olaf

    2014-08-24

    A cross-sectional study of 77 chronic HIV-infected children revealed higher levels of biomarkers of inflammation (ultrasensitive C-reactive protein, D-dimer and ?-2-microglobulin), immune activation (HLA-DR+ CD38+ CD4+ and CD8+ T cells) and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] than 32 healthy controls. Immune activation was higher in viremic children, but microbial translocation occurred independently of viraemia and T cell activation. Our results do not support a relevant role of microbial translocation in T cell activation in chronic HIV-infected children, proposing a need to develop strategies to minimize microbial translocation in the future. PMID:25259707

  20. Immobilization of the Plug Domain Inside the SecY Channel Allows Unrestricted Protein Translocation*

    PubMed Central

    Lycklama a Nijeholt, Jelger A.; Bulacu, Monica; Marrink, Siewert Jan; Driessen, Arnold J. M.

    2010-01-01

    The SecYEG complex forms a protein-conducting channel in the inner membrane of Escherichia coli to support the translocation of secretory proteins in their unfolded state. The SecY channel is closed at the periplasmic face of the membrane by a small re-entrance loop that connects transmembrane segment 1 with 2b. This helical domain 2a is termed the plug domain. By the introduction of pairs of cysteines and crosslinkers, the plug domain was immobilized inside the channel and connected to transmembrane segment 10. Translocation was inhibited to various degrees depending on the position and crosslinker spacer length. With one of the crosslinked mutants translocation occurred unrestricted. Biochemical characterization of this mutant as well as molecular dynamics simulations suggest that only a limited movement of the plug domain suffices for translocation. PMID:20489195

  1. Assessing the benefits and risks of translocations in changing environments: a genetic perspective

    PubMed Central

    Weeks, Andrew R; Sgro, Carla M; Young, Andrew G; Frankham, Richard; Mitchell, Nicki J; Miller, Kim A; Byrne, Margaret; Coates, David J; Eldridge, Mark D B; Sunnucks, Paul; Breed, Martin F; James, Elizabeth A; Hoffmann, Ary A

    2011-01-01

    Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on ‘genetic rescue’ of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework. PMID:22287981

  2. Conformation of a Peptide Encompassing the Proton Translocation Channel of Vacuolar H1

    E-print Network

    Hemminga, Marcus A.

    of subunit a from the yeast Saccharomyces cerevisiae vacuolar proton-translocating ATPase that contains two they function in processes such as renal acidification (3), pH homeostasis of macrophages (4), and bone

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

    EPA Science Inventory

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

  4. Cotranslational folding inhibits translocation from within the ribosome-Sec61 translocon complex.

    PubMed

    Conti, Brian J; Elferich, Johannes; Yang, Zhongying; Shinde, Ujwal; Skach, William R

    2014-03-01

    Eukaryotic secretory proteins cross the endoplasmic reticulum (ER) membrane through a protein-conducting channel contained within the ribosome-Sec61translocon complex (RTC). Using a zinc-finger sequence as a folding switch, we show that cotranslational folding of a secretory passenger inhibits translocation in canine ER microsomes and in human cells. Folding occurs within a cytosolically inaccessible environment, after ER targeting but before initiation of translocation, and it is most effective when the folded domain is 15-54 residues beyond the signal sequence. Under these conditions, substrate is diverted into cytosol at the stage of synthesis in which unfolded substrate enters the ER lumen. Moreover, the translocation block is reversed by passenger unfolding even after cytosol emergence. These studies identify an enclosed compartment within the assembled RTC that allows a short span of nascent chain to reversibly abort translocation in a substrate-specific manner. PMID:24561504

  5. Sequence dependence of the binding energy in chaperone-driven polymer translocation through a nanopore

    NASA Astrophysics Data System (ADS)

    Abdolvahab, Rouhollah Haji; Ejtehadi, Mohammad Reza; Metzler, Ralf

    2011-01-01

    We study the translocation of stiff polymers through a nanopore, driven by the chemical-potential gradient exerted by binding proteins (chaperones) on the trans side of the pore. Bound chaperones prevent backsliding through the pore and, therefore, partially rectify the polymer passage. We show that the sequence of chain monomers with different binding affinity for the chaperones significantly affects the translocation dynamics. In particular, we investigate the effect of the nearest-neighbor adjacency probability of the two monomer types. Depending on the magnitude of the involved binding energies, the translocation speed may either increase or decrease with the adjacency probability. We determine the mean first passage time and show that, by tuning the effective binding energy, the motion changes continuously from purely diffusive to ballistic translocation.

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

    EPA Science Inventory

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

  7. Metaphase association in microsporocytes of Sorghym bicolor (L) Moench with heterozygous translocations

    E-print Network

    Al-Tayar, Fadhel Abdulredha

    1972-01-01

    method (Schertz, 1970). Schertz sub jected pollen grains and seeds of ~Sh b' 1 (1) 6 h, ' t. y 6 b' 7976, t gamma irradiation and obtained translocated stocks (Schertz, 1970). Certain chemicals, such as Phenols, Coumarin, Sodium citrate, Aluminum...

  8. Effects of translocation and deer-vehicle collision mitigation on Florida Key deer

    E-print Network

    Parker, Israel David

    2009-06-02

    attribute differences in ranges to differences in habitat quality between the core habitat and destination islands and to use of soft releases. Presence of fawns and yearlings indicated successful reproduction of translocated deer. Overall, the project...

  9. Translocation of cave fish (Poecilia mexicana) within and between natural habitats along a

    E-print Network

    Schlupp, Ingo

    Translocation of cave fish (Poecilia mexicana) within and between natural habitats along a toxicity. In a system where incipient speciation of populations of the Atlantic molly (Poecilia mexicana) appears (Poecilia mexicana) from Ta

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

    E-print Network

    Aubin-Tam, Marie-Eve

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

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

    NASA Astrophysics Data System (ADS)

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

    1999-06-01

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

  12. Stochastic Background Search Correlating ALLEGRO with LIGO Engineering Data

    E-print Network

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

    2003-08-14

    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.

  13. Radiative emission of neutrino pair free of quantum electrodynamic backgrounds

    E-print Network

    M. Yoshimura; N. Sasao; M. Tanaka

    2015-01-23

    A scheme of quantum electrodynamic (QED) background-free radiative emission of neutrino pair (RENP) is proposed in order to achieve precision determination of neutrino properties so far not accessible. The important point for the background rejection is the fact that the dispersion relation between wave vector along propagating direction in wave guide (and in a photonic-crystal type fiber) and frequency is modified by a discretized non-vanishing effective mass. This effective mass acts as a cutoff of allowed frequencies, and one may select the RENP photon energy region free of all macro-coherently amplified QED processes by choosing the cutoff larger than the mass of neutrinos.

  14. Radiative emission of neutrino pair free of quantum electrodynamic backgrounds

    E-print Network

    Yoshimura, M; Tanaka, M

    2015-01-01

    A scheme of quantum electrodynamic (QED) background-free radiative emission of neutrino pair (RENP) is proposed in order to achieve precision determination of neutrino properties so far not accessible. The important point for the background rejection is the fact that the dispersion relation between wave vector along propagating direction in wave guide (and in a photonic-crystal type fiber) and frequency is modified by a discretized non-vanishing effective mass. This effective mass acts as a cutoff of allowed frequencies, and one may select the RENP photon energy region free of all macro-coherently amplified QED processes by choosing the cutoff larger than the mass of neutrinos.

  15. Phosphatidylserine Membrane Translocation in Human Spermatozoa: Topography in Membrane Domains and Relation to Cell Vitality

    Microsoft Academic Search

    Malgorzata Kotwicka; Magdalena Jendraszak; Piotr Jedrzejczak

    2011-01-01

    The complex structure of the human spermatozoa membrane comprises five topographic domains. Transmembrane asymmetry of the\\u000a distribution of phospholipids including phosphatidylserine (PS) is considered a marker of cell activity. The objective of\\u000a the study was to determine which cytomembrane domains of human spermatozoa are involved in PS membrane translocation and to\\u000a identify the possible relationship of PS translocation with spermatozoa

  16. Cytological Study of an X-Autosome Translocation in Mus musculus

    Microsoft Academic Search

    S. Ohno; B. M. Cattanach

    1962-01-01

    Earlier genetic studies on this stock of mice with an X-autosome translocation revealed that wild-type alleles of pink-eye and chinchilla of linkage group I have been translocated to the X. When the Xt was accompanied by an Xn, animals heterozygous for pp and cchcch showed variegated coat colors but the Xt alone led only to the wild-type coat color. The

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

    Microsoft Academic Search

    Stacey L. Lance; Jesús E. Maldonado; Carol I. Bocetti; O. H. Pattee; Jonathan D. Ballou; Robert C. Fleischer

    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\\u000a size and range, translocation sites were established beginning in the 1960's by moving squirrels from the natural range to\\u000a sites outside the current range. Although translocations have served as the primary component of

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

    NASA Astrophysics Data System (ADS)

    Polson, James M.; Dunn, Taylor R.

    2014-05-01

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

  19. Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization.

    PubMed Central

    Kuwano, A; Ledbetter, S A; Dobyns, W B; Emanuel, B S; Ledbetter, D H

    1991-01-01

    Fluorescence in situ hybridization (FISH) using two cosmid probes (41A and P13) from the Miller-Dieker syndrome (MDS) critical region in 17p13.3 was performed in a blinded comparison of three MDS patients with submicroscopic deletions and in four normal relatives used as controls. The controls showed both chromosome 17 homologues labeled in 85%-95% of cells, while each patient showed only one homologue labeled in 75%-80% of cells. Two MDS patients with cryptic translocations were also studied. In one case, a patient and her mother had the same der(17) (p+), but the reciprocal product of the translocation could not be identified in the mother by G-banding (i.e., it was a "half-cryptic" translocation). FISH revealed a 3q;17p translocation. The other case involved a patient with apparently normal karyotype. Because a large molecular deletion was found, a translocation involving two G-negative telomeres (i.e., a "full-cryptic" translocation) was postulated. FISH studies on her father and normal brother showed an 8q;17p translocation. These studies demonstrate that in situ hybridization is an efficient method for deletion detection in Miller-Dieker syndrome. More important, parental studies by FISH on patients demonstrating molecular deletions and a normal karyotype may identify cryptic translocation events, which cannot be detected by other molecular genetic strategies. Similar in situ strategies for deletion detection can be developed for other microdeletion syndromes, such as Prader-Willi/Angelman syndrome or DiGeorge syndrome. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1897521

  20. Absorption, translocation, and metabolism of propoxycarbazone-sodium in ALS-inhibitor resistant Bromus tectorum biotypes

    Microsoft Academic Search

    Kee Woong Park; Lynn Fandrich; Carol A. Mallory-Smith

    2004-01-01

    Experiments were conducted to investigate the absorption, translocation, and metabolism of propoxycarbazone-sodium in acetolactate synthase-inhibitor resistant (AR and MR) and susceptible (AS and MS) Bromus tectorum biotypes. Absorption and translocation of l4C-propoxycarbazone-sodium were similar in all biotypes. One major and three minor metabolites were identified using reverse-phase high performance liquid chromatography. In all biotypes, 80% of the propoxycarbazone-sodium was metabolized

  1. Evaluating the Applicability of the Fokker-Planck Equation in Polymer Translocation: A Brownian Dynamics Study

    E-print Network

    James M. Polson; Taylor Dunn

    2014-03-28

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

  2. Familial translocation involving chromosomes 1 and 9 in a patient with Philadelphia-positive CML

    Microsoft Academic Search

    K. Rehman; F. Rosner; A. Shanske

    1994-01-01

    CML has provided a model for understanding the genetic basis of neoplasia. Approximately 5% of Philadelphia-positive patients have a variant chromosome rearrangement. We recently evaluated a patient with a previously unreported simple variant translocation that is part of a familial rearrangement. He had a constitutional translocation, t(1;9)(p21;p22), which was initially identified after his wife had a routine amniocentesis. Case report:

  3. Disruption of two novel genes by a translocation co-segregating with schizophrenia

    Microsoft Academic Search

    J. Kirsty Millar; Julie C. Wilson-Annan; Susan Anderson; Sheila Christie; M artin S. Taylor; Colin A. M. Semple; Rebecca S. Devon; D avid M. St Clair; W alter J. Muir; Douglas H. R. Blackwood; David J. Porteous

    2000-01-01

    A balanced (1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related psychiatric disorders in a large Scottish family (maximum LOD = 6.0). We hypoth- esize that the translocation is the causative event and that it directly disrupts gene function. We previously reported a dearth of genes in the breakpoint region of chromosome 11 and it is therefore unlikely that the expression of

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

    SciTech Connect

    Resta, R.G.; Luthardt, F. [Swedish Medical Center, Seattle, WA (United States)] [Swedish Medical Center, Seattle, WA (United States); Kapur, R. [Univ. of Washington, Seattle, WA (United States)] [Univ. of Washington, Seattle, WA (United States)

    1996-05-17

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

  5. Determinants of the rate of mRNA translocation in bacterial protein synthesis.

    PubMed

    Borg, Anneli; Ehrenberg, Måns

    2015-05-01

    Studying the kinetics of translocation of mRNA and tRNAs on the translating ribosome is technically difficult since the rate-limiting steps involve large conformational changes without covalent bond formation or disruption. Here, we have developed a unique assay system for precise estimation of the full translocation cycle time at any position in any type of open reading frame (ORF). Using a buffer system optimized for high accuracy of tRNA selection together with high concentration of elongation factor G, we obtained in vivo compatible translocation rates. We found that translocation was comparatively slow early in the ORF and faster further downstream of the initiation codon. The maximal translocation rate decreased from the in vivo compatible value of 30s(-1) at 1mM free Mg(2+) concentration to the detrimentally low value of 1s(-1) at 6mM free Mg(2+) concentration. Thus, high and in vivo compatible accuracy of codon translation, as well as high and in vivo compatible translocation rate, required a remarkably low Mg(2+) concentration. Finally, we found that the rate of translocation deep inside an ORF was not significantly affected upon variation of the standard free energy of interaction between a 6-nt upstream Shine-Dalgarno (SD)-like sequence and the anti-SD sequence of 16S rRNA in a range of 0-6kcal/mol. Based on these experiments, we discuss the optimal choice of Mg(2+) concentration for maximal fitness of the living cell by taking its effects on the accuracy of translation, the peptide bond formation rate and the translocation rate into account. PMID:25451025

  6. DNA translocation across protein channels: How does a polymer worm through a hole?

    NASA Astrophysics Data System (ADS)

    Muthukumar, M.

    2001-03-01

    Free energy barriers control the translocation of polymers through narrow channels. Based on an analogy with the classical nucleation and growth process, we have calculated the translocation time and its dependencies on the length, stiffness, and sequence of the polymer, solution conditions, and the strength of the driving electrochemical potential gradient. Our predictions will be compared with experimental results and prospects of reading polymer sequences.

  7. Protein Translocation in Photoreceptor Light Adaptation: A Common Theme in Vertebrate and Invertebrate Vision

    NSDL National Science Digital Library

    Vadim Y. Arshavsky (Harvard Medical School and the Massachusetts Eye and Ear Infirmary; REV)

    2003-10-14

    How do our eyes adjust to daily light levels that vary by almost 11 orders of magnitude? Research shows that, in both vertebrates and invertebrates, signaling proteins are translocated in a light-dependent manner between the photoreceptor cellular compartments where visual transduction takes place, and the rest of the photoreceptor cell. Protein translocation is likely to contribute to photoreceptor light adaptation by adjusting the sensitivity and speed of photoresponse to ever-changing conditions of ambient illumination.

  8. Translocation of carnivores as a method for managing problem animals: a review

    Microsoft Academic Search

    JOHN D. C. LINNELL; RONNY AANES; JON E. SWENSON; JOHN ODDEN; MARTIN E. SMITH

    1997-01-01

    Translocation of individual carnivores has been a standard management tool for decades in North America and southern Africa\\u000a in response to livestock depredation and other conflict behaviours. As carnivore populations across Europe begin to increase\\u000a it is expected that management problems will also increase. Before translocation becomes established as a management tool\\u000a in Europe its success needs to be reviewed.

  9. IKCa1 activity is required for cell shrinkage, phosphatidylserine translocation and death in T lymphocyte apoptosis

    Microsoft Academic Search

    Christopher F. Higgins; James I. Elliott

    2003-01-01

    Apoptotic cell volume decrease (AVD) and exposure of phosphatidylserine (PtdSer) at the cell surface are early events in apoptosis. However, the ion channels responsible for AVD, and their relationship to PtdSer translocation and cell death are poorly understood. Real-time analysis of calcium-induced apoptosis in lymphocytes and thymocytes showed that AVD occurs rapidly, and precedes PtdSer translocation. Blockers of the K+

  10. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia

    Microsoft Academic Search

    Annelies De Klein; Ad Geurts Van Kessel; Gerard Grosveld; Claus R. Bartram; Anne Hagemeijer; Dirk Bootsma; Nigel K. Spurr; Nora Heisterkamp; John Groffen; John R. Stephenson

    1982-01-01

    The transforming genes of oncogenic retroviruses are homologous to a group of evolutionary conserved cellular onc genes1. The human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuLV) was recently shown2 to be located on chromosome 9. The long arm of this chromosome is involved in a specific translocation with chromosome 22, the Philadelphia translocation (Ph1),

  11. Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis

    Microsoft Academic Search

    Ting-Ting Yuan; Ying Huang; Ci-Xiang Zhou; Yun Yu; Li-Shun Wang; Han-Yi Zhuang; Guo-Qiang Chen

    2009-01-01

    Dihydrofolate reductase (DHFR) is a key enzyme for the synthesis of thymidylate, and therefore, of DNA. By applying subcellular\\u000a proteomic analysis, we identified that the DHFR protein was translocated from cytoplasm into the nucleus when apoptosis was\\u000a induced by NSC606985, a camptothecin analogue. The nuclear translocation of DHFR protein during apoptosis was independent\\u000a of the cellular context, but it was

  12. Studies of crossing-over in Heterozygous Translocations in Drosophila melanogaster

    Microsoft Academic Search

    G. W. Beadle

    1933-01-01

    locations in heterozygous condition generally reduce crossing-over in the broken chromosome or chromosomes. The reduction in crossing-over is greatest in the regions including and near breaks. In the autosomes, crossing-over is reduced only in the arm involved in the translocation. DOBZ~ANSKY (1931b) arrived at the above generalizations from a con- sideration of the known cases of translocation in Drosophila in

  13. Characterization of a wheat– Thinopyrum bessarabicum (T2JS-2BS·2BL) translocation line

    Microsoft Academic Search

    Zengjun Qi; Pei Du; Baoli Qian; Lifang Zhuang; Huafeng Chen; Tingting Chen; Jian Shen; Jie Guo; Yigao Feng; Ziyou Pei

    2010-01-01

    Thinopyrum bessarabicum (2n = 2x = 14, JJ or EbEb) is an important genetic resource for wheat improvement due to its salinity tolerance and disease resistance. Development\\u000a of wheat–Th. bessarabicum translocation lines will facilitate its practical utilization in wheat improvement. In this study, a novel wheat–Th. bessarabicum translocation line T2JS-2BS·2BL, which carries a segment of Th. bessarabicum chromosome arm 2JS was identified and further

  14. Background

    E-print Network

    Joe Martens

    2011-01-01

    This summary was completed upon request to provide information for the Town of Ancram for land use planning and decision-making. It identifies major natural features, as well as significant ecosystems and valuable stream, forest, wetland, and other habitats with important biological resources based on information available to the NYSDEC. It should not be considered a complete biological inventory because it is based only on existing information gleaned from various complementary, but not comprehensive, sources. In the case of Ancram, a large amount of information is available. However, there are areas for which we had no information, particularly in the western part of town. Additional general information about habitats can be found in the Wildlife and Habitat Conservation Framework developed by the Hudson River Estuary Program (Penhollow et al. 2006). If you have any questions about this summary, or want to know if it needs to be updated, please contact Karen Strong, Biodiversity Outreach Coordinator. NYSDEC’s Hudson River Estuary Program protects and improves the historic and scenic Hudson River watershed for all its residents. The program was created in 1987 and extends from the Troy dam to the Verrazano Narrows. Its core mission is to: • Ensure clean water; • Protect and restore fish and wildlife habitats;

  15. Background

    E-print Network

    Grazyna E Ptak; Jacek A Modlinski; Grazyna E Ptak; Jacek A Modlinski; Pasqualino Loi

    2013-01-01

    This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. Embryonic diapause in humans: time to consider?

  16. 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.

  17. Stochastic background from extra-galactic double neutron stars

    E-print Network

    T. Regimbau; B. Chauvineau

    2007-07-30

    We present Monte Carlo simulations of the extra galactic population of inspiralling double neutron stars, and estimate its contribution to the astrophysical gravitational wave background, in the frequency range of ground based interferometers, corresponding to the last thousand seconds before the last stable orbit when more than 96 percent of the signal is released. We show that sources at redshift z>0.5 contribute to a truly continuous background which may be detected by correlating third generation interferometers.

  18. The translocation selectivity of the kinesins that mediate neuronal organelle transport.

    PubMed

    Huang, Chun-Fang; Banker, Gary

    2012-04-01

    Polarized kinesin-driven transport is crucial for development and maintenance of neuronal polarity. Kinesins are thought to recognize biochemical differences between axonal and dendritic microtubules in order to deliver their cargoes to the appropriate domain. To identify kinesins that mediate polarized transport, we prepared constitutively active versions of all the kinesins implicated in vesicle transport and expressed them in cultured hippocampal neurons. Seven kinesins translocated preferentially to axons and five translocated into both axons and dendrites. None translocated selectively to dendrites. Highly homologous members of the same subfamily displayed distinctly different translocation preferences and were differentially regulated during development. By expressing chimeric kinesins, we identified two microtubule-binding elements within the motor domain that are important for selective translocation. We also discovered elements in the dimerization domain of kinesin-2 motors that contribute to their selective translocation. These observations indicate that selective interactions between kinesin motor domains and microtubules can account for polarized transport to the axon, but not for selective dendritic transport. PMID:22212743

  19. Mapping polypeptide interactions of the SecA ATPase during translocation

    PubMed Central

    Bauer, Benedikt W.; Rapoport, Tom A.

    2009-01-01

    Many bacterial proteins, including most secretory proteins, are translocated across the plasma membrane by the interplay of the cytoplasmic SecA ATPase and a protein-conducting channel formed by the SecY complex. SecA catalyzes the sequential movement of polypeptide segments through the SecY channel. How SecA interacts with a broad range of polypeptide segments is unclear, but structural data raise the possibility that translocation substrates bind into a “clamp” of SecA. Here, we have used disulfide bridge cross-linking to test this hypothesis. To analyze polypeptide interactions of SecA during translocation, two cysteines were introduced into a translocation intermediate: one that cross-links to the SecY channel and the other one for cross-linking to a cysteine placed at various positions in SecA. Our results show that a translocating polypeptide is indeed captured inside SecA's clamp and moves in an extended conformation through the clamp into the SecY channel. These results define the polypeptide path during SecA-mediated protein translocation and suggest a mechanism by which ATP hydrolysis by SecA is used to move a polypeptide chain through the SecY channel. PMID:19933328

  20. Different Aneuploidies Arise From the Same Bridge-Induced Chromosomal Translocation Event in Saccharomyces cerevisiae

    PubMed Central

    Rossi, Beatrice; Noel, Pawan; Bruschi, Carlo V.

    2010-01-01

    Chromosome translocations are gross chromosomal rearrangements that have often been associated with cancer development in mammalian cells. The feasibility of drastically reshaping the genome with a single translocation event also gives this molecular event a powerful capacity to drive evolution. Despite these implications and their role in genome instability, very little is known about the molecular mechanisms that promote and accompany these events. Here, at the molecular level, we describe 10 morphologically and physiologically different translocants ensuing from the induction of the same bridge-induced translocation (BIT) event in the budding yeast Saccharomyces cerevisiae. We have demonstrated that, despite their common origin from the integration of the same linear DNA construct, all 10 translocation mutant strains have different phenotypes and the ability to sporulate and regulate gene expression and morphology. We also provide insights into how heterogeneous phenotypic variations originate from the same initial genomic event. Here we show eight different ways in which yeast cells have dealt with a single initial event inducing translocation. Our results are in agreement with the formation of complex rearrangements and abnormal karyotypes described in many leukemia patients, thus confirming the modellistic value of the yeast BIT system for mammalian cells. PMID:20805555