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Sample records for reveals multiple spatiotemporal

  1. A Multiple Regression Approach to Normalization of Spatiotemporal Gait Features.

    PubMed

    Wahid, Ferdous; Begg, Rezaul; Lythgo, Noel; Hass, Chris J; Halgamuge, Saman; Ackland, David C

    2016-04-01

    Normalization of gait data is performed to reduce the effects of intersubject variations due to physical characteristics. This study reports a multiple regression normalization approach for spatiotemporal gait data that takes into account intersubject variations in self-selected walking speed and physical properties including age, height, body mass, and sex. Spatiotemporal gait data including stride length, cadence, stance time, double support time, and stride time were obtained from healthy subjects including 782 children, 71 adults, 29 elderly subjects, and 28 elderly Parkinson's disease (PD) patients. Data were normalized using standard dimensionless equations, a detrending method, and a multiple regression approach. After normalization using dimensionless equations and the detrending method, weak to moderate correlations between walking speed, physical properties, and spatiotemporal gait features were observed (0.01 < |r| < 0.88), whereas normalization using the multiple regression method reduced these correlations to weak values (|r| <0.29). Data normalization using dimensionless equations and detrending resulted in significant differences in stride length and double support time of PD patients; however the multiple regression approach revealed significant differences in these features as well as in cadence, stance time, and stride time. The proposed multiple regression normalization may be useful in machine learning, gait classification, and clinical evaluation of pathological gait patterns.

  2. Artificial spatiotemporal touch inputs reveal complementary decoding in neocortical neurons

    PubMed Central

    Oddo, Calogero M.; Mazzoni, Alberto; Spanne, Anton; Enander, Jonas M. D.; Mogensen, Hannes; Bengtsson, Fredrik; Camboni, Domenico; Micera, Silvestro; Jörntell, Henrik

    2017-01-01

    Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons in vivo, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models. PMID:28374841

  3. Asynchronous Visualization of Spatiotemporal Information for Multiple Moving Targets

    ERIC Educational Resources Information Center

    Wang, Huadong

    2013-01-01

    In the modern information age, the quantity and complexity of spatiotemporal data is increasing both rapidly and continuously. Sensor systems with multiple feeds that gather multidimensional spatiotemporal data will result in information clusters and overload, as well as a high cognitive load for users of these systems. To meet future…

  4. Spatiotemporal rogue events in optical multiple filamentation.

    PubMed

    Birkholz, Simon; Nibbering, Erik T J; Brée, Carsten; Skupin, Stefan; Demircan, Ayhan; Genty, Goëry; Steinmeyer, Günter

    2013-12-13

    The transient appearance of bright spots in the beam profile of optical filaments formed in xenon is experimentally investigated. Fluence profiles are recorded with high-speed optical cameras at the kilohertz repetition rate of the laser source. A statistical analysis reveals a thresholdlike appearance of heavy-tailed fluence distributions together with the transition from single to multiple filamentation. The multifilament scenario exhibits near-exponential probability density functions, with extreme events exceeding the significant wave height by more than a factor of 10. The extreme events are isolated in space and in time. The macroscopic origin of these experimentally observed heavy-tail statistics is shown to be local refractive index variations inside the nonlinear medium, induced by multiphoton absorption and subsequent plasma thermalization. Microscopically, mergers between filament strings appear to play a decisive role in the observed rogue wave statistics.

  5. Multiple movement modes by large herbivores at multiple spatiotemporal scales

    PubMed Central

    Fryxell, John M.; Hazell, Megan; Börger, Luca; Dalziel, Ben D.; Haydon, Daniel T.; Morales, Juan M.; McIntosh, Therese; Rosatte, Rick C.

    2008-01-01

    Recent theory suggests that animals should switch facultatively among canonical movement modes as a complex function of internal state, landscape characteristics, motion capacity, and navigational capacity. We tested the generality of this paradigm for free-ranging elk (Cervus elaphus) over 5 orders of magnitude in time (minutes to years) and space (meters to 100 km). At the coarsest spatiotemporal scale, elk shifted from a dispersive to a home-ranging phase over the course of 1–3 years after introduction into a novel environment. At intermediate spatiotemporal scales, elk continued to alternate between movement modes. During the dispersive phase, elk alternated between encamped and exploratory modes, possibly linked to changes in motivational goals from foraging to social bonding. During the home-ranging phase, elk movements were characterized by a complex interplay between attraction to preferred habitat types and memory of previous movements across the home-range. At the finest temporal and spatial scale, elk used area-restricted search while browsing, interspersed with less sinuous paths when not browsing. Encountering a patch of high-quality food plants triggered the switch from one mode to the next, creating biphasic movement dynamics that were reinforced by local resource heterogeneity. These patterns suggest that multiphasic structure is fundamental to the movement patterns of elk at all temporal and spatial scales tested. PMID:19060190

  6. Spatio-temporal Linear Stability Analysis of Multiple Reacting Wakes

    NASA Astrophysics Data System (ADS)

    Kunnumpuram Sebastian, Jacob; Emerson, Benjamin; Lieuwen, Tim

    2016-11-01

    Hydrodynamic stability of reacting shear flows plays a key role in controlling a variety of combustor behaviors, such as combustion instability, mixing and entrainment, and blowoff. A significant literature exists on the hydrodynamics of single bluff body flows, but not the multi-bluff body flows that are found in applications. The objective of this work was to compare the spatio-temporal stability of multiple reacting wakes and single reacting wakes, within the framework of linear stability theory. Spatio-temporal stability analyses are conducted on model velocity and density profiles, with key parameters being the density ratio across the flame, bluff body spacing, dimensionless shear, and asymmetry parameters (if the two wakes are dissimilar). The introduction of the additional bluff body can exert both a stabilizing and destabilizing effect on the combined two-wake system, depending on the spatial separation between the bluff bodies. Furthermore, while the most rapidly amplified mode of the single wake mode is the sinuous (asymmetric) one, in the two wake system, the most rapidly amplified mode can be either sinuous or varicose (symmetric), also depending on spatial separation.

  7. Enzyme-Responsive Delivery of Multiple Proteins with Spatiotemporal Control

    PubMed Central

    Zhu, Suwei; Nih, Lina; Carmichael, S. Thomas; Lu, Yunfeng; Segura, Tatiana

    2015-01-01

    The growth of tissues and organs is regulated by orchestrated signals from biomolecules such as enzymes and growth factors. The ability to deliver signal molecules in response to particular biological events (e.g., enzyme expression and activation) holds great promise towards tissue healing and regeneration. The current delivery vehicles mainly rely on hydrolysable scaffolds and thin films of protein-containing polymers, which cannot be programmed to respond to biological signals. We report herein an injectable delivery platform based on enantiomeric protein nanocapsules, which can deliver multiple proteins with spatiotemporal control in response to the tissue proteases secreted during wound healing. Exemplified by stroke and diabetic wound healing in mice, sequential delivery of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) greatly enhances tissue revascularization and vessel maturation, providing effective delivery vehicles for tissue engineering and reparative medicine. PMID:25962336

  8. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

    PubMed Central

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal

    2016-01-01

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. PMID:26728857

  9. Spatio-temporal variation in European starling reproductive success at multiple small spatial scales.

    PubMed

    Brickhill, Daisy; Evans, Peter Gh; Reid, Jane M

    2015-08-01

    Understanding population dynamics requires spatio-temporal variation in demography to be measured across appropriate spatial and temporal scales. However, the most appropriate spatial scale(s) may not be obvious, few datasets cover sufficient time periods, and key demographic rates are often incompletely measured. Consequently, it is often assumed that demography will be spatially homogeneous within populations that lack obvious subdivision. Here, we quantify small-scale spatial and temporal variation in a key demographic rate, reproductive success (RS), within an apparently contiguous population of European starlings. We used hierarchical cluster analysis to define spatial clusters of nest sites at multiple small spatial scales and long-term data to test the hypothesis that small-scale spatio-temporal variation in RS occurred. RS was measured as the number of chicks alive ca. 12 days posthatch either per first brood or per nest site per breeding season (thereby incorporating multiple breeding attempts). First brood RS varied substantially among spatial clusters and years. Furthermore, the pattern of spatial variation was stable across years; some nest clusters consistently produced more chicks than others. Total seasonal RS also varied substantially among spatial clusters and years. However, the magnitude of variation was much larger and the pattern of spatial variation was no longer temporally consistent. Furthermore, the estimated magnitude of spatial variation in RS was greater at smaller spatial scales. We thereby demonstrate substantial spatial, temporal, and spatio-temporal variation in RS occurring at very small spatial scales. We show that the estimated magnitude of this variation depended on spatial scale and that spatio-temporal variation would not have been detected if season-long RS had not been measured. Such small-scale spatio-temporal variation should be incorporated into empirical and theoretical treatments of population dynamics.

  10. Spatio-temporal variation in European starling reproductive success at multiple small spatial scales

    PubMed Central

    Brickhill, Daisy; Evans, Peter GH; Reid, Jane M

    2015-01-01

    Understanding population dynamics requires spatio-temporal variation in demography to be measured across appropriate spatial and temporal scales. However, the most appropriate spatial scale(s) may not be obvious, few datasets cover sufficient time periods, and key demographic rates are often incompletely measured. Consequently, it is often assumed that demography will be spatially homogeneous within populations that lack obvious subdivision. Here, we quantify small-scale spatial and temporal variation in a key demographic rate, reproductive success (RS), within an apparently contiguous population of European starlings. We used hierarchical cluster analysis to define spatial clusters of nest sites at multiple small spatial scales and long-term data to test the hypothesis that small-scale spatio-temporal variation in RS occurred. RS was measured as the number of chicks alive ca. 12 days posthatch either per first brood or per nest site per breeding season (thereby incorporating multiple breeding attempts). First brood RS varied substantially among spatial clusters and years. Furthermore, the pattern of spatial variation was stable across years; some nest clusters consistently produced more chicks than others. Total seasonal RS also varied substantially among spatial clusters and years. However, the magnitude of variation was much larger and the pattern of spatial variation was no longer temporally consistent. Furthermore, the estimated magnitude of spatial variation in RS was greater at smaller spatial scales. We thereby demonstrate substantial spatial, temporal, and spatio-temporal variation in RS occurring at very small spatial scales. We show that the estimated magnitude of this variation depended on spatial scale and that spatio-temporal variation would not have been detected if season-long RS had not been measured. Such small-scale spatio-temporal variation should be incorporated into empirical and theoretical treatments of population dynamics. PMID:26380670

  11. Reliability of the Spatiotemporal Determinants of Maximal Sprint Speed in Adolescent Boys Over Single and Multiple Steps.

    PubMed

    Meyers, Robert W; Oliver, Jon L; Hughes, Michael G; Lloyd, Rhodri Steffan; Cronin, John

    2015-08-01

    The purpose of this study was to examine the reliability of the spatiotemporal determinants of maximal sprinting speed in boys over single and multiple steps. Fifty-four adolescent boys (age = 14.1 ± 0.7 years [range = 12.9-15.7 years]; height = 1.63 ± 0.09 m; body mass = 55.3 ± 13.3 kg; -0.31 ± 0.90 age from Peak Height Velocity (PHV) in years; mean ± s) volunteered to complete a 30 m sprint test on 3 occasions over a 2-week period. Speed, step length, step frequency, contact time, and flight time were assessed via an optical measurement system. Speed and step characteristics were obtained from the single-fastest step and average of the 2 and 4 fastest consecutive steps. Pairwise comparison of consecutive trials revealed the coefficient of variation (CV) for speed was greater in 4-step (CV = 7.3 & 7.5%) compared with 2-step (CV = 4.2 & 4.1%) and 1-step (CV = 4.8 & 4.6%) analysis. The CV of step length, step frequency and contact time ranged from 4.8 to 7.5% for 1-step, 3.8-5.0% for 2-step and 4.2-7.5% for 4-step analyses across all trials. An acceptable degree of reliability was achieved for the spatiotemporal and performance variables assessed in this study. Two-step analysis demonstrated the highest degree of reliability for the key spatiotemporal variables, and therefore may be the most suitable approach to monitor the spatiotemporal characteristics of maximal sprint speed in boys.

  12. Spatiotemporal analysis with a genetically encoded fluorescent RNA probe reveals TERRA function around telomeres

    PubMed Central

    Yamada, Toshimichi; Yoshimura, Hideaki; Shimada, Rintaro; Hattori, Mitsuru; Eguchi, Masatoshi; Fujiwara, Takahiro K.; Kusumi, Akihiro; Ozawa, Takeaki

    2016-01-01

    Telomeric repeat-containing RNA (TERRA) controls the structure and length of telomeres through interactions with numerous telomere-binding proteins. However, little is known about the mechanism by which TERRA regulates the accessibility of the proteins to telomeres, mainly because of the lack of spatiotemporal information of TERRA and its-interacting proteins. We developed a fluorescent probe to visualize endogenous TERRA to investigate its dynamics in living cells. Single-particle fluorescence imaging revealed that TERRA accumulated in a telomere-neighboring region and trapped diffusive heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), thereby inhibiting hnRNPA1 localization to the telomere. These results suggest that TERRA regulates binding of hnRNPA1 to the telomere in a region surrounding the telomere, leading to a deeper understanding of the mechanism of TERRA function. PMID:27958374

  13. Spatiotemporal Coherent Control of Light through a Multiple Scattering Medium with the Multispectral Transmission Matrix

    NASA Astrophysics Data System (ADS)

    Mounaix, Mickael; Andreoli, Daria; Defienne, Hugo; Volpe, Giorgio; Katz, Ori; Grésillon, Samuel; Gigan, Sylvain

    2016-06-01

    We report the broadband characterization of the propagation of light through a multiple scattering medium by means of its multispectral transmission matrix. Using a single spatial light modulator, our approach enables the full control of both the spatial and spectral properties of an ultrashort pulse transmitted through the medium. We demonstrate spatiotemporal focusing of the pulse at any arbitrary position and time with any desired spectral shape. Our approach opens new perspectives for fundamental studies of light-matter interaction in disordered media, and has potential applications in sensing, coherent control, and imaging.

  14. Multiple dipole modeling and localization from spatio-temporal MEG data

    SciTech Connect

    Mosher, J.C. ); Lewis, P.S. ); Leahy, R. )

    1992-06-01

    An array of biomagnetometers may be used to measure the spatio-temporal neuromagnetic field or magnetoencephalogram (MEG) produced by neural activity in the brain. A popular model for the neural activity produced in response to a given sensory stimulus is a set of current dipoles, where each dipole represents the primary current associated with the combined activation of a large number of neutrons located in a small volume of the brain. An important problem in the interpretation of MEG data from evoked response experiments is the localization of these neural current dipoles. The authors present here a linear algebraic framework for three common spatio-temporal dipole models: (i) unconstrained dipoles, (ii) dipoles with a fixed location, and (iii) dipoles with a fixed orientation and location. In all cases, they assume that the location, orientation, and magnitude of the dipoles are unknown. With a common model, they show how the parameter estimation problem may be decomposed into the estimation of the time invariant parameter using nonlinear least-squares minimization, followed by linear estimation of the associated time varying parameters. A subspace formulation is presented and used to derive a suboptimal least-squares subspace scanning method. The resulting algorithm is a special case of the well-known MUltiple SIgnal Classification (MUSIC) method, in which the solution (multiple dipole locations) is found by scanning potential locations using a simple one dipole model.

  15. Whole-community DNA barcoding reveals a spatio-temporal continuum of biodiversity at species and genetic levels.

    PubMed

    Baselga, Andrés; Fujisawa, Tomochika; Crampton-Platt, Alexandra; Bergsten, Johannes; Foster, Peter G; Monaghan, Michael T; Vogler, Alfried P

    2013-01-01

    A correlation of species and genetic diversity has been proposed but not uniformly supported. Large-scale DNA barcoding provides qualitatively novel data to test for correlations across hierarchical levels (genes, genealogies and species), and may help to unveil the underlying processes. Here we analyse sequence variation in communities of aquatic beetles across Europe (>5,000 individuals) to test for self-similarity of beta diversity patterns at multiple hierarchical levels. We show that community similarity at all levels decreases exponentially with geographic distance, and initial similarity is correlated with the lineage age, consistent with a molecular clock. Log-log correlations between lineage age, number of lineages, and range sizes, reveal a fractal geometry in time and space, indicating a spatio-temporal continuum of biodiversity across scales. Simulations show that these findings mirror dispersal-constrained models of haplotype distributions. These novel macroecological patterns may be explained by neutral evolutionary processes, acting continuously over time to produce multi-scale regularities of biodiversity.

  16. Electrical brain imaging reveals spatio-temporal dynamics of timbre perception in humans.

    PubMed

    Meyer, Martin; Baumann, Simon; Jancke, Lutz

    2006-10-01

    Timbre is a major attribute of sound perception and a key feature for the identification of sound quality. Here, we present event-related brain potentials (ERPs) obtained from sixteen healthy individuals while they discriminated complex instrumental tones (piano, trumpet, and violin) or simple sine wave tones that lack the principal features of timbre. Data analysis yielded enhanced N1 and P2 responses to instrumental tones relative to sine wave tones. Furthermore, we applied an electrical brain imaging approach using low-resolution electromagnetic tomography (LORETA) to estimate the neural sources of N1/P2 responses. Separate significance tests of instrumental vs. sine wave tones for N1 and P2 revealed distinct regions as principally governing timbre perception. In an initial stage (N1), timbre perception recruits left and right (peri-)auditory fields with an activity maximum over the right posterior Sylvian fissure (SF) and the posterior cingulate (PCC) territory. In the subsequent stage (P2), we uncovered enhanced activity in the vicinity of the entire cingulate gyrus. The involvement of extra-auditory areas in timbre perception may imply the presence of a highly associative processing level which might be generally related to musical sensations and integrates widespread medial areas of the human cortex. In summary, our results demonstrate spatio-temporally distinct stages in timbre perception which not only involve bilateral parts of the peri-auditory cortex but also medially situated regions of the human brain associated with emotional and auditory imagery functions.

  17. Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

    NASA Astrophysics Data System (ADS)

    Huang, Chien-Lin; Hsu, Nien-Sheng

    2016-04-01

    This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

  18. Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals

    PubMed Central

    Koos, Tibor; Buzsáki, György

    2012-01-01

    Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions. PMID:22496529

  19. Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence

    PubMed Central

    Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Torralba, Antonio; Oliva, Aude

    2016-01-01

    The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain. PMID:27282108

  20. Statistical evaluation of biogeochemical variables affecting spatiotemporal distributions of multiple free metal ion concentrations in an urban estuary.

    PubMed

    Dong, Zhao; Lewis, Christopher G; Burgess, Robert M; Coull, Brent; Shine, James P

    2016-05-01

    Free metal ion concentrations have been recognized as a better indicator of metal bioavailability in aquatic environments than total dissolved metal concentrations. However, our understanding of the determinants of free ion concentrations, especially in a metal mixture, is limited, due to underexplored techniques for measuring multiple free metal ions simultaneously. In this work, we performed statistical analyses on a large dataset containing repeated measurements of free ion concentrations of Cu, Zn, Pb, Ni, and Cd, the most commonly measured metals in seawater, at five inshore locations in Boston Harbor, previously collected using an in-situ equilibrium-based multi-metal free ion sampler, the 'Gellyfish'. We examined correlations among these five metals by season, and evaluated effects of 10 biogeochemical variables on free ion concentrations over time and location through multivariate regressions. We also explored potential clustering among the five metals through a principal component analysis. We found significant correlations among metals, with varying patterns over season. Our regression results suggest that instead of dissolved metals, pH, salinity, temperature and rainfall were the most significant determinants of free metal ion concentrations. For example, a one-unit decrease in pH was associated with a 2.2 (Cd) to 99 (Cu) times increase in free ion concentrations. This work is among the first to reveal key contributors to spatiotemporal variations in free ion concentrations, and demonstrated the usefulness of the Gellyfish sampler in routine sampling of free ions within metal mixtures and in generating data for statistical analyses.

  1. Spatiotemporal Patterns of Evapotranspiration in Response to Multiple Environmental Factors Simulated by the Community Land Model

    SciTech Connect

    Shi, Xiaoying; Mao, Jiafu; Thornton, P.; Huang, Maoyi

    2013-04-25

    Spatiotemporal patterns of evapotranspiration (ET) over the period from 1982 to 2008 are investigated and attributed to multiple environmental factors using the Community Land Model version 4 (CLM4). Our results show that CLM4 captures the spatial distribution and interannual variability of ET well when compared to observation-based estimates. We find that climate dominates the predicted variability in ET. Elevated atmospheric CO2 concentration also plays an important role in modulating the trend of predicted ET over most land areas, and replaces climate to function as the dominant factor controlling ET changes over the North America, South America and Asia regions. Compared to the effect of climate and CO2 concentration, the roles of other factors such as nitrogen deposition, land use change and aerosol deposition are less pronounced and regionally dependent. The aerosol deposition contribution is the third most important factor for trends of ET over Europe, while it has the smallest impact over other regions. As ET is a dominant component of the terrestrial water cycle, our results suggest that environmental factors like elevated CO2, nitrogen and aerosol depositions, and land use change, in addition to climate, could have significant impact on future projections of water resources and water cycle dynamics at global and regional scales.

  2. Computational EEG modelling of decision making under ambiguity reveals spatio-temporal dynamics of outcome evaluation.

    PubMed

    Jollans, Lee; Whelan, Robert; Venables, Louise; Turnbull, Oliver H; Cella, Matteo; Dymond, Simon

    2017-03-15

    Complex human cognition, such as decision-making under ambiguity, is reflected in dynamic spatio-temporal activity in the brain. Here, we combined event-related potentials with computational modelling of the time course of decision-making and outcome evaluation during the Iowa Gambling Task. Measures of choice probability generated using the Prospect Valence Learning Delta (PVL-Delta) model, in addition to objective trial outcomes (outcome magnitude and valence), were applied as regressors in a general linear model of the EEG signal. The resulting three-dimensional spatio-temporal characterization of task-related neural dynamics demonstrated that outcome valence, outcome magnitude, and PVL-Delta choice probability were expressed in distinctly separate event related potentials. Our findings showed that the P3 component was associated with an experience-based measure of outcome expectancy.

  3. Spatiotemporal patterns of evapotranspiration along the North American east coast as influenced by multiple environmental changes

    DOE PAGES

    Yang, Qichun; Tian, Hanqin; Li, Xia; ...

    2014-08-08

    The North American east coast has experienced significant land-use and climate changes since the beginning of the 20th century. In this study, using the Dynamic Land Ecosystem Model 2.0 driven by time-series input data of land use, climate and atmospheric CO2, we examined how these driving forces have affected the spatiotemporal trends and variability of evapotranspiration (ET) in this region during 1901–2008. Annual ET in the North American east coast during this period was 648.3 ± 38.6 mm/year and demonstrated an increasing trend. Factorial model simulations indicated that climate variability explained 76% of the inter-annual ET variability. Although land-use changemore » only explained 16% of the ET temporal variability, afforestation induced the upward trend of ET and increased annual ET by 12.8 mm/year. Elevated atmospheric CO2 reduced annual ET by 0.84 mm, and its potential impacts under future atmospheric CO2 levels could be much larger than estimates for the historical 1901–2008 period. Climate change determined the spatial pattern of ET changes across the entire study area, whereas land-use changes dramatically affected ET in watersheds with significant land conversions. In spite of the multiple benefits from afforestation, its impacts on water resources should be considered in future land-use policy making. As a result, elevated ET may also affect fresh water availability for the increasing social and economic water demands.« less

  4. Spatiotemporal patterns of evapotranspiration along the North American east coast as influenced by multiple environmental changes

    SciTech Connect

    Yang, Qichun; Tian, Hanqin; Li, Xia; Tao, Bo; Ren, Wei; Chen, Guangsheng; Lu, Chaoqun; Yang, Jia; Pan, Shufen; Banger, Kamaljit; Zhang, Bowen

    2014-08-08

    The North American east coast has experienced significant land-use and climate changes since the beginning of the 20th century. In this study, using the Dynamic Land Ecosystem Model 2.0 driven by time-series input data of land use, climate and atmospheric CO2, we examined how these driving forces have affected the spatiotemporal trends and variability of evapotranspiration (ET) in this region during 1901–2008. Annual ET in the North American east coast during this period was 648.3 ± 38.6 mm/year and demonstrated an increasing trend. Factorial model simulations indicated that climate variability explained 76% of the inter-annual ET variability. Although land-use change only explained 16% of the ET temporal variability, afforestation induced the upward trend of ET and increased annual ET by 12.8 mm/year. Elevated atmospheric CO2 reduced annual ET by 0.84 mm, and its potential impacts under future atmospheric CO2 levels could be much larger than estimates for the historical 1901–2008 period. Climate change determined the spatial pattern of ET changes across the entire study area, whereas land-use changes dramatically affected ET in watersheds with significant land conversions. In spite of the multiple benefits from afforestation, its impacts on water resources should be considered in future land-use policy making. As a result, elevated ET may also affect fresh water availability for the increasing social and economic water demands.

  5. Spatiotemporal variations of Venus middle atmosphere revealed by Subaru/COMICS

    NASA Astrophysics Data System (ADS)

    Sato, T. M.; Sagawa, H.; Kouyama, T.; Imamura, T.; Satoh, T.

    2013-09-01

    We report the spatiotemporal variations of brightness temperatures of Venus at cloud top altitudes (~70 km) obtained by the Cooled Mid-Infrared Camera and Spectrometer (COMICS), mounted on the 8.2-m Subaru Telescope. The two important findings are (1) the brightness temperatures at north polar regions were synchronized with those at south polar regions at least in the three observation nights and (2) there were some streaky patterns as were seen in UV and these patterns varied from day to day.

  6. Spatiotemporal variations of phytoplankton in the East China Sea and the Yellow Sea revealed by lipid biomarkers

    NASA Astrophysics Data System (ADS)

    Wu, Peng; Bi, Rong; Duan, Shanshan; Jin, Haiyan; Chen, Jianfang; Hao, Qiang; Cai, Yuming; Mao, Xinyan; Zhao, Meixun

    2016-01-01

    The East China Sea (ECS) and the Southern Yellow Sea (SYS) ecosystem is undergoing dramatic changes, but the spatiotemporal patterns and forcing mechanisms of phytoplankton variations remain understudied. Phytoplankton lipid biomarkers are useful proxies for productivity and community structure changes, and they were measured in suspended particles of more than 81 sites from spring and summer of 2011 in the ECS and SYS. In spring, the concentrations of brassicasterol (4.7-127 ng L-1) and dinosterol (0.7-37 ng L-1) were markedly higher in the northern and central SYS, while C37 alkenones (0-15 ng L-1) were detected at only seven sites in the ECS. In summer, brassicasterol (25.3-1178 ng L-1) and dinosterol (0-125 ng L-1) showed high values off the Changjiang River Estuary (CRE), while C37 alkenones (0-410 ng L-1) had high values in the northwest and central SYS. The mean concentrations of the three lipid biomarkers in summer were 3 to 61 times higher than those in spring. Spatiotemporal patterns of biomarkers reveal higher ratios of diatom/dinoflagellate and diatom/haptophyte in higher productivity areas, off the CRE in summer and the northern and central SYS in spring. This study validates the applicability of brassicasterol, dinosterol, and alkenones as proxies of productivity and community structure of the three phytoplankton taxa: diatoms, dinoflagellates, and haptophytes. The results indicate that nutrients (in summer) and turbidity-induced photosynthetic available radiation (in spring) play important roles in regulating spatiotemporal variations of phytoplankton in the ECS and SYS.

  7. High-resolution spatiotemporal strain mapping reveals non-uniform deformation in micropatterned elastomers

    NASA Astrophysics Data System (ADS)

    Aksoy, B.; Rehman, A.; Bayraktar, H.; Alaca, B. E.

    2017-04-01

    Micropatterns are generated on a vast selection of polymeric substrates for various applications ranging from stretchable electronics to cellular mechanobiological systems. When these patterned substrates are exposed to external loading, strain field is primarily affected by the presence of microfabricated structures and similarly by fabrication-related defects. The capturing of such nonhomogeneous strain fields is of utmost importance in cases where study of the mechanical behavior with a high spatial resolution is necessary. Image-based non-contact strain measurement techniques are favorable and have recently been extended to scanning tunneling microscope and scanning electron microscope images for the characterization of mechanical properties of metallic materials, e.g. steel and aluminum, at the microscale. A similar real-time analysis of strain heterogeneity in elastomers is yet to be achieved during the entire loading sequence. The available measurement methods for polymeric materials mostly depend on cross-head displacement or precalibrated strain values. Thus, they suffer either from the lack of any real-time analysis, spatiotemporal distribution or high resolution in addition to a combination of these factors. In this work, these challenges are addressed by integrating a tensile stretcher with an inverted optical microscope and developing a subpixel particle tracking algorithm. As a proof of concept, the patterns with a critical dimension of 200 µm are generated on polydimethylsiloxane substrates and strain distribution in the vicinity of the patterns is captured with a high spatiotemporal resolution. In the field of strain measurement, there is always a tradeoff between minimum measurable strain value and spatial resolution. Current noncontact techniques on elastomers can deliver a strain resolution of 0.001% over a minimum length of 5 cm. More importantly, inhomogeneities within this quite large region cannot be captured. The proposed technique can

  8. iRaster: a novel information visualization tool to explore spatiotemporal patterns in multiple spike trains.

    PubMed

    Somerville, J; Stuart, L; Sernagor, E; Borisyuk, R

    2010-12-15

    Over the last few years, simultaneous recordings of multiple spike trains have become widely used by neuroscientists. Therefore, it is important to develop new tools for analysing multiple spike trains in order to gain new insight into the function of neural systems. This paper describes how techniques from the field of visual analytics can be used to reveal specific patterns of neural activity. An interactive raster plot called iRaster has been developed. This software incorporates a selection of statistical procedures for visualization and flexible manipulations with multiple spike trains. For example, there are several procedures for the re-ordering of spike trains which can be used to unmask activity propagation, spiking synchronization, and many other important features of multiple spike train activity. Additionally, iRaster includes a rate representation of neural activity, a combined representation of rate and spikes, spike train removal and time interval removal. Furthermore, it provides multiple coordinated views, time and spike train zooming windows, a fisheye lens distortion, and dissemination facilities. iRaster is a user friendly, interactive, flexible tool which supports a broad range of visual representations. This tool has been successfully used to analyse both synthetic and experimentally recorded datasets. In this paper, the main features of iRaster are described and its performance and effectiveness are demonstrated using various types of data including experimental multi-electrode array recordings from the ganglion cell layer in mouse retina. iRaster is part of an ongoing research project called VISA (Visualization of Inter-Spike Associations) at the Visualization Lab in the University of Plymouth. The overall aim of the VISA project is to provide neuroscientists with the ability to freely explore and analyse their data. The software is freely available from the Visualization Lab website (see www.plymouth.ac.uk/infovis).

  9. Stable isotope analysis of precipitation samples obtained via crowdsourcing reveals the spatiotemporal evolution of Superstorm Sandy.

    PubMed

    Good, Stephen P; Mallia, Derek V; Lin, John C; Bowen, Gabriel J

    2014-01-01

    Extra-tropical cyclones, such as 2012 Superstorm Sandy, pose a significant climatic threat to the northeastern United Sates, yet prediction of hydrologic and thermodynamic processes within such systems is complicated by their interaction with mid-latitude water patterns as they move poleward. Fortunately, the evolution of these systems is also recorded in the stable isotope ratios of storm-associated precipitation and water vapor, and isotopic analysis provides constraints on difficult-to-observe cyclone dynamics. During Superstorm Sandy, a unique crowdsourced approach enabled 685 precipitation samples to be obtained for oxygen and hydrogen isotopic analysis, constituting the largest isotopic sampling of a synoptic-scale system to date. Isotopically, these waters span an enormous range of values (> 21‰ for δ(18)O, > 160‰ for δ(2)H) and exhibit strong spatiotemporal structure. Low isotope ratios occurred predominantly in the west and south quadrants of the storm, indicating robust isotopic distillation that tracked the intensity of the storm's warm core. Elevated values of deuterium-excess (> 25‰) were found primarily in the New England region after Sandy made landfall. Isotope mass balance calculations and Lagrangian back-trajectory analysis suggest that these samples reflect the moistening of dry continental air entrained from a mid-latitude trough. These results demonstrate the power of rapid-response isotope monitoring to elucidate the structure and dynamics of water cycling within synoptic-scale systems and improve our understanding of storm evolution, hydroclimatological impacts, and paleo-storm proxies.

  10. Spatiotemporal variation in avian migration phenology: citizen science reveals effects of climate change.

    PubMed

    Hurlbert, Allen H; Liang, Zhongfei

    2012-01-01

    A growing number of studies have documented shifts in avian migratory phenology in response to climate change, and yet there is a large amount of unexplained variation in the magnitude of those responses across species and geographic regions. We use a database of citizen science bird observations to explore spatiotemporal variation in mean arrival dates across an unprecedented geographic extent for 18 common species in North America over the past decade, relating arrival dates to mean minimum spring temperature. Across all species and geographic locations, species shifted arrival dates 0.8 days earlier for every °C of warming of spring temperature, but it was common for some species in some locations to shift as much as 3-6 days earlier per °C. Species that advanced arrival dates the earliest in response to warming were those that migrate more slowly, short distance migrants, and species with broader climatic niches. These three variables explained 63% of the interspecific variation in phenological response. We also identify a latitudinal gradient in the average strength of phenological response, with species shifting arrival earlier at southern latitudes than northern latitudes for the same degree of warming. This observation is consistent with the idea that species must be more phenologically sensitive in less seasonal environments to maintain the same degree of precision in phenological timing.

  11. Attentional Signatures of Perception: Multiple Object Tracking Reveals the Automaticity of Contour Interpolation

    ERIC Educational Resources Information Center

    Keane, Brian P.; Mettler, Everett; Tsoi, Vicky; Kellman, Philip J.

    2011-01-01

    Multiple object tracking (MOT) is an attentional task wherein observers attempt to track multiple targets among moving distractors. Contour interpolation is a perceptual process that fills-in nonvisible edges on the basis of how surrounding edges (inducers) are spatiotemporally related. In five experiments, we explored the automaticity of…

  12. Tectonic environments of South American porphyry copper magmatism through time revealed by spatiotemporal data mining

    NASA Astrophysics Data System (ADS)

    Butterworth, N.; Steinberg, D.; Müller, R. D.; Williams, S.; Merdith, A. S.; Hardy, S.

    2016-12-01

    Porphyry ore deposits are known to be associated with arc magmatism on the overriding plate at subduction zones. While general mechanisms for driving magmatism are well established, specific subduction-related parameters linking episodes of ore deposit formation to specific tectonic environments have only been qualitatively inferred and have not been formally tested. We develop a four-dimensional approach to reconstruct age-dated ore deposits, with the aim of isolating the tectonomagmatic parameters leading to the formation of copper deposits during subduction. We use a plate tectonic model with continuously closing plate boundaries, combined with reconstructions of the spatiotemporal distribution of the ocean floor, including subducted portions of the Nazca/Farallon plates. The models compute convergence rates and directions, as well as the age of the downgoing plate through time. To identify and quantify tectonic parameters that are robust predictors of Andean porphyry copper magmatism and ore deposit formation, we test two alternative supervised machine learning methods; the "random forest" (RF) ensemble and "support vector machines" (SVM). We find that a combination of rapid convergence rates ( 100 km/Myr), subduction obliquity of 15°, a subducting plate age between 25-70 Myr old, and a location far from the subducting trench boundary (>2000 km) represents favorable conditions for porphyry magmatism and related ore deposits to occur. These parameters are linked to the availability of oceanic sediments, the changing small-scale convection around the subduction zone, and the availability of the partial melt in the mantle wedge. When coupled, these parameters could influence the genesis and exhumation of porphyry copper deposits.

  13. Spatio-Temporal Cellular Dynamics of the Arabidopsis Flagellin Receptor Reveal Activation Status-Dependent Endosomal Sorting[C][W

    PubMed Central

    Beck, Martina; Zhou, Ji; Faulkner, Christine; MacLean, Daniel; Robatzek, Silke

    2012-01-01

    The activity of surface receptors is location specific, dependent upon the dynamic membrane trafficking network and receptor-mediated endocytosis (RME). Therefore, the spatio-temporal dynamics of RME are critical to receptor function. The plasma membrane receptor FLAGELLIN SENSING2 (FLS2) confers immunity against bacterial infection through perception of flagellin (flg22). Following elicitation, FLS2 is internalized into vesicles. To resolve FLS2 trafficking, we exploited quantitative confocal imaging for colocalization studies and chemical interference. FLS2 localizes to bona fide endosomes via two distinct endocytic trafficking routes depending on its activation status. FLS2 receptors constitutively recycle in a Brefeldin A (BFA)–sensitive manner, while flg22-activated receptors traffic via ARA7/Rab F2b– and ARA6/Rab F1–positive endosomes insensitive to BFA. FLS2 endocytosis required a functional Rab5 GTPase pathway as revealed by dominant-negative ARA7/Rab F2b. Flg22-induced FLS2 endosomal numbers were increased by Concanamycin A treatment but reduced by Wortmannin, indicating that activated FLS2 receptors are targeted to late endosomes. RME inhibitors Tyrphostin A23 and Endosidin 1 altered but did not block induced FLS2 endocytosis. Additional inhibitor studies imply the involvement of the actin-myosin system in FLS2 internalization and trafficking. Altogether, we report a dynamic pattern of subcellular trafficking for FLS2 and reveal a defined framework for ligand-dependent endocytosis of this receptor. PMID:23085733

  14. Diet of a piscivorous seabird reveals spatiotemporal variation in abundance of forage fishes in the Monterey Bay region

    NASA Astrophysics Data System (ADS)

    Webb, Lisa A.; Harvey, James T.

    2015-06-01

    Brandt's Cormorant (Phalacrocorax penicillatus) diet was investigated using regurgitated pellets (n = 285) collected on 19 sampling days at three locations during the 2006-07 and 2007-08 nonbreeding seasons in the Monterey Bay region. The efficacy of using nested sieves and the all-structure technique to facilitate prey detection in the pellets was evaluated, but this method did not increase prey enumeration and greatly decreased efficiency. Although 29 prey species were consumed, northern anchovy (Engraulis mordax) dominated and speckled sanddab (Citharichthys stigmaeus) also was important in the diet. Few rockfishes (Sebastes spp.) and market squid (Doryteuthis opalescens) were consumed compared with great prevalence in previous studies during the 1970s. El Niño and La Niña during the study provided a unique opportunity to examine predator response to variation in prey availability. Patterns of prey number and diversity were not consistent among locations. Greatest number and diversity of prey occurred at locations within Monterey Bay during La Niña, results not evident at the outer coast location. Short-term specialization occurred but mean prey diversity indicated a generalist feeding mode. This study demonstrated the importance of periodic sampling at multiple locations within a region to detect spatiotemporal variability in the diet of opportunistic generalists.

  15. Long-Term Spatiotemporal Reconfiguration of Neuronal Activity Revealed by Voltage-Sensitive Dye Imaging in the Cerebellar Granular Layer

    PubMed Central

    Gandolfi, Daniela; Mapelli, Jonathan; D'Angelo, Egidio

    2015-01-01

    Understanding the spatiotemporal organization of long-term synaptic plasticity in neuronal networks demands techniques capable of monitoring changes in synaptic responsiveness over extended multineuronal structures. Among these techniques, voltage-sensitive dye imaging (VSD imaging) is of particular interest due to its good spatial resolution. However, improvements of the technique are needed in order to overcome limits imposed by its low signal-to-noise ratio. Here, we show that VSD imaging can detect long-term potentiation (LTP) and long-term depression (LTD) in acute cerebellar slices. Combined VSD imaging and patch-clamp recordings revealed that the most excited regions were predominantly associated with granule cells (GrCs) generating EPSP-spike complexes, while poorly responding regions were associated with GrCs generating EPSPs only. The correspondence with cellular changes occurring during LTP and LTD was highlighted by a vector representation obtained by combining amplitude with time-to-peak of VSD signals. This showed that LTP occurred in the most excited regions lying in the core of activated areas and increased the number of EPSP-spike complexes, while LTD occurred in the less excited regions lying in the surround. VSD imaging appears to be an efficient tool for investigating how synaptic plasticity contributes to the reorganization of multineuronal activity in neuronal circuits. PMID:26294979

  16. Spatio-Temporal Analysis of Micro Economic Activities in Rome Reveals Patterns of Mixed-Use Urban Evolution.

    PubMed

    Fiasconaro, Alessandro; Strano, Emanuele; Nicosia, Vincenzo; Porta, Sergio; Latora, Vito

    2016-01-01

    Understanding urban growth is one with understanding how society evolves to satisfy the needs of its individuals in sharing a common space and adapting to the territory. We propose here a quantitative analysis of the historical development of a large urban area by investigating the spatial distribution and the age of commercial activities in the whole city of Rome. We find that the age of activities of various categories presents a very interesting double exponential trend, with a transition possibly related to the long-term economical effects determined by the oil crisis of the Seventies. The diversification of commercial categories, studied through various measures of entropy, shows, among other interesting features, a saturating behaviour with the density of activities. Moreover, different couples of commercial categories exhibit over the years a tendency to attract in space. Our results demonstrate that the spatio-temporal distribution of commercial activities can provide important insights on the urbanisation processes at work, revealing specific and non trivial socio-economical dynamics, as the presence of crisis periods and expansion trends, and contributing to the characterisation of the maturity of urban areas.

  17. Spatio-Temporal Analysis of Micro Economic Activities in Rome Reveals Patterns of Mixed-Use Urban Evolution

    PubMed Central

    Fiasconaro, Alessandro; Strano, Emanuele; Nicosia, Vincenzo; Porta, Sergio; Latora, Vito

    2016-01-01

    Understanding urban growth is one with understanding how society evolves to satisfy the needs of its individuals in sharing a common space and adapting to the territory. We propose here a quantitative analysis of the historical development of a large urban area by investigating the spatial distribution and the age of commercial activities in the whole city of Rome. We find that the age of activities of various categories presents a very interesting double exponential trend, with a transition possibly related to the long-term economical effects determined by the oil crisis of the Seventies. The diversification of commercial categories, studied through various measures of entropy, shows, among other interesting features, a saturating behaviour with the density of activities. Moreover, different couples of commercial categories exhibit over the years a tendency to attract in space. Our results demonstrate that the spatio-temporal distribution of commercial activities can provide important insights on the urbanisation processes at work, revealing specific and non trivial socio-economical dynamics, as the presence of crisis periods and expansion trends, and contributing to the characterisation of the maturity of urban areas. PMID:26982028

  18. Wavelet-based regularity analysis reveals Recurrent Spatiotemporal Behavior in Resting-state fMRI

    PubMed Central

    Smith, Robert X.; Jann, Kay; Ances, Beau; Wang, Danny J.J.

    2015-01-01

    One of the major findings from multi-modal neuroimaging studies in the past decade is that the human brain is anatomically and functionally organized into large-scale networks. In resting state fMRI (rs-fMRI), spatial patterns emerge when temporal correlations between various brain regions are tallied, evidencing networks of ongoing intercortical cooperation. However, the dynamic structure governing the brain’s spontaneous activity is far less understood due to the short and noisy nature of the rs-fMRI signal. Here we develop a wavelet-based regularity analysis based on noise estimation capabilities of the wavelet transform to measure recurrent temporal pattern stability within the rs-fMRI signal across multiple temporal scales. The method consists of performing a stationary wavelet transform (SWT) to preserve signal structure, followed by construction of “lagged” subsequences to adjust for correlated features, and finally the calculation of sample entropy across wavelet scales based on an “objective” estimate of noise level at each scale. We found that the brain’s default mode network (DMN) areas manifest a higher level of irregularity in rs-fMRI time series than rest of the brain. In 25 aged subjects with mild cognitive impairment and 25 matched healthy controls, wavelet based regularity analysis showed improved sensitivity in detecting changes in the regularity of rs-fMRI signals between the two groups within the DMN and executive control networks, compared to standard multiscale entropy analysis. Wavelet based regularity analysis based on noise estimation capabilities of the wavelet transform is a promising technique to characterize the dynamic structure of rs-fMRI as well as other biological signals. PMID:26096080

  19. Elicitation interval dependent spatiotemporal evolution of cortical spreading depression waves revealed by optical intrinsic signal imaging

    NASA Astrophysics Data System (ADS)

    Chen, Shangbin; Gong, Hui; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2007-02-01

    This study aimed to investigate the variation of propagation patterns of successive cortical spreading depression (CSD) waves induced by K + or pinprick in rat cortex. In the K + induction group, 18 Sprague-Dawley rats under Î+/--chloralose/urethane anesthesia were used to elicit CSD by 1 M KCl solution in the frontal cortex. Optical intrinsic signal imaging (OISI) at an isosbestic point of hemoglobin (550 nm) was applied to examine regional cerebral blood volume (CBV) changes in the parieto-occipital cortex. In 6 of the 18 rats, OISI was performed in conjunction with DC potential recording of the cortex. The results of this group were reported previously. In the pinprick group, 6 rats were used to induce CSD by pinprick with 8 min interval, and the other 6 rats were pricked with 4 min. CBV changes during CSD appeared as repetitive propagation of wave-like hyperemia at a speed of 3.7+/-0.4 mm/min, which was characterized by a significant negative peak (-14.3+/-3.2%) in the reflectance signal. Except for the first CSD wave, the following waves don't spread fully in the observed cortex all the time and they might abort in the medial area. Independent on the stimulation of pinprick or K+, a short interval of the current CSD to the last CSD no more than 4 min would induce the current CSD be partially propagated. For the first time, the data reveals the time-varying propagation patterns of CSD waves might be affected by the interval between CSD waves. The results suggest that the propagation patterns of a series of CSD waves are time-varying in different regions of rat cortex, and the variation is related to the interval between CSD waves.

  20. Spontaneous switching among multiple spatio-temporal patterns in three-oscillator systems constructed with oscillatory cells of true slime mold

    NASA Astrophysics Data System (ADS)

    Takamatsu, Atsuko

    2006-11-01

    Three-oscillator systems with plasmodia of true slime mold, Physarum polycephalum, which is an oscillatory amoeba-like unicellular organism, were experimentally constructed and their spatio-temporal patterns were investigated. Three typical spatio-temporal patterns were found: rotation ( R), partial in-phase ( PI), and partial anti-phase with double frequency ( PA). In pattern R, phase differences between adjacent oscillators were almost 120 ∘. In pattern PI, two oscillators were in-phase and the third oscillator showed anti-phase against the two oscillators. In pattern PA, two oscillators showed anti-phase and the third oscillator showed frequency doubling oscillation with small amplitude. Actually each pattern is not perfectly stable but quasi-stable. Interestingly, the system shows spontaneous switching among the multiple quasi-stable patterns. Statistical analyses revealed a characteristic in the residence time of each pattern: the histograms seem to have Gamma-like distribution form but with a sharp peak and a tail on the side of long period. That suggests the attractor of this system has complex structure composed of at least three types of sub-attractors: a “Gamma attractor”-involved with several Poisson processes, a “deterministic attractor”-the residence time is deterministic, and a “stable attractor”-each pattern is stable. When the coupling strength was small, only the Gamma attractor was observed and switching behavior among patterns R, PI, and PA almost always via an asynchronous pattern named O. A conjecture is as follows: Internal/external noise exposes each pattern of R, PI, and PA coexisting around bifurcation points: That is observed as the Gamma attractor. As coupling strength increases, the deterministic attractor appears then followed by the stable attractor, always accompanied with the Gamma attractor. Switching behavior could be caused by regular existence of the Gamma attractor.

  1. Spatiotemporal regulation of multiple overlapping sense and novel natural antisense transcripts at the Nrgn and Camk2n1 gene loci during mouse cerebral corticogenesis.

    PubMed

    Ling, King-Hwa; Hewitt, Chelsee A; Beissbarth, Tim; Hyde, Lavinia; Cheah, Pike-See; Smyth, Gordon K; Tan, Seong-Seng; Hahn, Christopher N; Thomas, Tim; Thomas, Paul Q; Scott, Hamish S

    2011-03-01

    Nrgn and Camk2n1 are highly expressed in the brain and play an important role in synaptic long-term potentiation via regulation of Ca(2+)/calmodulin-dependent protein kinase II. We have shown that the gene loci for these 2 proteins are actively transcribed in the adult cerebral cortex and feature multiple overlapping transcripts in both the sense and antisense orientations with alternative polyadenylation. These transcripts were upregulated in the adult compared with embryonic and P1.5 mouse cerebral cortices, and transcripts with different 3' untranslated region lengths showed differing expression profiles. In situ hybridization (ISH) analysis revealed spatiotemporal regulation of the Nrgn and Camk2n1 sense and natural antisense transcripts (NATs) throughout cerebral corticogenesis. In addition, we also demonstrated that the expression of these transcripts was organ-specific. Both Nrgn and Camk2n1 sense and NATs were also upregulated in differentiating P19 teratocarcinoma cells. RNA fluorescent ISH analysis confirmed the capability of these NATs to form double-stranded RNA aggregates with the sense transcripts in the cytoplasm of cells obtained from the brain. We propose that the differential regulation of multiple sense and novel overlapping NATs at the Nrgn and Camk2n1 loci will increase the diversity of posttranscriptional regulation, resulting in cell- and time-specific regulation of their gene products during cerebral corticogenesis and function.

  2. Mitogenome revealed multiple postdomestication genetic mixtures of West African sheep.

    PubMed

    Brahi, O H D; Xiang, H; Chen, X; Farougou, S; Zhao, X

    2015-10-01

    Notable diversity observed within African ovine breeds makes them of great interests, but limited studies on genetic origins and domestications remain poorly understood. Here, we investigate the evolutionary status of West African native breeds, Djallonke and Sahelian sheep using mitogenome sequencing. Compared with other ovine mitogenome sequences, West African sheep were revealed a Eurasian origin, and the initially tamed sheep breeds in West Africa have been genetically mixed with each other and mixed with European breeds. Worldwide domestic sheep is deemed the Eurasian origin and migrated west to Europe and Africa and east to the Far East, in which dispersed and received selection for acclimation to autochthonic environment independently and ultimately evolved into different native breeds, respectively. Our results contribute to the comprehensive understanding of the domestic sheep origin and reveal multiple postdomestication genetic amelioration processes.

  3. The influence of weather and lemmings on spatiotemporal variation in the abundance of multiple avian guilds in the arctic.

    PubMed

    Robinson, Barry G; Franke, Alastair; Derocher, Andrew E

    2014-01-01

    Climate change is occurring more rapidly in the Arctic than other places in the world, which is likely to alter the distribution and abundance of migratory birds breeding there. A warming climate can provide benefits to birds by decreasing spring snow cover, but increases in the frequency of summer rainstorms, another product of climate change, may reduce foraging opportunities for insectivorous birds. Cyclic lemming populations in the Arctic also influence bird abundance because Arctic foxes begin consuming bird eggs when lemmings decline. The complex interaction between summer temperature, precipitation, and the lemming cycle hinder our ability to predict how Arctic-breeding birds will respond to climate change. The main objective of this study was to investigate the relationship between annual variation in weather, spring snow cover, lemming abundance and spatiotemporal variation in the abundance of multiple avian guilds in a tundra ecosystem in central Nunavut, Canada: songbirds, shorebirds, gulls, loons, and geese. We spatially stratified our study area based on vegetation productivity, terrain ruggedness, and freshwater abundance, and conducted distance sampling to estimate strata-specific densities of each guild during the summers of 2010-2012. We also monitored temperature, rainfall, spring snow cover, and lemming abundance each year. Spatial variation in bird abundance matched what was expected based on previous ecological knowledge, but weather and lemming abundance also significantly influenced the abundance of some guilds. In particular, songbirds were less abundant during the cool, wet summer with moderate snow cover, and shorebirds and gulls declined with lemming abundance. The abundance of geese did not vary over time, possibly because benefits created by moderate spring snow cover were offset by increased fox predation when lemmings were scarce. Our study provides an example of a simple way to monitor the correlation between weather, spring snow

  4. Multiple-Parameter Estimation Method Based on Spatio-Temporal 2-D Processing for Bistatic MIMO Radar.

    PubMed

    Yang, Shouguo; Li, Yong; Zhang, Kunhui; Tang, Weiping

    2015-12-14

    A novel spatio-temporal 2-dimensional (2-D) processing method that can jointly estimate the transmitting-receiving azimuth and Doppler frequency for bistatic multiple-input multiple-output (MIMO) radar in the presence of spatial colored noise and an unknown number of targets is proposed. In the temporal domain, the cross-correlation of the matched filters' outputs for different time-delay sampling is used to eliminate the spatial colored noise. In the spatial domain, the proposed method uses a diagonal loading method and subspace theory to estimate the direction of departure (DOD) and direction of arrival (DOA), and the Doppler frequency can then be accurately estimated through the estimation of the DOD and DOA. By skipping target number estimation and the eigenvalue decomposition (EVD) of the data covariance matrix estimation and only requiring a one-dimensional search, the proposed method achieves low computational complexity. Furthermore, the proposed method is suitable for bistatic MIMO radar with an arbitrary transmitted and received geometrical configuration. The correction and efficiency of the proposed method are verified by computer simulation results.

  5. Multiple-Parameter Estimation Method Based on Spatio-Temporal 2-D Processing for Bistatic MIMO Radar

    PubMed Central

    Yang, Shouguo; Li, Yong; Zhang, Kunhui; Tang, Weiping

    2015-01-01

    A novel spatio-temporal 2-dimensional (2-D) processing method that can jointly estimate the transmitting-receiving azimuth and Doppler frequency for bistatic multiple-input multiple-output (MIMO) radar in the presence of spatial colored noise and an unknown number of targets is proposed. In the temporal domain, the cross-correlation of the matched filters’ outputs for different time-delay sampling is used to eliminate the spatial colored noise. In the spatial domain, the proposed method uses a diagonal loading method and subspace theory to estimate the direction of departure (DOD) and direction of arrival (DOA), and the Doppler frequency can then be accurately estimated through the estimation of the DOD and DOA. By skipping target number estimation and the eigenvalue decomposition (EVD) of the data covariance matrix estimation and only requiring a one-dimensional search, the proposed method achieves low computational complexity. Furthermore, the proposed method is suitable for bistatic MIMO radar with an arbitrary transmitted and received geometrical configuration. The correction and efficiency of the proposed method are verified by computer simulation results. PMID:26694385

  6. Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient.

    PubMed

    Weavers, Helen; Liepe, Juliane; Sim, Aaron; Wood, Will; Martin, Paul; Stumpf, Michael P H

    2016-08-08

    In the acute inflammatory phase following tissue damage, cells of the innate immune system are rapidly recruited to sites of injury by pro-inflammatory mediators released at the wound site. Although advances in live imaging allow us to directly visualize this process in vivo, the precise identity and properties of the primary immune damage attractants remain unclear, as it is currently impossible to directly observe and accurately measure these signals in tissues. Here, we demonstrate that detailed information about the attractant signals can be extracted directly from the in vivo behavior of the responding immune cells. By applying inference-based computational approaches to analyze the in vivo dynamics of the Drosophila inflammatory response, we gain new detailed insight into the spatiotemporal properties of the attractant gradient. In particular, we show that the wound attractant is released by wound margin cells, rather than by the wounded tissue per se, and that it diffuses away from this source at rates far slower than those of previously implicated signals such as H2O2 and ATP, ruling out these fast mediators as the primary chemoattractant. We then predict, and experimentally test, how competing attractant signals might interact in space and time to regulate multi-step cell navigation in the complex environment of a healing wound, revealing a period of receptor desensitization after initial exposure to the damage attractant. Extending our analysis to model much larger wounds, we uncover a dynamic behavioral change in the responding immune cells in vivo that is prognostic of whether a wound will subsequently heal or not. VIDEO ABSTRACT.

  7. Multiple spatio-temporal scale modeling of composites subjected to cyclic loading

    NASA Astrophysics Data System (ADS)

    Crouch, Robert; Oskay, Caglar; Clay, Stephen

    2013-01-01

    This manuscript presents a multiscale modeling methodology for failure analysis of composites subjected to cyclic loading conditions. Computational homogenization theory with multiple spatial and temporal scales is employed to devise the proposed methodology. Multiple spatial scales address the disparity between the length scale of material heterogeneities and the overall structure, whereas multiple temporal scales with almost periodic fields address the disparity between the load period and overall life under cyclic loading. The computational complexity of the multiscale modeling approach is reduced by employing a meso-mechanical model based on eigendeformation based homogenization with symmetric coefficients in the space domain, and an adaptive time stepping strategy based on a quadratic multistep method with error control in the time domain. The proposed methodology is employed to simulate the response of graphite fiber-reinforced epoxy composites. Model parameters are calibrated using a suite of experiments conducted on unidirectionally reinforced specimens subjected to monotonic and cyclic loading. The calibrated model is employed to predict damage progression in quasi-isotropic specimens. The capabilities of the model are validated using acoustic emission testing.

  8. Spatiotemporal synchronization of biped walking patterns with multiple external inputs by style-phase adaptation.

    PubMed

    Matsubara, Takamitsu; Uchikata, Akimasa; Morimoto, Jun

    2015-12-01

    In this paper, we propose a framework for generating coordinated periodic movements of robotic systems with multiple external inputs. We developed an adaptive pattern generator model that is composed of a two-factor observation model with a style parameter and phase dynamics with a phase variable. The style parameter controls the spatial patterns of the generated trajectories, and the phase variable manages its temporal profiles. By exploiting the style-phase separation in the pattern generation, we can independently design adaptation schemes for the spatial and temporal profiles of the pattern generator to multiple external inputs. To validate the effectiveness of our proposed method, we applied it to a user-exoskeleton model to achieve user-adaptive walking assistance for which the exoskeleton robot's movements need to be coordinated with the user walking patterns and environment. As a result, the exoskeleton robot successfully performed stable biped walking behaviors for walking assistance even when the style of the observed walking pattern and the period were suddenly changed.

  9. Dynamic multiple-target tracing to probe spatiotemporal cartography of cell membranes.

    PubMed

    Sergé, Arnauld; Bertaux, Nicolas; Rigneault, Hervé; Marguet, Didier

    2008-08-01

    Although the highly dynamic and mosaic organization of the plasma membrane is well-recognized, depicting a resolved, global view of this organization remains challenging. We present an analytical single-particle tracking (SPT) method and tool, multiple-target tracing (MTT), that takes advantage of the high spatial resolution provided by single-fluorophore sensitivity. MTT can be used to generate dynamic maps at high densities of tracked particles, thereby providing global representation of molecular dynamics in cell membranes. Deflation by subtracting detected peaks allows detection of lower-intensity peaks. We exhaustively detected particles using MTT, with performance reaching theoretical limits, and then reconnected trajectories integrating the statistical information from past trajectories. We demonstrate the potential of this method by applying it to the epidermal growth factor receptor (EGFR) labeled with quantum dots (Qdots), in the plasma membrane of live cells. We anticipate the use of MTT to explore molecular dynamics and interactions at the cell membrane.

  10. Connexin43 null mice reveal that astrocytes express multiple connexins.

    PubMed

    Dermietzel, R; Gao, Y; Scemes, E; Vieira, D; Urban, M; Kremer, M; Bennett, M V; Spray, D C

    2000-04-01

    The gap junction protein connexin43 (Cx43) is the primary component of intercellular channels in cardiac tissue and in astrocytes, the most abundant type of glial cells in the brain. Mice in which the gene for Cx43 is deleted by homologous recombination die at birth, due to profound hypertrophy of the ventricular outflow tract and stenosis of the pulmonary artery. Despite this significant cardiovascular abnormality, brains of connexin43 null [Cx43 (-/-)] animals are shown to be macroscopically normal and to display a pattern of cortical lamination that is not detectably different from wildtype siblings. Presence of Cx40 and Cx45 in brains and astrocytes cultured from both Cx43 (-/-) mice and wildtype littermates was confirmed by RT-PCR, Northern blot analyses and by immunostaining; Cx46 was detected by RT-PCR and Northern blot analyses. Presence of Cx26 in astrocyte cultures was indicated by RT-PCR and by Western blot analysis, although we were unable to resolve whether it was contributed by contaminating cells; Cx30 mRNA was detected by Northern blot in long term (2 weeks) but not fresh cultures of astrocytes. These studies thus reveal that astrocyte gap junctions may be formed of multiple connexins. Presumably, the metabolic and ionic coupling provided by these diverse gap junction types may functionally compensate for the absence of the major astrocyte gap junction protein in Cx43 (-/-) mice, providing whatever intercellular signaling is necessary for brain development and cortical lamination.

  11. Spatiotemporal registration of multiple three-dimensional echocardiographic recordings for enhanced field of view imaging.

    PubMed

    Danudibroto, Adriyana; Bersvendsen, Jørn; Gérard, Olivier; Mirea, Oana; D'hooge, Jan; Samset, Eigil

    2016-07-01

    The use of three-dimensional (3-D) echocardiography is limited by signal dropouts and narrow field of view. Data compounding is proposed as a solution to overcome these limitations by combining multiple 3-D recordings to form a wide field of view. The first step of the solution requires registration between the recordings both in the spatial and temporal dimension for dynamic organs such as the heart. Accurate registration between the individual echo recordings is crucial for the quality of compounded volumes. A temporal registration method based on a piecewise one-dimensional cubic B-spline in combination with multiscale iterative Farnebäck optic flow method for spatial registration was described. The temporal registration method was validated on in vivo data sets with annotated timing of mitral valve opening. The spatial registration method was validated using in vivo data and compared to registration with Procrustes analysis using manual contouring as a benchmark. The spatial accuracy was assessed in terms of mean of absolute distance and Hausdorff distance between the left ventricular contours. The results showed that the temporal registration accuracy is in the range of half the time resolution of the echo recordings and the achieved spatial accuracy of the proposed method is comparable to manual registration.

  12. Analysing Spatio-Temporal Clustering of Meningococcal Meningitis Outbreaks in Niger Reveals Opportunities for Improved Disease Control

    PubMed Central

    Paireau, Juliette; Girond, Florian; Collard, Jean-Marc; Maïnassara, Halima B.; Jusot, Jean-François

    2012-01-01

    Background Meningococcal meningitis is a major health problem in the “African Meningitis Belt” where recurrent epidemics occur during the hot, dry season. In Niger, a central country belonging to the Meningitis Belt, reported meningitis cases varied between 1,000 and 13,000 from 2003 to 2009, with a case-fatality rate of 5–15%. Methodology/Principal Findings In order to gain insight in the epidemiology of meningococcal meningitis in Niger and to improve control strategies, the emergence of the epidemics and their diffusion patterns at a fine spatial scale have been investigated. A statistical analysis of the spatio-temporal distribution of confirmed meningococcal meningitis cases was performed between 2002 and 2009, based on health centre catchment areas (HCCAs) as spatial units. Anselin's local Moran's I test for spatial autocorrelation and Kulldorff's spatial scan statistic were used to identify spatial and spatio-temporal clusters of cases. Spatial clusters were detected every year and most frequently occurred within nine southern districts. Clusters most often encompassed few HCCAs within a district, without expanding to the entire district. Besides, strong intra-district heterogeneity and inter-annual variability in the spatio-temporal epidemic patterns were observed. To further investigate the benefit of using a finer spatial scale for surveillance and disease control, we compared timeliness of epidemic detection at the HCCA level versus district level and showed that a decision based on threshold estimated at the HCCA level may lead to earlier detection of outbreaks. Conclusions/Significance Our findings provide an evidence-based approach to improve control of meningitis in sub-Saharan Africa. First, they can assist public health authorities in Niger to better adjust allocation of resources (antibiotics, rapid diagnostic tests and medical staff). Then, this spatio-temporal analysis showed that surveillance at a finer spatial scale (HCCA) would be more

  13. Spatiotemporal characteristics of form analysis in the human visual cortex revealed by rapid event-related fMRI adaptation.

    PubMed

    Kourtzi, Zoe; Huberle, Elisabeth

    2005-11-01

    The integration of local elements to coherent forms is at the core of understanding visual perception. Accumulating evidence suggests that both early retinotopic and higher occipitotemporal areas contribute to the integration of local elements to global forms. However, the spatiotemporal characteristics of form analysis in the human visual cortex remain largely unknown. The aim of this study was to investigate form analysis at different spatial (global vs. local structure) and temporal (different stimulus presentation rates) scales across stages of visual analysis (from V1 to the lateral occipital complex-LOC) in the human brain. We used closed contours rendered by Gabor elements and manipulated either the global contour structure or the orientation of the local Gabor elements. Our rapid event-related fMRI adaptation studies suggest that contour integration and form processing in early visual areas is transient and limited within the local neighborhood of their cells' receptive field. In contrast, higher visual areas appear to process the perceived global form in a more sustained manner. Finally, we demonstrate that these spatiotemporal properties of form processing in the visual cortex are modulated by attention. Attention to the global form maintains sustained processing in occipitotemporal areas, whereas attention to local elements enhances their integration in early visual areas. These findings provide novel neuroimaging evidence for form analysis at different spatiotemporal scales across human visual areas and validate the use of rapid event-related fMRI adaptation for investigating processing across stages of visual analysis in the human brain.

  14. Vestibular influences on human postural control in combinations of pitch and roll planes reveal differences in spatiotemporal processing.

    PubMed

    Carpenter, M G; Allum, J H; Honegger, F

    2001-09-01

    destabilize the body. As a result of these changes in response amplitudes, BVL patients had reduced balance correcting ankle torque between 160 and 260 ms and increased torque between 280 and 380 ms compared to normals. There were no differences in the orientation of the resultant ankle torque vectors between BVL and normals, both of which were oriented primarily along the pitch plane. For combinations of backward (toe-up) and roll perturbations BVL patients had larger balance correcting and stabilizing reactions (between 350 and 700 ms) in PARAS than normals and these corresponded to excessive trunk pitch and roll velocities. During roll perturbations, trunk velocities in BVL subjects after 200 ms were directed along directions different from those of normals. Furthermore, roll instabilities appeared later than those of pitch particularly for backward roll perturbations. The results of the study show that combinations of roll and pitch surface rotations yield important spatiotemporal information, especially with respect to trunk response strategies changed by BVL which are not revealed by pitch plane perturbations alone. Our results indicate that vestibular influences are earlier for the pitch plane and are directed to leg muscles, whereas roll control is later and focused on trunk muscles.

  15. Atypical Functional Brain Activation during a Multiple Object Tracking Task in Girls with Turner Syndrome: Neurocorrelates of Reduced Spatiotemporal Resolution

    ERIC Educational Resources Information Center

    Beaton, Elliott A.; Stoddard, Joel; Lai, Song; Lackey, John; Shi, Jianrong; Ross, Judith L.; Simon, Tony J.

    2010-01-01

    Turner syndrome is associated with spatial and numerical cognitive impairments. We hypothesized that these nonverbal cognitive impairments result from limits in spatial and temporal processing, particularly as it affects attention. To examine spatiotemporal attention in girls with Turner syndrome versus typically developing controls, we used a…

  16. Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome.

    PubMed

    Pack, Chan-Gi; Yukii, Haruka; Toh-e, Akio; Kudo, Tai; Tsuchiya, Hikaru; Kaiho, Ai; Sakata, Eri; Murata, Shigeo; Yokosawa, Hideyoshi; Sako, Yasushi; Baumeister, Wolfgang; Tanaka, Keiji; Saeki, Yasushi

    2014-03-06

    The 26S proteasome is a 2.5-MDa multisubunit protease complex that degrades polyubiquitylated proteins. Although its functions and structure have been extensively characterized, little is known about its dynamics in living cells. Here, we investigate the absolute concentration, spatio-temporal dynamics and complex formation of the proteasome in living cells using fluorescence correlation spectroscopy. We find that the 26S proteasome complex is highly mobile, and that almost all proteasome subunits throughout the cell are stably incorporated into 26S proteasomes. The interaction between 19S and 20S particles is stable even in an importin-α mutant, suggesting that the 26S proteasome is assembled in the cytoplasm. Furthermore, a genetically stabilized 26S proteasome mutant is able to enter the nucleus. These results suggest that the 26S proteasome completes its assembly process in the cytoplasm and translocates into the nucleus through the nuclear pore complex as a holoenzyme.

  17. Eyetracking Reveals Multiple-Category Use in Induction

    ERIC Educational Resources Information Center

    Chen, Stephanie Y.; Ross, Brian H.; Murphy, Gregory L.

    2016-01-01

    Category information is used to predict properties of new category members. When categorization is uncertain, people often rely on only one, most likely category to make predictions. Yet studies of perception and action often conclude that people combine multiple sources of information near-optimally. We present a perception-action analog of…

  18. Probe-inspired nano-prodrug with dual-color fluorogenic property reveals spatiotemporal drug release in living cells.

    PubMed

    Xue, Xiangdong; Jin, Shubin; Zhang, Chunqiu; Yang, Keni; Huo, Shuaidong; Chen, Fei; Zou, Guozhang; Liang, Xing-Jie

    2015-03-24

    The versatility of the fluorescent probes inspires us to design fluorescently traceable prodrugs, which enables tracking the drug delivery kinetics in living cells. Herein, we constructed a self-indicating nanoprodrug with two fluorescent moieties, an aggregation-induced emission molecule (tetraphenylethylene, TPE) and a luminant anticancer drug (doxorubicin, DOX), with a pH-responsive linker between them. Except when a low pH environment is encountered, an energy-transfer relay (ETR) occurs and inactivates the fluorescence of both, showing a dark background. Otherwise, the ETR would be interrupted and evoke a dual-color fluorogenic process, giving distinct fluorogenic read out. By observing the dual-color fluorogenic scenario, we captured the kinetics of the drug release process in living cells. Because the separated TPE and DOX are both fluorescent but have a distinct spectrum, by examining the spatiotemporal pattern of TPE and DOX, we were able to precisely disclose the drug-releasing site, the releasing time, the destinations of the carriers, and the executing site of the drugs at subcellular level. Furthermore, different intracellular drug release kinetics between free doxorubicin and its nanoformulations were also observed in a real-time manner.

  19. Kidney tumor biomarkers revealed by simultaneous multiple matrix metabolomics analysis.

    PubMed

    Ganti, Sheila; Taylor, Sandra L; Abu Aboud, Omran; Yang, Joy; Evans, Christopher; Osier, Michael V; Alexander, Danny C; Kim, Kyoungmi; Weiss, Robert H

    2012-07-15

    Metabolomics is increasingly being used in cancer biology for biomarker discovery and identification of potential novel therapeutic targets. However, a systematic metabolomics study of multiple biofluids to determine their interrelationships and to describe their use as tumor proxies is lacking. Using a mouse xenograft model of kidney cancer, characterized by subcapsular implantation of Caki-1 clear cell human kidney cancer cells, we examined tissue, serum, and urine all obtained simultaneously at baseline (urine) and at, or close to, animal sacrifice (urine, tissue, and plasma). Uniform metabolomics analysis of all three "matrices" was accomplished using gas chromatography- and liquid chromatography-mass spectrometry. Of all the metabolites identified (267 in tissue, 246 in serum, and 267 in urine), 89 were detected in all 3 matrices, and the majority was altered in the same direction. Heat maps of individual metabolites showed that alterations in serum were more closely related to tissue than was urine. Two metabolites, cinnamoylglycine and nicotinamide, were concordantly and significantly (when corrected for multiple testing) altered in tissue and serum, and cysteine-glutathione disulfide showed the highest change (232.4-fold in tissue) of any metabolite. On the basis of these and other considerations, three pathways were chosen for biologic validation of the metabolomic data, resulting in potential therapeutic target identification. These data show that serum metabolomics analysis is a more accurate proxy for tissue changes than urine and that tryptophan degradation (yielding anti-inflammatory metabolites) is highly represented in renal cell carcinoma, and support the concept that PPAR-α antagonism may be a potential therapeutic approach for this disease.

  20. Biosensor reveals multiple sources for mitochondrial NAD⁺.

    PubMed

    Cambronne, Xiaolu A; Stewart, Melissa L; Kim, DongHo; Jones-Brunette, Amber M; Morgan, Rory K; Farrens, David L; Cohen, Michael S; Goodman, Richard H

    2016-06-17

    Nicotinamide adenine dinucleotide (NAD(+)) is an essential substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases (PARPs), which are NAD(+)-consuming enzymes localized in the nucleus, cytosol, and mitochondria. Fluctuations in NAD(+) concentrations within these subcellular compartments are thought to regulate the activity of NAD(+)-consuming enzymes; however, the challenge in measuring compartmentalized NAD(+) in cells has precluded direct evidence for this type of regulation. We describe the development of a genetically encoded fluorescent biosensor for directly monitoring free NAD(+) concentrations in subcellular compartments. We found that the concentrations of free NAD(+) in the nucleus, cytoplasm, and mitochondria approximate the Michaelis constants for sirtuins and PARPs in their respective compartments. Systematic depletion of enzymes that catalyze the final step of NAD(+) biosynthesis revealed cell-specific mechanisms for maintaining mitochondrial NAD(+) concentrations.

  1. Invariants reveal multiple forms of robustness in bifunctional enzyme systems.

    PubMed

    Dexter, Joseph P; Dasgupta, Tathagata; Gunawardena, Jeremy

    2015-08-01

    Experimental and theoretical studies have suggested that bifunctional enzymes catalyzing opposing modification and demodification reactions can confer steady-state concentration robustness to their substrates. However, the types of robustness and the biochemical basis for them have remained elusive. Here we report a systematic study of the most general biochemical reaction network for a bifunctional enzyme acting on a substrate with one modification site, along with eleven sub-networks with more specialized biochemical assumptions. We exploit ideas from computational algebraic geometry, introduced in previous work, to find a polynomial expression (an invariant) between the steady state concentrations of the modified and unmodified substrate for each network. We use these invariants to identify five classes of robust behavior: robust upper bounds on concentration, robust two-sided bounds on concentration ratio, hybrid robustness, absolute concentration robustness (ACR), and robust concentration ratio. This analysis demonstrates that robustness can take a variety of forms and that the type of robustness is sensitive to many biochemical details, with small changes in biochemistry leading to very different steady-state behaviors. In particular, we find that the widely-studied ACR requires highly specialized assumptions in addition to bifunctionality. An unexpected result is that the robust bounds derived from invariants are strictly tighter than those derived by ad hoc manipulation of the underlying differential equations, confirming the value of invariants as a tool to gain insight into biochemical reaction networks. Furthermore, invariants yield multiple experimentally testable predictions and illuminate new strategies for inferring enzymatic mechanisms from steady-state measurements.

  2. Plastome data reveal multiple geographic origins of Quercus Group Ilex

    PubMed Central

    Grimm, Guido W.; Papini, Alessio; Vessella, Federico; Cardoni, Simone; Tordoni, Enrico; Piredda, Roberta; Franc, Alain; Denk, Thomas

    2016-01-01

    Nucleotide sequences from the plastome are currently the main source for assessing taxonomic and phylogenetic relationships in flowering plants and their historical biogeography at all hierarchical levels. One major exception is the large and economically important genus Quercus (oaks). Whereas differentiation patterns of the nuclear genome are in agreement with morphology and the fossil record, diversity patterns in the plastome are at odds with established taxonomic and phylogenetic relationships. However, the extent and evolutionary implications of this incongruence has yet to be fully uncovered. The DNA sequence divergence of four Euro-Mediterranean Group Ilex oak species (Quercus ilex L., Q. coccifera L., Q. aucheri Jaub. & Spach., Q. alnifolia Poech.) was explored at three chloroplast markers (rbcL, trnK/matK, trnH-psbA). Phylogenetic relationships were reconstructed including worldwide members of additional 55 species representing all Quercus subgeneric groups. Family and order sequence data were harvested from gene banks to better frame the observed divergence in larger taxonomic contexts. We found a strong geographic sorting in the focal group and the genus in general that is entirely decoupled from species boundaries. High plastid divergence in members of Quercus Group Ilex, including haplotypes shared with related, but long isolated oak lineages, point towards multiple geographic origins of this group of oaks. The results suggest that incomplete lineage sorting and repeated phases of asymmetrical introgression among ancestral lineages of Group Ilex and two other main Groups of Eurasian oaks (Cyclobalanopsis and Cerris) caused this complex pattern. Comparison with the current phylogenetic synthesis also suggests an initial high- versus mid-latitude biogeographic split within Quercus. High plastome plasticity of Group Ilex reflects geographic area disruptions, possibly linked with high tectonic activity of past and modern distribution ranges, that did not

  3. Multiple etiologies for Alzheimer disease are revealed by segregation analysis

    SciTech Connect

    Rao, V.S.; Connor-Lacke, L.; Cupplies, L.A.; Growdon, J.H.; Farrer, L.A.; Duijn, C.M. van

    1994-11-01

    We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.

  4. Microsatellite markers reveal multiple origins for Italian weedy rice

    PubMed Central

    Grimm, Annabelle; Fogliatto, Silvia; Nick, Peter; Ferrero, Aldo; Vidotto, Francesco

    2013-01-01

    Weedy rice (Oryza sativa L.) is one of the major issues of rice cultivation worldwide. In Italy, it infests about 70% of the total rice area. Different Weedy Rice populations can be distinguished based on variable morphological and physiological traits; however, little is known about genetic differentiation and origin of Italian weedy rice populations. The objective of this study was to genetically and morphologically characterize and compare different Italian weedy rice populations selected on the basis of different phenotypes. The main Italian rice territory was divided into 10 geographical areas in which 40 weedy rice populations were collected and grouped according to the awn traits. All the individuals of the populations were morphologically characterized according to plant and seed traits. Genetic characterization was performed using 19 SSR markers on all the collected accessions, and several rice cultivars, including some very old (late 19th century), nowadays are no longer cultivated. ANOVA showed that morphological plant and seed traits were significantly affected by the collection area and awnedness group. The importance of the awn morphology was also reflected in the Bayesian clustering where, despite a relatively low genetic diversity, the clusters displayed different awn types. An UPGMA dendrogram confirmed the clusters detected in STRUCTURE analysis and also revealed a grouping of certain old cultivars with the weedy rice, suggesting a common origin. PMID:24363904

  5. Molecular and morphologic data reveal multiple species in Peromyscus pectoralis

    PubMed Central

    Bradley, Robert D.; Schmidly, David J.; Amman, Brian R.; Platt, Roy N.; Neumann, Kathy M.; Huynh, Howard M.; Muñiz-Martínez, Raúl; López-González, Celia; Ordóñez-Garza, Nicté

    2015-01-01

    DNA sequence and morphometric data were used to re-evaluate the taxonomy and systematics of Peromyscus pectoralis. Phylogenetic analyses (maximum likelihood and Bayesian inference) of DNA sequences from the mitochondrial cytochrome-b gene in 44 samples of P. pectoralis indicated 2 well-supported monophyletic clades. The 1st clade contained specimens from Texas historically assigned to P. p. laceianus; the 2nd was comprised of specimens previously referable to P. p. collinus, P. p. laceianus, and P. p. pectoralis obtained from northern and eastern Mexico. Levels of genetic variation (~7%) between these 2 clades indicated that the genetic divergence typically exceeded that reported for other species of Peromyscus. Samples of P. p. laceianus north and south of the Río Grande were not monophyletic. In addition, samples representing P. p. collinus and P. p. pectoralis formed 2 clades that differed genetically by 7.14%. Multivariate analyses of external and cranial measurements from 63 populations of P. pectoralis revealed 4 morpho-groups consistent with clades in the DNA sequence analysis: 1 from Texas and New Mexico assignable to P. p. laceianus; a 2nd from western and southern Mexico assignable to P. p. pectoralis; a 3rd from northern and central Mexico previously assigned to P. p. pectoralis but herein shown to represent an undescribed taxon; and a 4th from southeastern Mexico assignable to P. p. collinus. Based on the concordance of these results, populations from the United States are referred to as P. laceianus, whereas populations from Mexico are referred to as P. pectoralis (including some samples historically assigned to P. p. collinus, P. p. laceianus, and P. p. pectoralis). A new subspecies is described to represent populations south of the Río Grande in northern and central Mexico. Additional research is needed to discern if P. p. collinus warrants species recognition. PMID:26937045

  6. Spatio-temporal analysis reveals active control of both task-relevant and task-irrelevant variables

    PubMed Central

    Rácz, Kornelius; Valero-Cuevas, Francisco J.

    2013-01-01

    redundancy. Instead of a dichotomy of presence vs. absence of control, we should speak of a continuum of weaker to stronger—and potentially different—control strategies in specific spatiotemporal domains, indicated here by the magnitude of deviation from the 0.5 scaling exponent. Moreover, these results are counter examples to the UCM hypothesis and the Minimal Intervention principle, and the similar nature of control actions across time scales in both task-relevant and task-irrelevant spaces points to a level of modularity not previously recognized. PMID:24312045

  7. Defining multiple, distinct, and shared spatiotemporal patterns of DNA replication and endoreduplication from 3D image analysis of developing maize (Zea mays L.) root tip nuclei.

    PubMed

    Bass, Hank W; Hoffman, Gregg G; Lee, Tae-Jin; Wear, Emily E; Joseph, Stacey R; Allen, George C; Hanley-Bowdoin, Linda; Thompson, William F

    2015-11-01

    Spatiotemporal patterns of DNA replication have been described for yeast and many types of cultured animal cells, frequently after cell cycle arrest to aid in synchronization. However, patterns of DNA replication in nuclei from plants or naturally developing organs remain largely uncharacterized. Here we report findings from 3D quantitative analysis of DNA replication and endoreduplication in nuclei from pulse-labeled developing maize root tips. In both early and middle S phase nuclei, flow-sorted on the basis of DNA content, replicative labeling was widely distributed across euchromatic regions of the nucleoplasm. We did not observe the perinuclear or perinucleolar replicative labeling patterns characteristic of middle S phase in mammals. Instead, the early versus middle S phase patterns in maize could be distinguished cytologically by correlating two quantitative, continuous variables, replicative labeling and DAPI staining. Early S nuclei exhibited widely distributed euchromatic labeling preferentially localized to regions with weak DAPI signals. Middle S nuclei also exhibited widely distributed euchromatic labeling, but the label was preferentially localized to regions with strong DAPI signals. Highly condensed heterochromatin, including knobs, replicated during late S phase as previously reported. Similar spatiotemporal replication patterns were observed for both mitotic and endocycling maize nuclei. These results revealed that maize euchromatin exists as an intermingled mixture of two components distinguished by their condensation state and replication timing. These different patterns might reflect a previously described genome organization pattern, with "gene islands" mostly replicating during early S phase followed by most of the intergenic repetitive regions replicating during middle S phase.

  8. Spatiotemporal Regulation of Synaptic Vesicle Fusion Sites in Central Synapses.

    PubMed

    Maschi, Dario; Klyachko, Vitaly A

    2017-04-05

    The number and availability of vesicle release sites at the synaptic active zone (AZ) are critical factors governing neurotransmitter release; yet, these fundamental synaptic parameters have remained undetermined. Moreover, how neural activity regulates the spatiotemporal properties of the release sites within individual central synapses is unknown. Here, we combined a nanoscale imaging approach with advanced image analysis to detect individual vesicle fusion events with ∼27 nm localization precision at single hippocampal synapses under physiological conditions. Our results revealed the presence of multiple distinct release sites within individual hippocampal synapses. Release sites were distributed throughout the AZ and underwent repeated reuse. Furthermore, the spatiotemporal properties of the release sites were activity dependent with a reduction in reuse frequency and a shift in location toward the AZ periphery during high-frequency stimulation. These findings have revealed fundamental spatiotemporal properties of individual release sites in small central synapses and their activity-dependent modulation.

  9. A novel dendrochronological approach reveals drivers of carbon sequestration in tree species of riparian forests across spatiotemporal scales.

    PubMed

    Rieger, Isaak; Kowarik, Ingo; Cherubini, Paolo; Cierjacks, Arne

    2017-01-01

    Aboveground carbon (C) sequestration in trees is important in global C dynamics, but reliable techniques for its modeling in highly productive and heterogeneous ecosystems are limited. We applied an extended dendrochronological approach to disentangle the functioning of drivers from the atmosphere (temperature, precipitation), the lithosphere (sedimentation rate), the hydrosphere (groundwater table, river water level fluctuation), the biosphere (tree characteristics), and the anthroposphere (dike construction). Carbon sequestration in aboveground biomass of riparian Quercus robur L. and Fraxinus excelsior L. was modeled (1) over time using boosted regression tree analysis (BRT) on cross-datable trees characterized by equal annual growth ring patterns and (2) across space using a subsequent classification and regression tree analysis (CART) on cross-datable and not cross-datable trees. While C sequestration of cross-datable Q. robur responded to precipitation and temperature, cross-datable F. excelsior also responded to a low Danube river water level. However, CART revealed that C sequestration over time is governed by tree height and parameters that vary over space (magnitude of fluctuation in the groundwater table, vertical distance to mean river water level, and longitudinal distance to upstream end of the study area). Thus, a uniform response to climatic drivers of aboveground C sequestration in Q. robur was only detectable in trees of an intermediate height class and in taller trees (>21.8m) on sites where the groundwater table fluctuated little (≤0.9m). The detection of climatic drivers and the river water level in F. excelsior depended on sites at lower altitudes above the mean river water level (≤2.7m) and along a less dynamic downstream section of the study area. Our approach indicates unexploited opportunities of understanding the interplay of different environmental drivers in aboveground C sequestration. Results may support species-specific and

  10. Multiple cis-elements and trans-acting factors regulate dynamic spatio-temporal transcription of let-7 in Caenorhabditis elegans.

    PubMed

    Kai, Zoya S; Finnegan, Emily F; Huang, Stacey; Pasquinelli, Amy E

    2013-02-01

    The let-7 microRNA (miRNA) is highly conserved across animal phyla and generally regulates cellular differentiation and developmental timing pathways. In Caenorhabditis elegans, the mature let-7 miRNA starts to accumulate in the last stages of larval development where it directs cellular differentiation programs required for adult fates. Here, we show that expression of the let-7 gene in C. elegans is under complex transcriptional control. The onset of let-7 transcription begins as early as the first larval stage in some tissues, and as late as the third larval stage in others, and is abrogated at the gravid adult stage. Transcription from two different start sites in the let-7 promoter oscillates during each larval stage. We show that transcription is regulated by two distinct cis-elements in the promoter of let-7, the previously described temporal regulatory element (TRE), and a novel element downstream of the TRE that we have named the let-7 transcription element (LTE). These elements play distinct and redundant roles in regulating let-7 expression in specific tissues. In the absence of the TRE and LTE, transcription of let-7 is undetectable and worms exhibit the lethal phenotype characteristic of let-7 null mutants. We also identify several genes that affect the transcription of let-7 generally and tissue-specifically. Overall, spatio-temporal regulation of let-7 transcription is orchestrated by multiple cis- and trans-acting factors to ensure appropriate expression of this essential miRNA during worm development.

  11. Spatiotemporal characteristics of the geomagnetic diurnal variation anomalies prior to the 2011 Tohoku earthquake (Mw 9.0) and the possible coupling of multiple pre-earthquake phenomena

    NASA Astrophysics Data System (ADS)

    Han, Peng; Hattori, Katsumi; Huang, Qinghua; Hirooka, Shinji; Yoshino, Chie

    2016-11-01

    Xu et al. (2013) and Han et al. (2015) have reported unusual behaviors of geomagnetic diurnal variation (GDV) in the vertical component prior to the 2011 off the Pacific coast of Tohoku earthquake (Mw 9.0). To make a better understanding of this phenomenon, temporal-spatial analyses of GDV have been applied in this study. Geomagnetic data of long-term observations at 17 stations in Japan have been analyzed using the same method in Han et al. (2015). Ratios of diurnal variation range between the reference station KAK and the target stations have been computed. After removing seasonal variations, the 15-day backward running mean values of the ratios in the vertical component shows a clear anomaly exceeding the statistical threshold about 2 months before the mega event at both ESA and MIZ stations in the Tohoku Region. Locations of anomalies in spatial distribution show a good correlation with the epicenter of the Mw 9.0 earthquake. These spatiotemporal results are consistent with those obtained from other independent observations such as groundwater level and GPS displacements. The coupling of multiple pre-earthquake phenomena may help to understand the preparation process of a mega earthquake in the subduction zone.

  12. Collective synchronization of self/non-self discrimination in T cell activation, across multiple spatio-temporal scales

    NASA Astrophysics Data System (ADS)

    Altan-Bonnet, Gregoire

    The immune system is a collection of cells whose function is to eradicate pathogenic infections and malignant tumors while protecting healthy tissues. Recent work has delineated key molecular and cellular mechanisms associated with the ability to discriminate self from non-self agents. For example, structural studies have quantified the biophysical characteristics of antigenic molecules (those prone to trigger lymphocyte activation and a subsequent immune response). However, such molecular mechanisms were found to be highly unreliable at the individual cellular level. We will present recent efforts to build experimentally validated computational models of the immune responses at the collective cell level. Such models have become critical to delineate how higher-level integration through nonlinear amplification in signal transduction, dynamic feedback in lymphocyte differentiation and cell-to-cell communication allows the immune system to enforce reliable self/non-self discrimination at the organism level. In particular, we will present recent results demonstrating how T cells tune their antigen discrimination according to cytokine cues, and how competition for cytokine within polyclonal populations of cells shape the repertoire of responding clones. Additionally, we will present recent theoretical and experimental results demonstrating how competition between diffusion and consumption of cytokines determine the range of cell-cell communications within lymphoid organs. Finally, we will discuss how biochemically explicit models, combined with quantitative experimental validation, unravel the relevance of new feedbacks for immune regulations across multiple spatial and temporal scales.

  13. Cerebral and subdural abscess with spatio-temporal multiplicity 12 years after initial craniotomy for acute subdural hematoma. Case report.

    PubMed

    Wakui, Daisuke; Nagashima, Goro; Takada, Tatsuro; Ueda, Toshihiro; Itoh, Hidemichi; Tanaka, Yuichiro; Hashimoto, Takuo

    2012-01-01

    A 34-year-old man presented with a case of subdural empyema and cerebral abscess that developed 12 years after initial neurosurgical intervention for a traffic accident in 1998. Under a diagnosis of acute subdural hematoma and cerebral contusion, several neurosurgical procedures were performed at another hospital, including hematoma removal by craniotomy, external decompression, duraplasty, and cranioplasty. The patient experienced an epileptic seizure, and was referred to our hospital in March 2010. Magnetic resonance imaging revealed a cerebral abscess extending to the subdural space just under the previous surgical field. Surgical intervention was refused and antimicrobial treatment was initiated, but proved ineffective. Surgical removal of artificial dura and cranium with subdural empyema, and resection of a cerebral abscess were performed on May 12, 2010. No organism was recovered from the surgical samples. Meropenem and vancomycin were selected as perioperative antimicrobial agents. No recurrence of infection has been observed. Postneurosurgical subdural empyema and cerebral abscess are recently emerging problems. Infections of neurosurgical sites containing implanted materials occur in 6% of cases, usually within several months of the surgery. Subdural empyema and cerebral abscess developing 12 years after neurosurgical interventions are extremely rare. The long-term clinical course suggests less pathogenic organisms as a cause of infection, and further investigations to develop appropriate antimicrobial selection and adequate duration of antimicrobial administration for these cases are needed.

  14. Historical comparisons reveal multiple drivers of decadal change of an ecosystem engineer at the range edge.

    PubMed

    Firth, Louise B; Mieszkowska, Nova; Grant, Lisa M; Bush, Laura E; Davies, Andrew J; Frost, Matthew T; Moschella, Paula S; Burrows, Michael T; Cunningham, Paul N; Dye, Stephen R; Hawkins, Stephen J

    2015-08-01

    Biogenic reefs are important for habitat provision and coastal protection. Long-term datasets on the distribution and abundance of Sabellaria alveolata (L.) are available from Britain. The aim of this study was to combine historical records and contemporary data to (1) describe spatiotemporal variation in winter temperatures, (2) document short-term and long-term changes in the distribution and abundance of S. alveolata and discuss these changes in relation to extreme weather events and recent warming, and (3) assess the potential for artificial coastal defense structures to function as habitat for S. alveolata. A semi-quantitative abundance scale (ACFOR) was used to compare broadscale, long-term and interannual abundance of S. alveolata near its range edge in NW Britain. S. alveolata disappeared from the North Wales and Wirral coastlines where it had been abundant prior to the cold winter of 1962/1963. Population declines were also observed following the recent cold winters of 2009/2010 and 2010/2011. Extensive surveys in 2004 and 2012 revealed that S. alveolata had recolonized locations from which it had previously disappeared. Furthermore, it had increased in abundance at many locations, possibly in response to recent warming. S. alveolata was recorded on the majority of artificial coastal defense structures surveyed, suggesting that the proliferation of artificial coastal defense structures along this stretch of coastline may have enabled S. alveolata to spread across stretches of unsuitable natural habitat. Long-term and broadscale contextual monitoring is essential for monitoring responses of organisms to climate change. Historical data and gray literature can be invaluable sources of information. Our results support the theory that Lusitanian species are responding positively to climate warming but also that short-term extreme weather events can have potentially devastating widespread and lasting effects on organisms. Furthermore, the proliferation of

  15. On the potentials of multiple climate variables in assessing the spatio-temporal characteristics of hydrological droughts over the Volta Basin.

    PubMed

    Ndehedehe, Christopher E; Awange, Joseph L; Corner, Robert J; Kuhn, Michael; Okwuashi, Onuwa

    2016-07-01

    Multiple drought episodes over the Volta basin in recent reports may lead to food insecurity and loss of revenue. However, drought studies over the Volta basin are rather generalised and largely undocumented due to sparse ground observations and unsuitable framework to determine their space-time occurrence. In this study, we examined the utility of standardised indicators (standardised precipitation index (SPI), standardised runoff index (SRI), standardised soil moisture index (SSI), and multivariate standardised drought index (MSDI)) and Gravity Recovery and Climate Experiment (GRACE) derived terrestrial water storage to assess hydrological drought characteristics over the basin. In order to determine the space-time patterns of hydrological drought in the basin, Independent Component Analysis (ICA), a higher order statistical technique was employed. The results show that SPI and SRI exhibit inconsistent behaviour in observed wet years presupposing a non-linear relationship that reflects the slow response of river discharge to precipitation especially after a previous extreme dry period. While the SPI and SSI show a linear relationship with a correlation of 0.63, the correlation between the MSDIs derived from combining precipitation/river discharge and precipitation/soil moisture indicates a significant value of 0.70 and shows an improved skill in hydrological drought monitoring over the Volta basin during the study period. The ICA-derived spatio-temporal hydrological drought patterns show Burkina Faso and the Lake Volta areas as predominantly drought zones. Further, the statistically significant negative correlations of pacific decadal oscillations (0.39 and 0.25) with temporal evolutions of drought in Burkina Faso and Ghana suggest the possible influence of low frequency large scale oscillations in the observed wet and dry regimes over the basin. Finally, our approach in drought assessment over the Volta basin contributes to a broad framework for hydrological

  16. Similarity-Based Fusion of MEG and fMRI Reveals Spatio-Temporal Dynamics in Human Cortex During Visual Object Recognition

    PubMed Central

    Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

    2016-01-01

    Every human cognitive function, such as visual object recognition, is realized in a complex spatio-temporal activity pattern in the brain. Current brain imaging techniques in isolation cannot resolve the brain's spatio-temporal dynamics, because they provide either high spatial or temporal resolution but not both. To overcome this limitation, we developed an integration approach that uses representational similarities to combine measurements of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to yield a spatially and temporally integrated characterization of neuronal activation. Applying this approach to 2 independent MEG–fMRI data sets, we observed that neural activity first emerged in the occipital pole at 50–80 ms, before spreading rapidly and progressively in the anterior direction along the ventral and dorsal visual streams. Further region-of-interest analyses established that dorsal and ventral regions showed MEG–fMRI correspondence in representations later than early visual cortex. Together, these results provide a novel and comprehensive, spatio-temporally resolved view of the rapid neural dynamics during the first few hundred milliseconds of object vision. They further demonstrate the feasibility of spatially unbiased representational similarity-based fusion of MEG and fMRI, promising new insights into how the brain computes complex cognitive functions. PMID:27235099

  17. Cascade of Spatio-Temporal Period-Doubling Bifurcations in Connection with the Appearance and Dynamics of Non-Concentric Multiple Double Layers in Plasma

    SciTech Connect

    Dimitriu, D. G.; Ivan, L. M.

    2008-03-19

    Experimental results are presented that reveal a complex route to chaos in plasma, in which a Feigenbaum scenario (cascade of temporal period-doubling bifurcation) develops simultaneously with a cascade of spatial period-doubling bifurcations, in connection with the appearance of a non-concentric multiple double layers structure. The Feigenbaum scenario is identified in the time series of the oscillations of the current through the plasma conductor.

  18. Lung Postmortem Autopsy Revealing Extramedullary Involvement in Multiple Myeloma Causing Acute Respiratory Distress Syndrome

    PubMed Central

    Ravinet, Aurélie; Perbet, Sébastien; Guièze, Romain; Guérin, Renaud; Gayraud, Guillaume; Aliane, Jugurtha; Tremblay, Aymeric; Pascal, Julien; Ledoux, Albane; Chaleteix, Carine; Dechelotte, Pierre; Bay, Jacques-Olivier; Bazin, Jean-Etienne; Constantin, Jean-Michel

    2014-01-01

    Pulmonary involvement with multiple myeloma is rare. We report the case of a 61-year-old man with past medical history of chronic respiratory failure with emphysema, and a known multiple myeloma (Durie and Salmon stage III B and t(4;14) translocation). Six months after diagnosis and first line of treatment, he presented acute dyspnea with interstitial lung disease. Computed tomography showed severe bullous emphysema and diffuse, patchy, multifocal infiltrations bilaterally with nodular character, small bilateral pleural effusions, mediastinal lymphadenopathy, and a known lytic lesion of the 12th vertebra. He was treated with piperacillin-tazobactam, amikacin, oseltamivir, and methylprednisolone. Finally, outcome was unfavourable. Postmortem analysis revealed diffuse and nodular infracentimetric infiltration of the lung parenchyma by neoplastic plasma cells. Physicians should be aware that acute respiratory distress syndrome not responding to treatment of common causes could be a manifestation of the disease, even with negative BAL or biopsy and could be promptly treated with salvage therapy. PMID:25165587

  19. Historical comparisons reveal multiple drivers of decadal change of an ecosystem engineer at the range edge

    PubMed Central

    Firth, Louise B; Mieszkowska, Nova; Grant, Lisa M; Bush, Laura E; Davies, Andrew J; Frost, Matthew T; Moschella, Paula S; Burrows, Michael T; Cunningham, Paul N; Dye, Stephen R; Hawkins, Stephen J

    2015-01-01

    Biogenic reefs are important for habitat provision and coastal protection. Long-term datasets on the distribution and abundance of Sabellaria alveolata (L.) are available from Britain. The aim of this study was to combine historical records and contemporary data to (1) describe spatiotemporal variation in winter temperatures, (2) document short-term and long-term changes in the distribution and abundance of S. alveolata and discuss these changes in relation to extreme weather events and recent warming, and (3) assess the potential for artificial coastal defense structures to function as habitat for S. alveolata. A semi-quantitative abundance scale (ACFOR) was used to compare broadscale, long-term and interannual abundance of S. alveolata near its range edge in NW Britain. S. alveolata disappeared from the North Wales and Wirral coastlines where it had been abundant prior to the cold winter of 1962/1963. Population declines were also observed following the recent cold winters of 2009/2010 and 2010/2011. Extensive surveys in 2004 and 2012 revealed that S. alveolata had recolonized locations from which it had previously disappeared. Furthermore, it had increased in abundance at many locations, possibly in response to recent warming. S. alveolata was recorded on the majority of artificial coastal defense structures surveyed, suggesting that the proliferation of artificial coastal defense structures along this stretch of coastline may have enabled S. alveolata to spread across stretches of unsuitable natural habitat. Long-term and broadscale contextual monitoring is essential for monitoring responses of organisms to climate change. Historical data and gray literature can be invaluable sources of information. Our results support the theory that Lusitanian species are responding positively to climate warming but also that short-term extreme weather events can have potentially devastating widespread and lasting effects on organisms. Furthermore, the proliferation of

  20. HUBBLE SPACE TELESCOPE REVEALS MULTIPLE SUB-GIANT BRANCH IN EIGHT GLOBULAR CLUSTERS

    SciTech Connect

    Piotto, G.; Nascimbeni, V.; Milone, A. P.; Aparicio, A.; Anderson, J.; Bellini, A.; Bedin, L. R.; Cassisi, S.; Marino, A. F. E-mail: luigi.bedin@oapd.inaf.it E-mail: aparicio@iac.es E-mail: bellini@stsci.edu E-mail: amarino@MPA-Garching.MPG.DE

    2012-11-20

    In the last few years many globular clusters (GCs) have revealed complex color-magnitude diagrams, with the presence of multiple main sequences (MSs), broad or multiple sub-giant branches (SGBs) and MS turnoffs, and broad or split red giant branches (RGBs). After a careful correction for differential reddening, high-accuracy photometry with the Hubble Space Telescope (HST) presented in this paper reveals a broadened or even split SGB in five additional Milky Way GCs: NGC 362, NGC 5286, NGC 6656, NGC 6715, and NGC 7089. In addition, we confirm (with new and archival HST data) the presence of a split SGB in 47 Tuc, NGC 1851, and NGC 6388. The fraction of faint SGB stars with respect to the entire SGB population varies from one cluster to another and ranges from {approx}0.03 for NGC 362 to {approx}0.50 for NGC 6715. The average magnitude difference between the bright SGB and the faint SGB is almost the same at different wavelengths. This peculiarity is consistent with the presence of two groups of stars with either an age difference of about 1-2 Gyr or a significant difference in their overall C+N+O content.

  1. High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Campylobacter jejuni Isolates

    PubMed Central

    Förstner, Konrad U.; Heidrich, Nadja; Reinhardt, Richard; Nieselt, Kay; Sharma, Cynthia M.

    2013-01-01

    Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA–seq (dRNA–seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA–seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA–seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA–seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into

  2. Proteomic Profiling in Multiple Sclerosis Clinical Courses Reveals Potential Biomarkers of Neurodegeneration

    PubMed Central

    Liguori, Maria; Qualtieri, Antonio; Tortorella, Carla; Direnzo, Vita; Bagalà, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

    2014-01-01

    The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000–25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS. PMID:25098164

  3. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

    PubMed

    Liguori, Maria; Qualtieri, Antonio; Tortorella, Carla; Direnzo, Vita; Bagalà, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

    2014-01-01

    The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  4. Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase

    SciTech Connect

    Duan, Hongying; Takagi, Akira; Kayano, Hidekazu; Koyama, Isamu; Morisseau, Christophe; Hammock, Bruce D.; Akatsuka, Toshitaka

    2012-04-01

    In a previous study, we developed five kinds of monoclonal antibodies against different portions of human mEH: three, anti-N-terminal; one, anti-C-terminal; one, anti-conformational epitope. Using them, we stained the intact and the permeabilized human cells of various kinds and performed flow cytometric analysis. Primary hepatocytes and peripheral blood mononuclear cells (PBMC) showed remarkable differences. On the surface, hepatocytes exhibited 4 out of 5 epitopes whereas PBMC did not show any of the epitopes. mEH was detected inside both cell types, but the most prominent expression was observed for the conformational epitope in the hepatocytes and the two N-terminal epitopes in PBMC. These differences were also observed between hepatocyte-derived cell lines and mononuclear cell-derived cell lines. In addition, among each group, there were several differences which may be related to the cultivation, the degree of differentiation, or the original cell subsets. We also noted that two glioblastoma cell lines reveal marked expression of the conformational epitope on the surface which seemed to correlate with the brain tumor-associated antigen reported elsewhere. Several cell lines also underwent selective permeabilization before flow cytometric analysis, and we noticed that the topological orientation of mEH on the ER membrane in those cells was in accordance with the previous report. However, the orientation on the cell surface was inconsistent with the report and had a great variation between the cells. These findings show the multiple mode of expression of mEH which may be possibly related to the multiple roles that mEH plays in different cells. -- Highlights: ► We examine expression of five mEH epitopes in human cells. ► Remarkable differences exist between hepatocytes and PBMC. ► mEH expression in cell lines differs depending on several factors. ► Some glioblastoma cell lines reveal marked surface expression of mEH. ► Topology of mEH on the cell

  5. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

    PubMed Central

    Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

    2016-01-01

    ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

  6. Phylogeography of the widespread African puff adder (Bitis arietans) reveals multiple Pleistocene refugia in southern Africa.

    PubMed

    Barlow, Axel; Baker, Karis; Hendry, Catriona R; Peppin, Lindsay; Phelps, Tony; Tolley, Krystal A; Wüster, Catharine E; Wüster, Wolfgang

    2013-02-01

    Evidence from numerous Pan-African savannah mammals indicates that open-habitat refugia existed in Africa during the Pleistocene, isolated by expanding tropical forests during warm and humid interglacial periods. However, comparative data from other taxonomic groups are currently lacking. We present a phylogeographic investigation of the African puff adder (Bitis arietans), a snake that occurs in open-habitat formations throughout sub-Saharan Africa. Multiple parapatric mitochondrial clades occur across the current distribution of B. arietans, including a widespread southern African clade that is subdivided into four separate clades. We investigated the historical processes responsible for generating these phylogeographic patterns in southern Africa using species distribution modelling and genetic approaches. Our results show that interior regions of South Africa became largely inhospitable for B. arietans during glacial maxima, whereas coastal and more northerly areas remained habitable. This corresponds well with the locations of refugia inferred from mitochondrial data using a continuous phylogeographic diffusion model. Analysis of data from five anonymous nuclear loci revealed broadly similar patterns to mtDNA. Secondary admixture was detected between previously isolated refugial populations. In some cases, this is limited to individuals occurring near mitochondrial clade contact zones, but in other cases, more extensive admixture is evident. Overall, our study reveals a complex history of refugial isolation and secondary expansion for puff adders and a mosaic of isolated refugia in southern Africa. We also identify key differences between the processes that drove isolation in B. arietans and those hypothesized for sympatric savannah mammals.

  7. Comparisons of Caenorhabditis Fucosyltransferase Mutants Reveal a Multiplicity of Isomeric N-Glycan Structures.

    PubMed

    Yan, Shi; Jin, Chunsheng; Wilson, Iain B H; Paschinger, Katharina

    2015-12-04

    Recent studies have shown a remarkable degree of plasticity in the N-glycome of the model nematode Caenorhabditis elegans; ablation of glycosylation-relevant genes can result in radically altered N-glycan profiles despite only minor biological phenotypic effects. Up to four fucose residues and five different linkages of fucose are known on the N-glycans of C. elegans. Due to the complexity in the wild type, we established three mutant strains defective in two core fucosyltransferases each (fut-1;fut-6, fut-1;fut-8, and fut-6;fut-8). Enzymatically released N-glycans were subject to HPLC and MALDI-TOF MS/MS, in combination with various treatments, to verify structural details. The N-glycome of the fut-1;fut-6 mutant was the most complex of the three double-mutant strains due to the extension of the core α1,6-fucose as well as the presence of fucose on the bisecting galactose. In contrast, maximally two fucoses were found on N-glycans of the fut-1;fut-8 and fut-6;fut-8 strains. The different locations and capping of fucose meant that up to 13 isomeric structures, many highly galactosylated, were determined for some single masses. These data not only show the high variability of the N-glycomic capacity of a "simple" nematode but also exemplify the need for multiple approaches to reveal individual glycan structures within complex invertebrate glycomes.

  8. Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers.

    PubMed

    Agirre, Xabier; Castellano, Giancarlo; Pascual, Marien; Heath, Simon; Kulis, Marta; Segura, Victor; Bergmann, Anke; Esteve, Anna; Merkel, Angelika; Raineri, Emanuele; Agueda, Lidia; Blanc, Julie; Richardson, David; Clarke, Laura; Datta, Avik; Russiñol, Nuria; Queirós, Ana C; Beekman, Renée; Rodríguez-Madoz, Juan R; San José-Enériz, Edurne; Fang, Fang; Gutiérrez, Norma C; García-Verdugo, José M; Robson, Michael I; Schirmer, Eric C; Guruceaga, Elisabeth; Martens, Joost H A; Gut, Marta; Calasanz, Maria J; Flicek, Paul; Siebert, Reiner; Campo, Elías; Miguel, Jesús F San; Melnick, Ari; Stunnenberg, Hendrik G; Gut, Ivo G; Prosper, Felipe; Martín-Subero, José I

    2015-04-01

    While analyzing the DNA methylome of multiple myeloma (MM), a plasma cell neoplasm, by whole-genome bisulfite sequencing and high-density arrays, we observed a highly heterogeneous pattern globally characterized by regional DNA hypermethylation embedded in extensive hypomethylation. In contrast to the widely reported DNA hypermethylation of promoter-associated CpG islands (CGIs) in cancer, hypermethylated sites in MM, as opposed to normal plasma cells, were located outside CpG islands and were unexpectedly associated with intronic enhancer regions defined in normal B cells and plasma cells. Both RNA-seq and in vitro reporter assays indicated that enhancer hypermethylation is globally associated with down-regulation of its host genes. ChIP-seq and DNase-seq further revealed that DNA hypermethylation in these regions is related to enhancer decommissioning. Hypermethylated enhancer regions overlapped with binding sites of B cell-specific transcription factors (TFs) and the degree of enhancer methylation inversely correlated with expression levels of these TFs in MM. Furthermore, hypermethylated regions in MM were methylated in stem cells and gradually became demethylated during normal B-cell differentiation, suggesting that MM cells either reacquire epigenetic features of undifferentiated cells or maintain an epigenetic signature of a putative myeloma stem cell progenitor. Overall, we have identified DNA hypermethylation of developmentally regulated enhancers as a new type of epigenetic modification associated with the pathogenesis of MM.

  9. Novel centrosomal protein reveals the presence of multiple centrosomes in turkey (Meleagris gallopavo) bnbn binucleated erythrocytes.

    PubMed

    Woods, C M; Zhu, J; Coleman, T; Bloom, S E; Lazarides, E

    1995-02-01

    The phenotype of the bnbn hemolytic anemia mutation in the domestic turkey is manifested as binucleation specifically in the definitive erythrocyte lineage, most likely as the consequence of anomolous centrosomal activity (Bloom et al., 1970; Searle and Bloom, 1979). Here we have identified in turkey two variants of the novel, centrosomally-associated erythroid-specific protein p23. One variant is Ca(2+)-sensitive and is highly homologous to its chick counterpart (Zhu et al., 1995, accompanying paper). The other, p21 is a truncated form resulting from a 62 amino acid deletion from the 3' end and a 40 amino acid insertion at the 5' end, and appears to lack Ca(2+)-sensitivity. These proteins are localized at the marginal band, centrosomes and nuclear membrane of differentiated erythrocytes. Anti-p23/p21 immunofluorescence revealed the presence of multiple centrosomes in bnbn erythrocytes. We therefore undertook a detailed genetic analysis to determine whether the p21 variant represented the bn mutation. Initial tests of normal BnBn and mutant bnbn individuals suggested that the p23/p21 proteins might be encoded by the Bn/bn genes. However, further genetic tests demonstrated independent segregation for these two genetic loci. Thus, these proteins are encoded by the heretofore undescribed genes, p23/p21, mapping to an autosomal locus in the turkey genome.

  10. Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers

    PubMed Central

    Castellano, Giancarlo; Pascual, Marien; Heath, Simon; Kulis, Marta; Segura, Victor; Bergmann, Anke; Esteve, Anna; Merkel, Angelika; Raineri, Emanuele; Agueda, Lidia; Blanc, Julie; Richardson, David; Clarke, Laura; Datta, Avik; Russiñol, Nuria; Queirós, Ana C.; Beekman, Renée; Rodríguez-Madoz, Juan R.; José-Enériz, Edurne San; Fang, Fang; Gutiérrez, Norma C.; García-Verdugo, José M.; Robson, Michael I.; Schirmer, Eric C.; Guruceaga, Elisabeth; Martens, Joost H.A.; Gut, Marta; Calasanz, Maria J.; Flicek, Paul; Siebert, Reiner; Campo, Elías; Miguel, Jesús F. San; Melnick, Ari; Stunnenberg, Hendrik G.; Gut, Ivo G.

    2015-01-01

    While analyzing the DNA methylome of multiple myeloma (MM), a plasma cell neoplasm, by whole-genome bisulfite sequencing and high-density arrays, we observed a highly heterogeneous pattern globally characterized by regional DNA hypermethylation embedded in extensive hypomethylation. In contrast to the widely reported DNA hypermethylation of promoter-associated CpG islands (CGIs) in cancer, hypermethylated sites in MM, as opposed to normal plasma cells, were located outside CpG islands and were unexpectedly associated with intronic enhancer regions defined in normal B cells and plasma cells. Both RNA-seq and in vitro reporter assays indicated that enhancer hypermethylation is globally associated with down-regulation of its host genes. ChIP-seq and DNase-seq further revealed that DNA hypermethylation in these regions is related to enhancer decommissioning. Hypermethylated enhancer regions overlapped with binding sites of B cell-specific transcription factors (TFs) and the degree of enhancer methylation inversely correlated with expression levels of these TFs in MM. Furthermore, hypermethylated regions in MM were methylated in stem cells and gradually became demethylated during normal B-cell differentiation, suggesting that MM cells either reacquire epigenetic features of undifferentiated cells or maintain an epigenetic signature of a putative myeloma stem cell progenitor. Overall, we have identified DNA hypermethylation of developmentally regulated enhancers as a new type of epigenetic modification associated with the pathogenesis of MM. PMID:25644835

  11. Phylogeny of a Genomically Diverse Group of Elymus (Poaceae) Allopolyploids Reveals Multiple Levels of Reticulation

    PubMed Central

    Mason-Gamer, Roberta J.

    2013-01-01

    The grass tribe Triticeae (=Hordeeae) comprises only about 300 species, but it is well known for the economically important crop plants wheat, barley, and rye. The group is also recognized as a fascinating example of evolutionary complexity, with a history shaped by numerous events of auto- and allopolyploidy and apparent introgression involving diploids and polyploids. The genus Elymus comprises a heterogeneous collection of allopolyploid genome combinations, all of which include at least one set of homoeologs, designated St, derived from Pseudoroegneria. The current analysis includes a geographically and genomically diverse collection of 21 tetraploid Elymus species, and a single hexaploid species. Diploid and polyploid relationships were estimated using four molecular data sets, including one that combines two regions of the chloroplast genome, and three from unlinked nuclear genes: phosphoenolpyruvate carboxylase, β-amylase, and granule-bound starch synthase I. Four gene trees were generated using maximum likelihood, and the phylogenetic placement of the polyploid sequences reveals extensive reticulation beyond allopolyploidy alone. The trees were interpreted with reference to numerous phenomena known to complicate allopolyploid phylogenies, and introgression was identified as a major factor in their history. The work illustrates the interpretation of complicated phylogenetic results through the sequential consideration of numerous possible explanations, and the results highlight the value of careful inspection of multiple independent molecular phylogenetic estimates, with particular focus on the differences among them. PMID:24302986

  12. Multiple mating reveals complex patterns of assortative mating by personality and body size.

    PubMed

    Montiglio, Pierre-Olivier; Wey, Tina W; Chang, Ann T; Fogarty, Sean; Sih, Andrew

    2016-01-01

    Understanding patterns of non-random mating is central to predicting the consequences of sexual selection. Most studies quantifying assortative mating focus on testing for correlations among partners' phenotypes in mated pairs. Few studies have distinguished between assortative mating arising from preferences for similar partners (expressed by all or a subset of the population) vs. from phenotypic segregation in the environment. Also, few studies have assessed the robustness of assortative mating against temporal changes in social conditions. We tracked multiple matings by stream water striders (Aquarius remigis) across variable social conditions to investigate mating patterns by both body size and behavioural type (personality). We documented temporal changes in partner availability and used a mixed model approach to analyse individual behaviours and changes in mating status recorded on an hourly basis. We assessed whether all or only a subset of individuals in the population expressed a tendency to mate with similar phenotypes. Our analyses took into account variation in the level of competition and in the phenotypes of available partners. Males and females exhibited significant assortative mating by body size: the largest males and females, and the smallest males and females mated together more often than random. However, individuals of intermediate size were equally likely to mate with small, intermediate or large partners. Individuals also displayed two contrasting patterns of assortative mating by personality (activity level). Individuals generally mated preferentially with partners of similar activity level. However, beyond that general trend, individuals with more extreme personalities tended to exhibit disassortative mating: the most active males mated disproportionately with less active females and the least active males tended to mate with more active females. Our analyses thus revealed multiple, distinct patterns of nonrandom mating. These mating

  13. How Do Multiple-Star Systems Form? VLA Study Reveals "Smoking Gun"

    NASA Astrophysics Data System (ADS)

    2006-12-01

    system, all the antennas could provide data for us. In addition, we improved the level of detail by using the Pie Town, NM, antenna of the Very Long Baseline Array, as part of an expanded system," Lim said. The implementation and improvement of the 43 GHz receiving system was a collaborative program among the German Max Planck Institute, the Mexican National Autonomous University, and the U.S. National Radio Astronomy Observatory. Two popular theoretical models for the formation of multiple-star systems are, first, that the two protostars and their surrounding dusty disks fragment from a larger parent disk, and, second, that the protostars form independently and then one captures the other into a mutual orbit. "Our new study shows that the disks of the two main protostars are aligned with each other, and also are aligned with the larger, surrounding disk. In addition, their orbital motion resembles the rotation of the larger disk. This is a 'smoking gun' supporting the fragmentation model," Lim said. However, the new study also revealed a third young star with a dust disk. "The disk of this one is misaligned with those of the other two, so it may be the result of either fragmentation or capture," Takakuwa said. The misalignment of the third disk could have come through gravitational interactions with the other two, larger, protostars, the scientists said. They plan further observations to try to resolve the question. "We have a very firm indication that two of these protostars and their dust disks formed from the same, larger disk-like cloud, then broke out from it in a fragmentation process. That strongly supports one theoretical model for how multiple-star systems are formed. The misalignment of the third protostar and its disk leaves open the possibility that it could have formed elsewhere and been captured, and we'll continue to work on reconstructing the history of this fascinating system," Lim summarized. The National Radio Astronomy Observatory is a facility of

  14. Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family

    SciTech Connect

    Vanderslice, P.; Ballinger, S.M., Tam, E.K.; Goldstein, S.M.; Craik, C.S.; Caughey, G.H. )

    1990-05-01

    Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the {approx}1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5{prime} regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family.

  15. Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family.

    PubMed Central

    Vanderslice, P; Ballinger, S M; Tam, E K; Goldstein, S M; Craik, C S; Caughey, G H

    1990-01-01

    Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C-terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the approximately 1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5' regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family. Images PMID:2187193

  16. Spatiotemporal Wave Patterns: Information Dynamics

    SciTech Connect

    Mikhail Rabinovich; Lev Tsimring

    2006-01-20

    Pattern formation has traditionally been studied in non-equilibrium physics from the viewpoint of describing the basic structures and their interactions. While this is still an important area of research, the emphasis in the last few years has shifted towards analysis of specific properties of patterns in various complex media. For example, diverse and unexpected phenomena occur in neuro-like media that are characterized by highly non-trivial local dynamics. We carried out an active research program on analysis of spatio-temporal patterns in various physical systems (convection, oscillating fluid layer, soap film), as well as in neuro-like media, with an emphasis on informational aspects of the dynamics. Nonlinear nonequilibrium media and their discrete analogs have a unique ability to represent, memorize, and process the information contained in spatio-temporal patterns. Recent neurophysiological experiments demonstrated a certain universality of spatio-temporal representation of information by neural ensembles. Information processing is also revealed in the spatio-temporal dynamics of cellular patterns in nonequilibrium media. It is extremely important for many applications to study the informational aspects of these dynamics, including the origins and mechanisms of information generation, propagation and storage. Some of our results are: the discovery of self-organization of periodically oscillatory patterns in chaotic heterogeneous media; the analysis of the propagation of the information along a chaotic media as function of the entropy of the signal; the analysis of wave propagation in discrete non-equilibrium media with autocatalytic properties, which simulates the calcium dynamics in cellular membranes. Based on biological experiments we suggest the mechanism by which the spatial sensory information is transferred into the spatio-temporal code in the neural media. We also found a new mechanism of self-pinning in cellular structures and the related phenomenon

  17. Xenon and iodine reveal multiple distinct exotic xenon components in Efremovka "nanodiamonds"

    NASA Astrophysics Data System (ADS)

    Gilmour, J. D.; Holland, G.; Verchovsky, A. B.; Fisenko, A. V.; Crowther, S. A.; Turner, G.

    2016-03-01

    We identify new xenon components in a nanodiamond-rich residue from the reduced CV3 chondrite Efremovka. We demonstrate for the first time that these, and the previously identified xenon components Xe-P3 and Xe-P6, are associated with elevated I/Xe ratios. The 129I/127I ratio associated with xenon loss from these presolar compositions during processing on planetesimals in the early solar system was (0.369 ± 0.019) × 10-4, a factor of 3-4 lower than the canonical value. This suggests either incorporation of iodine into carbonaceous grains before the last input of freshly synthesized 129I to the solar system's precursor material, or loss of noble gases during processing of planetesimals around 30 Myr after solar system formation. The xenon/iodine ratios and model closure ages were revealed by laser step pyrolysis analysis of a neutron-irradiated, coarse-grained nanodiamond separate. Three distinct low temperature compositions are identified by characteristic I/Xe ratios and 136Xe/132Xe ratios. There is some evidence of multiple compositions with distinct I/Xe ratios in the higher temperature releases associated with Xe-P6. The presence of iodine alongside Q-Xe and these components in nanodiamonds constrains the pathway by which extreme volatiles entered the solid phase and may facilitate the identification of their carriers. There is no detectable iodine contribution to the presolar Xe-HL component, which is released at intermediate temperatures; this suggests a distinct trapping process. Releases associated with the other components all include significant contributions of 128Xe produced from iodine by neutron capture during reactor irradiation. We propose a revised model relating the origin of Xe-P3 (which exhibits an s-process deficit) through a ;Q-process; to the Q component (which makes the dominant contribution to the heavy noble gas budget of primitive material). The Q-process incorporates noble gases and iodine into specific carbonaceous phases with mass

  18. Phenotypic detection of clonotypic B cells in multiple myeloma by specific immunoglobulin ligands reveals their rarity in multiple myeloma.

    PubMed

    Trepel, Martin; Martens, Victoria; Doll, Christian; Rahlff, Janina; Gösch, Barbara; Loges, Sonja; Binder, Mascha

    2012-01-01

    In multiple myeloma, circulating "clonotypic" B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential "feeder" cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10(-3), this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology.

  19. Dynamics of multiple phases in a colossal-magnetoresistive manganite as revealed by dielectric spectroscopy.

    PubMed

    Sheng, Zhigao; Nakamura, Masao; Kagawa, Fumitaka; Kawasaki, Masashi; Tokura, Yoshinori

    2012-07-10

    Electronic phase separation is one of the key features in correlated electron oxides. The coexistence and competition of multiple phases give rise to gigantic responses to tiny stimuli producing dramatic changes in magnetic, transport and other properties of these compounds. To probe the physical properties of each phase separately is crucial for a comprehensive understanding of phase separation phenomena and for designing their device functions. Here we unravel, using a unique p-n junction configuration, dynamic properties of multiple phases in manganite thin films. The multiple dielectric relaxations have been detected and their corresponding multiple phases have been identified, while the activation energies of dielectric responses from different phases were extracted separately. Their phase evolutions with changing both temperature and applied magnetic field have been demonstrated by dielectric response. These results provide a guideline for exploring the electronic phase separation phenomena in correlated electron oxides.

  20. Quantitative 3D Fluorescence Imaging of Single Catalytic Turnovers Reveals Spatiotemporal Gradients in Reactivity of Zeolite H-ZSM-5 Crystals upon Steaming.

    PubMed

    Ristanović, Zoran; Hofmann, Jan P; De Cremer, Gert; Kubarev, Alexey V; Rohnke, Marcus; Meirer, Florian; Hofkens, Johan; Roeffaers, Maarten B J; Weckhuysen, Bert M

    2015-05-27

    Optimizing the number, distribution, and accessibility of Brønsted acid sites in zeolite-based catalysts is of a paramount importance to further improve their catalytic performance. However, it remains challenging to measure real-time changes in reactivity of single zeolite catalyst particles by ensemble-averaging characterization methods. In this work, a detailed 3D single molecule, single turnover sensitive fluorescence microscopy study is presented to quantify the reactivity of Brønsted acid sites in zeolite H-ZSM-5 crystals upon steaming. This approach, in combination with the oligomerization of furfuryl alcohol as a probe reaction, allowed the stochastic behavior of single catalytic turnovers and temporally resolved turnover frequencies of zeolite domains smaller than the diffraction limited resolution to be investigated with great precision. It was found that the single turnover kinetics of the parent zeolite crystal proceeds with significant spatial differences in turnover frequencies on the nanoscale and noncorrelated temporal fluctuations. Mild steaming of zeolite H-ZSM-5 crystals at 500 °C led to an enhanced surface reactivity, with up to 4 times higher local turnover rates than those of the parent H-ZSM-5 crystals, and revealed remarkable heterogeneities in surface reactivity. In strong contrast, severe steaming at 700 °C significantly dealuminated the zeolite H-ZSM-5 material, leading to a 460 times lower turnover rate. The differences in measured turnover activities are explained by changes in the 3D aluminum distribution due to migration of extraframework Al-species and their subsequent effect on pore accessibility, as corroborated by time-of-flight secondary ion mass spectrometry (TOF-SIMS) sputter depth profiling data.

  1. Quantitative 3D Fluorescence Imaging of Single Catalytic Turnovers Reveals Spatiotemporal Gradients in Reactivity of Zeolite H-ZSM-5 Crystals upon Steaming

    PubMed Central

    2015-01-01

    Optimizing the number, distribution, and accessibility of Brønsted acid sites in zeolite-based catalysts is of a paramount importance to further improve their catalytic performance. However, it remains challenging to measure real-time changes in reactivity of single zeolite catalyst particles by ensemble-averaging characterization methods. In this work, a detailed 3D single molecule, single turnover sensitive fluorescence microscopy study is presented to quantify the reactivity of Brønsted acid sites in zeolite H-ZSM-5 crystals upon steaming. This approach, in combination with the oligomerization of furfuryl alcohol as a probe reaction, allowed the stochastic behavior of single catalytic turnovers and temporally resolved turnover frequencies of zeolite domains smaller than the diffraction limited resolution to be investigated with great precision. It was found that the single turnover kinetics of the parent zeolite crystal proceeds with significant spatial differences in turnover frequencies on the nanoscale and noncorrelated temporal fluctuations. Mild steaming of zeolite H-ZSM-5 crystals at 500 °C led to an enhanced surface reactivity, with up to 4 times higher local turnover rates than those of the parent H-ZSM-5 crystals, and revealed remarkable heterogeneities in surface reactivity. In strong contrast, severe steaming at 700 °C significantly dealuminated the zeolite H-ZSM-5 material, leading to a 460 times lower turnover rate. The differences in measured turnover activities are explained by changes in the 3D aluminum distribution due to migration of extraframework Al-species and their subsequent effect on pore accessibility, as corroborated by time-of-flight secondary ion mass spectrometry (TOF-SIMS) sputter depth profiling data. PMID:25867455

  2. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    PubMed

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras.

  3. Multiple oxygen entry pathways in globin proteins revealed by intrinsic pathway identification method

    NASA Astrophysics Data System (ADS)

    Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

    2015-12-01

    Each subunit of human hemoglobin (HbA) stores an oxygen molecule (O2) in the binding site (BS) cavity near the heme group. The BS is buried in the interior of the subunit so that there is a debate over the O2 entry pathways from solvent to the BS; histidine gate or multiple pathways. To elucidate the O2 entry pathways, we executed ensemble molecular dynamics (MD) simulations of T-state tetramer HbA in high concentration O2 solvent to simulate spontaneous O2 entry from solvent into the BS. By analyzing 128 independent 8 ns MD trajectories by intrinsic pathway identification by clustering (IPIC) method, we found 141 and 425 O2 entry events into the BS of the α and β subunits, respectively. In both subunits, we found that multiple O2 entry pathways through inside cavities play a significant role for O2 entry process of HbA. The rate constants of O2 entry estimated from the MD trajectories correspond to the experimentally observed values. In addition, by analyzing monomer myoglobin, we verified that the high O2 concentration condition can reproduce the ratios of each multiple pathway in the one-tenth lower O2 concentration condition. These indicate the validity of the multiple pathways obtained in our MD simulations.

  4. Ar-Ar Age of the L Chondrite Northwest Africa 091: More Evidence that Multiple Isochrons Reveal a Link to Fossil Meteorites

    NASA Astrophysics Data System (ADS)

    Weirich, J. R.; Isachsen, C. E.; Swindle, T. D.

    2011-03-01

    The multiple isochron approach on NWA 091 reveals impacts at 472 ± 6 and 799 ± 71 Ma, with different trapped components at different release temperatures. Two trapped components >1000°C suggests multiple high temperature K domains.

  5. Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.

    PubMed

    Nakaya, Helder I; Hagan, Thomas; Duraisingham, Sai S; Lee, Eva K; Kwissa, Marcin; Rouphael, Nadine; Frasca, Daniela; Gersten, Merril; Mehta, Aneesh K; Gaujoux, Renaud; Li, Gui-Mei; Gupta, Shakti; Ahmed, Rafi; Mulligan, Mark J; Shen-Orr, Shai; Blomberg, Bonnie B; Subramaniam, Shankar; Pulendran, Bali

    2015-12-15

    Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza.

  6. Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions

    PubMed Central

    Garone, Caterina; Bordoni, Andreina; Gutierrez Rios, Purificacion; Calvo, Sarah E.; Ripolone, Michela; Ranieri, Michela; Rizzuti, Mafalda; Villa, Luisa; Magri, Francesca; Corti, Stefania; Bresolin, Nereo; Mootha, Vamsi K.; Moggio, Maurizio; DiMauro, Salvatore; Comi, Giacomo P.; Sciacco, Monica

    2012-01-01

    The molecular diagnosis of mitochondrial disorders still remains elusive in a large proportion of patients, but advances in next generation sequencing are significantly improving our chances to detect mutations even in sporadic patients. Syndromes associated with mitochondrial DNA multiple deletions are caused by different molecular defects resulting in a wide spectrum of predominantly adult-onset clinical presentations, ranging from progressive external ophthalmoplegia to multi-systemic disorders of variable severity. The mutations underlying these conditions remain undisclosed in half of the affected subjects. We applied next-generation sequencing of known mitochondrial targets (MitoExome) to probands presenting with adult-onset mitochondrial myopathy and harbouring mitochondrial DNA multiple deletions in skeletal muscle. We identified autosomal recessive mutations in the DGUOK gene (encoding mitochondrial deoxyguanosine kinase), which has previously been associated with an infantile hepatocerebral form of mitochondrial DNA depletion. Mutations in DGUOK occurred in five independent subjects, representing 5.6% of our cohort of patients with mitochondrial DNA multiple deletions, and impaired both muscle DGUOK activity and protein stability. Clinical presentations were variable, including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis in a young female who had received a liver transplant at 9 months of age and adult-onset lower motor neuron syndrome with mild cognitive impairment. These findings reinforce the concept that mutations in genes involved in deoxyribonucleotide metabolism can cause diverse clinical phenotypes and suggest that DGUOK should be screened in patients harbouring mitochondrial DNA deletions in skeletal muscle. PMID:23043144

  7. Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers.

    PubMed

    Grossman, Iris; Avidan, Nili; Singer, Clara; Goldstaub, Dan; Hayardeny, Liat; Eyal, Eli; Ben-Asher, Edna; Paperna, Tamar; Pe'er, Itsik; Lancet, Doron; Beckmann, Jacques S; Miller, Ariel

    2007-08-01

    Genetic-based optimization of treatment prescription is becoming a central research focus in the management of chronic diseases, such as multiple sclerosis, which incur a prolonged drug-regimen adjustment. This study was aimed to identify genetic markers that can predict response to glatiramer acetate (Copaxone) immunotherapy for relapsing multiple sclerosis. For this purpose, we genotyped fractional cohorts of two glatiramer acetate clinical trials for HLA-DRB1*1501 and 61 single nucleotide polymorphisms within a total of 27 candidate genes. Statistical analyses included single nucleotide polymorphism-by-single nucleotide polymorphism and haplotype tests of drug-by-genotype effects in drug-treated versus placebo-treated groups. We report the detection of a statistically significant association between glatiramer acetate response and a single nucleotide polymorphism in a T-cell receptor beta (TRB@) variant replicated in the two independent cohorts (odds ratio=6.85). Findings in the Cathepsin S (CTSS) gene (P=0.049 corrected for all single nucleotide polymorphisms and definitions tested, odds ratio=11.59) in one of the cohorts indicate a possible association that needs to be further investigated. Additionally, we recorded nominally significant associations of response with five other genes, MBP, CD86, FAS, IL1R1 and IL12RB2, which are likely to be involved in glatiramer acetate's mode-of-action, both directly and indirectly. Each of these association signals in and of itself is consistent with the no-association null-hypothesis, but the number of detected associations is surprising vis-à-vis chance expectation. Moreover, the restriction of these associations to the glatiramer acetate-treated group, rather than the placebo group, clearly demonstrates drug-specific genetic effects. These findings provide additional progress toward development of pharmacogenetics-based personalized treatment for multiple sclerosis.

  8. Transcriptome analysis reveals crosstalk of responsive genes to multiple abiotic stresses in cotton (Gossypium hirsutum L.).

    PubMed

    Zhu, Ya-Na; Shi, Dong-Qiao; Ruan, Meng-Bin; Zhang, Li-Li; Meng, Zhao-Hong; Liu, Jie; Yang, Wei-Cai

    2013-01-01

    Abiotic stress is a major environmental factor that limits cotton growth and yield, moreover, this problem has become more and more serious recently, as multiple stresses often occur simultaneously due to the global climate change and environmental pollution. In this study, we sought to identify genes involved in diverse stresses including abscisic acid (ABA), cold, drought, salinity and alkalinity by comparative microarray analysis. Our result showed that 5790, 3067, 5608, 778 and 6148 transcripts, were differentially expressed in cotton seedlings under treatment of ABA (1 μM ABA), cold (4°C), drought (200 mM mannitol), salinity (200 mM NaCl) and alkalinity (pH=11) respectively. Among the induced or suppressed genes, 126 transcripts were shared by all of the five kinds of abiotic stresses, with 64 up-regulated and 62 down-regulated. These common members are grouped as stress signal transduction, transcription factors (TFs), stress response/defense proteins, metabolism, transport facilitation, as well as cell wall/structure, according to the function annotation. We also noticed that large proportion of significant differentially expressed genes specifically regulated in response to different stress. Nine of the common transcripts of multiple stresses were selected for further validation with quantitative real time RT-PCR (qRT-PCR). Furthermore, several well characterized TF families, for example, WRKY, MYB, NAC, AP2/ERF and zinc finger were shown to be involved in different stresses. As an original report using comparative microarray to analyze transcriptome of cotton under five abiotic stresses, valuable information about functional genes and related pathways of anti-stress, and/or stress tolerance in cotton seedlings was unveiled in our result. Besides this, some important common factors were focused for detailed identification and characterization. According to our analysis, it suggested that there was crosstalk of responsive genes or pathways to multiple

  9. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism

    PubMed Central

    Wang, Lijie; Zhang, Tong; Watson, David G.; Silva, Ana Marta; Coombs, Graham H.

    2015-01-01

    Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts. PMID:26368322

  10. Multiple bases of human intelligence revealed by cortical thickness and neural activation.

    PubMed

    Choi, Yu Yong; Shamosh, Noah A; Cho, Sun Hee; DeYoung, Colin G; Lee, Min Joo; Lee, Jong-Min; Kim, Sun I; Cho, Zang-Hee; Kim, Kyungjin; Gray, Jeremy R; Lee, Kun Ho

    2008-10-08

    We hypothesized that individual differences in intelligence (Spearman's g) are supported by multiple brain regions, and in particular that fluid (gF) and crystallized (gC) components of intelligence are related to brain function and structure with a distinct profile of association across brain regions. In 225 healthy young adults scanned with structural and functional magnetic resonance imaging sequences, regions of interest (ROIs) were defined on the basis of a correlation between g and either brain structure or brain function. In these ROIs, gC was more strongly related to structure (cortical thickness) than function, whereas gF was more strongly related to function (blood oxygenation level-dependent signal during reasoning) than structure. We further validated this finding by generating a neurometric prediction model of intelligence quotient (IQ) that explained 50% of variance in IQ in an independent sample. The data compel a nuanced view of the neurobiology of intelligence, providing the most persuasive evidence to date for theories emphasizing multiple distributed brain regions differing in function.

  11. Integrated Multiple “-omics” Data Reveal Subtypes of Hepatocellular Carcinoma

    PubMed Central

    Liu, Gang; Dong, Chuanpeng; Liu, Lei

    2016-01-01

    Hepatocellular carcinoma is one of the most heterogeneous cancers, as reflected by its multiple grades and difficulty to subtype. In this study, we integrated copy number variation, DNA methylation, mRNA, and miRNA data with the developed “cluster of cluster” method and classified 256 HCC samples from TCGA (The Cancer Genome Atlas) into five major subgroups (S1-S5). We observed that this classification was associated with specific mutations and protein expression, and we detected that each subgroup had distinct molecular signatures. The subclasses were associated not only with survival but also with clinical observations. S1 was characterized by bulk amplification on 8q24, TP53 mutation, low lipid metabolism, highly expressed onco-proteins, attenuated tumor suppressor proteins and a worse survival rate. S2 and S3 were characterized by telomere hypomethylation and a low expression of TERT and DNMT1/3B. Compared to S2, S3 was associated with less copy number variation and some good prognosis biomarkers, including CRP and CYP2E1. In contrast, the mutation rate of CTNNB1 was higher in S3. S4 was associated with bulk amplification and various molecular characteristics at different biological levels. In summary, we classified the HCC samples into five subgroups using multiple “-omics” data. Each subgroup had a distinct survival rate and molecular signature, which may provide information about the pathogenesis of subtypes in HCC. PMID:27806083

  12. Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes.

    PubMed

    Paraboschi, Elvezia Maria; Cardamone, Giulia; Rimoldi, Valeria; Gemmati, Donato; Spreafico, Marta; Duga, Stefano; Soldà, Giulia; Asselta, Rosanna

    2015-09-30

    Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p=0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

  13. Three-Dimensional Structures Reveal Multiple ADP/ATP Binding Modes

    SciTech Connect

    C Simmons; C Magee; D Smith; L Lauman; J Chaput; J Allen

    2011-12-31

    The creation of synthetic enzymes with predefined functions represents a major challenge in future synthetic biology applications. Here, we describe six structures of de novo proteins that have been determined using protein crystallography to address how simple enzymes perform catalysis. Three structures are of a protein, DX, selected for its stability and ability to tightly bind ATP. Despite the addition of ATP to the crystallization conditions, the presence of a bound but distorted ATP was found only under excess ATP conditions, with ADP being present under equimolar conditions or when crystallized for a prolonged period of time. A bound ADP cofactor was evident when Asp was substituted for Val at residue 65, but ATP in a linear configuration is present when Phe was substituted for Tyr at residue 43. These new structures complement previously determined structures of DX and the protein with the Phe 43 to Tyr substitution [Simmons, C. R., et al. (2009) ACS Chem. Biol. 4, 649-658] and together demonstrate the multiple ADP/ATP binding modes from which a model emerges in which the DX protein binds ATP in a configuration that represents a transitional state for the catalysis of ATP to ADP through a slow, metal-free reaction capable of multiple turnovers. This unusual observation suggests that design-free methods can be used to generate novel protein scaffolds that are tailor-made for catalysis.

  14. Spatio-temporal clustering

    NASA Astrophysics Data System (ADS)

    Kisilevich, Slava; Mansmann, Florian; Nanni, Mirco; Rinzivillo, Salvatore

    Spatio-temporal clustering is a process of grouping objects based on their spatial and temporal similarity. It is relatively new subfield of data mining which gained high popularity especially in geographic information sciences due to the pervasiveness of all kinds of location-based or environmental devices that record position, time or/and environmental properties of an object or set of objects in real-time. As a consequence, different types and large amounts of spatio-temporal data became available that introduce new challenges to data analysis and require novel approaches to knowledge discovery. In this chapter we concentrate on the spatio-temporal clustering in geographic space. First, we provide a classification of different types of spatio-temporal data. Then, we focus on one type of spatio-temporal clustering - trajectory clustering, provide an overview of the state-of-the-art approaches and methods of spatio-temporal clustering and finally present several scenarios in different application domains such as movement, cellular networks and environmental studies.

  15. Single-molecule analysis reveals widespread structural variation in multiple myeloma

    PubMed Central

    Gupta, Aditya; Place, Michael; Goldstein, Steven; Sarkar, Deepayan; Zhou, Shiguo; Potamousis, Konstantinos; Kim, Jaehyup; Flanagan, Claire; Li, Yang; Newton, Michael A.; Callander, Natalie S.; Hematti, Peiman; Bresnick, Emery H.; Ma, Jian; Asimakopoulos, Fotis; Schwartz, David C.

    2015-01-01

    Multiple myeloma (MM), a malignancy of plasma cells, is characterized by widespread genomic heterogeneity and, consequently, differences in disease progression and drug response. Although recent large-scale sequencing studies have greatly improved our understanding of MM genomes, our knowledge about genomic structural variation in MM is attenuated due to the limitations of commonly used sequencing approaches. In this study, we present the application of optical mapping, a single-molecule, whole-genome analysis system, to discover new structural variants in a primary MM genome. Through our analysis, we have identified and characterized widespread structural variation in this tumor genome. Additionally, we describe our efforts toward comprehensive characterization of genome structure and variation by integrating our findings from optical mapping with those from DNA sequencing-based genomic analysis. Finally, by studying this MM genome at two time points during tumor progression, we have demonstrated an increase in mutational burden with tumor progression at all length scales of variation. PMID:26056298

  16. Streptococcus pneumoniae causing septic arthritis with shock and revealing multiple myeloma

    PubMed Central

    Riachy, Moussa Albert

    2011-01-01

    The authors present the case of a 43-year-old male who presented at the emergency department, with a mean arterial pressure of 48 mm of Hg, a sinus tachycardia of 142/min and shallow breathing at 30/min. Two days previously, he started a high-grade fever with a concomitant reddish and painful left knee and right elbow, without any treatment. Septic shock was diagnosed and the patient was started on empiric antibiotics combining ceftriaxone and vancomycin and vasopressors (norepinephrine). The painful knee and elbow joints were aspirated and cultures grew Streptococcus pneumoniae. The patient’s clinical condition improved progressively and after investigation, the diagnosis of multiple myeloma was concluded. Pneumococcal septic arthritis, an extraordinary cause of septic arthritis, is a manifestation of an underlying disease and can be responsible for septic shock. Its diagnosis should direct further investigations. It can occur in patients with joint disease but should emphasise the search of systemic immunosuppression. PMID:22694889

  17. Multiple time scales of adaptation in the auditory system as revealed by human evoked potentials.

    PubMed

    Costa-Faidella, Jordi; Grimm, Sabine; Slabu, Lavinia; Díaz-Santaella, Francisco; Escera, Carles

    2011-06-01

    Single neurons in the primary auditory cortex of the cat show faster adaptation time constants to short- than long-term stimulus history. This ability to encode the complex past auditory stimulation in multiple time scales would enable the auditory system to generate expectations of the incoming stimuli. Here, we tested whether large neural populations exhibit this ability as well, by recording human auditory evoked potentials (AEP) to pure tones in a sequence embedding short- and long-term aspects of stimulus history. Our results yielded dynamic amplitude modulations of the P2 AEP to stimulus repetition spanning from milliseconds to tens of seconds concurrently, as well as amplitude modulations of the mismatch negativity AEP to regularity violations. A simple linear model of expectancy accounting for both short- and long-term stimulus history described our results, paralleling the behavior of neurons in the primary auditory cortex.

  18. Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.

    PubMed

    Huang, Shengfeng; Chen, Zelin; Yan, Xinyu; Yu, Ting; Huang, Guangrui; Yan, Qingyu; Pontarotti, Pierre Antoine; Zhao, Hongchen; Li, Jie; Yang, Ping; Wang, Ruihua; Li, Rui; Tao, Xin; Deng, Ting; Wang, Yiquan; Li, Guang; Zhang, Qiujin; Zhou, Sisi; You, Leiming; Yuan, Shaochun; Fu, Yonggui; Wu, Fenfang; Dong, Meiling; Chen, Shangwu; Xu, Anlong

    2014-12-19

    Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE). Modern vertebrates also lost substantial transposable element (TE) diversity, whereas lancelets preserve high TE diversity that includes even the long-sought RAG transposon. Lancelets also exhibit rapid gene turnover, pervasive transcription, fastest exon shuffling in metazoans and substantial TE methylation not observed in other invertebrates. These new lancelet genome sequences provide new insights into the chordate ancestral state and the vertebrate evolution.

  19. Genetic analysis reveals multiple parentage in captive reared eastern hellbender salamanders (Cryptobranchus alleganiensis).

    PubMed

    Unger, Shem D; Williams, Rod N

    2015-11-01

    Information on the parentage of captive reared clutches is vital for conservation head-starting programs. Molecular methods, such as genotyping individuals with hyper-variable markers, can elucidate the genealogical contribution of captive-reared, reintroduced individuals to native populations. In this study, we used 12 polymorphic microsatellite loci to infer parentage of a clutch of 18 eastern hellbenders collected from a single nest from Buffalo Creek, West Virginia, subsequently reared in captivity, and used for translocations in Indiana. Collectively, these markers successfully detected the presence of multiple parentage for this species of conservation concern presently used in captive management programs in zoos across many states. This study highlights the need for genetic analysis of captive reared clutches used in translocations to minimize the loss of genetic diversity and potential for genetic swamping at release sites.

  20. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.

    PubMed

    Zahid, Henna; Miah, Layeque; Lau, Andy M; Brochard, Lea; Hati, Debolina; Bui, Tam T T; Drake, Alex F; Gor, Jayesh; Perkins, Stephen J; McDermott, Lindsay C

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.

  1. The visual pulvinar in tree shrews I. Multiple subdivisions revealed through acetylcholinesterase and Cat-301 chemoarchitecture.

    PubMed

    Lyon, David C; Jain, Neeraj; Kaas, Jon H

    2003-12-22

    Tree shrews are highly visual mammals closely related to primates. They have a large visual pulvinar complex, but its organization and relation to visual cortex is only partly known. We processed brain sections through the pulvinar with seven different procedures in an effort to reveal histologically distinct compartments. The results revealed three major subdivisions. A dorsal subdivision, Pd, stains darkly for acetylcholinesterase (AChE) and occupies the dorsoposterior one-third of the pulvinar complex. A ventral subdivision, Pv, stains darkly when processed with the Cat-301 antibody and occupies the ventroanterior fifth of the pulvinar complex along the brachium of the superior colliculus. Unexpectedly, part of Pv is ventral to the brachium. A large central subdivision, Pc, stains moderately dark for AChE and cytochrome oxidase (CO), and very light for Cat-301. Pc includes about half of the pulvinar complex, with parts on both sides of the brachium of the superior colliculus. These architectonic results demonstrate that the pulvinar complex of tree shrews is larger and has more subdivisions than previously described. The complex resembles the pulvinar of primates by having a portion ventral to the brachium and by having histochemically distinct nuclei; the number of nuclei is less than in primates, however.

  2. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    PubMed

    Benitez, Cecil M; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H Efsun; Zhang, Jiajing; Dekker, Joseph D; Tucker, Haley O; Chang, Howard Y; Kim, Seung K

    2014-10-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  3. Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications

    PubMed Central

    Burks, Scott R.; Ziadloo, Ali; Kim, Saejeong J.; Nguyen, Ben A.; Frank, Joseph A.

    2013-01-01

    Stem cells are promising therapeutics for cardiovascular diseases and intravenous injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemo attractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (plus), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemo attractant expression in plus-treated tissue prior to cell infusions. We demonstrate that plus is nondestructive to marine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate local up regulation of chemo attractants in plus-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when plus treatments and cell infusions were repeated daily. This study demonstrates that plus defines transient “molecular zip codes” of elevated chemo attractants in targeted muscle tissue, which effectively provides spatiotemporal control and tenability of the homing process for multiple stem cell types. plus is a clinically-translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. PMID:23922277

  4. Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning.

    PubMed

    Frank, Michael J; Moustafa, Ahmed A; Haughey, Heather M; Curran, Tim; Hutchison, Kent E

    2007-10-09

    What are the genetic and neural components that support adaptive learning from positive and negative outcomes? Here, we show with genetic analyses that three independent dopaminergic mechanisms contribute to reward and avoidance learning in humans. A polymorphism in the DARPP-32 gene, associated with striatal dopamine function, predicted relatively better probabilistic reward learning. Conversely, the C957T polymorphism of the DRD2 gene, associated with striatal D2 receptor function, predicted the degree to which participants learned to avoid choices that had been probabilistically associated with negative outcomes. The Val/Met polymorphism of the COMT gene, associated with prefrontal cortical dopamine function, predicted participants' ability to rapidly adapt behavior on a trial-to-trial basis. These findings support a neurocomputational dissociation between striatal and prefrontal dopaminergic mechanisms in reinforcement learning. Computational maximum likelihood analyses reveal independent gene effects on three reinforcement learning parameters that can explain the observed dissociations.

  5. Mutual information reveals multiple structural relaxation mechanisms in a model glass former

    PubMed Central

    Dunleavy, Andrew J.; Wiesner, Karoline; Yamamoto, Ryoichi; Royall, C. Patrick

    2015-01-01

    Among the key challenges to our understanding of solidification in the glass transition is that it is accompanied by little apparent change in structure. Recently, geometric motifs have been identified in glassy liquids, but a causal link between these motifs and solidification remains elusive. One ‘smoking gun’ for such a link would be identical scaling of structural and dynamic lengthscales on approaching the glass transition, but this is highly controversial. Here we introduce an information theoretic approach to determine correlations in displacement for particle relaxation encoded in the initial configuration of a glass-forming liquid. We uncover two populations of particles, one inclined to relax quickly, the other slowly. Each population is correlated with local density and geometric motifs. Our analysis further reveals a dynamic lengthscale similar to that associated with structural properties, which may resolve the discrepancy between structural and dynamic lengthscales. PMID:25608791

  6. Genome Mining for Radical SAM Protein Determinants Reveals Multiple Sactibiotic-Like Gene Clusters

    PubMed Central

    Murphy, Kiera; O'Sullivan, Orla; Rea, Mary C.; Cotter, Paul D.; Ross, R. Paul; Hill, Colin

    2011-01-01

    Thuricin CD is a two-component bacteriocin produced by Bacillus thuringiensis that kills a wide range of clinically significant Clostridium difficile. This bacteriocin has recently been characterized and consists of two distinct peptides, Trnβ and Trnα, which both possess 3 intrapeptide sulphur to α-carbon bridges and act synergistically. Indeed, thuricin CD and subtilosin A are the only antimicrobials known to possess these unusual structures and are known as the sactibiotics (sulplur to alpha carbon-containing antibiotics). Analysis of the thuricin CD-associated gene cluster revealed the presence of genes encoding two highly unusual SAM proteins (TrnC and TrnD) which are proposed to be responsible for these unusual post-translational modifications. On the basis of the frequently high conservation among enzymes responsible for the post-translational modification of specific antimicrobials, we performed an in silico screen for novel thuricin CD–like gene clusters using the TrnC and TrnD radical SAM proteins as driver sequences to perform an initial homology search against the complete non-redundant database. Fifteen novel thuricin CD–like gene clusters were identified, based on the presence of TrnC and TrnD homologues in the context of neighbouring genes encoding potential bacteriocin structural peptides. Moreover, metagenomic analysis revealed that TrnC or TrnD homologs are present in a variety of metagenomic environments, suggesting a widespread distribution of thuricin-like operons in a variety of environments. In-silico analysis of radical SAM proteins is sufficient to identify novel putative sactibiotic clusters. PMID:21760885

  7. Whole population cell analysis of a landmark-rich mammalian epithelium reveals multiple elongation mechanisms

    PubMed Central

    Economou, Andrew D.; Brock, Lara J.; Cobourne, Martyn T.; Green, Jeremy B. A.

    2013-01-01

    Tissue elongation is a fundamental component of developing and regenerating systems. Although localised proliferation is an important mechanism for tissue elongation, potentially important contributions of other elongation mechanisms, specifically cell shape change, orientated cell division and cell rearrangement, are rarely considered or quantified, particularly in mammalian systems. Their quantification, together with proliferation, provides a rigorous framework for the analysis of elongation. The mammalian palatal epithelium is a landmark-rich tissue, marked by regularly spaced ridges (rugae), making it an excellent model in which to analyse the contributions of cellular processes to directional tissue growth. We captured confocal stacks of entire fixed mouse palate epithelia throughout the mid-gestation growth period, labelled with membrane, nuclear and cell proliferation markers and segmented all cells (up to ∼20,000 per palate), allowing the quantification of cell shape and proliferation. Using the rugae as landmarks, these measures revealed that the so-called growth zone is a region of proliferation that is intermittently elevated at ruga initiation. The distribution of oriented cell division suggests that it is not a driver of tissue elongation, whereas cell shape analysis revealed that both elongation of cells leaving the growth zone and apico-basal cell rearrangements do contribute significantly to directional growth. Quantitative comparison of elongation processes indicated that proliferation contributes most to elongation at the growth zone, but cell shape change and rearrangement contribute as much as 40% of total elongation. We have demonstrated the utility of an approach to analysing the cellular mechanisms underlying tissue elongation in mammalian tissues. It should be broadly applied to higher-resolution analysis of links between genotypes and malformation phenotypes. PMID:24173805

  8. Comparative Genomics Revealed Multiple Helicobacter pylori Genes Associated with Biofilm Formation In Vitro

    PubMed Central

    Chua, Eng Guan; Tay, Alfred Chin Yen; Peters, Fanny; Marshall, Barry J.; Ho, Bow; Goh, Khean Lee; Vadivelu, Jamuna; Loke, Mun Fai

    2016-01-01

    Background Biofilm formation by Helicobacter pylori may be one of the factors influencing eradication outcome. However, genetic differences between good and poor biofilm forming strains have not been studied. Materials and Methods Biofilm yield of 32 Helicobacter pylori strains (standard strain and 31 clinical strains) were determined by crystal-violet assay and grouped into poor, moderate and good biofilm forming groups. Whole genome sequencing of these 32 clinical strains was performed on the Illumina MiSeq platform. Annotation and comparison of the differences between the genomic sequences were carried out using RAST (Rapid Annotation using Subsystem Technology) and SEED viewer. Genes identified were confirmed using PCR. Results Genes identified to be associated with biofilm formation in H. pylori includes alpha (1,3)-fucosyltransferase, flagellar protein, 3 hypothetical proteins, outer membrane protein and a cag pathogenicity island protein. These genes play a role in bacterial motility, lipopolysaccharide (LPS) synthesis, Lewis antigen synthesis, adhesion and/or the type-IV secretion system (T4SS). Deletion of cagA and cagPAI confirmed that CagA and T4SS were involved in H. pylori biofilm formation. Conclusions Results from this study suggest that biofilm formation in H. pylori might be genetically determined and might be influenced by multiple genes. Good, moderate and poor biofilm forming strain might differ during the initiation of biofilm formation. PMID:27870886

  9. Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis

    PubMed Central

    Carroll, James A.; Olano, L. Rennee; Sturdevant, Daniel E.; Rosa, Patricia A.

    2015-01-01

    The saprophyte Leptospira biflexa is an excellent model for studying the physiology of the medically important Leptospira genus, the pathogenic members of which are more recalcitrant to genetic manipulation and have significantly slower in vitro growth. However, relatively little is known regarding the proteome of L. biflexa, limiting its utility as a model for some studies. Therefore, we have generated a proteomic map of both soluble and membrane-associated proteins of L. biflexa during exponential growth and in stationary phase. Using these data, we identified abundantly produced proteins in each cellular fraction and quantified the transcript levels from a subset of these genes using quantitative reverse transcription-PCR (RT-PCR). These proteins should prove useful as cellular markers and as controls for gene expression studies. We also observed a significant number of L. biflexa membrane-associated proteins with multiple isoforms, each having unique isoelectric focusing points. L. biflexa cell lysates were examined for several posttranslational modifications suggested by the protein patterns. Methylation and acetylation of lysine residues were predominately observed in the proteins of the membrane-associated fraction, while phosphorylation was detected mainly among soluble proteins. These three posttranslational modification systems appear to be conserved between the free-living species L. biflexa and the pathogenic species Leptospira interrogans, suggesting an important physiological advantage despite the varied life cycles of the different species. PMID:26655756

  10. Ecosystem service tradeoff analysis reveals the value of marine spatial planning for multiple ocean uses.

    PubMed

    White, Crow; Halpern, Benjamin S; Kappel, Carrie V

    2012-03-20

    Marine spatial planning (MSP) is an emerging responsibility of resource managers around the United States and elsewhere. A key proposed advantage of MSP is that it makes tradeoffs in resource use and sector (stakeholder group) values explicit, but doing so requires tools to assess tradeoffs. We extended tradeoff analyses from economics to simultaneously assess multiple ecosystem services and the values they provide to sectors using a robust, quantitative, and transparent framework. We used the framework to assess potential conflicts among offshore wind energy, commercial fishing, and whale-watching sectors in Massachusetts and identify and quantify the value from choosing optimal wind farm designs that minimize conflicts among these sectors. Most notably, we show that using MSP over conventional planning could prevent >$1 million dollars in losses to the incumbent fishery and whale-watching sectors and could generate >$10 billion in extra value to the energy sector. The value of MSP increased with the greater the number of sectors considered and the larger the area under management. Importantly, the framework can be applied even when sectors are not measured in dollars (e.g., conservation). Making tradeoffs explicit improves transparency in decision-making, helps avoid unnecessary conflicts attributable to perceived but weak tradeoffs, and focuses debate on finding the most efficient solutions to mitigate real tradeoffs and maximize sector values. Our analysis demonstrates the utility, feasibility, and value of MSP and provides timely support for the management transitions needed for society to address the challenges of an increasingly crowded ocean environment.

  11. Hydrodynamics of horseradish peroxidase revealed by global analysis of multiple fluorescence probes.

    PubMed Central

    Brunet, J E; Vargas, V; Gratton, E; Jameson, D M

    1994-01-01

    Previous fluorescence studies of horseradish peroxidase conjugated with protoporphyrin IX suggested that the protein behaved hydrodynamically as a prolate ellipsoid of axial ratio 3 to 1. The present study, designed to further investigate the hydrodynamics of this protein, exploits a series of probes, noncovalently bound to the heme binding site of apo-horseradish peroxidase, having different orientations of the excitation and emission transition dipoles with respect to the protein's rotational axes. The probes utilized included protoporphyrin IX and the naphthalene probes 1-anilino-8-naphthalene sulfonate, 2-p-toluidinyl-6-naphthalene sulfonate, and 4,4'-bis(1-anilino-8-naphthalene sulfonate). Time-resolved data were obtained using multifrequency phase fluorometry. The global analysis approach to the determination of molecular shape using multiple probes was evaluated by utilizing all data sets while maintaining a constant molecular shape for the protein. The results indicated that, in such analyses, probes exhibiting a single exponential decay and limited local motion have the major weight in the evaluation of the axial ratio. Probes that show complex decay patterns and local motions, such as the naphthalene derivatives, give rise to significant uncertainties in such global treatments. By explicitly accounting for the effect of such local motion, however, the shape of the protein can be reliably recovered. PMID:8161698

  12. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism.

    PubMed Central

    Umezu, K; Sugawara, N; Chen, C; Haber, J E; Kolodner, R D

    1998-01-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10(4) to 10(5) times increased sensitivity to these agents. Some of the UV- and MMS-sensitive mutants were killed by an HO-induced double-strand break at MAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. PMID:9539419

  13. Multiple-stage ambiguity in motion perception reveals global computation of local motion directions.

    PubMed

    Rider, Andrew T; Nishida, Shin'ya; Johnston, Alan

    2016-12-01

    The motion of a 1D image feature, such as a line, seen through a small aperture, or the small receptive field of a neural motion sensor, is underconstrained, and it is not possible to derive the true motion direction from a single local measurement. This is referred to as the aperture problem. How the visual system solves the aperture problem is a fundamental question in visual motion research. In the estimation of motion vectors through integration of ambiguous local motion measurements at different positions, conventional theories assume that the object motion is a rigid translation, with motion signals sharing a common motion vector within the spatial region over which the aperture problem is solved. However, this strategy fails for global rotation. Here we show that the human visual system can estimate global rotation directly through spatial pooling of locally ambiguous measurements, without an intervening step that computes local motion vectors. We designed a novel ambiguous global flow stimulus, which is globally as well as locally ambiguous. The global ambiguity implies that the stimulus is simultaneously consistent with both a global rigid translation and an infinite number of global rigid rotations. By the standard view, the motion should always be seen as a global translation, but it appears to shift from translation to rotation as observers shift fixation. This finding indicates that the visual system can estimate local vectors using a global rotation constraint, and suggests that local motion ambiguity may not be resolved until consistencies with multiple global motion patterns are assessed.

  14. Ecosystem service tradeoff analysis reveals the value of marine spatial planning for multiple ocean uses

    PubMed Central

    White, Crow; Halpern, Benjamin S.; Kappel, Carrie V.

    2012-01-01

    Marine spatial planning (MSP) is an emerging responsibility of resource managers around the United States and elsewhere. A key proposed advantage of MSP is that it makes tradeoffs in resource use and sector (stakeholder group) values explicit, but doing so requires tools to assess tradeoffs. We extended tradeoff analyses from economics to simultaneously assess multiple ecosystem services and the values they provide to sectors using a robust, quantitative, and transparent framework. We used the framework to assess potential conflicts among offshore wind energy, commercial fishing, and whale-watching sectors in Massachusetts and identify and quantify the value from choosing optimal wind farm designs that minimize conflicts among these sectors. Most notably, we show that using MSP over conventional planning could prevent >$1 million dollars in losses to the incumbent fishery and whale-watching sectors and could generate >$10 billion in extra value to the energy sector. The value of MSP increased with the greater the number of sectors considered and the larger the area under management. Importantly, the framework can be applied even when sectors are not measured in dollars (e.g., conservation). Making tradeoffs explicit improves transparency in decision-making, helps avoid unnecessary conflicts attributable to perceived but weak tradeoffs, and focuses debate on finding the most efficient solutions to mitigate real tradeoffs and maximize sector values. Our analysis demonstrates the utility, feasibility, and value of MSP and provides timely support for the management transitions needed for society to address the challenges of an increasingly crowded ocean environment. PMID:22392996

  15. Phylogenetic relationships of rat lungworm, Angiostrongylus cantonensis, isolated from different geographical regions revealed widespread multiple lineages.

    PubMed

    Tokiwa, Toshihiro; Harunari, Tsunehito; Tanikawa, Tsutomu; Komatsu, Noriyuki; Koizumi, Nobuo; Tung, Kwong-Chung; Suzuki, Jun; Kadosaka, Teruki; Takada, Nobuhiro; Kumagai, Takashi; Akao, Nobuaki; Ohta, Nobuo

    2012-09-01

    We conducted a pilot survey of genetic variation of A. cantonensis using small subunit (SSU) ribosomal (r) RNA and mitochondrial cytochrome c oxidase subunit I (coxI) gene sequences. Two distinct SSU genotypes (G1 and G2) were identified among 17 individual A. cantonensis worms from 17 different geographical localities in Japan, Mainland China, Taiwan, and Thailand. The partial coxI sequences were determined for 83 worms from 18 different geographical localities from Japan, Mainland China, Taiwan, and Thailand. Phylogenetic analysis showed eight distinct coxI haplotypes (ac1 to ac8). In 16 out of 18 localities, only a single coxI haplotype was found. However, in two localities, two coxI haplotypes coexisted. The common haplotypes found were: haplotype ac1 (Tokyo, Chiba, Kanagawa, Amamioshima Island, and Taichung), haplotype ac2 (Ishikawa, Shenzhen, and Lianjiang), haplotype ac5 (the Okinawa and the Ogasawara Islands), and haplotype ac7 (Miyagi, Aichi, and Kanagawa). Each of these regions is separated from the others by high mountain ranges or oceans. In addition, the lower genetic variation and particular geographical distribution of A. cantonensis in each location could indicate a founder effect, which may have resulted from multiple independent origins, and suggests that haplotypes migrated from endemic areas via human-related transportation.

  16. Accelerometry reveals differences in gait variability between patients with multiple sclerosis and healthy controls

    PubMed Central

    Huisinga, Jessie M.; Mancini, Martina; St. George, Rebecca; Horak, Fay

    2014-01-01

    Variability of movement reflects important information for the maintenance of the health of the system. For pathological populations, changes in variability during gait signal the presence of abnormal motor control strategies. For persons with multiple sclerosis (PwMS), extensive gait problems have been reported including changes in gait variability. While previous studies have focused on footfall variability, the present study used accelerometers on the trunk to measure variability during walking. Thus, the purpose of this study was to examine the variability of the acceleration pattern of the upper and lower trunk in PwMS compared to healthy controls. We extracted linear and nonlinear measures of gait variability from 30s of steady state walking for 15 PwMS and 15 age-matched healthy controls. PwMS had altered variability compared to controls with greater Lyapunov exponent in the ML (p < 0.001) and AP (p < 0.001) directions, and greater frequency dispersion in the ML direction (p = 0.034). PwMS also demonstrated greater mean velocity in the ML direction (p = 0.045) and lower root mean square of acceleration in the AP direction (p = 0.040). These findings indicate that PwMS have altered structure of variability of the trunk during gait compared to healthy controls and agree with previous findings related to changes in gait variability in PwMS. PMID:23161166

  17. Multiple b-jets reveal top superpartners and the 125 GeV Higgs

    NASA Astrophysics Data System (ADS)

    Berenstein, David; Liu, Tao; Perkins, Erik

    2013-06-01

    We demonstrate that in supersymmetry with relatively light top superpartners, h→bb¯ can be a very promising channel to discover the Standard Model (SM)-like Higgs resonance at the LHC; although in general contexts, it is thought to be challenging because of its huge QCD background. In this scenario, the SM-like Higgs boson is mainly produced via cascade decays initiated by pair-produced stop or sbottom squarks. The good sensitivity to h→bb¯ owes a great deal to the application of multiple (≥4) b-jet tagging in removing the QCD background and color-flow variables for reconstructing the Higgs resonance. We show in two benchmark points that a SM-like Higgs resonance can be discovered at the 14 TeV LHC (with a signal-to-background ratio as high as 0.35), with ˜40fb-1 of data. Potentially, this strategy can be also applied to nonsupersymmetry theories with cascade decays of top partners for the SM-like Higgs search, such as little Higgs, composite Higgs, and Randall-Sundrum models.

  18. Benznidazole Biotransformation and Multiple Targets in Trypanosoma cruzi Revealed by Metabolomics

    PubMed Central

    Trochine, Andrea; Creek, Darren J.; Faral-Tello, Paula; Barrett, Michael P.; Robello, Carlos

    2014-01-01

    Background The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn. Methodology/Principal findings Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected. Conclusions/significance Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi. PMID:24853684

  19. Multiple LacI-mediated loops revealed by Bayesian statistics and tethered particle motion

    PubMed Central

    Johnson, Stephanie; van de Meent, Jan-Willem; Phillips, Rob; Wiggins, Chris H.; Lindén, Martin

    2014-01-01

    The bacterial transcription factor LacI loops DNA by binding to two separate locations on the DNA simultaneously. Despite being one of the best-studied model systems for transcriptional regulation, the number and conformations of loop structures accessible to LacI remain unclear, though the importance of multiple coexisting loops has been implicated in interactions between LacI and other cellular regulators of gene expression. To probe this issue, we have developed a new analysis method for tethered particle motion, a versatile and commonly used in vitro single-molecule technique. Our method, vbTPM, performs variational Bayesian inference in hidden Markov models. It learns the number of distinct states (i.e. DNA–protein conformations) directly from tethered particle motion data with better resolution than existing methods, while easily correcting for common experimental artifacts. Studying short (roughly 100 bp) LacI-mediated loops, we provide evidence for three distinct loop structures, more than previously reported in single-molecule studies. Moreover, our results confirm that changes in LacI conformation and DNA-binding topology both contribute to the repertoire of LacI-mediated loops formed in vitro, and provide qualitatively new input for models of looping and transcriptional regulation. We expect vbTPM to be broadly useful for probing complex protein–nucleic acid interactions. PMID:25120267

  20. Gene and Network Analysis of Common Variants Reveals Novel Associations in Multiple Complex Diseases

    PubMed Central

    Nakka, Priyanka; Raphael, Benjamin J.; Ramachandran, Sohini

    2016-01-01

    Genome-wide association (GWA) studies typically lack power to detect genotypes significantly associated with complex diseases, where different causal mutations of small effect may be present across cases. A common, tractable approach for identifying genomic elements associated with complex traits is to evaluate combinations of variants in known pathways or gene sets with shared biological function. Such gene-set analyses require the computation of gene-level P-values or gene scores; these gene scores are also useful when generating hypotheses for experimental validation. However, commonly used methods for generating GWA gene scores are computationally inefficient, biased by gene length, imprecise, or have low true positive rate (TPR) at low false positive rates (FPR), leading to erroneous hypotheses for functional validation. Here we introduce a new method, PEGASUS, for analytically calculating gene scores. PEGASUS produces gene scores with as much as 10 orders of magnitude higher numerical precision than competing methods. In simulation, PEGASUS outperforms existing methods, achieving up to 30% higher TPR when the FPR is fixed at 1%. We use gene scores from PEGASUS as input to HotNet2 to identify networks of interacting genes associated with multiple complex diseases and traits; this is the first application of HotNet2 to common variation. In ulcerative colitis and waist–hip ratio, we discover networks that include genes previously associated with these phenotypes, as well as novel candidate genes. In contrast, existing methods fail to identify these networks. We also identify networks for attention-deficit/hyperactivity disorder, in which GWA studies have yet to identify any significant SNPs. PMID:27489002

  1. Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points.

    PubMed

    Vainieri, Maria L; Blagborough, Andrew M; MacLean, Adam L; Haltalli, Myriam L R; Ruivo, Nicola; Fletcher, Helen A; Stumpf, Michael P H; Sinden, Robert E; Celso, Cristina Lo

    2016-06-01

    Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1(+) progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host.

  2. Mitochondrial DNA reveals multiple Northern Hemisphere introductions of Caprella mutica (Crustacea, Amphipoda).

    PubMed

    Ashton, Gail V; Stevens, Mark I; Hart, Mark C; Green, David H; Burrows, Michael T; Cook, Elizabeth J; Willis, Kate J

    2008-03-01

    Caprella mutica (Crustacea, Amphipoda) has been widely introduced to non-native regions in the last 40 years. Its native habitat is sub-boreal northeast Asia, but in the Northern Hemisphere, it is now found on both coasts of North America, and North Atlantic coastlines of Europe. Direct sequencing of mitochondrial DNA (cytochrome c oxidase subunit I gene) was used to compare genetic variation in native and non-native populations of C. mutica. These data were used to investigate the invasion history of C. mutica and to test potential source populations in Japan. High diversity (31 haplotypes from 49 individuals), but no phylogeographical structure, was identified in four populations in the putative native range. In contrast, non-native populations showed reduced genetic diversity (7 haplotypes from 249 individuals) and informative phylogeographical structure. Grouping of C. mutica populations into native, east Pacific, and Atlantic groups explained the most among-region variation (59%). This indicates independent introduction pathways for C. mutica to the Pacific and Atlantic coasts of North America. Two dominant haplotypes were identified in eastern and western Atlantic coastal populations, indicating several dispersal routes within the Atlantic. The analysis indicated that several introductions from multiple sources were likely to be responsible for the observed global distribution of C. mutica, but the pathways were least well defined among the Atlantic populations. The four sampled populations of C. mutica in Japan could not be identified as the direct source of the non-native populations examined in this study. The high diversity within the Japan populations indicates that the native range needs to be assessed at a far greater scale, both within and among populations, to accurately assess the source of the global spread of C. mutica.

  3. Functional somatotopy revealed across multiple cortical regions using a model of complex motor task

    PubMed Central

    Cunningham, David A.; Machado, Andre; Yue, Guang H.; Carey, Jim R.; Plow, Ela B.

    2014-01-01

    The primary motor cortex (M1) possesses a functional somatotopic structure -representations of adjacent within-limb joints overlap to facilitate coordination while maintaining discrete centers for individuated movement. We examined whether similar organization exists across other sensorimotor cortices. Twenty-four right-handed healthy subjects underwent functional Magnetic Resonance Imaging (fMRI) while tracking complex targets with flexion/extension at right finger, elbow and ankle separately. Activation related to each joint at false discovery rate of .005 served as its representation across multiple regions. Within each region, we identified the Center of Mass (COM) for each representation, and overlap between representations of within-limb (finger and elbow) and between-limb joints (finger and ankle). Somatosensory (S1) and premotor cortices (PMC) demonstrated greater distinction of COM and minimal overlap for within- and between-limb representations. Contrarily, M1 and supplementary motor area (SMA) showed more integrative somatotopy with higher sharing for within-limb representations. Superior and inferior parietal lobule (SPL and IPL) possessed both types of structure. Some clusters exhibited extensive overlap of within- and between-limb representations, while others showed discrete COMs for within-limb representations. Our results help infer hierarchy in motor control. Areas as S1 may be associated with individuated movements, while M1 may be more integrative for coordinated motion; parietal associative regions may allow switch between both modes of control. Such hierarchy creates redundant opportunities to exploit in stroke rehabilitation. Use of complex rather than traditionally used simple movements was integral to illustrating comprehensive somatotopic structure; complex tasks can potentially help understand cortical representation of skill and learning-related plasticity. PMID:23920009

  4. Gene and Network Analysis of Common Variants Reveals Novel Associations in Multiple Complex Diseases.

    PubMed

    Nakka, Priyanka; Raphael, Benjamin J; Ramachandran, Sohini

    2016-10-01

    Genome-wide association (GWA) studies typically lack power to detect genotypes significantly associated with complex diseases, where different causal mutations of small effect may be present across cases. A common, tractable approach for identifying genomic elements associated with complex traits is to evaluate combinations of variants in known pathways or gene sets with shared biological function. Such gene-set analyses require the computation of gene-level P-values or gene scores; these gene scores are also useful when generating hypotheses for experimental validation. However, commonly used methods for generating GWA gene scores are computationally inefficient, biased by gene length, imprecise, or have low true positive rate (TPR) at low false positive rates (FPR), leading to erroneous hypotheses for functional validation. Here we introduce a new method, PEGASUS, for analytically calculating gene scores. PEGASUS produces gene scores with as much as 10 orders of magnitude higher numerical precision than competing methods. In simulation, PEGASUS outperforms existing methods, achieving up to 30% higher TPR when the FPR is fixed at 1%. We use gene scores from PEGASUS as input to HotNet2 to identify networks of interacting genes associated with multiple complex diseases and traits; this is the first application of HotNet2 to common variation. In ulcerative colitis and waist-hip ratio, we discover networks that include genes previously associated with these phenotypes, as well as novel candidate genes. In contrast, existing methods fail to identify these networks. We also identify networks for attention-deficit/hyperactivity disorder, in which GWA studies have yet to identify any significant SNPs.

  5. Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points

    PubMed Central

    Vainieri, Maria L.; Blagborough, Andrew M.; MacLean, Adam L.; Haltalli, Myriam L. R.; Ruivo, Nicola; Fletcher, Helen A.; Stumpf, Michael P. H.; Sinden, Robert E.; Celso, Cristina Lo

    2016-01-01

    Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1+ progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host. PMID:27335321

  6. Proteomic analysis reveals complex metabolic regulation in Saccharomyces cerevisiae cells against multiple inhibitors stress.

    PubMed

    Lv, Ya-Jin; Wang, Xin; Ma, Qian; Bai, Xue; Li, Bing-Zhi; Zhang, Weiwen; Yuan, Ying-Jin

    2014-03-01

    Toxic compounds including acids, furans, and phenols (AFP) were generated from the pretreatment of lignocellulose. We cultivated Saccharomyces cerevisiae cells in a batch mode, besides the cell culture of original yeast strain in AFP-free medium which was referred as C0, three independent subcultures were cultivated under multiple inhibitors AFP and were referred as C1, C2, and C3 in time sequence. Comparing to C0, the cell density was lowered while the ethanol yield was maintained stably in the three yeast cultures under AFP stress, and the lag phase of C1 was extended while the lag phases of C2 and C3 were not extended. In proteomic analysis, 194 and 215 unique proteins were identified as differently expressed proteins at lag phase and exponential phase, respectively. Specifically, the yeast cells co-regulated protein folding and protein synthesis process to prevent the generation of misfolded proteins and to save cellular energy, they increased the activity of glycolysis, redirected metabolic flux towards phosphate pentose pathway and the biosynthesis of ethanol instead of the biosynthesis of glycerol and acetic acid, and they upregulated several oxidoreductases especially at lag phase and induced programmed cell death at exponential phase. When the yeast cells were cultivated under AFP stress, the new metabolism homeostasis in favor of cellular energy and redox homeostasis was generated in C1, then it was inherited and optimized in C2 and C3, enabling the yeast cells in C2 and C3 to enter the exponential phase in a short period after inoculation, which thus significantly shortened the fermentation time.

  7. Multiple genome sequences reveal adaptations of a phototrophic bacterium to sediment microenvironments.

    SciTech Connect

    Oda, Yasuhiro; Larimer, Frank W; Chain, Patrick S. G.; Malfatti, Stephanie; Shin, Maria V; Vergez, Lisa; Hauser, Loren John; Land, Miriam L; Braatsch, Stephan; Beatty, Thomas; Pelletier, Dale A; Schaefer, Amy L; Harwood, Caroline S

    2008-11-01

    The bacterial genus Rhodopseudomonas is comprised of photosynthetic bacteria found widely distributed in aquatic sediments. Members of the genus catalyze hydrogen gas production, carbon dioxide sequestration, and biomass turnover. The genome sequence of Rhodopseudomonas palustris CGA009 revealed a surprising richness of metabolic versatility that would seem to explain its ability to live in a heterogeneous environment like sediment. However, there is considerable genotypic diversity among Rhodopseudomonas isolates. Here we report the complete genome sequences of four additional members of the genus isolated from a restricted geographical area. The sequences confirm that the isolates belong to a coherent taxonomic unit, but they also have significant differences. Whole genome alignments show that the circular chromosomes of the isolates consist of a collinear backbone with a moderate number of genomic rearrangements that impact local gene order and orientation. There are 3,319 genes, 70% of the genes in each genome, shared by four or more strains. Between 10% and 18% of the genes in each genome are strain specific. Some of these genes suggest specialized physiological traits, which we verified experimentally, that include expanded light harvesting, oxygen respiration, and nitrogen fixation capabilities, as well as anaerobic fermentation. Strain-specific adaptations include traits that may be useful in bioenergy applications. This work suggests that against a backdrop of metabolic versatility that is a defining characteristic of Rhodopseudomonas, different ecotypes have evolved to take advantage of physical and chemical conditions in sediment microenvironments that are too small for human observation.

  8. Targeted next-generation sequencing reveals multiple deleterious variants in OPLL-associated genes

    PubMed Central

    Chen, Xin; Guo, Jun; Cai, Tao; Zhang, Fengshan; Pan, Shengfa; Zhang, Li; Wang, Shaobo; Zhou, Feifei; Diao, Yinze; Zhao, Yanbin; Chen, Zhen; Liu, Xiaoguang; Chen, Zhongqiang; Liu, Zhongjun; Sun, Yu; Du, Jie

    2016-01-01

    Ossification of the posterior longitudinal ligament of the spine (OPLL), which is characterized by ectopic bone formation in the spinal ligaments, can cause spinal-cord compression. To date, at least 11 susceptibility genes have been genetically linked to OPLL. In order to identify potential deleterious alleles in these OPLL-associated genes, we designed a capture array encompassing all coding regions of the target genes for next-generation sequencing (NGS) in a cohort of 55 unrelated patients with OPLL. By bioinformatics analyses, we successfully identified three novel and five extremely rare variants (MAF < 0.005). These variants were predicted to be deleterious by commonly used various algorithms, thereby resulting in missense mutations in four OPLL-associated genes (i.e., COL6A1, COL11A2, FGFR1, and BMP2). Furthermore, potential effects of the patient with p.Q89E of BMP2 were confirmed by a markedly increased BMP2 level in peripheral blood samples. Notably, seven of the variants were found to be associated with the patients with continuous subtype changes by cervical spinal radiological analyses. Taken together, our findings revealed for the first time that deleterious coding variants of the four OPLL-associated genes are potentially pathogenic in the patients with OPLL. PMID:27246988

  9. A single-cell imaging screen reveals multiple effects of secreted small molecules on bacteria

    PubMed Central

    Salje, Jeanne

    2014-01-01

    Bacteria cells exist in close proximity to other cells of both the same and different species. Bacteria secrete a large number of different chemical species, and the local concentrations of these compounds at the surfaces of nearby cells may reach very high levels. It is fascinating to imagine how individual cells might sense and respond to the complex mix of signals at their surface. However, it is difficult to measure exactly what the local environmental composition looks like, or what the effects of individual compounds on nearby cells are. Here, an electron microscopy imaging screen was designed that would detect morphological changes induced by secreted small molecules. This differs from conventional approaches by detecting structural changes in individual cells rather than gene expression or growth rate changes at the population level. For example, one of the changes detected here was an increase in outer membrane vesicle production, which does not necessarily correspond to a change in gene expression. This initial study focussed on Pseudomonas aeruginosa, Escherichia coli, and Burkholderia dolosa, and revealed an intriguing range of effects of secreted small molecules on cells both within and between species. PMID:24910069

  10. Relative time scales reveal multiple origins of parallel disjunct distributions of African caecilian amphibians.

    PubMed

    Loader, Simon P; Pisani, Davide; Cotton, James A; Gower, David J; Day, Julia J; Wilkinson, Mark

    2007-10-22

    Parallel patterns of distribution in different lineages suggest a common cause. Explanations in terms of a single biogeographic event often imply contemporaneous diversifications. Phylogenies with absolute time scales provide the most obvious means of testing temporal components of biogeographic hypotheses but, in their absence, the sequence of diversification events and whether any could have been contemporaneous can be tested with relative date estimates. Tests using relative time scales have been largely overlooked, but because they do not require the calibration upon which absolute time scales depend, they make a large amount of existing molecular data of use to historical biogeography and may also be helpful when calibration is possible but uncertain. We illustrate the use of relative dating by testing the hypothesis that parallel, disjunct east/west distributions in three independent lineages of African caecilians have a common cause. We demonstrate that at least two biogeographic events are implied by molecular data. Relative dating analysis reveals the potential complexity of causes of parallel distributions and cautions against inferring common cause from common spatial patterns without considering the temporal dimension.

  11. Coast-wide recruitment dynamics of Olympia oysters reveal limited synchrony and multiple predictors of failure.

    PubMed

    Wasson, Kerstin; Hughes, Brent B; Berriman, John S; Chang, Andrew L; Deck, Anna K; Dinnel, Paul A; Endris, Charlie; Espinoza, Michael; Dudas, Sarah; Ferner, Matthew C; Grosholz, Edwin D; Kimbro, David; Ruesink, Jennifer L; Trimble, Alan C; Vander Schaaf, Dick; Zabin, Chela J; Zacherl, Danielle C

    2016-12-01

    Recruitment of new propagules into a population can be a critical determinant of adult density. We examined recruitment dynamics in the Olympia oyster (Ostrea lurida), a species occurring almost entirely in estuaries. We investigated spatial scales of interannual synchrony across 37 sites in eight estuaries along 2,500 km of Pacific North American coastline, predicting that high vs. low recruitment years would coincide among neighboring estuaries due to shared exposure to regional oceanographic factors. Such synchrony in recruitment has been found for many marine species and some migratory estuarine species, but has never been examined across estuaries in a species that can complete its entire life cycle within the same estuary. To inform ongoing restoration efforts for Olympia oysters, which have declined in abundance in many estuaries, we also investigated predictors of recruitment failure. We found striking contrasts in absolute recruitment rate and frequency of recruitment failure among sites, estuaries, and years. Although we found a positive relationship between upwelling and recruitment, there was little evidence of synchrony in recruitment among estuaries along the coast, and only limited synchrony of sites within estuaries, suggesting recruitment rates are affected more strongly by local dynamics within estuaries than by regional oceanographic factors operating at scales encompassing multiple estuaries. This highlights the importance of local wetland and watershed management for the demography of oysters, and perhaps other species that can complete their entire life cycle within estuaries. Estuaries with more homogeneous environmental conditions had greater synchrony among sites, and this led to the potential for estuary-wide failure when all sites had no recruitment in the same year. Environmental heterogeneity within estuaries may thus buffer against estuary-wide recruitment failure, analogous to the portfolio effect for diversity. Recruitment failure

  12. Transcriptome Sequencing Reveals the Character of Incomplete Dosage Compensation across Multiple Tissues in Flycatchers

    PubMed Central

    Uebbing, Severin; Künstner, Axel; Mäkinen, Hannu; Ellegren, Hans

    2013-01-01

    Sex chromosome divergence, which follows the cessation of recombination and degeneration of the sex-limited chromosome, can cause a reduction in expression level for sex-linked genes in the heterozygous sex, unless some mechanisms of dosage compensation develops to counter the reduction in gene dose. Because large-scale perturbations in expression levels arising from changes in gene dose might have strong deleterious effects, the evolutionary response should be strong. However, in birds and in at least some other female heterogametic organisms, wholesale sex chromosome dosage compensation does not seem to occur. Using RNA-seq of multiple tissues and individuals, we investigated male and female expression levels of Z-linked and autosomal genes in the collared flycatcher, a bird for which a draft genome sequence recently has been reported. We found that male expression of Z-linked genes was on average 50% higher than female expression, although there was considerable variation in the male-to-female ratio among genes. The ratio for individual genes was well correlated among tissues and there was also a correlation in the extent of compensation between flycatcher and chicken orthologs. The relative excess of male expression was positively correlated with expression breadth, expression level, and number of interacting proteins (protein connectivity), and negatively correlated with variance in expression. These observations lead to a model of compensation occurring on a gene-by-gene basis, supported by an absence of clustering of genes on the Z chromosome with respect to the extent of compensation. Equal mean expression level of autosomal and Z-linked genes in males, and 50% higher expression of autosomal than Z-linked genes in females, is compatible with that partial compensation is achieved by hypertranscription from females’ single Z chromosome. A comparison with male-to-female expression ratios in orthologous Z-linked genes of ostriches, where Z–W recombination

  13. Integrative taxonomy of root-knot nematodes reveals multiple independent origins of mitotic parthenogenesis

    PubMed Central

    Janssen, Toon; Karssen, Gerrit; Topalović, Olivera; Coyne, Danny; Bert, Wim

    2017-01-01

    During sampling of several Coffea arabica plantations in Tanzania severe root galling, caused by a root-knot nematode was observed. From pure cultures, morphology and morphometrics of juveniles and females matched perfectly with Meloidogyne africana, whereas morphology of the males matched identically with those of Meloidogyne decalineata. Based on their Cox1 sequence, however, the recovered juveniles, females and males were confirmed to belong to the same species, creating a taxonomic conundrum. Adding further to this puzzle, re-examination of M. oteifae type material showed insufficient morphological evidence to maintain its status as a separate species. Consequently, M. decalineata and M. oteifae are synonymized with M. africana, which is herewith redescribed based on results of light and scanning electron microscopy, ribosomal and mitochondrial DNA sequences, isozyme electrophoresis, along with bionomic and cytogenetic features. Multi-gene phylogenetic analysis placed M. africana outside of the three major clades, together with M. coffeicola, M. ichinohei and M. camelliae. This phylogenetic position was confirmed by several morphological features, including cellular structure of the spermatheca, egg mass position, perineal pattern and head shape. Moreover, M. africana was found to be a polyphagous species, demonstrating that “early-branching” Meloidogyne spp. are not as oligophagous as had previously been assumed. Cytogenetic information indicates M. africana (2n = 21) and M. ardenensis (2n = 51–54) to be a triploid mitotic parthenogenetic species, revealing at least four independent origins of mitotic parthenogenesis within the genus Meloidogyne. Furthermore, M. mali (n = 12) was found to reproduce by amphimixis, indicating that amphimictic species with a limited number of chromosomes are widespread in the genus, potentially reflecting the ancestral state of the genus. The wide variation in chromosome numbers and associated changes in reproduction modes

  14. Boron isotopes reveal multiple metasomatic events in the mantle beneath the eastern North China Craton

    NASA Astrophysics Data System (ADS)

    Li, Hong-Yan; Zhou, Zhou; Ryan, Jeffrey G.; Wei, Gang-Jian; Xu, Yi-Gang

    2016-12-01

    additions to the mantle. We thus call upon multiple metasomatic events in the mantle beneath the eastern NCC in order to interpret its observed radiogenic and boron isotopic variability. The heavier δ11B, FME-enriched mantle source developed during an older event, while metasomatism by melts from the stagnant Pacific plate in the MTZ led to the development of a FME-depleted mantle source at greater depths with a lower δ11B.

  15. Cross-class metallo-β-lactamase inhibition by bisthiazolidines reveals multiple binding modes

    PubMed Central

    Hinchliffe, Philip; González, Mariano M.; Mojica, Maria F.; González, Javier M.; Castillo, Valerie; Saiz, Cecilia; Kosmopoulou, Magda; Tooke, Catherine L.; Llarrull, Leticia I.; Mahler, Graciela; Bonomo, Robert A.; Vila, Alejandro J.; Spencer, James

    2016-01-01

    Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, and B3), complicating development of βLIs effective against all enzymes. Bisthiazolidines (BTZs) are carboxylate-containing, bicyclic compounds, considered as penicillin analogs with an additional free thiol. Here, we show both l- and d-BTZ enantiomers are micromolar competitive βLIs of all MBL classes in vitro, with Kis of 6–15 µM or 36–84 µM for subclass B1 MBLs (IMP-1 and BcII, respectively), and 10–12 µM for the B3 enzyme L1. Against the B2 MBL Sfh-I, the l-BTZ enantiomers exhibit 100-fold lower Kis (0.26–0.36 µM) than d-BTZs (26–29 µM). Importantly, cell-based time-kill assays show BTZs restore β-lactam susceptibility of Escherichia coli-producing MBLs (IMP-1, Sfh-1, BcII, and GOB-18) and, significantly, an extensively drug-resistant Stenotrophomonas maltophilia clinical isolate expressing L1. BTZs therefore inhibit the full range of MBLs and potentiate β-lactam activity against producer pathogens. X-ray crystal structures reveal insights into diverse BTZ binding modes, varying with orientation of the carboxylate and thiol moieties. BTZs bind the di-zinc centers of B1 (IMP-1; BcII) and B3 (L1) MBLs via the free thiol, but orient differently depending upon stereochemistry. In contrast, the l-BTZ carboxylate dominates interactions with the monozinc B2 MBL Sfh-I, with the thiol uninvolved. d-BTZ complexes most closely resemble β-lactam binding to B1 MBLs, but feature an unprecedented disruption of the D120–zinc interaction. Cross-class MBL inhibition therefore arises from the unexpected versatility of BTZ binding. PMID:27303030

  16. Multi-gene phylogenetic analysis reveals the multiple origin and evolution of mangrove physiological traits through exaptation

    NASA Astrophysics Data System (ADS)

    Sahu, Sunil Kumar; Singh, Reena; Kathiresan, Kandasamy

    2016-12-01

    Mangroves are taxonomically diverse group of salt-tolerant, mainly arboreal, flowering plants that grow in tropical and sub-tropical regions and have adapted themselves to thrive in such obdurate surroundings. While evolution is often understood exclusively in terms of adaptation, innovation often begins when a feature adapted for one function is co-opted for a different purpose and the co-opted features are called exaptations. Thus, one of the fundamental issues is what features of mangroves have evolved through exaptation. We attempt to address these questions through molecular phylogenetic approach using chloroplast and nuclear markers. First, we determined if these mangroves specific traits have evolved multiple times in the phylogeny. Once the multiple origins were established, we then looked at related non-mangrove species for characters that could have been co-opted by mangrove species. We also assessed the efficacy of these molecular sequences in distinguishing mangroves at the species level. This study revealed the multiple origin of mangroves and shed light on the ancestral characters that might have led certain lineages of plants to adapt to estuarine conditions and also traces the evolutionary history of mangroves and hitherto unexplained theory that mangroves traits (aerial roots and viviparous propagules) evolved as a result of exaptation rather than adaptation to saline habitats.

  17. Hierarchical Spatio-Temporal Probabilistic Graphical Model with Multiple Feature Fusion for Binary Facial Attribute Classification in Real-World Face Videos.

    PubMed

    Demirkus, Meltem; Precup, Doina; Clark, James J; Arbel, Tal

    2016-06-01

    Recent literature shows that facial attributes, i.e., contextual facial information, can be beneficial for improving the performance of real-world applications, such as face verification, face recognition, and image search. Examples of face attributes include gender, skin color, facial hair, etc. How to robustly obtain these facial attributes (traits) is still an open problem, especially in the presence of the challenges of real-world environments: non-uniform illumination conditions, arbitrary occlusions, motion blur and background clutter. What makes this problem even more difficult is the enormous variability presented by the same subject, due to arbitrary face scales, head poses, and facial expressions. In this paper, we focus on the problem of facial trait classification in real-world face videos. We have developed a fully automatic hierarchical and probabilistic framework that models the collective set of frame class distributions and feature spatial information over a video sequence. The experiments are conducted on a large real-world face video database that we have collected, labelled and made publicly available. The proposed method is flexible enough to be applied to any facial classification problem. Experiments on a large, real-world video database McGillFaces [1] of 18,000 video frames reveal that the proposed framework outperforms alternative approaches, by up to 16.96 and 10.13%, for the facial attributes of gender and facial hair, respectively.

  18. Gait Analysis at Multiple Speeds Reveals Differential Functional and Structural Outcomes in Response to Graded Spinal Cord Injury

    PubMed Central

    Krizsan-Agbas, Dora; Winter, Michelle K.; Eggimann, Linda S.; Meriwether, Judith; Berman, Nancy E.; McCarson, Kenneth E.

    2014-01-01

    Abstract Open-field behavioral scoring is widely used to assess spinal cord injury (SCI) outcomes, but has limited usefulness in describing subtle changes important for posture and locomotion. Additional quantitative methods are needed to increase the resolution of locomotor outcome assessment. This study used gait analysis at multiple speeds (GAMS) across a range of mild-to-severe intensities of thoracic SCI in the rat. Overall, Basso, Beattie, and Bresnahan (BBB) scores and subscores were assessed, and detailed automated gait analysis was performed at three fixed walking speeds (3.5, 6.0, and 8.5 cm/sec). Variability in hindpaw brake, propel, and stance times were analyzed further by integrating across the stance phase of stepping cycles. Myelin staining of spinal cord sections was used to quantify white matter loss at the injury site. Varied SCI intensity produced graded deficits in BBB score, BBB subscores, and spinal cord white matter and total volume loss. GAMS measures of posture revealed decreased paw area, increased limb extension, altered stance width, and decreased values for integrated brake, propel, and stance. Measures of coordination revealed increased stride frequency concomitant with decreased stride length, resulting in deviation from consistent forelimb/hindlimb coordination. Alterations in posture and coordination were correlated to impact severity. GAMS results correlated highly with functional and histological measures and revealed differential relationships between sets of GAMS dynamics and cord total volume loss versus epicenter myelin loss. Automated gait analysis at multiple speeds is therefore a useful tool for quantifying nuanced changes in gait as an extension of histological and observational methods in assessing SCI outcomes. PMID:24405378

  19. Gait analysis at multiple speeds reveals differential functional and structural outcomes in response to graded spinal cord injury.

    PubMed

    Krizsan-Agbas, Dora; Winter, Michelle K; Eggimann, Linda S; Meriwether, Judith; Berman, Nancy E; Smith, Peter G; McCarson, Kenneth E

    2014-05-01

    Open-field behavioral scoring is widely used to assess spinal cord injury (SCI) outcomes, but has limited usefulness in describing subtle changes important for posture and locomotion. Additional quantitative methods are needed to increase the resolution of locomotor outcome assessment. This study used gait analysis at multiple speeds (GAMS) across a range of mild-to-severe intensities of thoracic SCI in the rat. Overall, Basso, Beattie, and Bresnahan (BBB) scores and subscores were assessed, and detailed automated gait analysis was performed at three fixed walking speeds (3.5, 6.0, and 8.5 cm/sec). Variability in hindpaw brake, propel, and stance times were analyzed further by integrating across the stance phase of stepping cycles. Myelin staining of spinal cord sections was used to quantify white matter loss at the injury site. Varied SCI intensity produced graded deficits in BBB score, BBB subscores, and spinal cord white matter and total volume loss. GAMS measures of posture revealed decreased paw area, increased limb extension, altered stance width, and decreased values for integrated brake, propel, and stance. Measures of coordination revealed increased stride frequency concomitant with decreased stride length, resulting in deviation from consistent forelimb/hindlimb coordination. Alterations in posture and coordination were correlated to impact severity. GAMS results correlated highly with functional and histological measures and revealed differential relationships between sets of GAMS dynamics and cord total volume loss versus epicenter myelin loss. Automated gait analysis at multiple speeds is therefore a useful tool for quantifying nuanced changes in gait as an extension of histological and observational methods in assessing SCI outcomes.

  20. Molecular genetic analysis and ecological evidence reveals multiple cryptic species among thynnine wasp pollinators of sexually deceptive orchids.

    PubMed

    Griffiths, Kate E; Trueman, John W H; Brown, Graham R; Peakall, Rod

    2011-04-01

    Sexually deceptive Chiloglottis orchids lure their male thynnine wasp pollinators to the flower by emitting semiochemicals that mimic the specific sex pheromone of the wasp. Sexual deception is possible because chemical rather than visual cues play the key role in wasp mate search, suggesting that cryptic wasp species may be frequent. We investigated this prospect among Neozeleboria wasp pollinators of Chiloglottis orchids, drawing on evidence from molecular phylogenetic analysis at three genes (CO1, rhodopsin and wingless), population genetic and statistical parsimony analysis at CO1, orchid associations and their semiochemicals, and geographic ranges. We found a compelling relationship between genetically defined wasp groups, orchid associations, semiochemicals and geographic range, despite a frequent lack of detectable morphological differences. Our findings reveal multiple cryptic species among orchid pollinators and indicate that chemical changes are important for wasp reproductive isolation and speciation. The diversity of Neozeleboria may have enabled, rather than constrained, pollinator-driven speciation in these orchids.

  1. Acoustic telemetry and network analysis reveal the space use of multiple reef predators and enhance marine protected area design.

    PubMed

    Lea, James S E; Humphries, Nicolas E; von Brandis, Rainer G; Clarke, Christopher R; Sims, David W

    2016-07-13

    Marine protected areas (MPAs) are commonly employed to protect ecosystems from threats like overfishing. Ideally, MPA design should incorporate movement data from multiple target species to ensure sufficient habitat is protected. We used long-term acoustic telemetry and network analysis to determine the fine-scale space use of five shark and one turtle species at a remote atoll in the Seychelles, Indian Ocean, and evaluate the efficacy of a proposed MPA. Results revealed strong, species-specific habitat use in both sharks and turtles, with corresponding variation in MPA use. Defining the MPA's boundary from the edge of the reef flat at low tide instead of the beach at high tide (the current best in Seychelles) significantly increased the MPA's coverage of predator movements by an average of 34%. Informed by these results, the larger MPA was adopted by the Seychelles government, demonstrating how telemetry data can improve shark spatial conservation by affecting policy directly.

  2. Genome-wide allelic methylation analysis reveals disease-specific susceptibility to multiple methylation defects in imprinting syndromes.

    PubMed

    Court, Franck; Martin-Trujillo, Alex; Romanelli, Valeria; Garin, Intza; Iglesias-Platas, Isabel; Salafsky, Ira; Guitart, Miriam; Perez de Nanclares, Guiomar; Lapunzina, Pablo; Monk, David

    2013-04-01

    Genomic imprinting is the parent-of-origin-specific allelic transcriptional silencing observed in mammals, which is governed by DNA methylation established in the gametes and maintained throughout the development. The frequency and extent of epimutations associated with the nine reported imprinting syndromes varies because it is evident that aberrant preimplantation maintenance of imprinted differentially methylated regions (DMRs) may affect multiple loci. Using a custom Illumina GoldenGate array targeting 27 imprinted DMRs, we profiled allelic methylation in 65 imprinting defect patients. We identify multilocus hypomethylation in numerous Beckwith-Wiedemann syndrome, transient neonatal diabetes mellitus (TNDM), and pseudohypoparathyroidism 1B patients, and an individual with Silver-Russell syndrome. Our data reveal a broad range of epimutations exist in certain imprinting syndromes, with the exception of Prader-Willi syndrome and Angelman syndrome patients that are associated with solitary SNRPN-DMR defects. A mutation analysis identified a 1 bp deletion in the ZFP57 gene in a TNDM patient with methylation defects at multiple maternal DMRs. In addition, we observe missense variants in ZFP57, NLRP2, and NLRP7 that are not consistent with maternal effect and aberrant establishment or methylation maintenance, and are likely benign. This work illustrates that further extensive molecular characterization of these rare patients is required to fully understand the mechanism underlying the etiology of imprint establishment and maintenance.

  3. Expression profiling reveals functionally redundant multiple-copy genes related to zinc, iron and cadmium responses in Brassica rapa.

    PubMed

    Li, Jimeng; Liu, Bo; Cheng, Feng; Wang, Xiaowu; Aarts, Mark G M; Wu, Jian

    2014-07-01

    Genes underlying environmental adaptability tend to be over-retained in polyploid plant species. Zinc deficiency (ZnD) and iron deficiency (FeD), excess Zn (ZnE) and cadmium exposure (CdE) are major environmental problems for crop cultivation, but little is known about the differential expression of duplicated genes upon these stress conditions. Applying Tag-Seq technology to leaves of Brassica rapa grown under FeD, ZnD, ZnE or CdE conditions, with normal conditions as a control, we examined global gene expression changes and compared the expression patterns of multiple paralogs. We identified 812, 543, 331 and 447 differentially expressed genes under FeD, ZnD, ZnE and CdE conditions, respectively, in B. rapa leaves. Genes involved in regulatory networks centered on the transcription factors bHLH038 or bHLH100 were differentially expressed under (ZnE-induced) FeD. Further analysis revealed that genes associated with Zn, Fe and Cd responses tended to be over-retained in the B. rapa genome. Most of these multiple-copy genes showed the same direction of expression change under stress conditions. We conclude that the duplicated genes involved in trace element responses in B. rapa are functionally redundant, making the regulatory network more complex in B. rapa than in Arabidopsis thaliana.

  4. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics

    PubMed Central

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-01-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae–Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. PMID:27604225

  5. Comparative analysis of SET domain proteins in maize and Arabidopsis reveals multiple duplications preceding the divergence of monocots and dicots.

    PubMed

    Springer, Nathan M; Napoli, Carolyn A; Selinger, David A; Pandey, Ritu; Cone, Karen C; Chandler, Vicki L; Kaeppler, Heidi F; Kaeppler, Shawn M

    2003-06-01

    Histone proteins play a central role in chromatin packaging, and modification of histones is associated with chromatin accessibility. SET domain [Su(var)3-9, Enhancer-of-zeste, Trithorax] proteins are one class of proteins that have been implicated in regulating gene expression through histone methylation. The relationships of 22 SET domain proteins from maize (Zea mays) and 32 SET domain proteins from Arabidopsis were evaluated by phylogenetic analysis and domain organization. Our analysis reveals five classes of SET domain proteins in plants that can be further divided into 19 orthology groups. In some cases, such as the Enhancer of zeste-like and trithorax-like proteins, plants and animals contain homologous proteins with a similar organization of domains outside of the SET domain. However, a majority of plant SET domain proteins do not have an animal homolog with similar domain organization, suggesting that plants have unique mechanisms to establish and maintain chromatin states. Although the domains present in plant and animal SET domain proteins often differ, the domains found in the plant proteins have been generally implicated in protein-protein interactions, indicating that most SET domain proteins operate in complexes. Combined analysis of the maize and Arabidopsis SET domain proteins reveals that duplication of SET domain proteins in plants is extensive and has occurred via multiple mechanisms that preceded the divergence of monocots and dicots.

  6. A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors

    PubMed Central

    Vicente-Dueñas, Carolina; Romero-Camarero, Isabel; González-Herrero, Inés; Alonso-Escudero, Esther; Abollo-Jiménez, Fernando; Jiang, Xiaoyu; Gutierrez, Norma C; Orfao, Alberto; Marín, Nieves; Villar, Luisa María; Criado, Ma Carmen Fernández; Pintado, Belén; Flores, Teresa; Alonso-López, Diego; De Las Rivas, Javier; Jiménez, Rafael; Criado, Francisco Javier García; Cenador, María Begoña García; Lossos, Izidore S; Cobaleda, César; Sánchez-García, Isidro

    2012-01-01

    Understanding the cellular origin of cancer can help to improve disease prevention and therapeutics. Human plasma cell neoplasias are thought to develop from either differentiated B cells or plasma cells. However, when the expression of Maf oncogenes (associated to human plasma cell neoplasias) is targeted to mouse B cells, the resulting animals fail to reproduce the human disease. Here, to explore early cellular changes that might take place in the development of plasma cell neoplasias, we engineered transgenic mice to express MafB in haematopoietic stem/progenitor cells (HS/PCs). Unexpectedly, we show that plasma cell neoplasias arise in the MafB-transgenic mice. Beyond their clinical resemblance to human disease, these neoplasias highly express genes that are known to be upregulated in human multiple myeloma. Moreover, gene expression profiling revealed that MafB-expressing HS/PCs were more similar to B cells and tumour plasma cells than to any other subset, including wild-type HS/PCs. Consistent with this, genome-scale DNA methylation profiling revealed that MafB imposes an epigenetic program in HS/PCs, and that this program is preserved in mature B cells of MafB-transgenic mice, demonstrating a novel molecular mechanism involved in tumour initiation. Our findings suggest that, mechanistically, the haematopoietic progenitor population can be the target for transformation in MafB-associated plasma cell neoplasias. PMID:22903061

  7. Single-Copy Nuclear Genes Place Haustorial Hydnoraceae within Piperales and Reveal a Cretaceous Origin of Multiple Parasitic Angiosperm Lineages

    PubMed Central

    Naumann, Julia; Salomo, Karsten; Der, Joshua P.; Wafula, Eric K.; Bolin, Jay F.; Maass, Erika; Frenzke, Lena; Samain, Marie-Stéphanie; Neinhuis, Christoph

    2013-01-01

    Extreme haustorial parasites have long captured the interest of naturalists and scientists with their greatly reduced and highly specialized morphology. Along with the reduction or loss of photosynthesis, the plastid genome often decays as photosynthetic genes are released from selective constraint. This makes it challenging to use traditional plastid genes for parasitic plant phylogenetics, and has driven the search for alternative phylogenetic and molecular evolutionary markers. Thus, evolutionary studies, such as molecular clock-based age estimates, are not yet available for all parasitic lineages. In the present study, we extracted 14 nuclear single copy genes (nSCG) from Illumina transcriptome data from one of the “strangest plants in the world”, Hydnora visseri (Hydnoraceae). A ∼15,000 character molecular dataset, based on all three genomic compartments, shows the utility of nSCG for reconstructing phylogenetic relationships in parasitic lineages. A relaxed molecular clock approach with the same multi-locus dataset, revealed an ancient age of ∼91 MYA for Hydnoraceae. We then estimated the stem ages of all independently originated parasitic angiosperm lineages using a published dataset, which also revealed a Cretaceous origin for Balanophoraceae, Cynomoriaceae and Apodanthaceae. With the exception of Santalales, older parasite lineages tend to be more specialized with respect to trophic level and have lower species diversity. We thus propose the “temporal specialization hypothesis” (TSH) implementing multiple independent specialization processes over time during parasitic angiosperm evolution. PMID:24265760

  8. Spatiotemporal Optical Vortices

    NASA Astrophysics Data System (ADS)

    Jhajj, N.; Larkin, I.; Rosenthal, E. W.; Zahedpour, S.; Wahlstrand, J. K.; Milchberg, H. M.

    2016-07-01

    We present the first experimental evidence, supported by theory and simulation, of spatiotemporal optical vortices (STOVs). A STOV is an optical vortex with phase and energy circulation in a spatiotemporal plane. Depending on the sign of the material dispersion, the local electromagnetic energy flow is saddle or spiral about the STOV. STOVs are a fundamental element of the nonlinear collapse and subsequent propagation of short optical pulses in material media, and conserve topological charge, constraining their birth, evolution, and annihilation. We measure a self-generated STOV consisting of a ring-shaped null in the electromagnetic field about which the phase is spiral, forming a dynamic torus that is concentric with and tracks the propagating pulse. Our results, here obtained for optical pulse collapse and filamentation in air, are generalizable to a broad class of nonlinearly propagating waves.

  9. Spatiotemporal multipartite entanglement

    SciTech Connect

    Kolobov, Mikhail I.; Patera, Giuseppe

    2011-05-15

    In this Rapid Communication, we propose, following the spirit of quantum imaging, to generalize the theory of multipartite entanglement for the continuous-variable Gaussian states by considering, instead of the global covariance matrix, the local correlation matrix at two different spatiotemporal points ({rho}-vector,t) and ({rho}-vector{sup '},t{sup '}), with {rho}-vector being the transverse coordinate. Our approach makes it possible to introduce the characteristic spatial length and the characteristic time of the multipartite entanglement, which in general depend on the number of 'parties' in the system. As an example, we consider tripartite entanglement in spontaneous parametric down-conversion with a spatially structured pump. We investigate spatiotemporal properties of such entanglement and calculate its characteristic spatial length and time.

  10. Characterizing spatiotemporal non-stationarity in vegetation dynamics in China using MODIS EVI dataset.

    PubMed

    Qiu, Bingwen; Zeng, Canying; Tang, Zhenghong; Chen, Chongcheng

    2013-11-01

    This paper evaluated the spatiotemporal non-stationarity in the vegetation dynamic based on 1-km resolution 16-day composite Moderate Resolution Imaging Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI) datasets in China during 2001-2011 through a wavelet transform method. First, it revealed from selected pixels that agricultural crops, natural forests, and meadows were characterized by their distinct intra-annual temporal variation patterns in different climate regions. The amplitude of intra-annual variability generally increased with latitude. Second, parameters calculated using a per-pixel strategy indicated that the natural forests had the strongest variation pattern from seasonal to semiannual scales, and the multiple-cropping croplands typically showed almost equal variances distributed at monthly, seasonal, and semiannual scales. Third, spatiotemporal non-stationarity induced from cloud cover was also evaluated. It revealed that the EVI temporal profiles were significantly distorted with regular summer cloud cover in tropical and subtropical regions. Nevertheless, no significant differences were observed from those statistical parameters related to the interannual and interannual components between the de-clouded and the original MODIS EVI datasets across the whole country. Finally, 12 vegetation zones were proposed based on spatiotemporal variability, as indicated by the magnitude of interannual and intra-annual dynamic components, normalized wavelet variances of detailed components from monthly to semiannual scale, and proportion of cloud cover in summer. This paper provides insightful solutions for addressing spatiotemporal non-stationarity by evaluating the magnitude and frequency of vegetation variability using monthly, seasonal, semiannual to interannual scales across the whole study area.

  11. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison).

    PubMed

    Noer, Christina Lehmkuhl; Needham, Esther Kjær; Wiese, Ann-Sophie; Balsby, Thorsten Johannes Skovbjerg; Dabelsteen, Torben

    2015-01-01

    Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits.

  12. Context Matters: Multiple Novelty Tests Reveal Different Aspects of Shyness-Boldness in Farmed American Mink (Neovison vison)

    PubMed Central

    Noer, Christina Lehmkuhl; Needham, Esther Kjær; Wiese, Ann-Sophie; Balsby, Thorsten Johannes Skovbjerg; Dabelsteen, Torben

    2015-01-01

    Animal personality research is receiving increasing interest from related fields, such as evolutionary personality psychology. By merging the conceptual understanding of personality, the contributions to both fields of research may be enhanced. In this study, we investigate animal personality based on the definition of personality traits as underlying dispositional factors, which are not directly measurable, but which predispose individuals to react through different behavioural patterns. We investigated the shyness-boldness continuum reflected in the consistency of inter-individual variation in behavioural responses towards novelty in 47 farmed American mink (Neovison vison), which were raised in identical housing conditions. Different stages of approach behaviour towards novelty, and how these related within and across contexts, were explored. Our experimental design contained four tests: two novel object tests (non-social contexts) and two novel animated stimuli tests (social contexts). Our results showed consistency in shyness measures across multiple tests, indicating the existence of personality in farmed American mink. It was found that consistency in shyness measures differs across non-social and social contexts, as well as across the various stages in the approach towards novel objects, revealing that different aspects of shyness exist in the farmed American mink. To our knowledge this is the first study to reveal aspects of the shyness-boldness continuum in the American mink. Since the mink were raised in identical housing conditions, inherited factors may have been important in shaping the consistent inter-individual variation. Body weight and sex had no effect on the personality of the mink. Altogether, our results suggest that the shyness-boldness continuum cannot be explained by a simple underlying dispositional factor, but instead encompasses a broader term of hesitating behaviour that might comprise several different personality traits. PMID

  13. Structural and Functional Characterization of CRM1-Nup214 Interactions Reveals Multiple FG-Binding Sites Involved in Nuclear Export.

    PubMed

    Port, Sarah A; Monecke, Thomas; Dickmanns, Achim; Spillner, Christiane; Hofele, Romina; Urlaub, Henning; Ficner, Ralf; Kehlenbach, Ralph H

    2015-10-27

    CRM1 is the major nuclear export receptor. During translocation through the nuclear pore, transport complexes transiently interact with phenylalanine-glycine (FG) repeats of multiple nucleoporins. On the cytoplasmic side of the nuclear pore, CRM1 tightly interacts with the nucleoporin Nup214. Here, we present the crystal structure of a 117-amino-acid FG-repeat-containing fragment of Nup214, in complex with CRM1, Snurportin 1, and RanGTP at 2.85 Å resolution. The structure reveals eight binding sites for Nup214 FG motifs on CRM1, with intervening stretches that are loosely attached to the transport receptor. Nup214 binds to N- and C-terminal regions of CRM1, thereby clamping CRM1 in a closed conformation and stabilizing the export complex. The role of conserved hydrophobic pockets for the recognition of FG motifs was analyzed in biochemical and cell-based assays. Comparative studies with RanBP3 and Nup62 shed light on specificities of CRM1-nucleoporin binding, which serves as a paradigm for transport receptor-nucleoporin interactions.

  14. Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.

    PubMed

    Sathitruangsak, Chirawadee; Righolt, Christiaan H; Klewes, Ludger; Tammur, Pille; Ilus, Tiiu; Tamm, Anu; Punab, Mari; Olujohungbe, Adebayo; Mai, Sabine

    2015-05-01

    The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM.

  15. Phylogeography of Nanorana parkeri (Anura: Ranidae) and multiple refugia on the Tibetan Plateau revealed by mitochondrial and nuclear DNA

    PubMed Central

    Liu, Jun; Wang, Cuimin; Fu, Dongli; Hu, Xiaoju; Xie, Xiangmo; Liu, Pengfei; Zhang, Qiong; Li, Meng-Hua

    2015-01-01

    Quaternary climatic changes have been recognized to influence the distribution patterns and evolutionary histories of extant organisms, but their effects on alpine species are not well understood. To investigate the Pleistocene climatic oscillations on the genetic structure of amphibians, we sequenced one mitochondrial and three nuclear DNA fragments in Nanorana parkeri, a frog endemic to the Tibetan Plateau, across its distribution range in the southern plateau. Mitochondrial cytochrome b (Cytb) and three nuclear genes (c-Myc2, Rhod, and Tyr) revealed two distinct lineages (i.e. the lineages East and West), which were strongly geographically structured. The split of the two divergent lineages was dated back earlier than the Middle Pleistocene, probably being associated with climatic and ecological factors. Species distribution modeling, together with the phylogeographic structuring, supported the hypothesis of multiple refugia for N. parkeri on the Tibetan Plateau during the Pleistocene glaciations, and suggested the Yarlung Zangbo valley and the Kyichu catchment to be the potential refugia. Our findings indicate that Pleistocene climatic changes have had a great impact on the evolution and demographic history of N. parkeri. Our study has important implications for conservation of this and other frog species in the Tibetan Plateau. PMID:25985205

  16. Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy

    PubMed Central

    Wrobel, Tomasz; Usnarska-Zubkiewicz, Lidia; Brzezniakiewicz, Katarzyna; Jamroziak, Krzysztof; Giannopoulos, Krzysztof; Przybylowicz-Chalecka, Anna; Ratajczak, Blazej; Czerwinska-Rybak, Joanna; Nowicki, Adam; Joks, Monika; Czechowska, Elzbieta; Zawartko, Magdalena; Szczepaniak, Tomasz; Grzasko, Norbert; Morawska, Marta; Bochenek, Maciej; Kubicki, Tadeusz; Morawska, Michalina; Tusznio, Katarzyna; Jakubowiak, Andrzej; Komarnicki, Mieczysław

    2016-01-01

    Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance. PMID:27527861

  17. A functional dissociation between language and multiple-demand systems revealed in patterns of BOLD signal fluctuations.

    PubMed

    Blank, Idan; Kanwisher, Nancy; Fedorenko, Evelina

    2014-09-01

    What is the relationship between language and other high-level cognitive functions? Neuroimaging studies have begun to illuminate this question, revealing that some brain regions are quite selectively engaged during language processing, whereas other "multiple-demand" (MD) regions are broadly engaged by diverse cognitive tasks. Nonetheless, the functional dissociation between the language and MD systems remains controversial. Here, we tackle this question with a synergistic combination of functional MRI methods: we first define candidate language-specific and MD regions in each subject individually (using functional localizers) and then measure blood oxygen level-dependent signal fluctuations in these regions during two naturalistic conditions ("rest" and story-comprehension). In both conditions, signal fluctuations strongly correlate among language regions as well as among MD regions, but correlations across systems are weak or negative. Moreover, data-driven clustering analyses based on these inter-region correlations consistently recover two clusters corresponding to the language and MD systems. Thus although each system forms an internally integrated whole, the two systems dissociate sharply from each other. This independent recruitment of the language and MD systems during cognitive processing is consistent with the hypothesis that these two systems support distinct cognitive functions.

  18. Preliminary whole-exome sequencing reveals mutations that imply common tumorigenicity pathways in multiple endocrine neoplasia type 1 patients

    PubMed Central

    Arenas, Minerva Angélica Romero; Fowler, Richard G.; Lucas, F. Anthony San; Shen, Jie; Rich, Thereasa A.; Grubbs, Elizabeth G.; Lee, Jeffrey E.; Scheet, Paul; Perrier, Nancy D.; Zhao, Hua

    2016-01-01

    Background Whole-exome sequencing studies have not established definitive somatic mutation patterns among patients with sporadic hyperparathyroidism (HPT). No sequencing has evaluated multiple endocrine neoplasia type 1 (MEN1)-related HPT. We sought to perform whole-exome sequencing in HPT patients to identify somatic mutations and associated biological pathways and tumorigenic networks. Methods Whole-exome sequencing was performed on blood and tissue from HPT patients (MEN1 and sporadic) and somatic single nucleotide variants (SNVs) were identified. Stop-gain and stop-loss SNVs were analyzed with Ingenuity Pathways Analysis (IPA). Loss of heterozygosity (LOH) was also assessed. Results Sequencing was performed on 4 MEN1 and 10 sporadic cases. Eighteen stop-gain/stop-loss SNV mutations were identified in 3 MEN1 patients. One complex network was identified on IPA: Cellular function and maintenance, tumor morphology, and cardiovascular disease (IPA score = 49). A nonsynonymous SNV of TP53 (lysine-to-glutamic acid change at codon 81) identified in a MEN1 patient was suggested to be a driver mutation (Cancer-specific High-throughput Annotation of Somatic Mutations; P = .002). All MEN1 and 3/10 sporadic specimens demonstrated LOH of chromosome 11. Conclusion Whole-exome sequencing revealed somatic mutations in MEN1 associated with a single tumorigenic network, whereas sporadic pathogenesis seemed to be more diverse. A somatic TP53 mutation was also identified. LOH of chromosome 11 was seen in all MEN1 and 3 of 10 sporadic patients. PMID:25456907

  19. Quantitative proteome analysis of an antibiotic resistant Escherichia coli exposed to tetracycline reveals multiple affected metabolic and peptidoglycan processes.

    PubMed

    Jones-Dias, Daniela; Carvalho, Ana Sofia; Moura, Inês Barata; Manageiro, Vera; Igrejas, Gilberto; Caniça, Manuela; Matthiesen, Rune

    2017-03-06

    Tetracyclines are among the most commonly used antibiotics administrated to farm animals for disease treatment and prevention, contributing to the worldwide increase in antibiotic resistance in animal and human pathogens. Although tetracycline mechanisms of resistance are well known, the role of metabolism in bacterial reaction to antibiotic stress is still an important assignment and could contribute to the understanding of tetracycline related stress response. In this study, spectral counts-based label free quantitative proteomics has been applied to study the response to tetracycline of the environmental-borne Escherichia coli EcAmb278 isolate soluble proteome. A total of 1484 proteins were identified by high resolution mass spectrometry at a false discovery rate threshold of 1%, of which 108 were uniquely identified under absence of tetracycline whereas 126 were uniquely identified in presence of tetracycline. These proteins revealed interesting difference in e.g. proteins involved in peptidoglycan-based cell wall proteins and energy metabolism. Upon treatment, 12 proteins were differentially regulated showing more than 2-fold change and p<0.05 (p value corrected for multiple testing). This integrated study using high resolution mass spectrometry based label-free quantitative proteomics to study tetracycline antibiotic response in the soluble proteome of resistant E. coli provides novel insight into tetracycline related stress.

  20. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    PubMed

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  1. Phylogeography of Nanorana parkeri (Anura: Ranidae) and multiple refugia on the Tibetan Plateau revealed by mitochondrial and nuclear DNA.

    PubMed

    Liu, Jun; Wang, Cuimin; Fu, Dongli; Hu, Xiaoju; Xie, Xiangmo; Liu, Pengfei; Zhang, Qiong; Li, Meng-Hua

    2015-05-18

    Quaternary climatic changes have been recognized to influence the distribution patterns and evolutionary histories of extant organisms, but their effects on alpine species are not well understood. To investigate the Pleistocene climatic oscillations on the genetic structure of amphibians, we sequenced one mitochondrial and three nuclear DNA fragments in Nanorana parkeri, a frog endemic to the Tibetan Plateau, across its distribution range in the southern plateau. Mitochondrial cytochrome b (Cytb) and three nuclear genes (c-Myc2, Rhod, and Tyr) revealed two distinct lineages (i.e. the lineages East and West), which were strongly geographically structured. The split of the two divergent lineages was dated back earlier than the Middle Pleistocene, probably being associated with climatic and ecological factors. Species distribution modeling, together with the phylogeographic structuring, supported the hypothesis of multiple refugia for N. parkeri on the Tibetan Plateau during the Pleistocene glaciations, and suggested the Yarlung Zangbo valley and the Kyichu catchment to be the potential refugia. Our findings indicate that Pleistocene climatic changes have had a great impact on the evolution and demographic history of N. parkeri. Our study has important implications for conservation of this and other frog species in the Tibetan Plateau.

  2. A functional dissociation between language and multiple-demand systems revealed in patterns of BOLD signal fluctuations

    PubMed Central

    Kanwisher, Nancy; Fedorenko, Evelina

    2014-01-01

    What is the relationship between language and other high-level cognitive functions? Neuroimaging studies have begun to illuminate this question, revealing that some brain regions are quite selectively engaged during language processing, whereas other “multiple-demand” (MD) regions are broadly engaged by diverse cognitive tasks. Nonetheless, the functional dissociation between the language and MD systems remains controversial. Here, we tackle this question with a synergistic combination of functional MRI methods: we first define candidate language-specific and MD regions in each subject individually (using functional localizers) and then measure blood oxygen level-dependent signal fluctuations in these regions during two naturalistic conditions (“rest” and story-comprehension). In both conditions, signal fluctuations strongly correlate among language regions as well as among MD regions, but correlations across systems are weak or negative. Moreover, data-driven clustering analyses based on these inter-region correlations consistently recover two clusters corresponding to the language and MD systems. Thus although each system forms an internally integrated whole, the two systems dissociate sharply from each other. This independent recruitment of the language and MD systems during cognitive processing is consistent with the hypothesis that these two systems support distinct cognitive functions. PMID:24872535

  3. Physiological Stress Responses in Amphibian Larvae to Multiple Stressors Reveal Marked Anthropogenic Effects even below Lethal Levels.

    PubMed

    Burraco, Pablo; Gomez-Mestre, Ivan

    Natural and anthropogenic disturbances cause profound alterations in organisms, inducing physiological adjustments to avoid, reduce, or remedy the impact of disturbances. In vertebrates, the stress response is regulated via neuroendocrine pathways, including the hypothalamic-pituitary-interrenal axis that regulates the secretion of glucocorticoids. Glucocorticoids have cascading effects on multiple physiological pathways, affecting the metabolic rate, reactive oxygen species production, or immune system. Determining the extent to which natural and anthropogenic environmental factors induce stress responses in vertebrates is of great importance in ecology and conservation biology. Here we study the physiological stress response in spadefoot toad tadpoles (Pelobates cultripes) against three levels of a series of natural and anthropogenic stressors common to many aquatic systems: salinity (0, 6, and 9 ppt), herbicide (0, 1, and 2 mg/L acid equivalent of glyphosate), water acidity (pH 4.5, 7.0, and 9.5), predators (absent, native, and invasive), and temperature (21°, 25°, and 29°C). The physiological stress response was assessed examining corticosterone levels, standard metabolic rate, activity of antioxidant enzymes, oxidative cellular damage in lipids, and immunological status. We found that common stressors substantially altered the physiological state of tadpoles. In particular, salinity and herbicides cause dramatic physiological changes in tadpoles. Moreover, tadpoles reduced corticosterone levels in the presence of natural predators but did not do so against invasive predators, indicating a lack of innate recognition. Corticosterone and the antioxidant enzyme glutathione reductase were the most sensitive parameters to stress in this study. Anthropogenic perturbations of aquatic systems pose serious threats to larval amphibians even at nonlethal concentrations, judging from the marked physiological stress responses generated, and reveal the importance of

  4. Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse

    PubMed Central

    Krzeminski, Patryk; Corchete, Luis A.; García, Juan L.; López-Corral, Lucía; Fermiñán, Encarna; García, Eva M.; Martín, Ana A.; Hernández-Rivas, Jesús M.; García-Sanz, Ramón; Miguel, Jesús F. San; Gutiérrez, Norma C.

    2016-01-01

    Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse. PMID:27811368

  5. Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.

    PubMed

    Krzeminski, Patryk; Corchete, Luis A; García, Juan L; López-Corral, Lucía; Fermiñán, Encarna; García, Eva M; Martín, Ana A; Hernández-Rivas, Jesús M; García-Sanz, Ramón; San Miguel, Jesús F; Gutiérrez, Norma C

    2016-12-06

    Multiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.

  6. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3.

    PubMed

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H; Poulsen, Per Løgstrup; Rolighed, Lars; Ladefoged, Søren A; Rejnmark, Lars

    2016-10-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies and for the worry of being diagnosed with a cancer susceptibility syndrome.

  7. Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

    PubMed Central

    2012-01-01

    Background Many marine meiofaunal species are reported to have wide distributions, which creates a paradox considering their hypothesized low dispersal abilities. Correlated with this paradox is an especially high taxonomic deficit for meiofauna, partly related to a lower taxonomic effort and partly to a high number of putative cryptic species. Molecular-based species delineation and barcoding approaches have been advocated for meiofaunal biodiversity assessments to speed up description processes and uncover cryptic lineages. However, these approaches show sensitivity to sampling coverage (taxonomic and geographic) and the success rate has never been explored on mesopsammic Mollusca. Results We collected the meiofaunal sea-slug Pontohedyle (Acochlidia, Heterobranchia) from 28 localities worldwide. With a traditional morphological approach, all specimens fall into two morphospecies. However, with a multi-marker genetic approach, we reveal multiple lineages that are reciprocally monophyletic on single and concatenated gene trees in phylogenetic analyses. These lineages are largely concordant with geographical and oceanographic parameters, leading to our primary species hypothesis (PSH). In parallel, we apply four independent methods of molecular based species delineation: General Mixed Yule Coalescent model (GMYC), statistical parsimony, Bayesian Species Delineation (BPP) and Automatic Barcode Gap Discovery (ABGD). The secondary species hypothesis (SSH) is gained by relying only on uncontradicted results of the different approaches (‘minimum consensus approach’), resulting in the discovery of a radiation of (at least) 12 mainly cryptic species, 9 of them new to science, some sympatric and some allopatric with respect to ocean boundaries. However, the meiofaunal paradox still persists in some Pontohedyle species identified here with wide coastal and trans-archipelago distributions. Conclusions Our study confirms extensive, morphologically cryptic diversity among

  8. Mercury Toolset for Spatiotemporal Metadata

    NASA Astrophysics Data System (ADS)

    Devarakonda, Ranjeet; Palanisamy, Giri; Green, James; Wilson, Bruce; Rhyne, B. Timothy; Lindsley, Chris

    2010-06-01

    Mercury (http://mercury.ornl.gov) is a set of tools for federated harvesting, searching, and retrieving metadata, particularly spatiotemporal metadata. Version 3.0 of the Mercury toolset provides orders of magnitude improvements in search speed, support for additional metadata formats, integration with Google Maps for spatial queries, facetted type search, support for RSS (Really Simple Syndication) delivery of search results, and enhanced customization to meet the needs of the multiple projects that use Mercury. It provides a single portal to very quickly search for data and information contained in disparate data management systems, each of which may use different metadata formats. Mercury harvests metadata and key data from contributing project servers distributed around the world and builds a centralized index. The search interfaces then allow the users to perform a variety of fielded, spatial, and temporal searches across these metadata sources. This centralized repository of metadata with distributed data sources provides extremely fast search results to the user, while allowing data providers to advertise the availability of their data and maintain complete control and ownership of that data. Mercury periodically (typically daily)harvests metadata sources through a collection of interfaces and re-indexes these metadata to provide extremely rapid search capabilities, even over collections with tens of millions of metadata records. A number of both graphical and application interfaces have been constructed within Mercury, to enable both human users and other computer programs to perform queries. Mercury was also designed to support multiple different projects, so that the particular fields that can be queried and used with search filters are easy to configure for each different project.

  9. Mercury Toolset for Spatiotemporal Metadata

    NASA Technical Reports Server (NTRS)

    Wilson, Bruce E.; Palanisamy, Giri; Devarakonda, Ranjeet; Rhyne, B. Timothy; Lindsley, Chris; Green, James

    2010-01-01

    Mercury (http://mercury.ornl.gov) is a set of tools for federated harvesting, searching, and retrieving metadata, particularly spatiotemporal metadata. Version 3.0 of the Mercury toolset provides orders of magnitude improvements in search speed, support for additional metadata formats, integration with Google Maps for spatial queries, facetted type search, support for RSS (Really Simple Syndication) delivery of search results, and enhanced customization to meet the needs of the multiple projects that use Mercury. It provides a single portal to very quickly search for data and information contained in disparate data management systems, each of which may use different metadata formats. Mercury harvests metadata and key data from contributing project servers distributed around the world and builds a centralized index. The search interfaces then allow the users to perform a variety of fielded, spatial, and temporal searches across these metadata sources. This centralized repository of metadata with distributed data sources provides extremely fast search results to the user, while allowing data providers to advertise the availability of their data and maintain complete control and ownership of that data. Mercury periodically (typically daily) harvests metadata sources through a collection of interfaces and re-indexes these metadata to provide extremely rapid search capabilities, even over collections with tens of millions of metadata records. A number of both graphical and application interfaces have been constructed within Mercury, to enable both human users and other computer programs to perform queries. Mercury was also designed to support multiple different projects, so that the particular fields that can be queried and used with search filters are easy to configure for each different project.

  10. An integrated data model to estimate spatiotemporal occupancy, abundance, and colonization dynamics.

    PubMed

    Williams, Perry J; Hooten, Mevin B; Womble, Jamie N; Esslinger, George G; Bower, Michael R; Hefley, Trevor J

    2017-02-01

    Ecological invasions and colonizations occur dynamically through space and time. Estimating the distribution and abundance of colonizing species is critical for efficient management or conservation. We describe a statistical framework for simultaneously estimating spatiotemporal occupancy and abundance dynamics of a colonizing species. Our method accounts for several issues that are common when modeling spatiotemporal ecological data including multiple levels of detection probability, multiple data sources, and computational limitations that occur when making fine-scale inference over a large spatiotemporal domain. We apply the model to estimate the colonization dynamics of sea otters (Enhydra lutris) in Glacier Bay, in southeastern Alaska.

  11. Spatiotemporal chaos from bursting dynamics

    SciTech Connect

    Berenstein, Igal; De Decker, Yannick

    2015-08-14

    In this paper, we study the emergence of spatiotemporal chaos from mixed-mode oscillations, by using an extended Oregonator model. We show that bursting dynamics consisting of fast/slow mixed mode oscillations along a single attractor can lead to spatiotemporal chaotic dynamics, although the spatially homogeneous solution is itself non-chaotic. This behavior is observed far from the Hopf bifurcation and takes the form of a spatiotemporal intermittency where the system locally alternates between the fast and the slow phases of the mixed mode oscillations. We expect this form of spatiotemporal chaos to be generic for models in which one or several slow variables are coupled to activator-inhibitor type of oscillators.

  12. Phylogeny and evolutionary histories of Pyrus L. revealed by phylogenetic trees and networks based on data from multiple DNA sequences

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reconstructing the phylogeny of Pyrus has been difficult due to the wide distribution of the genus and lack of informative data. In this study, we collected 110 accessions representing 25 Pyrus species and constructed both phylogenetic trees and phylogenetic networks based on multiple DNA sequence d...

  13. P-wave travel-time tomography reveals multiple mantle upwellings beneath the northern East-Africa Rift

    NASA Astrophysics Data System (ADS)

    Hammond, J. O. S.; Civiero, C.; Goes, S. D. B.; Ahmed, A.; Ayele, A.; Doubre, C.; Goitom, B.; Keir, D.; Kendall, M.; Leroy, S. D.; Ogubazghi, G.; Rumpker, G.; Stuart, G. W.

    2014-12-01

    The East African Rift (EAR) shows evidence for active magmatism from the eruption of flood basalts 30 Ma to active volcanism associated with rifting today. Mantle plumes have been invoked as the likely cause. However, the nature of mantle upwelling is debated, with proposed models ranging from a single broad plume, the African Superplume, connected to the LLSVP beneath Southern Africa, to multiple distinct sources of upwelling along the East-Africa Rift. We present a new relative travel-time tomography model that images detailed P-wave velocities below the northern East-African rift from the surface to lower mantle depths. Data comes from 439 stations that cover the area from Tanzania to Saudi Arabia. The aperture of the integrated dataset allows us to image for the first time low-velocity structures of ~ 100-km length scales down to depths of 900 km beneath this region. Our images provide evidence of at least two separate low-velocity structures with a diameter of ~200 km that continue through the transition zone and into the lower mantle: the first, and most pronounced, is beneath the Afar Depression, which extends to at least 900 km depth and a second is located beneath the Main Ethiopian Rift that extends to at least 750 km. Taking into account seismic sensitivity to temperature and thermally controlled phase boundary topography, we interpret these features as multiple focused upwellings from below the transition zone with excess temperatures of ~ 100-150 K. Such temperatures are also fully consistent with previous petrological and other geophysical estimates. Furthermore, the separate structures could explain differences in geochemistry of erupted magmas along the rift zone, as well as the dynamic topography seen at the surface. Our findings thus support the involvement of multiple plumes in the evolution of the EAR and a direct connection between lower mantle features and the volcanism at the surface.

  14. Analysis of Multiple Tsetse Fly Populations in Uganda Reveals Limited Diversity and Species-Specific Gut Microbiota

    PubMed Central

    Telleria, Erich L.; Echodu, Richard; Wu, Yineng; Okedi, Loyce M.; Weiss, Brian L.; Aksoy, Serap; Caccone, Adalgisa

    2014-01-01

    The invertebrate microbiome contributes to multiple aspects of host physiology, including nutrient supplementation and immune maturation processes. We identified and compared gut microbial abundance and diversity in natural tsetse flies from Uganda using five genetically distinct populations of Glossina fuscipes fuscipes and multiple tsetse species (Glossina morsitans morsitans, G. f. fuscipes, and Glossina pallidipes) that occur in sympatry in one location. We used multiple approaches, including deep sequencing of the V4 hypervariable region of the 16S rRNA gene, 16S rRNA gene clone libraries, and bacterium-specific quantitative PCR (qPCR), to investigate the levels and patterns of gut microbial diversity from a total of 151 individuals. Our results show extremely limited diversity in field flies of different tsetse species. The obligate endosymbiont Wigglesworthia dominated all samples (>99%), but we also observed wide prevalence of low-density Sodalis (tsetse's commensal endosymbiont) infections (<0.05%). There were also several individuals (22%) with high Sodalis density, which also carried coinfections with Serratia. Albeit in low density, we noted differences in microbiota composition among the genetically distinct G. f. fuscipes flies and between different sympatric species. Interestingly, Wigglesworthia density varied in different species (104 to 106 normalized genomes), with G. f. fuscipes having the highest levels. We describe the factors that may be responsible for the reduced diversity of tsetse's gut microbiota compared to those of other insects. Additionally, we discuss the implications of Wigglesworthia and Sodalis density variations as they relate to trypanosome transmission dynamics and vector competence variations associated with different tsetse species. PMID:24814785

  15. Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts

    PubMed Central

    Troupin, Cécile; Dacheux, Laurent; Tanguy, Marion; Sabeta, Claude; Blanc, Hervé; Bouchier, Christiane; Vignuzzi, Marco; Holmes, Edward C.; Bourhy, Hervé

    2016-01-01

    The natural evolution of rabies virus (RABV) provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence. Using 321 genome sequences spanning an unprecedented diversity of RABV, we compared evolutionary rates and selection pressures in viruses sampled from multiple primary host shifts that occurred on various continents. Two major phylogenetic groups, bat-related RABV and dog-related RABV, experiencing markedly different evolutionary dynamics were identified. While no correlation between time and genetic divergence was found in bat-related RABV, the evolution of dog-related RABV followed a generally clock-like structure, although with a relatively low evolutionary rate. Subsequent molecular clock dating indicated that dog-related RABV likely underwent a rapid global spread following the intensification of intercontinental trade starting in the 15th century. Strikingly, although dog RABV has jumped to various wildlife species from the order Carnivora, we found no clear evidence that these host-jumping events involved adaptive evolution, with RABV instead characterized by strong purifying selection, suggesting that ecological processes also play an important role in shaping patterns of emergence. However, specific amino acid changes were associated with the parallel emergence of RABV in ferret-badgers in Asia, and some host shifts were associated with increases in evolutionary rate, particularly in the ferret-badger and mongoose, implying that changes in host species can have important impacts on evolutionary dynamics. PMID:27977811

  16. Genetic analysis across different spatial scales reveals multiple dispersal mechanisms for the invasive hydrozoan Cordylophora in the Great Lakes.

    PubMed

    Darling, John A; Folino-Rorem, Nadine C

    2009-12-01

    Discerning patterns of post-establishment spread by invasive species is critically important for the design of effective management strategies and the development of appropriate theoretical models predicting spatial expansion of introduced populations. The globally invasive colonial hydrozoan Cordylophora produces propagules both sexually and vegetatively and is associated with multiple potential dispersal mechanisms, making it a promising system to investigate complex patterns of population structure generated throughout the course of rapid range expansion. Here, we explore genetic patterns associated with the spread of this taxon within the North American Great Lakes basin. We collected intensively from eight harbours in the Chicago area in order to conduct detailed investigation of local population expansion. In addition, we collected from Lakes Michigan, Erie, and Ontario, as well as Lake Cayuga in the Finger Lakes of upstate New York in order to assess genetic structure on a regional scale. Based on data from eight highly polymorphic microsatellite loci we examined the spatial extent of clonal genotypes, assessed levels of neutral genetic diversity, and explored patterns of migration and dispersal at multiple spatial scales through assessment of population level genetic differentiation (pairwise F(ST) and factorial correspondence analysis), Bayesian inference of population structure, and assignment tests on individual genotypes. Results of these analyses indicate that Cordylophora populations in this region spread predominantly through sexually produced propagules, and that while limited natural larval dispersal can drive expansion locally, regional expansion likely relies on anthropogenic dispersal vectors.

  17. A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle

    PubMed Central

    Chockalingam, Karuppiah; Simeon, Rudo L.; Rice, Charles M.; Chen, Zhilei

    2010-01-01

    The hepatitis C virus (HCV) life cycle involves multiple steps, but most current drug candidates target only viral replication. The inability to systematically discover inhibitors targeting multiple steps of the HCV life cycle has hampered antiviral development. We present a simple screen for HCV antivirals based on the alleviation of HCV-mediated cytopathic effect in an engineered cell line—n4mBid. This approach obviates the need for a secondary screen to avoid cytotoxic false-positive hits. Application of our screen to 1280 compounds, many in clinical trials or approved for therapeutic use, yielded >200 hits. Of the 55 leading hits, 47 inhibited one or more aspects of the HCV life cycle by >40%. Six compounds blocked HCV entry to levels similar to an antibody (JS-81) targeting the HCV entry receptor CD81. Seven hits inhibited HCV replication and/or infectious virus production by >100-fold, with one (quinidine) inhibiting infectious virus production by 450-fold relative to HCV replication levels. This approach is simple and inexpensive and should enable the rapid discovery of new classes of HCV life cycle inhibitors. PMID:20142494

  18. Multiple sulphur and oxygen isotopes reveal microbial sulphur cycling in spring waters in the Lower Engadin, Switzerland.

    PubMed

    Strauss, Harald; Chmiel, Hannah; Christ, Andreas; Fugmann, Artur; Hanselmann, Kurt; Kappler, Andreas; Königer, Paul; Lutter, Andreas; Siedenberg, Katharina; Teichert, Barbara M A

    2016-01-01

    Highly mineralized springs in the Scuol-Tarasp area of the Lower Engadin and in the Albula Valley near Alvaneu, Switzerland, display distinct differences with respect to the source and fate of their dissolved sulphur species. High sulphate concentrations and positive sulphur (δ(34)S) and oxygen (δ(18)O) isotopic compositions argue for the subsurface dissolution of Mesozoic evaporitic sulphate. In contrast, low sulphate concentrations and less positive or even negative δ(34)S and δ(18)O values indicate a substantial contribution of sulphate sulphur from the oxidation of sulphides in the crystalline basement rocks or the Jurassic sedimentary cover rocks. Furthermore, multiple sulphur (δ(34)S, Δ(33)S) isotopes support the identification of microbial sulphate reduction and sulphide oxidation in the subsurface, the latter is also evident through the presence of thick aggregates of sulphide-oxidizing Thiothrix bacteria.

  19. Fine mapping analysis of HLA-DP/DQ gene clusters on chromosome 6 reveals multiple susceptibility loci for HBV infection.

    PubMed

    Tao, Jingjing; Su, Kunkai; Yu, Chengbo; Liu, Xiaoli; Wu, Wei; Xu, Wei; Jiang, Bingxun; Luo, Rui; Yao, Jian; Zhou, Jiawei; Zhan, Yan; Ye, Chao; Yuan, Wenji; Jiang, Xianzhong; Cui, Wenyan; Li, Ming D; Li, Lianjuan

    2015-12-01

    Recent genome-wide association studies have revealed the HLA region on chromosome 6p21 as a susceptibility locus for hepatitis B virus (HBV) infection, a finding subsequently replicated in independent samples. However, only limited single nucleotide polymorphisms (SNPs) were analyzed in most of these studies, and it remains to be determined which SNPs contribute to the detected association. After genotyping 140 SNPs within this genomic region in a total of 1657 HBV-positive patients and 1456 HBV-negative controls, we conducted a series of genetic epidemiological and bioinformatics analysis, including individual SNP-based association analysis, haplotype-based association analysis, and conditional analysis. We identified 76 SNPs and 5 LD blocks in HLA-DP/DQ clusters that are significantly associated with HBV infection, with the smallest P value being 3.88 × 10(-18) for rs9277535 in HLA-DPB1. With conditional analysis, we further revealed that the genes contributing to the effects of variants in HLA-DP/DQ on infection are independent of each other, and the LD block 5 in the 3'-UTR region of HLA-DPB1 had a predominant effect in the association of HLA-DP with HBV infection. We also found that the SNPs in the 3'-UTR region of HLA-DPB1 were significant between the subgroups of inactive HBV carrier, chronic hepatitis B, or hepatic cirrhosis from the case group and the spontaneous HBV-clearance subgroup from the control group. Finally, we did further association analysis of SNPs in this region with different subgroups from the case group, which revealed no association of these SNPs with the progression of HBV-related diseases. In sum, we showed, for the first time, that the HLA-DP/DQ clusters contribute independently to HBV infection, and the 3'-UTR region of HLA-DPB1 represents an important functional region involved in HBV infection.

  20. Validation and Genotyping of Multiple Human Polymorphic Inversions Mediated by Inverted Repeats Reveals a High Degree of Recurrence

    PubMed Central

    Aguado, Cristina; Gayà-Vidal, Magdalena; Villatoro, Sergi; Oliva, Meritxell; Izquierdo, David; Giner-Delgado, Carla; Montalvo, Víctor; García-González, Judit; Martínez-Fundichely, Alexander; Capilla, Laia; Ruiz-Herrera, Aurora; Estivill, Xavier; Puig, Marta; Cáceres, Mario

    2014-01-01

    In recent years different types of structural variants (SVs) have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR) protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6–24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies. PMID:24651690

  1. Genetic Dissection of a Genomic Region with Pleiotropic Effects on Domestication Traits in Maize Reveals Multiple Linked QTL

    PubMed Central

    Lemmon, Zachary H.; Doebley, John F.

    2014-01-01

    The domesticated crop maize and its wild progenitor, teosinte, have been used in numerous experiments to investigate the nature of divergent morphologies. This study examines a poorly understood region on the fifth chromosome of maize associated with a number of traits under selection during domestication, using a quantitative trait locus (QTL) mapping population specific to the fifth chromosome. In contrast with other major domestication loci in maize where large-effect, highly pleiotropic, single genes are responsible for phenotypic effects, our study found the region on chromosome five fractionates into multiple-QTL regions, none with singularly large effects. The smallest 1.5-LOD support interval for a QTL contained 54 genes, one of which was a MADS MIKCC transcription factor, a family of proteins implicated in many developmental programs. We also used simulated trait data sets to investigate the power of our mapping population to identify QTL for which there is a single underlying causal gene. This analysis showed that while QTL for traits controlled by single genes can be accurately mapped, our population design can detect no more than ∼4.5 QTL per trait even when there are 100 causal genes. Thus when a trait is controlled by ≥5 genes in the simulated data, the number of detected QTL can represent a simplification of the underlying causative factors. Our results show how a QTL region with effects on several domestication traits may be due to multiple linked QTL of small effect as opposed to a single gene with large and pleiotropic effects. PMID:24950893

  2. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

    PubMed

    Kerr, Peter J; Cattadori, Isabella M; Rogers, Matthew B; Fitch, Adam; Geber, Adam; Liu, June; Sim, Derek G; Boag, Brian; Eden, John-Sebastian; Ghedin, Elodie; Read, Andrew F; Holmes, Edward C

    2017-03-01

    The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955) and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.

  3. LUT REVEALS AN ALGOL-TYPE ECLIPSING BINARY WITH THREE ADDITIONAL STELLAR COMPANIONS IN A MULTIPLE SYSTEM

    SciTech Connect

    Zhu, L.-Y.; Zhou, X.; Qian, S.-B.; Li, L.-J.; Liao, W.-P.; Tian, X.-M.; Wang, Z.-H.; Hu, J.-Y.

    2016-04-15

    A complete light curve of the neglected eclipsing binary Algol V548 Cygni in the UV band was obtained with the Lunar-based Ultraviolet Telescope in 2014 May. Photometric solutions are obtained using the Wilson–Devinney method. It is found that solutions with and without third light are quite different. The mass ratio without third light is determined to be q = 0.307, while that derived with third light is q = 0.606. It is shown that V548 Cygni is a semi-detached binary where the secondary component is filling the critical Roche lobe. An analysis of all available eclipse times suggests that there are three cyclic variations in the O–C diagram that are interpreted by the light travel-time effect via the presence of three additional stellar companions. This is in agreement with the presence of a large quantity of third light in the system. The masses of these companions are estimated as m sin i′ ∼ 1.09, 0.20, and 0.52 M{sub ⊙}. They are orbiting the central binary with orbital periods of about 5.5, 23.3, and 69.9 years, i.e., in 1:4:12 resonance orbit. Their orbital separations are about 4.5, 13.2, and 26.4 au, respectively. Our photometric solutions suggest that they contribute about 32.4% to the total light of the multiple system. No obvious long-term changes in the orbital period were found, indicating that the contributions of the mass transfer and the mass loss due to magnetic braking to the period variations are comparable. The detection of three possible additional stellar components orbiting a typical Algol in a multiple system make V548 Cygni a very interesting binary to study in the future.

  4. Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia

    PubMed Central

    Kerr, Peter J.; Cattadori, Isabella M.; Fitch, Adam; Geber, Adam; Liu, June; Sim, Derek G.; Boag, Brian; Ghedin, Elodie

    2017-01-01

    The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954–1955) and between 2008–2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms. PMID:28253375

  5. LUT Reveals an Algol-type Eclipsing Binary With Three Additional Stellar Companions in a Multiple System

    NASA Astrophysics Data System (ADS)

    Zhu, L.-Y.; Zhou, X.; Hu, J.-Y.; Qian, S.-B.; Li, L.-J.; Liao, W.-P.; Tian, X.-M.; Wang, Z.-H.

    2016-04-01

    A complete light curve of the neglected eclipsing binary Algol V548 Cygni in the UV band was obtained with the Lunar-based Ultraviolet Telescope in 2014 May. Photometric solutions are obtained using the Wilson-Devinney method. It is found that solutions with and without third light are quite different. The mass ratio without third light is determined to be q = 0.307, while that derived with third light is q = 0.606. It is shown that V548 Cygni is a semi-detached binary where the secondary component is filling the critical Roche lobe. An analysis of all available eclipse times suggests that there are three cyclic variations in the O-C diagram that are interpreted by the light travel-time effect via the presence of three additional stellar companions. This is in agreement with the presence of a large quantity of third light in the system. The masses of these companions are estimated as m sin i‧ ˜ 1.09, 0.20, and 0.52 M⊙. They are orbiting the central binary with orbital periods of about 5.5, 23.3, and 69.9 years, i.e., in 1:4:12 resonance orbit. Their orbital separations are about 4.5, 13.2, and 26.4 au, respectively. Our photometric solutions suggest that they contribute about 32.4% to the total light of the multiple system. No obvious long-term changes in the orbital period were found, indicating that the contributions of the mass transfer and the mass loss due to magnetic braking to the period variations are comparable. The detection of three possible additional stellar components orbiting a typical Algol in a multiple system make V548 Cygni a very interesting binary to study in the future.

  6. MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

    PubMed

    Hinsch, Andrea; Buchholz, Malte; Odinga, Sinje; Borkowski, Carina; Koop, Christina; Izbicki, Jacob R; Wurlitzer, Marcus; Krech, Till; Wilczak, Waldemar; Steurer, Stefan; Jacobsen, Frank; Burandt, Eike-Christian; Stahl, Phillip; Simon, Ronald; Sauter, Guido; Schlüter, Hartmut

    2017-01-24

    For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer we applied MALDI imaging mass spectrometry (IMS) to a tissue micro array (TMA) containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. 15 out of 27 IMS signals revealed a significant association with survival. For 7 signals (m/z 654, 776, 788, 904, 944, 975, and 1013) the absence, and for 8 signals (m/z 643, 678, 836, 886, 898, 1095, 1459, and 1477) the presence was associated with decreased life expectancy, including 5 masses (m/z 788, 836, 904, 944, and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these 5 masses resulted in a 3-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis, and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale TMAs to simultaneously identify and validate clinically useful molecular marker.

  7. Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales.

    PubMed

    Wehrl, Hans F; Hossain, Mosaddek; Lankes, Konrad; Liu, Chih-Chieh; Bezrukov, Ilja; Martirosian, Petros; Schick, Fritz; Reischl, Gerald; Pichler, Bernd J

    2013-09-01

    Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) is a new tool to study functional processes in the brain. Here we study brain function in response to a barrel-field stimulus simultaneously using PET, which traces changes in glucose metabolism on a slow time scale, and functional MRI (fMRI), which assesses fast vascular and oxygenation changes during activation. We found spatial and quantitative discrepancies between the PET and the fMRI activation data. The functional connectivity of the rat brain was assessed by both modalities: the fMRI approach determined a total of nine known neural networks, whereas the PET method identified seven glucose metabolism-related networks. These results demonstrate the feasibility of combined PET-MRI for the simultaneous study of the brain at activation and rest, revealing comprehensive and complementary information to further decode brain function and brain networks.

  8. A Quantitative Model of Motility Reveals Low-Dimensional Variation in Exploratory Behavior Across Multiple Nematode Species

    NASA Astrophysics Data System (ADS)

    Helms, Stephen; Avery, Leon; Stephens, Greg; Shimizu, Tom

    2014-03-01

    Animal behavior emerges from many layers of biological organization--from molecular signaling pathways and neuronal networks to mechanical outputs of muscles. In principle, the large number of interconnected variables at each of these layers could imply dynamics that are complex and hard to control or even tinker with. Yet, for organisms to survive in a competitive, ever-changing environment, behavior must readily adapt. We applied quantitative modeling to identify important aspects of behavior in chromadorean nematodes ranging from the lab strain C. elegans N2 to wild strains and distant species. We revealed subtle yet important features such as speed control and heavy-tailed directional changes. We found that the parameters describing this behavioral model varied among individuals and across species in a correlated way that is consistent with a trade-off between exploratory and exploitative behavior.

  9. Characterization of expressed class II MHC sequences in the banner-tailed kangaroo rat (Dipodomys spectabilis) reveals multiple DRB loci.

    PubMed

    Busch, Joseph D; Waser, Peter M; DeWoody, J Andrew

    2008-11-01

    Genes of the major histocompatibility complex (MHC) are exceptionally polymorphic due to the combined effects of natural and sexual selection. Most research in wild populations has focused on the second exon of a single class II locus (DRB), but complete gene sequences can provide an illuminating backdrop for studies of intragenic selection, recombination, and organization. To this end, we characterized class II loci in the banner-tailed kangaroo rat (Dipodomys spectabilis). Seven DRB-like sequences (provisionally named MhcDisp-DRB*01 through *07) were isolated from spleen cDNA and most likely comprise > or =5 loci; this multiformity is quite unlike the situation in muroid rodents such as Mus, Rattus, and Peromyscus. In silico translation revealed the presence of important structural residues for glycosylation sites, salt bonds, and CD4+ T-cell recognition. Amino-acid distances varied widely among the seven sequences (2-34%). Nuclear DNA sequences from the Disp-DRB*07 locus (approximately 10 kb) revealed a conventional exon/intron structure as well as a number of microsatellites and short interspersed nuclear elements (B4, Alu, and IDL-Geo subfamilies). Rates of nucleotide substitution at Disp-DRB*07 are similar in both exons and introns (pi = 0.015 and 0.012, respectively), which suggests relaxed selection and may indicate that this locus is an expressed pseudogene. Finally, we performed BLASTn searches against Dipodomys ordii genomic sequences (unassembled reads) and find 90-97% nucleotide similarity between the two kangaroo rat species. Collectively, these data suggest that class II diversity in heteromyid rodents is based on polylocism and departs from the muroid architecture.

  10. Multiple Sex-Associated Regions and a Putative Sex Chromosome in Zebrafish Revealed by RAD Mapping and Population Genomics

    PubMed Central

    Anderson, Jennifer L.; Rodríguez Marí, Adriana; Braasch, Ingo; Amores, Angel; Hohenlohe, Paul; Batzel, Peter; Postlethwait, John H.

    2012-01-01

    Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio), neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate), the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA) wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag) markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome. PMID:22792396

  11. Comparative analyses of lipidomes and transcriptomes reveal a concerted action of multiple defensive systems against photooxidative stress in Haematococcus pluvialis

    PubMed Central

    Gwak, Yunho; Hwang, Yong-sic; Wang, Baobei; Kim, Minju; Jeong, Jooyeon; Lee, Choul-Gyun; Hu, Qiang; Han, Danxiang; Jin, EonSeon

    2014-01-01

    Haematococcus pluvialis cells predominantly remain in the macrozooid stage under favourable environmental conditions but are rapidly differentiated into haematocysts upon exposure to various environmental stresses. Haematocysts are characterized by massive accumulations of astaxanthin sequestered in cytosolic oil globules. Lipidomic analyses revealed that synthesis of the storage lipid triacylglycerol (TAG) was substantially stimulated under high irradiance. Simultaneously, remodelling of membrane glycerolipids occurred as a result of dramatic reductions in chloroplast membrane glycolipids but remained unchanged or declined slightly in extraplastidic membrane glycerolipids. De novo assembly of transcriptomes revealed the genomic and metabolic features of this unsequenced microalga. Comparative transcriptomic analysis showed that so-called resting cells (haematocysts) may be more active than fast-growing vegetative cells (macrozooids) regarding metabolic pathways and functions. Comparative transcriptomic analyses of astaxanthin biosynthesis suggested that the non-mevalonate pathway mediated the synthesis of isopentenyl diphosphate, as the majority of genes involved in subsequent astaxanthin biosynthesis were substantially up-regulated under high irradiance, with the genes encoding phytoene synthase, phytoene desaturase, and β-carotene hydroxylase identified as the most prominent regulatory components. Accumulation of TAG under high irradiance was attributed to moderate up-regulation of de novo fatty acid biosynthesis at the gene level as well as to moderate elevation of the TAG assembly pathways. Additionally, inferred from transcriptomic differentiation, an increase in reactive oxygen species (ROS) scavenging activity, a decrease in ROS production, and the relaxation of over-reduction of the photosynthetic electron transport chain will work together to protect against photooxidative stress in H. pluvialis under high irradiance. PMID:24821952

  12. Comparative analyses of lipidomes and transcriptomes reveal a concerted action of multiple defensive systems against photooxidative stress in Haematococcus pluvialis.

    PubMed

    Gwak, Yunho; Hwang, Yong-sic; Wang, Baobei; Kim, Minju; Jeong, Jooyeon; Lee, Choul-Gyun; Hu, Qiang; Han, Danxiang; Jin, EonSeon

    2014-08-01

    Haematococcus pluvialis cells predominantly remain in the macrozooid stage under favourable environmental conditions but are rapidly differentiated into haematocysts upon exposure to various environmental stresses. Haematocysts are characterized by massive accumulations of astaxanthin sequestered in cytosolic oil globules. Lipidomic analyses revealed that synthesis of the storage lipid triacylglycerol (TAG) was substantially stimulated under high irradiance. Simultaneously, remodelling of membrane glycerolipids occurred as a result of dramatic reductions in chloroplast membrane glycolipids but remained unchanged or declined slightly in extraplastidic membrane glycerolipids. De novo assembly of transcriptomes revealed the genomic and metabolic features of this unsequenced microalga. Comparative transcriptomic analysis showed that so-called resting cells (haematocysts) may be more active than fast-growing vegetative cells (macrozooids) regarding metabolic pathways and functions. Comparative transcriptomic analyses of astaxanthin biosynthesis suggested that the non-mevalonate pathway mediated the synthesis of isopentenyl diphosphate, as the majority of genes involved in subsequent astaxanthin biosynthesis were substantially up-regulated under high irradiance, with the genes encoding phytoene synthase, phytoene desaturase, and β-carotene hydroxylase identified as the most prominent regulatory components. Accumulation of TAG under high irradiance was attributed to moderate up-regulation of de novo fatty acid biosynthesis at the gene level as well as to moderate elevation of the TAG assembly pathways. Additionally, inferred from transcriptomic differentiation, an increase in reactive oxygen species (ROS) scavenging activity, a decrease in ROS production, and the relaxation of over-reduction of the photosynthetic electron transport chain will work together to protect against photooxidative stress in H. pluvialis under high irradiance.

  13. The Distribution of Thermophilic Sulfate-reducing Bacteria Along an Estuarine Gradient Reveals Multiple Origins of Endospores in Estuarine Sediments

    NASA Astrophysics Data System (ADS)

    Bell, E.

    2015-12-01

    Cold marine sediments harbour inactive spores of thermophilic bacteria. These misplaced thermophiles are genetically similar to microorganisms detected in deep biosphere environments, leading to the hypothesis that seabed fluid flow transports thermophiles out of warm subsurface environments and into the ocean. Estuaries form the transition between the marine and the terrestrial biosphere and are influenced by tidal currents, surface run-off and groundwater seepage. Endospores from thermophilic bacteria present in estuarine sediments could therefore originate from a number of sources that may influence the estuary differently. We have therefore tested the hypothesis that this will lead to a gradient in the composition of thermophilic endospore populations in estuarine sediments. The distribution of thermophilic spore-forming sulfate-reducing bacteria along an estuarine gradient from freshwater (River Tyne, UK) to marine (North Sea) was investigated. Microbial community analysis by 16S rRNA gene amplicon sequencing revealed changes in the thermophilic population enriched at different locations within the estuary. Certain species were only detected at the marine end, highlighting possible links to deep marine biosphere habitats such as oil reservoirs that harbour closely related Desulfotomaculum spp. Conversely, other taxa were predominantly observed in the freshwater reaches of the estuary indicating dispersal from an upstream or terrestrial source. Different endospore populations were enriched dependent on incubation temperature and spore heat-resistance. Microcosms incubated at 50, 60 or 70°C showed a shift in the dominant species of Desulfotomaculum enriched as the temperature increased. Microcosms triple-autoclaved at 121°C prior to incubation still showed rapid and reproducible sulfate-reduction and some Desulfotomaculum spp. remained active after autoclaving at 130°C. These results show that temperature physiology and biogeographic patterns can be used to

  14. Large-scale phylogenetic analyses reveal multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms associated with climate change.

    PubMed

    Li, Hong-Lei; Wang, Wei; Mortimer, Peter E; Li, Rui-Qi; Li, De-Zhu; Hyde, Kevin D; Xu, Jian-Chu; Soltis, Douglas E; Chen, Zhi-Duan

    2015-09-10

    Nitrogen is fundamental to all life forms and is also one of the most limiting of nutrients for plant growth. Several clades of angiosperms have developed symbiotic relationships with actinorhizal bacteria that fix atmospheric nitrogen and increase access to this nutrient. However, the evolutionary patterns of actinorhizal nitrogen-fixing symbioses remain unclear to date. Furthermore the underlying environmental pressures that led to the gain of symbiotic actinorhizal nitrogen fixation have never been investigated. Here, we present the most comprehensive genus-level phylogenetic analysis of the nitrogen-fixing angiosperms based on three plastid loci. We found that actinorhizal nitrogen-fixing species are distributed in nine distinct lineages. By dating the branching events, we determined that seven actinorhizal nitrogen-fixing lineages originated during the Late Cretaceous, and two more emerged during the Eocene. We put forward a hypothesis that multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms may have been associated with increased global temperatures and high levels of atmospheric carbon dioxide during these two time periods, as well as the availability of open habitats with high light conditions. Our nearly complete genus-level time-tree for the nitrogen-fixing clade is a significant advance in understanding the evolutionary and ecological background of this important symbiosis between plants and bacteria.

  15. Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq

    SciTech Connect

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; Gaffrey, Matthew J.; Hu, Dehong; Szymanski, Craig J.; Xie, Yumei; Melby, Eric S.; Dohnalkova, Alice; Taylor, Ronald C.; Grate, Eva K.; Cooley, Scott K.; McDermott, Jason E.; Heredia-Langner, Alejandro; Orr, Galya

    2016-11-22

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. Here we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with upregulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly downregulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong upregulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis and organelle activities. In contrast, strategies unique to carboxylated QDs showed upregulation of DNA repair and RNA activities, and decreased regulation of cell division, coupled in some cases with upregulation of stress responses and ATP related functions. Together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified, proactive defenses or repairs of the NP insults.

  16. Pyrosequencing the Midgut Transcriptome of the Banana Weevil Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae) Reveals Multiple Protease-Like Transcripts

    PubMed Central

    Valencia, Arnubio; Wang, Haichuan; Soto, Alberto; Aristizabal, Manuel; Arboleda, Jorge W.; Eyun, Seong-il; Noriega, Daniel D.; Siegfried, Blair

    2016-01-01

    The banana weevil Cosmopolites sordidus is an important and serious insect pest in most banana and plantain-growing areas of the world. In spite of the economic importance of this insect pest very little genomic and transcriptomic information exists for this species. In the present study, we characterized the midgut transcriptome of C. sordidus using massive 454-pyrosequencing. We generated over 590,000 sequencing reads that assembled into 30,840 contigs with more than 400 bp, representing a significant expansion of existing sequences available for this insect pest. Among them, 16,427 contigs contained one or more GO terms. In addition, 15,263 contigs were assigned an EC number. In-depth transcriptome analysis identified genes potentially involved in insecticide resistance, peritrophic membrane biosynthesis, immunity-related function and defense against pathogens, and Bacillus thuringiensis toxins binding proteins as well as multiple enzymes involved with protein digestion. This transcriptome will provide a valuable resource for understanding larval physiology and for identifying novel target sites and management approaches for this important insect pest. PMID:26949943

  17. Sandcastle: software for revealing latent information in multiple experimental ChIP-chip datasets via a novel normalisation procedure

    PubMed Central

    Bennett, Mark; Evans, Katie Ellen; Yu, Shirong; Teng, Yumin; Webster, Richard M.; Powell, James; Waters, Raymond; Reed, Simon H.

    2015-01-01

    ChIP-chip is a microarray based technology for determining the genomic locations of chromatin bound factors of interest, such as proteins. Standard ChIP-chip analyses employ peak detection methodologies to generate lists of genomic binding sites. No previously published method exists to enable comparative analyses of enrichment levels derived from datasets examining different experimental conditions. This restricts the use of the technology to binary comparisons of presence or absence of features between datasets. Here we present the R package Sandcastle — Software for the Analysis and Normalisation of Data from ChIP-chip AssayS of Two or more Linked Experiments — which allows for comparative analyses of data from multiple experiments by normalising all datasets to a common background. Relative changes in binding levels between experimental datasets can thus be determined, enabling the extraction of latent information from ChIP-chip experiments. Novel enrichment detection and peak calling algorithms are also presented, with a range of graphical tools, which facilitate these analyses. The software and documentation are available for download from http://reedlab.cardiff.ac.uk/sandcastle. PMID:26307543

  18. Multilocus sequence analyses reveal extensive diversity and multiple origins of fluconazole resistance in Candida tropicalis from tropical China

    PubMed Central

    Wu, Jin-Yan; Guo, Hong; Wang, Hua-Min; Yi, Guo-Hui; Zhou, Li-Min; He, Xiao-Wen; Zhang, Ying; Xu, Jianping

    2017-01-01

    Candida tropicalis is among the most prevalent human pathogenic yeast species, second only to C. albicans in certain geographic regions such as East Asia and Brazil. However, compared to C. albicans, relatively little is known about the patterns of genetic variation in C. tropicalis. This study analyzed the genetic diversity and relationships among isolates of C. tropicalis from the southern Chinese island of Hainan. A total of 116 isolates were obtained from seven geographic regions located across the Island. For each isolate, a total of 2677 bp from six gene loci were sequenced and 79 (2.96%) polymorphic nucleotide sites were found in our sample. Comparisons with strains reported from other parts of the world identified significant novel diversities in Hainan, including an average of six novel sequences (with a range 1 to 14) per locus and 80 novel diploid sequence types. Most of the genetic variation was found within individual strains and there was abundant evidence for gene flow among the seven geographic locations within Hainan. Interestingly, our analyses identified no significant correlation between the diploid sequence types at the six loci and fluconazole susceptibility, consistent with multiple origins of fluconazole resistance in the Hainan population of C. tropicalis. PMID:28186162

  19. Analyses of transcriptome sequences reveal multiple ancient large-scale duplication events in the ancestor of Sphagnopsida (Bryophyta).

    PubMed

    Devos, Nicolas; Szövényi, Péter; Weston, David J; Rothfels, Carl J; Johnson, Matthew G; Shaw, A Jonathan

    2016-07-01

    The goal of this research was to investigate whether there has been a whole-genome duplication (WGD) in the ancestry of Sphagnum (peatmoss) or the class Sphagnopsida, and to determine if the timing of any such duplication(s) and patterns of paralog retention could help explain the rapid radiation and current ecological dominance of peatmosses. RNA sequencing (RNA-seq) data were generated for nine taxa in Sphagnopsida (Bryophyta). Analyses of frequency plots for synonymous substitutions per synonymous site (Ks ) between paralogous gene pairs and reconciliation of 578 gene trees were conducted to assess evidence of large-scale or genome-wide duplication events in each transcriptome. Both Ks frequency plots and gene tree-based analyses indicate multiple duplication events in the history of the Sphagnopsida. The most recent WGD event predates divergence of Sphagnum from the two other genera of Sphagnopsida. Duplicate retention is highly variable across species, which might be best explained by local adaptation. Our analyses indicate that the last WGD could have been an important factor underlying the diversification of peatmosses and facilitated their rise to ecological dominance in peatlands. The timing of the duplication events and their significance in the evolutionary history of peat mosses are discussed.

  20. Large-scale phylogenetic analyses reveal multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms associated with climate change

    PubMed Central

    Li, Hong-Lei; Wang, Wei; Mortimer, Peter E.; Li, Rui-Qi; Li, De-Zhu; Hyde, Kevin D.; Xu, Jian-Chu; Soltis, Douglas E.; Chen, Zhi-Duan

    2015-01-01

    Nitrogen is fundamental to all life forms and is also one of the most limiting of nutrients for plant growth. Several clades of angiosperms have developed symbiotic relationships with actinorhizal bacteria that fix atmospheric nitrogen and increase access to this nutrient. However, the evolutionary patterns of actinorhizal nitrogen-fixing symbioses remain unclear to date. Furthermore the underlying environmental pressures that led to the gain of symbiotic actinorhizal nitrogen fixation have never been investigated. Here, we present the most comprehensive genus-level phylogenetic analysis of the nitrogen-fixing angiosperms based on three plastid loci. We found that actinorhizal nitrogen-fixing species are distributed in nine distinct lineages. By dating the branching events, we determined that seven actinorhizal nitrogen-fixing lineages originated during the Late Cretaceous, and two more emerged during the Eocene. We put forward a hypothesis that multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms may have been associated with increased global temperatures and high levels of atmospheric carbon dioxide during these two time periods, as well as the availability of open habitats with high light conditions. Our nearly complete genus-level time-tree for the nitrogen-fixing clade is a significant advance in understanding the evolutionary and ecological background of this important symbiosis between plants and bacteria. PMID:26354898

  1. High-Throughput Analysis of Stimulus-Evoked Behaviors in Drosophila Larva Reveals Multiple Modality-Specific Escape Strategies

    PubMed Central

    Ohyama, Tomoko; Jovanic, Tihana; Denisov, Gennady; Dang, Tam C.; Hoffmann, Dominik; Kerr, Rex A.; Zlatic, Marta

    2013-01-01

    All organisms react to noxious and mechanical stimuli but we still lack a complete understanding of cellular and molecular mechanisms by which somatosensory information is transformed into appropriate motor outputs. The small number of neurons and excellent genetic tools make Drosophila larva an especially tractable model system in which to address this problem. We developed high throughput assays with which we can simultaneously expose more than 1,000 larvae per man-hour to precisely timed noxious heat, vibration, air current, or optogenetic stimuli. Using this hardware in combination with custom software we characterized larval reactions to somatosensory stimuli in far greater detail than possible previously. Each stimulus evoked a distinctive escape strategy that consisted of multiple actions. The escape strategy was context-dependent. Using our system we confirmed that the nociceptive class IV multidendritic neurons were involved in the reactions to noxious heat. Chordotonal (ch) neurons were necessary for normal modulation of head casting, crawling and hunching, in response to mechanical stimuli. Consistent with this we observed increases in calcium transients in response to vibration in ch neurons. Optogenetic activation of ch neurons was sufficient to evoke head casting and crawling. These studies significantly increase our understanding of the functional roles of larval ch neurons. More generally, our system and the detailed description of wild type reactions to somatosensory stimuli provide a basis for systematic identification of neurons and genes underlying these behaviors. PMID:23977118

  2. A comprehensive molecular phylogeny of dalytyphloplanida (platyhelminthes: rhabdocoela) reveals multiple escapes from the marine environment and origins of symbiotic relationships.

    PubMed

    Van Steenkiste, Niels; Tessens, Bart; Willems, Wim; Backeljau, Thierry; Jondelius, Ulf; Artois, Tom

    2013-01-01

    In this study we elaborate the phylogeny of Dalytyphloplanida based on complete 18S rDNA (156 sequences) and partial 28S rDNA (125 sequences), using a Maximum Likelihood and a Bayesian Inference approach, in order to investigate the origin of a limnic or limnoterrestrial and of a symbiotic lifestyle in this large group of rhabditophoran flatworms. The results of our phylogenetic analyses and ancestral state reconstructions indicate that dalytyphloplanids have their origin in the marine environment and that there was one highly successful invasion of the freshwater environment, leading to a large radiation of limnic and limnoterrestrial dalytyphloplanids. This monophyletic freshwater clade, Limnotyphloplanida, comprises the taxa Dalyelliidae, Temnocephalida, and most Typhloplanidae. Temnocephalida can be considered ectosymbiotic Dalyelliidae as they are embedded within this group. Secondary returns to brackish water and marine environments occurred relatively frequently in several dalyeliid and typhloplanid taxa. Our phylogenies also show that, apart from the Limnotyphloplanida, there have been only few independent invasions of the limnic environment, and apparently these were not followed by spectacular speciation events. The distinct phylogenetic positions of the symbiotic taxa also suggest multiple origins of commensal and parasitic life strategies within Dalytyphloplanida. The previously established higher-level dalytyphloplanid clades are confirmed in our topologies, but many of the traditional families are not monophyletic. Alternative hypothesis testing constraining the monophyly of these families in the topologies and using the approximately unbiased test, also statistically rejects their monophyly.

  3. Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects

    PubMed Central

    Jacobs, Russell E.; Lopez-Burks, Martha E.; Choi, Hojae; Wikenheiser, Jamie; Hallgrimsson, Benedikt; Jamniczky, Heather A.; Fraser, Scott E.; Lander, Arthur D.; Calof, Anne L.

    2016-01-01

    Elucidating the causes of congenital heart defects is made difficult by the complex morphogenesis of the mammalian heart, which takes place early in development, involves contributions from multiple germ layers, and is controlled by many genes. Here, we use a conditional/invertible genetic strategy to identify the cell lineage(s) responsible for the development of heart defects in a Nipbl-deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle transcriptional dysregulation leads to development of atrial septal defects (ASDs) at high frequency. Using an approach that allows for recombinase-mediated creation or rescue of Nipbl deficiency in different lineages, we uncover complex interactions between the cardiac mesoderm, endoderm, and the rest of the embryo, whereby the risk conferred by genetic abnormality in any one lineage is modified, in a surprisingly non-additive way, by the status of others. We argue that these results are best understood in the context of a model in which the risk of heart defects is associated with the adequacy of early progenitor cell populations relative to the sizes of the structures they must eventually form. PMID:27606604

  4. Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations.

    PubMed

    Wang, Beibei; Weng, Jingwei; Wang, Wenning

    2014-09-01

    Outer membrane protein TolC serves as an exit duct for exporting substances out of cell. The occluded periplasmic entrance of TolC is required to open for substrate transport, although the opening mechanism remains elusive. In this study, systematic molecular dynamics (MD) simulations for wild type TolC and six mutants were performed to explore the conformational dynamics of TolC. The periplasmic gate was shown to sample multiple conformational states with various degrees of gating opening. The gate opening was facilitated by all mutations except Y362F, which adopts an even more closed state than wild type TolC. The interprotomer salt-bridge R367-D153 is turned out to be crucial for periplasmic gate opening. The mutations that disrupt the interactions at the periplasmic tip may affect the stability of the trimeric assembly of TolC. Structural asymmetry of the periplasmic gate was observed to be opening size dependent. Asymmetric conformations are found in moderately opening states, while the most and the least opening states are often more symmetric. Finally, it is shown that lowering pH can remarkably stabilize the closed state of the periplasmic gate.

  5. Multiple causation of phylogeographical pattern as revealed by nested clade analysis of the bamboo viper (Trimeresurus stejnegeri) within Taiwan.

    PubMed

    Creer, S; Malhotra, A; Thorpe, R S; Chou, W H

    2001-08-01

    In order to assess the utility of nested clade analysis, both standard phylogenetic algorithms and nested clade analysis were performed on a geographically widespread survey of mitochondrial DNA haplotypes of the bamboo viper, Trimeresurus stejnegeri, within Taiwan. Gross tree topologies were congruent for all analyses and indicated the presence of two geographically overlapping clades within Taiwan. The smaller lineage was restricted to the north and east coasts, whereas the larger lineage occupied all but the northern range of the species within Taiwan including the Pacific offshore populations of Green and Orchid Islands. The phylogeographical pattern supports the existence of at least one colonization event from the continent since the initial isolation of Taiwan from the mainland in the Pliocene. However, determining the exact number of colonization events was not possible due to the simultaneous vicariant forces of hypothesized continental landbridge connections and the occurrence of dramatic in situ orogenesis throughout the Pleistocene. Nested clade analysis provided multiple temporal and spatial population historical inferences that are not possible with standard analyses and therefore should become widely applied to future phylogeographical studies.

  6. Systems responses of rats to aflatoxin B1 exposure revealed with metabonomic changes in multiple biological matrices.

    PubMed

    Zhang, Limin; Ye, Yangfang; An, Yanpeng; Tian, Yuan; Wang, Yulan; Tang, Huiru

    2011-02-04

    Exposure to aflatoxins causes liver fibrosis and hepatocellular carcinoma posing a significant health risk for human populations and livestock. To understand the mammalian systems responses to aflatoxin-B1 (AFB1) exposure, we analyzed the AFB1-induced metabonomic changes in multiple biological matrices (plasma, urine, and liver) of rats using (1)H NMR spectroscopy together with clinical biochemistry and histopathologic assessments. We found that AFB1 exposure caused significant elevation of glucose, amino acids, and choline metabolites (choline, phosphocholine, and glycerophosphocholine) in plasma but reduction of plasma lipids. AFB1 also induced elevation of liver lipids, amino acids (tyrosine, histidine, phenylalanine, leucine, isoleucine, and valine), choline, and nucleic acid metabolites (inosine, adenosine, and uridine) together with reduction of hepatic glycogen and glucose. AFB1 further caused decreases in urinary TCA cycle intermediates (2-oxoglutarate and citrate) and elevation of gut microbiota cometabolites (phenylacetylglycine and hippurate). These indicated that AFB1 exposure caused hepatic steatosis accompanied with widespread metabolic changes including lipid and cell membrane metabolisms, protein biosynthesis, glycolysis, TCA cycle, and gut microbiota functions. This implied that AFB1 exposure probably caused oxidative-stress-mediated impairments of mitochondria functions. These findings provide an overview of biochemical consequences of AFB1 exposure and comprehensive insights into the metabolic aspects of AFB1-induced hepatotoxicity in rats.

  7. Pyrosequencing the Midgut Transcriptome of the Banana Weevil Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae) Reveals Multiple Protease-Like Transcripts.

    PubMed

    Valencia, Arnubio; Wang, Haichuan; Soto, Alberto; Aristizabal, Manuel; Arboleda, Jorge W; Eyun, Seong-Il; Noriega, Daniel D; Siegfried, Blair

    2016-01-01

    The banana weevil Cosmopolites sordidus is an important and serious insect pest in most banana and plantain-growing areas of the world. In spite of the economic importance of this insect pest very little genomic and transcriptomic information exists for this species. In the present study, we characterized the midgut transcriptome of C. sordidus using massive 454-pyrosequencing. We generated over 590,000 sequencing reads that assembled into 30,840 contigs with more than 400 bp, representing a significant expansion of existing sequences available for this insect pest. Among them, 16,427 contigs contained one or more GO terms. In addition, 15,263 contigs were assigned an EC number. In-depth transcriptome analysis identified genes potentially involved in insecticide resistance, peritrophic membrane biosynthesis, immunity-related function and defense against pathogens, and Bacillus thuringiensis toxins binding proteins as well as multiple enzymes involved with protein digestion. This transcriptome will provide a valuable resource for understanding larval physiology and for identifying novel target sites and management approaches for this important insect pest.

  8. Spatiotemporal Variability of Soil Hydraulic Properties from Field Data and Remote Sensing in the Walnut Gulch Experimental Watershed

    NASA Astrophysics Data System (ADS)

    Becker, R.; Gebremichael, M.; Marker, M.

    2015-12-01

    reveal several interesting features on the spatiotemporal variability of soil moisture at multiple scales, and the capabilities and limitations of remote sensing derived products in reproducing them.

  9. The influence of spatiotemporal structure of noisy stimuli in decision making.

    PubMed

    Insabato, Andrea; Dempere-Marco, Laura; Pannunzi, Mario; Deco, Gustavo; Romo, Ranulfo

    2014-04-01

    Decision making is a process of utmost importance in our daily lives, the study of which has been receiving notable attention for decades. Nevertheless, the neural mechanisms underlying decision making are still not fully understood. Computational modeling has revealed itself as a valuable asset to address some of the fundamental questions. Biophysically plausible models, in particular, are useful in bridging the different levels of description that experimental studies provide, from the neural spiking activity recorded at the cellular level to the performance reported at the behavioral level. In this article, we have reviewed some of the recent progress made in the understanding of the neural mechanisms that underlie decision making. We have performed a critical evaluation of the available results and address, from a computational perspective, aspects of both experimentation and modeling that so far have eluded comprehension. To guide the discussion, we have selected a central theme which revolves around the following question: how does the spatiotemporal structure of sensory stimuli affect the perceptual decision-making process? This question is a timely one as several issues that still remain unresolved stem from this central theme. These include: (i) the role of spatiotemporal input fluctuations in perceptual decision making, (ii) how to extend the current results and models derived from two-alternative choice studies to scenarios with multiple competing evidences, and (iii) to establish whether different types of spatiotemporal input fluctuations affect decision-making outcomes in distinctive ways. And although we have restricted our discussion mostly to visual decisions, our main conclusions are arguably generalizable; hence, their possible extension to other sensory modalities is one of the points in our discussion.

  10. The Influence of Spatiotemporal Structure of Noisy Stimuli in Decision Making

    PubMed Central

    Deco, Gustavo; Romo, Ranulfo

    2014-01-01

    Decision making is a process of utmost importance in our daily lives, the study of which has been receiving notable attention for decades. Nevertheless, the neural mechanisms underlying decision making are still not fully understood. Computational modeling has revealed itself as a valuable asset to address some of the fundamental questions. Biophysically plausible models, in particular, are useful in bridging the different levels of description that experimental studies provide, from the neural spiking activity recorded at the cellular level to the performance reported at the behavioral level. In this article, we have reviewed some of the recent progress made in the understanding of the neural mechanisms that underlie decision making. We have performed a critical evaluation of the available results and address, from a computational perspective, aspects of both experimentation and modeling that so far have eluded comprehension. To guide the discussion, we have selected a central theme which revolves around the following question: how does the spatiotemporal structure of sensory stimuli affect the perceptual decision-making process? This question is a timely one as several issues that still remain unresolved stem from this central theme. These include: (i) the role of spatiotemporal input fluctuations in perceptual decision making, (ii) how to extend the current results and models derived from two-alternative choice studies to scenarios with multiple competing evidences, and (iii) to establish whether different types of spatiotemporal input fluctuations affect decision-making outcomes in distinctive ways. And although we have restricted our discussion mostly to visual decisions, our main conclusions are arguably generalizable; hence, their possible extension to other sensory modalities is one of the points in our discussion. PMID:24743140

  11. Pharmacogenomics and chemical library screens reveal a novel SCF(SKP2) inhibitor that overcomes Bortezomib resistance in multiple myeloma.

    PubMed

    Malek, E; Abdel-Malek, M A Y; Jagannathan, S; Vad, N; Karns, R; Jegga, A G; Broyl, A; van Duin, M; Sonneveld, P; Cottini, F; Anderson, K C; Driscoll, J J

    2017-03-01

    While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin ligase Skp1-Cullin-1-Skp2 (SCF(Skp2)) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCF(Skp2) activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B. Here we observed higher CUL1, COMMD1 and SKP2 mRNA levels in CD138(+) cells isolated from BTZ-resistant MM patients. Higher CUL1, COMMD1, SKP2 and CKS1B mRNA levels in patient CD138(+) cells correlated with decreased progression-free and overall survival. Genetic knockdown of CUL1, COMMD1 or SKP2 disrupted the SCF(Skp2) complex, stabilized p27 and increased the number of annexin-V-positive cells after BTZ treatment. Chemical library screens identified a novel compound, designated DT204, that reduced Skp2 binding to Cullin-1 and Commd1, and synergistically enhanced BTZ-induced apoptosis. DT204 co-treatment with BTZ overcame drug resistance and reduced the in vivo growth of myeloma tumors in murine models with survival benefit. Taken together, the results provide proof of concept for rationally designed drug combinations that incorporate SCF(Skp2) inhibitors to treat BTZ resistant disease.

  12. Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer

    PubMed Central

    Poczobutt, Joanna M.; De, Subhajyoti; Yadav, Vinod K.; Nguyen, Teresa T.; Li, Howard; Sippel, Trisha R.; Weiser-Evans, Mary C.M.; Nemenoff, Raphael A.

    2016-01-01

    Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. PMID:26873985

  13. Pharmacogenomics and chemical library screens reveal a novel SCFSKP2 inhibitor that overcomes Bortezomib resistance in multiple myeloma

    PubMed Central

    Malek, E; Abdel-Malek, M A Y; Jagannathan, S; Vad, N; Karns, R; Jegga, A G; Broyl, A; van Duin, M; Sonneveld, P; Cottini, F; Anderson, K C; Driscoll, J J

    2017-01-01

    While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin ligase Skp1–Cullin-1–Skp2 (SCFSkp2) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCFSkp2 activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B. Here we observed higher CUL1, COMMD1 and SKP2 mRNA levels in CD138+ cells isolated from BTZ-resistant MM patients. Higher CUL1, COMMD1, SKP2 and CKS1B mRNA levels in patient CD138+ cells correlated with decreased progression-free and overall survival. Genetic knockdown of CUL1, COMMD1 or SKP2 disrupted the SCFSkp2 complex, stabilized p27 and increased the number of annexin-V-positive cells after BTZ treatment. Chemical library screens identified a novel compound, designated DT204, that reduced Skp2 binding to Cullin-1 and Commd1, and synergistically enhanced BTZ-induced apoptosis. DT204 co-treatment with BTZ overcame drug resistance and reduced the in vivo growth of myeloma tumors in murine models with survival benefit. Taken together, the results provide proof of concept for rationally designed drug combinations that incorporate SCFSkp2 inhibitors to treat BTZ resistant disease. PMID:27677741

  14. Multiple open channel states revealed by lidocaine and QX-314 on rat brain voltage-dependent sodium channels

    PubMed Central

    1996-01-01

    We have recently reported that brain sodium channels display periods with high (low-Kd) and low (high-Kd) levels of lidocaine-induced open channel block (Salazar, B.C., D.O. Flash, J.L. Walewski, and E. Recio- Pinto. 1995. Brain Res. 699:305-314). In the present study, we further characterize this phenomenon by studying the effects of the permanently charged lidocaine analogue, QX-314. We found that the detection of high- and low-Kd periods does not require the presence of the uncharged form of lidocaine. The level of block, for either period, at various QX-314 concentrations indicated the presence of a single local anesthetic binding site. Increasing the concentration of QX-314 decreased the lifetime of the high-Kd periods while it increased the lifetime of the low-Kd periods. These results could be best fitted to a model with two open channel conformations that display different local anesthetic Kd values (low and high Kd), and in which the channel area defining the local anesthetic Kd consists of multiple interacting regions. Amplitude distribution analysis showed that changes in the Kd values reflected changes in the kon rates, without changes in the koff rates. Both lidocaine and QX-314 were found to be incapable of blocking small- channel subconductance states (5-6 pS). Changes in the local anesthetic kon rates for blocking the fully open state and the lack of local anesthetic block of the small subconductance state are consistent with the presence of channel conformational changes involving the intracellular permeation pathway leading to the local anesthetic binding site. PMID:8783074

  15. Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq.

    PubMed

    Mitchell, Hugh D; Markillie, Lye Meng; Chrisler, William B; Gaffrey, Matthew J; Hu, Dehong; Szymanski, Craig J; Xie, Yumei; Melby, Eric S; Dohnalkova, Alice; Taylor, Ronald C; Grate, Eva K; Cooley, Scott K; McDermott, Jason E; Heredia-Langner, Alejandro; Orr, Galya

    2016-11-22

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells "overloaded" while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. Here, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.

  16. Multiple Time Courses of Vestibular Set-Point Adaptation Revealed by Sustained Magnetic Field Stimulation of the Labyrinth.

    PubMed

    Jareonsettasin, Prem; Otero-Millan, Jorge; Ward, Bryan K; Roberts, Dale C; Schubert, Michael C; Zee, David S

    2016-05-23

    A major focus in neurobiology is how the brain adapts its motor behavior to changes in its internal and external environments [1, 2]. Much is known about adaptively optimizing the amplitude and direction of eye and limb movements, for example, but little is known about another essential form of learning, "set-point" adaptation. Set-point adaptation balances tonic activity so that reciprocally acting, agonist and antagonist muscles have a stable platform from which to launch accurate movements. Here, we use the vestibulo-ocular reflex-a simple behavior that stabilizes the position of the eye while the head is moving-to investigate how tonic activity is adapted toward a new set point to prevent eye drift when the head is still [3, 4]. Set-point adaptation was elicited with magneto-hydrodynamic vestibular stimulation (MVS) by placing normal humans in a 7T MRI for 90 min. MVS is ideal for prolonged labyrinthine activation because it mimics constant head acceleration and induces a sustained nystagmus similar to natural vestibular lesions [5, 6]. The MVS-induced nystagmus diminished slowly but incompletely over multiple timescales. We propose a new adaptation hypothesis, using a cascade of imperfect mathematical integrators, that reproduces the response to MVS (and more natural chair rotations), including the gradual decrease in nystagmus as the set point changes over progressively longer time courses. MVS set-point adaptation is a biological model with applications to basic neurophysiological research into all types of movements [7], functional brain imaging [8], and treatment of vestibular and higher-level attentional disorders by introducing new biases to counteract pathological ones [9].

  17. Population phylogenomic analysis of mitochondrial DNA in wild boars and domestic pigs revealed multiple domestication events in East Asia

    PubMed Central

    Wu, Gui-Sheng; Yao, Yong-Gang; Qu, Kai-Xing; Ding, Zhao-Li; Li, Hui; Palanichamy, Malliya G; Duan, Zi-Yuan; Li, Ning; Chen, Yao-Sheng; Zhang, Ya-Ping

    2007-01-01

    Background Previously reported evidence indicates that pigs were independently domesticated in multiple places throughout the world. However, a detailed picture of the origin and dispersal of domestic pigs in East Asia has not yet been reported. Results Population phylogenomic analysis was conducted in domestic pigs and wild boars by screening the haplogroup-specific mutation motifs inferred from a phylogenetic tree of pig complete mitochondrial DNA (mtDNA) sequences. All domestic pigs are clustered into single clade D (which contains subclades D1, D2, D3, and D4), with wild boars from East Asia being interspersed. Three haplogroups within D1 are dominant in the Mekong region (D1a2 and D1b) and the middle and downstream regions of the Yangtze River (D1a1a), and may represent independent founders of domestic pigs. None of the domestic pig samples from North East Asia, the Yellow River region, and the upstream region of the Yangtze River share the same haplogroup status with the local wild boars. The limited regional distributions of haplogroups D1 (including its subhaplogroups), D2, D3, and D4 in domestic pigs suggest at least two different in situ domestication events. Conclusion The use of fine-grained mtDNA phylogenomic analysis of wild boars and domestic pigs is a powerful tool with which to discern the origin of domestic pigs. Our findings show that pig domestication in East Asia mainly occurred in the Mekong region and the middle and downstream regions of the Yangtze River. PMID:18021448

  18. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    PubMed

    Mengoli, Valentina; Bucciarelli, Elisabetta; Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-10-01

    Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences

  19. Cells respond to distinct nanoparticle properties with multiple strategies as revealed by single-cell RNA-Seq

    DOE PAGES

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; ...

    2016-10-27

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. In this paper, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantummore » dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Finally, together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.« less

  20. Cells respond to distinct nanoparticle properties with multiple strategies as revealed by single-cell RNA-Seq

    SciTech Connect

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; Gaffrey, Matthew J.; Hu, Dehong; Szymanski, Craig J.; Xie, Yumei; Melby, Eric S.; Dohnalkova, Alice; Taylor, Ronald C.; Grate, Eva K.; Cooley, Scott K.; McDermott, Jason E.; Heredia-Langner, Alejandro; Orr, Galya

    2016-10-27

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. In this paper, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Finally, together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.

  1. Multiple isotope analyses of the pike tapeworm Triaenophorus nodulosus reveal peculiarities in consumer-diet discrimination patterns.

    PubMed

    Behrmann-Godel, J; Yohannes, E

    2015-03-01

    Previous studies of dietary isotope discrimination have led to the general expectation that a consumer will exhibit enriched stable isotope levels relative to its diet. Parasite-host systems are specific consumer-diet pairs in which the consumer (parasite) feeds exclusively on one dietary source: host tissue. However, the small numbers of studies previously carried out on isotopic discrimination in parasite-host (ΔXP-HT) systems have yielded controversial results, showing some parasites to be isotopically depleted relative to their food source, while others are enriched or in equilibrium with their hosts. Although the mechanism for these deviations from expectations remains to be understood, possible influences of specific feeding niche or selection for only a few nutritional components by the parasite are discussed. ΔXP-HT for multiple isotopes (δ13C, δ15N, δ34S) were measured in the pike tapeworm Triaenophorus nodulosus and two of its life-cycle fish hosts, perch Perca fluviatilis and pike Esox lucius, within which T. nodulosus occupies different feeding locations. Variability in the value of ΔXP-HT calculated for the parasite and its different hosts indicates an influence of feeding location on isotopic discrimination. In perch liver ΔXP-HT was relatively more negative for all three stable isotopes. In pike gut ΔXP-HT was more positive for δ13C, as expected in conventional consumer-diet systems. For parasites feeding on pike gut, however, the δ15N and δ34S isotope values were comparable with those of the host. We discuss potential causes of these deviations from expectations, including the effect of specific parasite feeding niches, and conclude that ΔXP-HT should be critically evaluated for trophic interactions between parasite and host before general patterns are assumed.

  2. Auditory Perception of Spatiotemporal Patterns

    ERIC Educational Resources Information Center

    Tolkmitt, Frank J.; Brindley, Robin

    1977-01-01

    To test the tendency of subjects to perceptually organize discrete temporal patterns with regard to runs of identical stimulus events, spatiotemporal patterns of white noise were presented for reproduction. It is suggested that changes in runs of auditory patterns are perceptually analogous to changes in contours of visual patterns. (Editor/RK)

  3. The gene orders on human chromosome 15 and chicken chromosome 10 reveal multiple inter- and intrachromosomal rearrangements.

    PubMed

    Crooijmans, R P; Dijkhof, R J; Veenendaal, T; van der Poel, J J; Nicholls, R D; Bovenhuis, H; Groenen, M A

    2001-11-01

    Comparative mapping between the human and chicken genomes has revealed a striking conservation of synteny between the genomes of these two species, but the results have been based on low-resolution comparative maps. To address this conserved synteny in much more detail, a high-resolution human-chicken comparative map was constructed from human chromosome 15. Mapping, sequencing, and ordering of specific chicken bacterial artificial chromosomes has improved the comparative map of chromosome 15 (Hsa15) and the homologous regions in chicken with almost 100 new genes and/or expressed sequence tags. A comparison of Hsa15 with chicken identified seven conserved chromosomal segments between the two species. In chicken, these were on chromosome 1 (Gga1; two segments), Gga5 (two segments), and Gga10 (three segments). Although four conserved segments were also observed between Hsa15 and mouse, only one of the underlying rearrangement breakpoints was located at the same position as in chicken, indicating that the rearrangements generating the other three breakpoints occurred after the divergence of the rodent and the primate lineages. A high-resolution comparison of Gga10 with Hsa15 identified 19 conserved blocks, indicating the presence of at least 16 intrachromosomal rearrangement breakpoints in the bird lineage after the separation of birds and mammals. These results improve our knowledge of the evolution and dynamics of the vertebrate genomes and will aid in the clarification of the mechanisms that underlie the differentiation between the vertebrate species.

  4. Systems Biology Approach in Chlamydomonas Reveals Connections between Copper Nutrition and Multiple Metabolic Steps[C][W][OA

    PubMed Central

    Castruita, Madeli; Casero, David; Karpowicz, Steven J.; Kropat, Janette; Vieler, Astrid; Hsieh, Scott I.; Yan, Weihong; Cokus, Shawn; Loo, Joseph A.; Benning, Christoph; Pellegrini, Matteo; Merchant, Sabeeha S.

    2011-01-01

    In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane protease in the thylakoid suggest a mechanism for blocking copper utilization in the chloroplast. We also found an example of copper sparing in the N assimilation pathway: the replacement of copper amine oxidase by a flavin-dependent backup enzyme. Forty percent of the targets are previously uncharacterized proteins, indicating considerable potential for new discovery in the biology of copper. PMID:21498682

  5. Phenotypic, histological and proteomic analyses reveal multiple differences associated with chloroplast development in yellow and variegated variants from Camellia sinensis

    PubMed Central

    Ma, Chengying; Cao, Junxi; Li, Jianke; Zhou, Bo; Tang, Jinchi; Miao, Aiqing

    2016-01-01

    Leaf colour variation is observed in several plants. We obtained two types of branches with yellow and variegated leaves from Camellia sinensis. To reveal the mechanisms that underlie the leaf colour variations, combined morphological, histological, ionomic and proteomic analyses were performed using leaves from abnormal branches (variants) and normal branches (CKs). The measurement of the CIE-Lab coordinates showed that the brightness and yellowness of the variants were more intense than the CKs. When chloroplast profiles were analysed, HY1 (branch with yellow leaves) and HY2 (branch with variegated leaves) displayed abnormal chloroplast structures and a reduced number and size compared with the CKs, indicating that the abnormal chloroplast development might be tightly linked to the leaf colour variations. Moreover, the concentration of elemental minerals was different between the variants and the CKs. Furthermore, DEPs (differentially expressed proteins) were identified in the variants and the CKs by a quantitative proteomics analysis using the label-free approach. The DEPs were significantly involved in photosynthesis and included PSI, PSII, cytochrome b6/f complex, photosynthetic electron transport, LHC and F-type ATPase. Our results suggested that a decrease in the abundance of photosynthetic proteins might be associated with the changes of leaf colours in tea plants. PMID:27633059

  6. Whole-genome sequencing of Bacillus subtilis XF-1 reveals mechanisms for biological control and multiple beneficial properties in plants.

    PubMed

    Guo, Shengye; Li, Xingyu; He, Pengfei; Ho, Honhing; Wu, Yixin; He, Yueqiu

    2015-06-01

    Bacillus subtilis XF-1 is a gram-positive, plant-associated bacterium that stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. In particular, it is especially highly efficient at controlling the clubroot disease of cruciferous crops. Its 4,061,186-bp genome contains an estimated 3853 protein-coding sequences and the 1155 genes of XF-1 are present in most genome-sequenced Bacillus strains: 3757 genes in B. subtilis 168, and 1164 in B. amyloliquefaciens FZB42. Analysis using the Cluster of Orthologous Groups database of proteins shows that 60 genes control bacterial mobility, 221 genes are related to cell wall and membrane biosynthesis, and more than 112 are genes associated with secondary metabolites. In addition, the genes contributed to the strain's plant colonization, bio-control and stimulation of plant growth. Sequencing of the genome is a fundamental step for developing a desired strain to serve as an efficient biological control agent and plant growth stimulator. Similar to other members of the taxon, XF-1 has a genome that contains giant gene clusters for the non-ribosomal synthesis of antifungal lipopeptides (surfactin and fengycin), the polyketides (macrolactin and bacillaene), the siderophore bacillibactin, and the dipeptide bacilysin. There are two synthesis pathways for volatile growth-promoting compounds. The expression of biosynthesized antibiotic peptides in XF-1 was revealed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

  7. Multiple cooling episodes in the Central Tarim (Northwest China) revealed by apatite fission track analysis and vitrinite reflectance data

    NASA Astrophysics Data System (ADS)

    Chang, Jian; Qiu, Nansheng; Song, Xinying; Li, Huili

    2016-06-01

    Apatite fission track and vitrinite reflectance are integrated for the first time to study the cooling history in the Central Tarim, northwest China. The paleo-temperature profiles from vitrinite reflectance data of the Z1 and Z11 wells showed a linear relationship with depth, suggesting an approximately 24.8 °C/km paleo-geothermal gradient and 2700-3900 m of erosion during the Early Mesozoic. The measured apatite fission track ages from well Z2 in the Central Tarim range from 39 to 159 Ma and effectively record the Meso-Cenozoic cooling events that occurred in Central Tarim. Moreover, two cooling events at 190-140 Ma in the Early Jurassic-Early Cretaceous and 80-45 Ma in the Late Cretaceous-Paleocene revealed by measured AFT data and thermal modeling results are related to the collisions of the Qiangtang-Lhasa terranes and the Greater India Plate with the southern margin of the Eurasian Plate, respectively. This study provides new insights into the tectonic evolution of the Tarim Basin (and more broadly Central Asia) and for hydrocarbon generation and exploration in the Central Tarim.

  8. Peptidome analysis of human milk from women delivering macrosomic fetuses reveals multiple means of protection for infants

    PubMed Central

    Cui, Xianwei; Li, Yun; Yang, Lei; You, Lianghui; Wang, Xing; Shi, Chunmei; Ji, Chenbo; Guo, Xirong

    2016-01-01

    Breastfeeding is associated with a lower incidence of obesity, diabetes, and cardiovascular disease later in life. While macrosomic infants have a higher risk of developing obesity and other metabolic disorders. Breast milk may contain special nutrients to meet the different growth needs of different infants. Whether mothers make breast milk different to meet the requirement of macrosomic infants is still unknown. Here, we conducted a comparison between mothers delivering macrosomic and non-macrosomic infants in colostrum endogenous peptides. More than 400 peptides, originating from at least 34 protein precursors, were identified by Liquid Chromatography/Mass Spectrometry (LC/MS). Out of these, 29 peptides found to be significant differently expressed (|fold change| ≥ 3, P < 0.01). Blastp analysis revealed 41 peptides may have established biological activities, which exhibit immunomodulating, antibacterial action, antioxidation, opioid agonist and antihypertensive activity. Furthermore, we found that peptide located at β-Casein 24-38 AA has antimicrobial effect against E. coli, Y. enterocolitica and S. aureus. While, κ-Casein 89-109 AA-derived peptide plays as a regulator of preadipocyte proliferation. The profile of endogenous peptides from macrosomic term infants is different from non-macrosomic terms. This different peptide expression potentially has specific physiological function to benefit macrosomic infants. Finally, we believe that our research is a meaningfull finding which may add to the understanding of milk peptide physiological action. PMID:27566575

  9. Deep sequencing of pyrethroid-resistant bed bugs reveals multiple mechanisms of resistance within a single population.

    PubMed

    Adelman, Zach N; Kilcullen, Kathleen A; Koganemaru, Reina; Anderson, Michelle A E; Anderson, Troy D; Miller, Dini M

    2011-01-01

    A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD(50) bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.

  10. Deep Sequencing of Pyrethroid-Resistant Bed Bugs Reveals Multiple Mechanisms of Resistance within a Single Population

    PubMed Central

    Adelman, Zach N.; Kilcullen, Kathleen A.; Koganemaru, Reina; Anderson, Michelle A. E.; Anderson, Troy D.; Miller, Dini M.

    2011-01-01

    A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD50 bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance. PMID:22039447

  11. The role of climate and socioeconomic factors on the spatiotemporal variability of cholera in Nigeria

    NASA Astrophysics Data System (ADS)

    Abdussalam, Auwal; Thornes, John; Leckebusch, Gregor

    2015-04-01

    Nigeria has a number of climate-sensitive infectious diseases; one of the most important of these diseases that remains a threat to public health is cholera. This study investigates the influences of both meteorological and socioeconomic factors on the spatiotemporal variability of cholera in Nigeria. A stepwise multiple regression models are used to estimate the influence of the year-to-year variations of cholera cases and deaths for individual states in the country and as well for three groups of states that are classified based on annual rainfall amount. Specifically, seasonal mean maximum and minimum temperatures and annual rainfall totals were analysed with annual aggregate count of cholera cases and deaths, taking into account of the socioeconomic factors that are potentially enhancing vulnerability such as: absolute poverty, adult literacy, access to pipe borne water and population density. Result reveals that the most important explanatory meteorological and socioeconomic variables in explaining the spatiotemporal variability of the disease are rainfall totals, seasonal mean maximum temperature, absolute poverty, and accessibility to pipe borne water. The influences of socioeconomic factors appeared to be more pronounced in the northern part of the country, and vice-versa in the case of meteorological factors. Also, cross validated models output suggests a strong possibility of disease prediction, which will help authorities to put effective control measures in place which depend on prevention, and or efficient response.

  12. Evolutionary history of the fish genus Astyanax Baird & Girard (1854) (Actinopterygii, Characidae) in Mesoamerica reveals multiple morphological homoplasies

    PubMed Central

    2008-01-01

    Mesoamerica apparently occurred by two independent routes, with lineage turnover over a large part of the region. Conclusion Our results support multiple, independent origins of morphological traits in Astyanax, whereby the morphotype associated with Bramocharax represents a recurrent trophic adaptation. Molecular clock estimates indicate that Astyanax was present in Mesoamerica during the Miocene (~8 Mya), which implies the existence of an incipient land-bridge connecting South America and Central America before the final closure of the Isthmus of Panama (~3.3 Mya). PMID:19102731

  13. Multiple paleopolyploidizations during the evolution of the Compositae reveal parallel patterns of duplicate gene retention after millions of years.

    PubMed

    Barker, Michael S; Kane, Nolan C; Matvienko, Marta; Kozik, Alexander; Michelmore, Richard W; Knapp, Steven J; Rieseberg, Loren H

    2008-11-01

    Of the approximately 250,000 species of flowering plants, nearly one in ten are members of the Compositae (Asteraceae), a diverse family found in almost every habitat on all continents except Antarctica. With an origin in the mid Eocene, the Compositae is also a relatively young family with remarkable diversifications during the last 40 My. Previous cytologic and systematic investigations suggested that paleopolyploidy may have occurred in at least one Compositae lineage, but a recent analysis of genomic data was equivocal. We tested for evidence of paleopolyploidy in the evolutionary history of the family using recently available expressed sequence tag (EST) data from the Compositae Genome Project. Combined with data available on GenBank, we analyzed nearly 1 million ESTs from 18 species representing seven genera and four tribes. Our analyses revealed at least three ancient whole-genome duplications in the Compositae-a paleopolyploidization shared by all analyzed taxa and placed near the origin of the family just prior to the rapid radiation of its tribes and independent genome duplications near the base of the tribes Mutisieae and Heliantheae. These results are consistent with previous research implicating paleopolyploidy in the evolution and diversification of the Heliantheae. Further, we observed parallel retention of duplicate genes from the basal Compositae genome duplication across all tribes, despite divergence times of 33-38 My among these lineages. This pattern of retention was also repeated for the paleologs from the Heliantheae duplication. Intriguingly, the categories of genes retained in duplicate were substantially different from those in Arabidopsis. In particular, we found that genes annotated to structural components or cellular organization Gene Ontology categories were significantly enriched among paleologs, whereas genes associated with transcription and other regulatory functions were significantly underrepresented. Our results suggest that

  14. Integration of the proteome and transcriptome reveals multiple levels of gene regulation in the rice dl2 mutant

    PubMed Central

    Peng, Xiaoyan; Qin, Zhongliang; Zhang, Guopeng; Guo, Yaomin; Huang, Junli

    2015-01-01

    Leaf vascular system differentiation and venation patterns play a key role in transporting nutrients and maintaining the plant shape, which is an important agronomic trait for improving photosynthetic efficiency. However, there is little knowledge about the regulation of leaf vascular specification and development. Here we utilized the rice midribless mutant (dl2) to investigate the molecular changes in transcriptome and proteome profiles during leaf vascular specification and differentiation. Using isobaric tags for relative and absolute quantification (iTRAQ) with digital gene expression (DGE) techniques, a nearly complete catalog of expressed protein and mRNA was acquired. From the catalog, we reliably identified 3172 proteins and 9,865,230 tags mapped to genes, and subsets of 141 proteins and 98 mRNAs, which were differentially expressed between the dl2 mutant and wild type. The correlation analysis between the abundance of differentially expressed mRNA and DEPs (differentially expressed proteins) revealed numerous discordant changes in mRNA/protein pairs and only a modest correlation was observed, indicative of divergent regulation of transcription and translational processes. The DEPs were analyzed for their involvement in biological processes and metabolic pathways. Up- or down- regulation of some key proteins confirmed that the physiological process of vascular differentiation is an active process. These key proteins included those not previously reported to be associated with vascular differentiation processes, and included proteins that are involved in the spliceosome pathway. Together, our results show that the developmental and physiological process of the leaf vascular system is a thoroughly regulated and complicated process and this work has identified potential targets for genetic modification that could be used to regulate the development of the leaf vasculature. PMID:26136752

  15. Phylogeography and niche modelling of the relict plant Amborella trichopoda (Amborellaceae) reveal multiple Pleistocene refugia in New Caledonia.

    PubMed

    Poncet, Valérie; Munoz, François; Munzinger, Jérôme; Pillon, Yohan; Gomez, Céline; Couderc, Marie; Tranchant-Dubreuil, Christine; Hamon, Serge; de Kochko, Alexandre

    2013-12-01

    Amborella trichopoda Baill. (Amborellaceae, Amborellales), the sole living member of the sister group to all other extant angiosperms, is endemic to New Caledonia. We addressed the intraspecific phylogeography of Amborella by investigating whether its present population genetic structure could be related to its current and past habitats. We found moderate range-wide genetic diversity based on nuclear microsatellite data and detected four well-differentiated, geographically distinct genetic groups using Bayesian clustering analyses. We modelled the ecological niche of Amborella based on the current climatic and environmental conditions. The predictive ability of the model was very good throughout the Central East mainland zone, but Amborella was predicted in the northern part of the island where this plant has not been reported. Furthermore, no significant barrier was detected based on habitat suitability that could explain the genetic differentiation across the area. Conversely, we found that the main genetic clusters could be related to the distribution of the suitable habitat at the last glacial maximum (LGM, c. 21,000 years BP), when Amborella experienced a dramatic 96.5% reduction in suitable area. At least two lineages survived in distinct putative refugia located in the Massif des Lèvres and in the vicinity of Mount Aoupinié. Our findings finally confirmed the importance of LGM rainforest refugia in shaping the current intra- and interspecific diversity in New Caledonian plants and revealed the possibility of an as yet unreported refugium. The combination of niche modelling and population genetics thereby offered novel insight into the biogeographical history of an emblematic taxon.

  16. Assessment of snake DNA barcodes based on mitochondrial COI and Cytb genes revealed multiple putative cryptic species in Thailand.

    PubMed

    Laopichienpong, Nararat; Muangmai, Narongrit; Supikamolseni, Arrjaree; Twilprawat, Panupon; Chanhome, Lawan; Suntrarachun, Sunutcha; Peyachoknagul, Surin; Srikulnath, Kornsorn

    2016-12-15

    DNA barcodes of mitochondrial cytochrome c oxidase I (COI), cytochrome b (Cytb) genes, and their combined data sets were constructed from 35 snake species in Thailand. No barcoding gap was detected in either of the two genes from the observed intra- and interspecific sequence divergences. Intra- and interspecific sequence divergences of the COI gene differed 14 times, with barcode cut-off scores ranging over 2%-4% for threshold values differentiated among most of the different species; the Cytb gene differed 6 times with cut-off scores ranging over 2%-6%. Thirty-five specific nucleotide mutations were also found at interspecific level in the COI gene, identifying 18 snake species, but no specific nucleotide mutation was observed for Cytb in any single species. This suggests that COI barcoding was a better marker than Cytb. Phylogenetic clustering analysis indicated that most species were represented by monophyletic clusters, suggesting that these snake species could be clearly differentiated using COI barcodes. However, the two-marker combination of both COI and Cytb was more effective, differentiating snake species by over 2%-4%, and reducing species numbers in the overlap value between intra- and interspecific divergences. Three species delimitation algorithms (general mixed Yule-coalescent, automatic barcoding gap detection, and statistical parsimony network analysis) were extensively applied to a wide range of snakes based on both barcodes. This revealed cryptic diversity for eleven snake species in Thailand. In addition, eleven accessions from the database previously grouped under the same species were represented at different species level, suggesting either high genetic diversity, or the misidentification of these sequences in the database as a consequence of cryptic species.

  17. Multiple Paleopolyploidizations during the Evolution of the Compositae Reveal Parallel Patterns of Duplicate Gene Retention after Millions of Years

    PubMed Central

    Barker, Michael S.; Kane, Nolan C.; Matvienko, Marta; Kozik, Alexander; Michelmore, Richard W.; Knapp, Steven J.; Rieseberg, Loren H.

    2008-01-01

    Of the approximately 250,000 species of flowering plants, nearly one in ten are members of the Compositae (Asteraceae), a diverse family found in almost every habitat on all continents except Antarctica. With an origin in the mid Eocene, the Compositae is also a relatively young family with remarkable diversifications during the last 40 My. Previous cytologic and systematic investigations suggested that paleopolyploidy may have occurred in at least one Compositae lineage, but a recent analysis of genomic data was equivocal. We tested for evidence of paleopolyploidy in the evolutionary history of the family using recently available expressed sequence tag (EST) data from the Compositae Genome Project. Combined with data available on GenBank, we analyzed nearly 1 million ESTs from 18 species representing seven genera and four tribes. Our analyses revealed at least three ancient whole-genome duplications in the Compositae—a paleopolyploidization shared by all analyzed taxa and placed near the origin of the family just prior to the rapid radiation of its tribes and independent genome duplications near the base of the tribes Mutisieae and Heliantheae. These results are consistent with previous research implicating paleopolyploidy in the evolution and diversification of the Heliantheae. Further, we observed parallel retention of duplicate genes from the basal Compositae genome duplication across all tribes, despite divergence times of 33–38 My among these lineages. This pattern of retention was also repeated for the paleologs from the Heliantheae duplication. Intriguingly, the categories of genes retained in duplicate were substantially different from those in Arabidopsis. In particular, we found that genes annotated to structural components or cellular organization Gene Ontology categories were significantly enriched among paleologs, whereas genes associated with transcription and other regulatory functions were significantly underrepresented. Our results suggest

  18. Multilocus assignment analyses reveal multiple units and rare migration events in the recently expanded yellow-eyed penguin (Megadyptes antipodes).

    PubMed

    Boessenkool, Sanne; Star, Bastiaan; Waters, Jonathan M; Seddon, Philip J

    2009-06-01

    The identification of demographically independent populations and the recognition of management units have been greatly facilitated by the continuing advances in genetic tools. Managements units now play a key role in short-term conservation management programmes of declining species, but their importance in expanding populations receives comparatively little attention. The endangered yellow-eyed penguin (Megadyptes antipodes) expanded its range from the subantarctic to New Zealand's South Island a few hundred years ago and this new population now represents almost half of the species' total census size. This dramatic expansion attests to M. antipodes' high dispersal abilities and suggests the species is likely to constitute a single demographic population. Here we test this hypothesis of panmixia by investigating genetic differentiation and levels of gene flow among penguin breeding areas using 12 autosomal microsatellite loci along with mitochondrial control region sequence analyses for 350 individuals. Contrary to our hypothesis, however, the analyses reveal two genetically and geographically distinct assemblages: South Island vs. subantarctic populations. Using assignment tests, we recognize just two first-generation migrants between these populations (corresponding to a migration rate of < 2%), indicating that ongoing levels of long-distance migration are low. Furthermore, the South Island population has low genetic variability compared to the subantarctic population. These results suggest that the South Island population was founded by only a small number of individuals, and that subsequent levels of gene flow have remained low. The demographic independence of the two populations warrants their designation as distinct management units and conservation efforts should be adjusted accordingly to protect both populations.

  19. Multidimensional High Spatiotemporal Resolution InSAR Time Series Assist Interdisciplinary Space- And Ground-Based Monitoring To Reveal Pre-Eruptive Signals At Nyamulagira Volcano (North Kivu, D.R.C.)

    NASA Astrophysics Data System (ADS)

    d'Oreye, N.; Smets, B.; Kervyn, F.; Kervyn, M.; Albino, F.; Arellano, S. R.; Arjona, A. A.; Carn, S. A.; Fernandez, J.; Galle, B.; Gonzalez, P. J.; Head, E.; Pallero, J.; Prieto, J. F.; Samsonov, S. V.; Tedesco, D.; Tiampo, K. F.; Wauthier, C.

    2013-12-01

    Interdisciplinary space- and ground-based monitoring systems allowed the quantitative and detailed study of the Nyamulagira 2010 eruption (Congo). Field observations revealed the event as 4 eruptive phases delimited by major changes in effusive activity. Signals from ground deformation, seismicity, SO2 emission and thermal flux correlate with these eruptive phases. Moreover, MSBAS InSAR time series combining data acquired under different geometries and with different satellites (Samsonov and d'Oreye, 2012) allowed the detection of pre-, co- and inter-eruptive deformation in the Nyamulagira volcanic field. Using 8 years of ENVISAT, RADARSAT2 and ALOS data, the MSBAS method reveals the first unambiguous pre-eruptive ground deformations in the Virunga Volcanic Province. Precursory ground deformations are detected up to 3 weeks prior the onset of the 2010 eruption by images acquired by 3 different sensors in different geometries. These deformations took place in the main crater and along the SE flank of the volcano, where eruptive fractures will ultimately opened. Deformations coincide with small, though clear, increase of the short period seismicity and SO2 emissions.These seismic and SO2 variations alone were too small, however, to raise attention. The pre-eruptive ground deformation signals revealed by InSAR are of about the same amplitude and spatial extent as atmospheric noise and therefore cannot be identified on individual differential interferograms. Conventional time-series methods based on single acquisition geometry do not have a sufficient time resolution to discriminate such a precursory signal from an atmospheric artifact. The 3-week precursors detected at Nyamulagira contrast with the only precursory signal previously recognized so far in the Virunga, namely the increase of tremors and long period seismicity no more than few hours or days before the eruption onset. In January 2010, such short-term seismic precursors were detected less than two hours

  20. Spatiotemporal Interpolation for Environmental Modelling

    PubMed Central

    Susanto, Ferry; de Souza, Paulo; He, Jing

    2016-01-01

    A variation of the reduction-based approach to spatiotemporal interpolation (STI), in which time is treated independently from the spatial dimensions, is proposed in this paper. We reviewed and compared three widely-used spatial interpolation techniques: ordinary kriging, inverse distance weighting and the triangular irregular network. We also proposed a new distribution-based distance weighting (DDW) spatial interpolation method. In this study, we utilised one year of Tasmania’s South Esk Hydrology model developed by CSIRO. Root mean squared error statistical methods were performed for performance evaluations. Our results show that the proposed reduction approach is superior to the extension approach to STI. However, the proposed DDW provides little benefit compared to the conventional inverse distance weighting (IDW) method. We suggest that the improved IDW technique, with the reduction approach used for the temporal dimension, is the optimal combination for large-scale spatiotemporal interpolation within environmental modelling applications. PMID:27509497

  1. Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

    PubMed

    Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

    2017-03-01

    In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases.

  2. Neural mechanisms of spatiotemporal signal processing

    NASA Astrophysics Data System (ADS)

    Khanbabaie Shoub, Shaban (Reza)

    We have studied the synaptic, dendritic, and network mechanisms of spatiotemporal signal processing underlying the computation of visual motion in the avian tectum. Such mechanisms are critical for information processing in all vertebrates, but have been difficult to elucidate in mammals because of anatomical limitations. We have therefore developed a chick tectal slice preparation, which has features that help us circumvent these limitations. Using single-electrode multi-pulse synaptic stimulation experiments we found that the SGC-I cell responds to synaptic stimulation in a binary manner and its response is phasic in a time dependent probabilistic manner over large time scales. Synaptic inputs at two locations typically interact in a mutually exclusive manner when delivered within the "interaction time" of approximately 30 ms. Then we constructed a model of SGC-I cell and the retinal inputs to examine the role of the observed non-linear cellular properties in shaping the response of SGC-I neurons to assumed retinal representations of dynamic spatiotemporal visual stimuli. We found that by these properties, SGC-I cells can classify different stimuli. Especially without the phasic synaptic signal transfer the model SGC-I cell fails to distinguish between the static stationary stimuli and dynamic spatiotemporal stimuli. Based on one-site synaptic response probability and the assumption of independent neighboring dendritic endings we predicted the response probability of SGC-I cells to multiple synaptic inputs. We tested this independence-based model prediction and found that the independency assumption is not valid. The measured SGC-I response probability to multiple synaptic inputs does not increase with the number of synaptic inputs. The presence of GABAergic horizontal cells in layer 5 suggest an inhibitory effect of these cells on the SGC-I retino-tectal synaptic responses. In our experiment we found that the measured SGC-I response probability to multiple

  3. Identification of peanut (Arachis hypogaea) chromosomes using a fluorescence in situ hybridization system reveals multiple hybridization events during tetraploid peanut formation.

    PubMed

    Zhang, Laining; Yang, Xiaoyu; Tian, Li; Chen, Lei; Yu, Weichang

    2016-09-01

    The cultivated peanut Arachis hypogaea (AABB) is thought to have originated from the hybridization of Arachis duranensis (AA) and Arachis ipaënsis (BB) followed by spontaneous chromosome doubling. In this study, we cloned and analyzed chromosome markers from cultivated peanut and its wild relatives. A fluorescence in situ hybridization (FISH)-based karyotyping cocktail was developed with which to study the karyotypes and chromosome evolution of peanut and its wild relatives. Karyotypes were constructed in cultivated peanut and its two putative progenitors using our FISH-based karyotyping system. Comparative karyotyping analysis revealed that chromosome organization was highly conserved in cultivated peanut and its two putative progenitors, especially in the B genome chromosomes. However, variations existed between A. duranensis and the A genome chromosomes in cultivated peanut, especially for the distribution of the interstitial telomere repeats (ITRs). A search of additional A. duranensis varieties from different geographic regions revealed both numeric and positional variations of ITRs, which were similar to the variations in tetraploid peanut varieties. The results provide evidence for the origin of cultivated peanut from the two diploid ancestors, and also suggest that multiple hybridization events of A. ipaënsis with different varieties of A. duranensis may have occurred during the origination of peanut.

  4. Transcriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome

    PubMed Central

    2010-01-01

    Background Glutamate plays a central position in the synthesis of a variety of organic molecules in plants and is synthesised from nitrate through a series of enzymatic reactions. Glutamate synthases catalyse the last step in this pathway and two types are present in plants: NADH- or ferredoxin-dependent. Here we report a genome wide microarray analysis of the transcriptional reprogramming that occurs in leaves and roots of the A. thaliana mutant glu1-2 knocked-down in the expression of Fd-GOGAT1 (GLU1; At5g04140), one of the two genes of A. thaliana encoding ferredoxin-dependent glutamate synthase. Results Transcriptional profiling of glu1-2 revealed extensive changes with the expression of more than 5500 genes significantly affected in leaves and nearly 700 in roots. Both genes involved in glutamate biosynthesis and transformation are affected, leading to changes in amino acid compositions as revealed by NMR metabolome analysis. An elevated glutamine level in the glu1-2 mutant was the most prominent of these changes. An unbiased analysis of the gene expression datasets allowed us to identify the pathways that constitute the secondary response of an FdGOGAT1/GLU1 knock-down. Among the most significantly affected pathways, photosynthesis, photorespiratory cycle and chlorophyll biosynthesis show an overall downregulation in glu1-2 leaves. This is in accordance with their slight chlorotic phenotype. Another characteristic of the glu1-2 transcriptional profile is the activation of multiple stress responses, mimicking cold, heat, drought and oxidative stress. The change in expression of genes involved in flavonoid biosynthesis is also revealed. The expression of a substantial number of genes encoding stress-related transcription factors, cytochrome P450 monooxygenases, glutathione S-transferases and UDP-glycosyltransferases is affected in the glu1-2 mutant. This may indicate an induction of the detoxification of secondary metabolites in the mutant. Conclusions Analysis

  5. Global Phylogenomic Analysis of Nonencapsulated Streptococcus pneumoniae Reveals a Deep-Branching Classic Lineage That Is Distinct from Multiple Sporadic Lineages

    PubMed Central

    Hilty, Markus; Wüthrich, Daniel; Salter, Susannah J.; Engel, Hansjürg; Campbell, Samuel; Sá-Leão, Raquel; de Lencastre, Hermínia; Hermans, Peter; Sadowy, Ewa; Turner, Paul; Chewapreecha, Claire; Diggle, Mathew; Pluschke, Gerd; McGee, Lesley; Köseoğlu Eser, Özgen; Low, Donald E.; Smith-Vaughan, Heidi; Endimiani, Andrea; Küffer, Marianne; Dupasquier, Mélanie; Beaudoing, Emmanuel; Weber, Johann; Bruggmann, Rémy; Hanage, William P.; Parkhill, Julian; Hathaway, Lucy J.; Mühlemann, Kathrin; Bentley, Stephen D.

    2014-01-01

    The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent. PMID:25480686

  6. Noise tolerant spatiotemporal chaos computing

    SciTech Connect

    Kia, Behnam; Kia, Sarvenaz; Ditto, William L.; Lindner, John F.; Sinha, Sudeshna

    2014-12-01

    We introduce and design a noise tolerant chaos computing system based on a coupled map lattice (CML) and the noise reduction capabilities inherent in coupled dynamical systems. The resulting spatiotemporal chaos computing system is more robust to noise than a single map chaos computing system. In this CML based approach to computing, under the coupled dynamics, the local noise from different nodes of the lattice diffuses across the lattice, and it attenuates each other's effects, resulting in a system with less noise content and a more robust chaos computing architecture.

  7. Enhancing chaoticity of spatiotemporal chaos.

    PubMed

    Li, Xiaowen; Zhang, Heqiao; Xue, Yu; Hu, Gang

    2005-01-01

    In some practical situations strong chaos is needed. This introduces the task of chaos control with enhancing chaoticity rather than suppressing chaoticity. In this paper a simple method of linear amplifications incorporating modulo operations is suggested to make spatiotemporal systems, which may be originally chaotic or nonchaotic, strongly chaotic. Specifically, this control can eliminate periodic windows, increase the values and the number of positive Lyapunov exponents, make the probability distributions of the output chaotic sequences more homogeneous, and reduce the correlations of chaotic outputs for different times and different space units. The applicability of the method to practical tasks, in particular to random number generators and secure communications, is briefly discussed.

  8. Noise tolerant spatiotemporal chaos computing.

    PubMed

    Kia, Behnam; Kia, Sarvenaz; Lindner, John F; Sinha, Sudeshna; Ditto, William L

    2014-12-01

    We introduce and design a noise tolerant chaos computing system based on a coupled map lattice (CML) and the noise reduction capabilities inherent in coupled dynamical systems. The resulting spatiotemporal chaos computing system is more robust to noise than a single map chaos computing system. In this CML based approach to computing, under the coupled dynamics, the local noise from different nodes of the lattice diffuses across the lattice, and it attenuates each other's effects, resulting in a system with less noise content and a more robust chaos computing architecture.

  9. Spatiotemporal chaos involving wave instability

    NASA Astrophysics Data System (ADS)

    Berenstein, Igal; Carballido-Landeira, Jorge

    2017-01-01

    In this paper, we investigate pattern formation in a model of a reaction confined in a microemulsion, in a regime where both Turing and wave instability occur. In one-dimensional systems, the pattern corresponds to spatiotemporal intermittency where the behavior of the systems alternates in both time and space between stationary Turing patterns and traveling waves. In two-dimensional systems, the behavior initially may correspond to Turing patterns, which then turn into wave patterns. The resulting pattern also corresponds to a chaotic state, where the system alternates in both space and time between standing wave patterns and traveling waves, and the local dynamics may show vanishing amplitude of the variables.

  10. Sensitivity to Spatiotemporal Percepts Predicts the Perception of Emotion

    PubMed Central

    Castro, Vanessa L.; Boone, R. Thomas

    2015-01-01

    The present studies examined how sensitivity to spatiotemporal percepts such as rhythm, angularity, configuration, and force predicts accuracy in perceiving emotion. In Study 1, participants (N = 99) completed a nonverbal test battery consisting of three nonverbal emotion perception tests and two perceptual sensitivity tasks assessing rhythm sensitivity and angularity sensitivity. Study 2 (N = 101) extended the findings of Study 1 with the addition of a fourth nonverbal test, a third configural sensitivity task, and a fourth force sensitivity task. Regression analyses across both studies revealed partial support for the association between perceptual sensitivity to spatiotemporal percepts and greater emotion perception accuracy. Results indicate that accuracy in perceiving emotions may be predicted by sensitivity to specific percepts embedded within channel- and emotion-specific displays. The significance of such research lies in the understanding of how individuals acquire emotion perception skill and the processes by which distinct features of percepts are related to the perception of emotion. PMID:26339111

  11. Multiple Loci and Complete Taxonomic Sampling Resolve the Phylogeny and Biogeographic History of Tenrecs (Mammalia: Tenrecidae) and Reveal Higher Speciation Rates in Madagascar's Humid Forests.

    PubMed

    Everson, Kathryn M; Soarimalala, Voahangy; Goodman, Steven M; Olson, Link E

    2016-09-01

    The family Tenrecidae (tenrecs) is one of only four extant terrestrial mammal lineages to have colonized and diversified on Madagascar. Over the last 15 years, several studies have disagreed on relationships among major tenrec lineages, resulting in multiple reinterpretations of the number and timing of historical transoceanic dispersal events between Africa and Madagascar. We reconstructed the phylogeny of Tenrecidae using multiple loci from all recognized extant species and estimated divergence timing using six fossil calibrations within Afrotheria. All phylogenetic analyses strongly support monophyly of the Malagasy tenrecs, and our divergence timing analysis places their colonization of the island at 30-56 Ma. Our comprehensive phylogeny supports three important taxonomic revisions that reflect the evolutionary history of tenrecs: (1) we formally elevate the African otter shrews to their own family Potamogalidae, thereby rendering extant Tenrecidae entirely endemic to Madagascar; (2) we subsume the semiaquatic genus Limnogale within the shrew tenrec genus Microgale; and (3) we re-elevate the two largest-bodied shrew tenrecs, Microgale dobsoni and Microgale talazaci, to the genus Nesogale Thomas (1918) Finally, we use recently summarized habitat data to test the hypothesis that diversification rates differ between humid and arid habitats on Madagascar, and we compare three common methods for ancestral biogeographic reconstruction. These analyses suggest higher speciation rates in humid habitats and reveal a minimum of three and more likely five independent transitions to arid habitats. Our results resolve the relationships among previously recalcitrant taxa, illuminate the timing and mechanisms of major biogeographic patterns in an extraordinary example of an island radiation, and permit the first comprehensive, phylogenetically consistent taxonomy of Madagascar's tenrecs.

  12. Real-time task recognition in cataract surgery videos using adaptive spatiotemporal polynomials.

    PubMed

    Quellec, Gwénolé; Lamard, Mathieu; Cochener, Béatrice; Cazuguel, Guy

    2015-04-01

    This paper introduces a new algorithm for recognizing surgical tasks in real-time in a video stream. The goal is to communicate information to the surgeon in due time during a video-monitored surgery. The proposed algorithm is applied to cataract surgery, which is the most common eye surgery. To compensate for eye motion and zoom level variations, cataract surgery videos are first normalized. Then, the motion content of short video subsequences is characterized with spatiotemporal polynomials: a multiscale motion characterization based on adaptive spatiotemporal polynomials is presented. The proposed solution is particularly suited to characterize deformable moving objects with fuzzy borders, which are typically found in surgical videos. Given a target surgical task, the system is trained to identify which spatiotemporal polynomials are usually extracted from videos when and only when this task is being performed. These key spatiotemporal polynomials are then searched in new videos to recognize the target surgical task. For improved performances, the system jointly adapts the spatiotemporal polynomial basis and identifies the key spatiotemporal polynomials using the multiple-instance learning paradigm. The proposed system runs in real-time and outperforms the previous solution from our group, both for surgical task recognition ( Az = 0.851 on average, as opposed to Az = 0.794 previously) and for the joint segmentation and recognition of surgical tasks ( Az = 0.856 on average, as opposed to Az = 0.832 previously).

  13. Spatiotemporal Thinking in the Geosciences

    NASA Astrophysics Data System (ADS)

    Shipley, T. F.; Manduca, C. A.; Ormand, C. J.; Tikoff, B.

    2011-12-01

    Reasoning about spatial relations is a critical skill for geoscientists. Within the geosciences different disciplines may reason about different sorts of relationships. These relationships may span vastly different spatial and temporal scales (from the spatial alignment in atoms in crystals to the changes in the shape of plates). As part of work in a research center on spatial thinking in STEM education, we have been working to classify the spatial skills required in geology, develop tests for each spatial skill, and develop the cognitive science tools to promote the critical spatial reasoning skills. Research in psychology, neurology and linguistics supports a broad classification of spatial skills along two dimensions: one versus many objects (which roughly translates to object- focused and navigation focused skills) and static versus dynamic spatial relations. The talk will focus on the interaction of space and time in spatial cognition in the geosciences. We are working to develop measures of skill in visualizing spatiotemporal changes. A new test developed to measure visualization of brittle deformations will be presented. This is a skill that has not been clearly recognized in the cognitive science research domain and thus illustrates the value of interdisciplinary work that combines geosciences with cognitive sciences. Teaching spatiotemporal concepts can be challenging. Recent theoretical work suggests analogical reasoning can be a powerful tool to aid student learning to reason about temporal relations using spatial skills. Recent work in our lab has found that progressive alignment of spatial and temporal scales promotes accurate reasoning about temporal relations at geological time scales.

  14. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation

    PubMed Central

    2014-01-01

    Background Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Methods Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10–40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. Results The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Conclusions Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis. PMID:25001852

  15. Dynamic nature of the proximal AZFc region of the human Y chromosome: multiple independent deletion and duplication events revealed by microsatellite analysis.

    PubMed

    Balaresque, Patricia; Bowden, Georgina R; Parkin, Emma J; Omran, Ghada A; Heyer, Evelyne; Quintana-Murci, Lluis; Roewer, Lutz; Stoneking, Mark; Nasidze, Ivan; Carvalho-Silva, Denise R; Tyler-Smith, Chris; de Knijff, Peter; Jobling, Mark A

    2008-10-01

    The human Y chromosome shows frequent structural variants, some of which are selectively neutral, while others cause impaired fertility due to the loss of spermatogenic genes. The large-scale use of multiple Y-chromosomal microsatellites in forensic and population genetic studies can reveal such variants, through the absence or duplication of specific markers in haplotypes. We describe Y chromosomes in apparently normal males carrying null and duplicated alleles at the microsatellite DYS448, which lies in the proximal part of the azoospermia factor c (AZFc) region, important in spermatogenesis, and made up of "ampliconic" repeats that act as substrates for nonallelic homologous recombination (NAHR). Physical mapping in 26 DYS448 deletion chromosomes reveals that only three cases belong to a previously described class, representing independent occurrences of an approximately 1.5-Mb deletion mediated by recombination between the b1 and b3 repeat units. The remainder belong to five novel classes; none appears to be mediated through homologous recombination, and all remove some genes, but are likely to be compatible with normal fertility. A combination of deletion analysis with binary-marker and microsatellite haplotyping shows that the 26 deletions represent nine independent events. Nine DYS448 duplication chromosomes can be explained by four independent events. Some lineages have risen to high frequency in particular populations, in particular a deletion within haplogroup (hg) C(*)(xC3a,C3c) found in 18 Asian males. The nonrandom phylogenetic distribution of duplication and deletion events suggests possible structural predisposition to such mutations in hgs C and G.

  16. Phylogeographic patterns of mtDNA variation revealed multiple glacial refugia for the frog species Feirana taihangnica endemic to the Qinling Mountains.

    PubMed

    Wang, Bin; Jiang, Jianping; Xie, Feng; Li, Cheng

    2013-03-01

    Diversification patterns and demography of montane species are affected by Pleistocene climate fluctuations. Empirical cases from the Qinling Mountains (QM) region, which is a major biogeographic divider of East Asia, are few. We used DNA sequence data of the complete mitochondrial ND2 gene to detect effects of the Pleistocene glaciations on phylogeographic profiles of a frog species, Feirana taihangnica, which is endemic to the QM. Four distinct lineages consisting of seven sublineages were revealed. The strongest signal of biogeographical structure (F(ct) = 0.971, P < 0.01) was found when populations were grouped according to these seven sublineages. One narrow secondary contact zone was detected in the middle QM between the lineage from middle QM and the lineage from eastern QM. Coalescent simulations indicated that this species colonized the QM region by a stepping-stone model. Divergences among lineages had likely been influenced by the uplift of the Tibetan Plateau during the late Miocene-to-late Pleistocene, as well as by the Pleistocene climatic cycles. Coalescent simulations also suggested that F. taihangnica populations have persisted through the Pleistocene glacial periods in multiple refugia across the QM region. Demographic analyses indicated that all lineages, except the lineage in the Funiu Mountains, have been experienced postglacial expansion of population size and distribution range. In conclusion, Pleistocene climate fluctuations and tectonic changes during the late Miocene-late Pleistocene have profoundly influenced the phylogeography and historical demography of F. taihangnica.

  17. Multiple-locus variable-number tandem repeat analysis (MLVA) of Leptospira interrogans serovar Pomona from Argentina reveals four new genotypes.

    PubMed

    Pavan, María Elisa; Cairó, Fabián; Brihuega, Bibiana; Samartino, Luis

    2008-01-01

    Outbreaks of leptospirosis occur regularly in Argentina, but little is known about their epidemiological relationships. We have analyzed the genetic diversity of a collection of 16 strains of Leptospira interrogans serovar Pomona isolated from animals and humans in Argentina during the past 45 years. Genotyping was performed by multiple-locus variable-number tandem repeat analysis (MLVA) using the loci VNTR4, VNTR7, VNTR9, VNTR10, VNTR19, VNTR23 and VNTR31, as described by Majed et al. [Identification of variable-number tandem-repeat loci in Leptospira interrogans sensu stricto. J Clin Microbiol 2005;43:539-45]. Clustering analysis revealed four new distinct MLVA genotypes, with a dominant one. Strains with this genotype were consistently isolated since 1960 to the present, mainly from cows and pigs, but also from humans, representing 75% of the total strains studied. These strains coexisted temporally and geographically with isolates presenting the other new genotypes. VNTR4 locus, with four different alleles, presented the highest diversity between the VNTR loci analyzed. MLVA patterns obtained will be useful for future diagnostic and epidemiological tracing analysis.

  18. Morphological and Proteomic Analyses Reveal that Unsaturated Guluronate Oligosaccharide Modulates Multiple Functional Pathways in Murine Macrophage RAW264.7 Cells

    PubMed Central

    Xu, Xu; Bi, De-Cheng; Li, Chao; Fang, Wei-Shan; Zhou, Rui; Li, Shui-Ming; Chi, Lian-Li; Wan, Min; Shen, Li-Ming

    2015-01-01

    Alginate is a natural polysaccharide extracted from various species of marine brown algae. Alginate-derived guluronate oligosaccharide (GOS) obtained by enzymatic depolymerization has various pharmacological functions. Previous studies have demonstrated that GOS can trigger the production of inducible nitric oxide synthase (iNOS)/nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor (TNF)-α by macrophages and that it is involved in the nuclear factor (NF)-κB and mitogen-activated protein (MAP) kinase signaling pathways. To expand upon the current knowledge regarding the molecular mechanisms associated with the GOS-induced immune response in macrophages, comparative proteomic analysis was employed together with two-dimensional electrophoresis (2-DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and Western blot verification. Proteins showing significant differences in expression in GOS-treated cells were categorized into multiple functional pathways, including the NF-κB signaling pathway and pathways involved in inflammation, antioxidant activity, glycolysis, cytoskeletal processes and translational elongation. Moreover, GOS-stimulated changes in the morphologies and actin cytoskeleton organization of RAW264.7 cells were also investigated as possible adaptations to GOS. This study is the first to reveal GOS as a promising agent that can modulate the proper balance between the pro- and anti-inflammatory immune responses, and it provides new insights into pharmaceutical applications of polysaccharides. PMID:25830683

  19. Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

    PubMed Central

    Miller, Nichole M.; Wang, Jun; Tan, Yanping; Dittel, Bonnie N.

    2015-01-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) mediated by T helper (h)1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE), indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB) and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on strong EAE data this view is being reevaluated by some investigators in the field. PMID:26347600

  20. Comparative genomic analysis reveals multiple long terminal repeats, lineage-specific amplification, and frequent interelement recombination for Cassandra retrotransposon in pear (Pyrus bretschneideri Rehd.).

    PubMed

    Yin, Hao; Du, Jianchang; Li, Leiting; Jin, Cong; Fan, Lian; Li, Meng; Wu, Jun; Zhang, Shaoling

    2014-06-04

    Cassandra transposable elements belong to a specific group of terminal-repeat retrotransposons in miniature (TRIM). Although Cassandra TRIM elements have been found in almost all vascular plants, detailed investigations on the nature, abundance, amplification timeframe, and evolution have not been performed in an individual genome. We therefore conducted a comprehensive analysis of Cassandra retrotransposons using the newly sequenced pear genome along with four other Rosaceae species, including apple, peach, mei, and woodland strawberry. Our data reveal several interesting findings for this particular retrotransposon family: 1) A large number of the intact copies contain three, four, or five long terminal repeats (LTRs) (∼20% in pear); 2) intact copies and solo LTRs with or without target site duplications are both common (∼80% vs. 20%) in each genome; 3) the elements exhibit an overall unbiased distribution among the chromosomes; 4) the elements are most successfully amplified in pear (5,032 copies); and 5) the evolutionary relationships of these elements vary among different lineages, species, and evolutionary time. These results indicate that Cassandra retrotransposons contain more complex structures (elements with multiple LTRs) than what we have known previously, and that frequent interelement unequal recombination followed by transposition may play a critical role in shaping and reshaping host genomes. Thus this study provides insights into the property, propensity, and molecular mechanisms governing the formation and amplification of Cassandra retrotransposons, and enhances our understanding of the structural variation, evolutionary history, and transposition process of LTR retrotransposons in plants.

  1. Tug-of-war between corrugation and binding energy: revealing the formation of multiple moiré patterns on a strongly interacting graphene-metal system.

    PubMed

    Martín-Recio, A; Romero-Muñiz, C; Martínez-Galera, A J; Pou, P; Pérez, R; Gómez-Rodríguez, J M

    2015-07-14

    The formation of multidomain epitaxial graphene on Rh(111) under ultra-high vacuum (UHV) conditions has been characterized by scanning tunnelling microscopy (STM) measurements and density functional theory (DFT) calculations. At variance with the accepted view for strongly interacting graphene-metal systems, we clearly demonstrate the formation of different rotational domains leading to multiple moiré structures with a wide distribution of surface periodicities. Experiments reveal a correlation between the STM apparent corrugation and the lattice parameter of the moiré unit cell, with corrugations of just 30-40 pm for the smallest moirés. DFT calculations for a relevant selection of these moiré patterns show much larger height differences and a non-monotonic behaviour with the moiré size. Simulations based on non-equilibrium Green's function (NEGF) methods reproduce quantitatively the experimental trend and provide a detailed understanding of the interplay between electronic and geometric contributions in the STM contrast of graphene systems. Our study sheds light on the subtle energy balance among strain, corrugation and binding that drives the formation of the moiré patterns in all graphene/metal systems and suggests an explanation for the success of an effective model only based on the lattice mismatch. Although low values of the strain energy are a necessary condition, it is the ability of graphene to corrugate in order to maximize the areas of favourable graphene-metal interactions that finally selects the stable configurations.

  2. Spatiotemporal Bayesian inference dipole analysis for MEG neuroimaging data.

    PubMed

    Jun, Sung C; George, John S; Paré-Blagoev, Juliana; Plis, Sergey M; Ranken, Doug M; Schmidt, David M; Wood, C C

    2005-10-15

    Recently, we described a Bayesian inference approach to the MEG/EEG inverse problem that used numerical techniques to estimate the full posterior probability distributions of likely solutions upon which all inferences were based [Schmidt, D.M., George, J.S., Wood, C.C., 1999. Bayesian inference applied to the electromagnetic inverse problem. Human Brain Mapping 7, 195; Schmidt, D.M., George, J.S., Ranken, D.M., Wood, C.C., 2001. Spatial-temporal bayesian inference for MEG/EEG. In: Nenonen, J., Ilmoniemi, R. J., Katila, T. (Eds.), Biomag 2000: 12th International Conference on Biomagnetism. Espoo, Norway, p. 671]. Schmidt et al. (1999) focused on the analysis of data at a single point in time employing an extended region source model. They subsequently extended their work to a spatiotemporal Bayesian inference analysis of the full spatiotemporal MEG/EEG data set. Here, we formulate spatiotemporal Bayesian inference analysis using a multi-dipole model of neural activity. This approach is faster than the extended region model, does not require use of the subject's anatomical information, does not require prior determination of the number of dipoles, and yields quantitative probabilistic inferences. In addition, we have incorporated the ability to handle much more complex and realistic estimates of the background noise, which may be represented as a sum of Kronecker products of temporal and spatial noise covariance components. This reduces the effects of undermodeling noise. In order to reduce the rigidity of the multi-dipole formulation which commonly causes problems due to multiple local minima, we treat the given covariance of the background as uncertain and marginalize over it in the analysis. Markov Chain Monte Carlo (MCMC) was used to sample the many possible likely solutions. The spatiotemporal Bayesian dipole analysis is demonstrated using simulated and empirical whole-head MEG data.

  3. An Adaptive Organization Method of Geovideo Data for Spatio-Temporal Association Analysis

    NASA Astrophysics Data System (ADS)

    Wu, C.; Zhu, Q.; Zhang, Y. T.; Du, Z. Q.; Zhou, Y.; Xie, X.; He, F.

    2015-07-01

    Public security incidents have been increasingly challenging to address with their new features, including large-scale mobility, multi-stage dynamic evolution, spatio-temporal concurrency and uncertainty in the complex urban environment, which require spatio-temporal association analysis among multiple regional video data for global cognition. However, the existing video data organizational methods that view video as a property of the spatial object or position in space dissever the spatio-temporal relationship of scattered video shots captured from multiple video channels, limit the query functions on interactive retrieval between a camera and its video clips and hinder the comprehensive management of event-related scattered video shots. GeoVideo, which maps video frames onto a geographic space, is a new approach to represent the geographic world, promote security monitoring in a spatial perspective and provide a highly feasible solution to this problem. This paper analyzes the large-scale personnel mobility in public safety events and proposes a multi-level, event-related organization method with massive GeoVideo data by spatio-temporal trajectory. This paper designs a unified object identify(ID) structure to implicitly store the spatio-temporal relationship of scattered video clips and support the distributed storage management of massive cases. Finally, the validity and feasibility of this method are demonstrated through suspect tracking experiments.

  4. Manipulating spatiotemporal degrees of freedom of waves in random media.

    PubMed

    Lemoult, Fabrice; Lerosey, Geoffroy; de Rosny, Julien; Fink, Mathias

    2009-10-23

    We show that all the spatiotemporal degrees of freedom available in a complex medium can be harnessed and converted into spatial ones. This is demonstrated experimentally through an instantaneous spatial inversion, using broadband ultrasonic waves in a multiple scattering sample. We show theoretically that the inversion convergence is governed by the total number of degrees of freedom available in the medium for a fixed bandwidth and demonstrate experimentally its use for complex media investigation. We believe our approach has potential in sensing, imagery, focusing, and telecommunication.

  5. Large scale stochastic spatio-temporal modelling with PCRaster

    NASA Astrophysics Data System (ADS)

    Karssenberg, Derek; Drost, Niels; Schmitz, Oliver; de Jong, Kor; Bierkens, Marc F. P.

    2013-04-01

    PCRaster is a software framework for building spatio-temporal models of land surface processes (http://www.pcraster.eu). Building blocks of models are spatial operations on raster maps, including a large suite of operations for water and sediment routing. These operations are available to model builders as Python functions. The software comes with Python framework classes providing control flow for spatio-temporal modelling, Monte Carlo simulation, and data assimilation (Ensemble Kalman Filter and Particle Filter). Models are built by combining the spatial operations in these framework classes. This approach enables modellers without specialist programming experience to construct large, rather complicated models, as many technical details of modelling (e.g., data storage, solving spatial operations, data assimilation algorithms) are taken care of by the PCRaster toolbox. Exploratory modelling is supported by routines for prompt, interactive visualisation of stochastic spatio-temporal data generated by the models. The high computational requirements for stochastic spatio-temporal modelling, and an increasing demand to run models over large areas at high resolution, e.g. in global hydrological modelling, require an optimal use of available, heterogeneous computing resources by the modelling framework. Current work in the context of the eWaterCycle project is on a parallel implementation of the modelling engine, capable of running on a high-performance computing infrastructure such as clusters and supercomputers. Model runs will be distributed over multiple compute nodes and multiple processors (GPUs and CPUs). Parallelization will be done by parallel execution of Monte Carlo realizations and sub regions of the modelling domain. In our approach we use multiple levels of parallelism, improving scalability considerably. On the node level we will use OpenCL, the industry standard for low-level high performance computing kernels. To combine multiple nodes we will use

  6. The spatiotemporal properties of visual completion measured by response classification.

    PubMed

    Gold, Jason M; Shubel, Erin

    2006-03-03

    A constant problem faced by the visual system is the identification of partly occluded objects within the visual scene. Recent experiments have demonstrated that the visual system engages in a process of visual completion, where the hidden parts of objects are filled into the visual representation. Recent experiments have also suggested that there may be a time course to this completion process. Here, we examined the spatiotemporal properties of visual completion by having observers classify figures defined by either luminance-defined or illusory contours and then correlating their decisions with externally added spatiotemporal visual noise. This "response classification" technique allowed us to derive a spatiotemporal correlation map (a "classification movie") that revealed the locations used by observers at each point in space and time during the stimulus presentation. We found that observers gradually became more influenced by noise at locations corresponding to illusory contours across the first 175 ms of stimulus presentation. Our results are consistent with the idea that there is a time course to the completion process on the order of approximately 175 ms.

  7. Plasticity of recurring spatiotemporal activity patterns in cortical networks

    NASA Astrophysics Data System (ADS)

    Madhavan, Radhika; Chao, Zenas C.; Potter, Steve M.

    2007-09-01

    How do neurons encode and store information for long periods of time? Recurring patterns of activity have been reported in various cortical structures and were suggested to play a role in information processing and memory. To study the potential role of bursts of action potentials in memory mechanisms, we investigated patterns of spontaneous multi-single-unit activity in dissociated rat cortical cultures in vitro. Spontaneous spikes were recorded from networks of approximately 50 000 neurons and glia cultured on a grid of 60 extracellular substrate- embedded electrodes (multi-electrode arrays). These networks expressed spontaneous culture- wide bursting from approximately one week in vitro. During bursts, a large portion of the active electrodes showed elevated levels of firing. Spatiotemporal activity patterns within spontaneous bursts were clustered using a correlation-based clustering algorithm, and the occurrences of these burst clusters were tracked over several hours. This analysis revealed spatiotemporally diverse bursts occurring in well-defined patterns, which remained stable for several hours. Activity evoked by strong local tetanic stimulation resulted in significant changes in the occurrences of spontaneous bursts belonging to different clusters, indicating that the dynamical flow of information in the neuronal network had been altered. The diversity of spatiotemporal structure and long-term stability of spontaneous bursts together with their plastic nature strongly suggests that such network patterns could be used as codes for information transfer and the expression of memories stored in cortical networks.

  8. Spatiotemporal Fluctuation Analysis: A Powerful Tool for the Future Nanoscopy of Molecular Processes.

    PubMed

    Di Rienzo, Carmine; Gratton, Enrico; Beltram, Fabio; Cardarelli, Francesco

    2016-08-23

    The enormous wealth of information available today from optical microscopy measurements on living samples is often underexploited. We argue that spatiotemporal analysis of fluorescence fluctuations using multiple detection channels can enhance the performance of current nanoscopy methods and provide further insight into dynamic molecular processes of high biological relevance.

  9. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion

    PubMed Central

    Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Raymond, F Lucy; Linglart, Agnès; Jüppner, Harald

    2016-01-01

    Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright’s Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but

  10. STPMiner: A Highperformance Spatiotemporal Pattern Mining Toolbox

    SciTech Connect

    Vatsavai, Raju

    2011-01-01

    The volume of spatiotemporal data being generated from scientific simulations and observations from sensors is growing at an astronomical rate. This data explosion is going to pose three challenges to the existing data mining infrastructure: algorithmic, computational, and I/O. Over the years we have implemented several spatiotemporal data mining algorithms including: outliers/anomalies, colocation patterns, change patterns, clustering, classification, and prediction algorithms. In this paper we briefly discuss the core spatiotemporal pattern mining algorithms along with some of the computational and I/O challenges associated with the big data.

  11. A Systems Biological Approach Reveals Multiple Crosstalk Mechanism between Gram-Positive and Negative Bacterial Infections: An Insight into Core Mechanism and Unique Molecular Signatures

    PubMed Central

    Thangam, Berla; Ahmed, Shiek S. S. J.

    2014-01-01

    Background Bacterial infections remain a major threat and a leading cause of death worldwide. Most of the bacterial infections are caused by gram-positive and negative bacteria, which are recognized by Toll-like receptor (TLR) 2 and 4, respectively. Activation of these TLRs initiates multiple pathways that subsequently lead to effective immune response. Although, both the TLRs share common signaling mechanism yet they may exhibit specificity as well, resulting in the release of diverse range of inflammatory mediators which could be used as candidate biomolecules for bacterial infections. Results We adopted systems biological approach to identify signaling pathways mediated by TLRs to determine candidate molecules associated with bacterial infections. We used bioinformatics concepts, including literature mining to construct protein-protein interaction network, prioritization of TLRs specific nodes using microarray data and pathway analysis. Our constructed PPI network for TLR 2 (nodes: 4091 and edges: 66068) and TLR 4 (node: 4076 and edges: 67898) showed 3207 common nodes, indicating that both the TLRs might share similar signaling events that are attributed to cell migration, MAPK pathway and several inflammatory cascades. Our results propose the potential collaboration between the shared signaling pathways of both the receptors may enhance the immune response against invading pathogens. Further, to identify candidate molecules, the TLRs specific nodes were prioritized using microarray differential expressed genes. Of the top prioritized TLR 2 molecules, 70% were co-expressed. A similar trend was also observed within TLR 4 nodes. Further, most of these molecules were preferentially found in blood plasma for feasible diagnosis. Conclusions The analysis reveals the common and unique mechanism regulated by both the TLRs that provide a broad perspective of signaling events in bacterial infections. Further, the identified candidate biomolecules could potentially aid

  12. An allelic series of mice reveals a role for RERE in the development of multiple organs affected in chromosome 1p36 deletions.

    PubMed

    Kim, Bum Jun; Zaveri, Hitisha P; Shchelochkov, Oleg A; Yu, Zhiyin; Hernández-García, Andrés; Seymour, Michelle L; Oghalai, John S; Pereira, Fred A; Stockton, David W; Justice, Monica J; Lee, Brendan; Scott, Daryl A

    2013-01-01

    Individuals with terminal and interstitial deletions of chromosome 1p36 have a spectrum of defects that includes eye anomalies, postnatal growth deficiency, structural brain anomalies, seizures, cognitive impairment, delayed motor development, behavior problems, hearing loss, cardiovascular malformations, cardiomyopathy, and renal anomalies. The proximal 1p36 genes that contribute to these defects have not been clearly delineated. The arginine-glutamic acid dipeptide (RE) repeats gene (RERE) is located in this region and encodes a nuclear receptor coregulator that plays a critical role in embryonic development as a positive regulator of retinoic acid signaling. Rere-null mice die of cardiac failure between E9.5 and E11.5. This limits their usefulness in studying the role of RERE in the latter stages of development and into adulthood. To overcome this limitation, we created an allelic series of RERE-deficient mice using an Rere-null allele, om, and a novel hypomorphic Rere allele, eyes3 (c.578T>C, p.Val193Ala), which we identified in an N-ethyl-N-nitrosourea (ENU)-based screen for autosomal recessive phenotypes. Analyses of these mice revealed microphthalmia, postnatal growth deficiency, brain hypoplasia, decreased numbers of neuronal nuclear antigen (NeuN)-positive hippocampal neurons, hearing loss, cardiovascular malformations-aortic arch anomalies, double outlet right ventricle, and transposition of the great arteries, and perimembranous ventricular septal defects-spontaneous development of cardiac fibrosis and renal agenesis. These findings suggest that RERE plays a critical role in the development and function of multiple organs including the eye, brain, inner ear, heart and kidney. It follows that haploinsufficiency of RERE may contribute-alone or in conjunction with other genetic, environmental, or stochastic factors-to the development of many of the phenotypes seen in individuals with terminal and interstitial deletions that include the proximal region of

  13. Whole genome analysis of Yersinia ruckeri isolated over 27 years in Australia and New Zealand reveals geographical endemism over multiple lineages and recent evolution under host selection

    PubMed Central

    Delamare-Deboutteville, Jerome; Gudkovs, Nicholas; Brosnahan, Cara; Morrison, Richard; Carson, Jeremy

    2016-01-01

    Yersinia ruckeri is a salmonid pathogen with widespread distribution in cool-temperate waters including Australia and New Zealand, two isolated environments with recently developed salmonid farming industries. Phylogenetic comparison of 58 isolates from Australia, New Zealand, USA, Chile, Finland and China based on non-recombinant core genome SNPs revealed multiple deep-branching lineages, with a most recent common ancestor estimated at 18 500 years BP (12 355–24 757 95% HPD) and evidence of Australasian endemism. Evolution within the Tasmanian Atlantic salmon serotype O1b lineage has been slow, with 63 SNPs describing the variance over 27 years. Isolates from the prevailing lineage are poorly/non-motile compared to a lineage pre-vaccination, introduced in 1997, which is highly motile but has not been isolated since from epizootics. A non-motile phenotype has arisen independently in Tasmania compared to Europe and USA through a frameshift in fliI, encoding the ATPase of the flagella cluster. We report for the first time lipopolysaccharide O-antigen serotype O2 isolates in Tasmania. This phenotype results from deletion of the O-antigen cluster and consequent loss of high-molecular-weight O-antigen. This phenomenon has occurred independently on three occasions on three continents (Australasia, North America and Asia) as O2 isolates from the USA, China and Tasmania share the O-antigen deletion but occupy distant lineages. Despite the European and North American origins of the Australasian salmonid stocks, the lineages of Y. ruckeri in Australia and New Zealand are distinct from those of the northern hemisphere, suggesting they are pre-existing ancient strains that have emerged and evolved with the introduction of susceptible hosts following European colonization. PMID:28348835

  14. PTCH 1 staining of pancreatic neuroendocrine tumor (PNET) samples from patients with and without multiple endocrine neoplasia (MEN-1) syndrome reveals a potential therapeutic target.

    PubMed

    Gurung, Buddha; Hua, Xianxin; Runske, Melissa; Bennett, Bonita; LiVolsi, Virginia; Roses, Robert; Fraker, Douglas A; Metz, David C

    2015-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare, indolent tumors that may occur sporadically or develop in association with well-recognized hereditary syndromes, particularly multiple endocrine neoplasia type 1 (MEN-1). We previously demonstrated that the hedgehog (HH) signaling pathway was aberrantly up-regulated in a mouse model that phenocopies the human MEN-1 syndrome, Men1l/l;RipCre, and that inhibition of this pathway suppresses MEN-1 tumor cell proliferation. We hypothesized that the HH signaling pathway is similarly upregulated in human PNETs. We performed immunohistochemical (IHC) staining for PTCH1 in human fresh and archival PNET specimens to examine whether human sporadic and MEN-1-associated PNETs revealed similar abnormalities as in our mouse model and correlated the results with clinical and demographic factors of the study cohort. PTCH1 staining was positive in 12 of 22 PNET patients (55%). Four of 5 MEN-1 patients stained for PTCH1 (p = 0.32 as compared with sporadic disease patients). Nine of 16 patients with metastatic disease stained for PTCH1 as compared with zero of 3 with localized disease only (p = 0.21). No demographic or clinical features appeared to be predictive of PTCH 1 positivity and PTCH 1 positivity per se was not predictive of clinical outcome. PTCH1, a marker of HH pathway up regulation, is detectable in both primary and metastatic tumors in more than 50% of PNET patients. Although no clinical or demographic factors predict PTCH1 positivity and PTCH1 positivity does not predict clinical outcome, the frequency of expression alone indicates that perturbation of this pathway with agents such as Vismodegib, an inhibitor of Smoothened (SMO), should be examined in future clinical trials.

  15. Phylogeographic study of Chinese seabuckthorn (Hippophae rhamnoides subsp. sinensis Rousi) reveals two distinct haplotype groups and multiple microrefugia on the Qinghai-Tibet Plateau

    PubMed Central

    Wang, Hongfang; Liu, Han; Yang, Mingbo; Bao, Lei; Ge, Jianping

    2014-01-01

    Historical climate change can shape the genetic pattern of a species. Studies on this phenomenon provide great advantage in predicting the response of species to current and future global climate change. Chinese seabuckthorn (Hippophae rhamnoides subsp. sinensis) is one of the most important cultivated plants in Northwest China. However, the subspecies history and the potential genetic resources within the subspecies range remain unclear. In this study, we utilized two intergenic chloroplast regions to characterize the spatial genetic distribution of the species. We found 19 haplotypes in total, 12 of which were unique to the Chinese seabuckthorn. The populations observed on the Qinghai-Tibet Plateau (QTP) consisted of most of the haplotypes, while in the northeast of the range of the subspecies, an area not on the QTP, only four haplotypes were detected. Our study also revealed two distinct haplotype groups of the subspecies with a sharp transition region located in the south of the Zoige Basin. 89.96% of the genetic variation located between the regions. Mismatch analysis indicated old expansions of these two haplotype groups, approximately around the early stage of Pleistocene. Additional morphological proofs from existing studies and habitat differentiation supported a long independent colonization history among the two regions. Potential adaptation probably occurred but needs more genome and morphology data in future. Chinese seabuckthorn have an older population expansion compared with subspecies in Europe. The lack of large land ice sheets and the heterogeneous landscape of the QTP could have provided extensive microrefugia for Chinese seabuckthorn during the glaciation period. Multiple localities sustaining high-frequency private haplotypes support this hypothesis. Our study gives clear insight into the distribution of genetic resources and the evolutionary history of Chinese seabuckthorn. PMID:25540697

  16. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.

    PubMed

    Rai, Rajani; Kim, Jong Joo; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

    2015-11-25

    Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene-gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  17. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    PubMed Central

    Rai, Rajani; Kim, Jong Joo; Misra, Sanjeev; Kumar, Ashok; Mittal, Balraj

    2015-01-01

    Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility. PMID:26602921

  18. Multisensory control of hippocampal spatiotemporal selectivity.

    PubMed

    Ravassard, Pascal; Kees, Ashley; Willers, Bernard; Ho, David; Aharoni, Daniel; Cushman, Jesse; Aghajan, Zahra M; Mehta, Mayank R

    2013-06-14

    The hippocampal cognitive map is thought to be driven by distal visual cues and self-motion cues. However, other sensory cues also influence place cells. Hence, we measured rat hippocampal activity in virtual reality (VR), where only distal visual and nonvestibular self-motion cues provided spatial information, and in the real world (RW). In VR, place cells showed robust spatial selectivity; however, only 20% were track active, compared with 45% in the RW. This indicates that distal visual and nonvestibular self-motion cues are sufficient to provide selectivity, but vestibular and other sensory cues present in RW are necessary to fully activate the place-cell population. In addition, bidirectional cells preferentially encoded distance along the track in VR, while encoding absolute position in RW. Taken together, these results suggest the differential contributions of these sensory cues in shaping the hippocampal population code. Theta frequency was reduced, and its speed dependence was abolished in VR, but phase precession was unaffected, constraining mechanisms governing both hippocampal theta oscillations and temporal coding. These results reveal cooperative and competitive interactions between sensory cues for control over hippocampal spatiotemporal selectivity and theta rhythm.

  19. Origin and Spatiotemporal Control of Cuspate Forelands

    NASA Astrophysics Data System (ADS)

    McNinch, J. E.

    2006-12-01

    Cuspate shoreline forms are ubiquitous throughout shorelines of the world and span a wide range in size from sub-meter to 102 kilometers; in grain size from fine to coarse; and in energetic settings from small lakes and lagoons to open ocean beaches with virtually unlimited fetch. Cuspate forelands, with wavelengths ranging from 1-120 km, are found worldwide and are the largest of the rhythmic coastal forms. The origin of cuspate forelands has been debated for well over a century but no theory has emerged that fully explains both the origin and the processes controlling the size and time necessary for development. Despite this uncertainty of spatiotemporal controls, large-scale rhythmic morphology of cuspate forelands strongly suggests that scaling and linkages between physical and sedimentary processes may span many orders of magnitude. The same hydrodynamic forces driving sediment transport at the granular scale, such as wave orbital motion and mean currents, likely play a role in shaping the much larger cuspate shorelines. A survey of passive margin, microtidal shorelines from the US and select locations around the world reveals that cuspate forelands are only found in regions where the predominant wind direction is shore-parallel. Modeling and observations of waves, currents, and sediment accumulation from Cape Lookout, North Carolina indicate that water and sediment are transported well seaward of cuspate foreland promontories by wind-driven and tidal residual currents leading to: 1) the rapid growth of spits and sub-aqueous shoals, 2) elimination of sediment exchange between adjacent littoral cells, and 3) control of the wave diffraction point around the promontories. These results and earlier modeling work related to high-angle waves suggest that wind leads to feedback between waves, currents, and promontory-shoal bathymetry and ultimately defines the size and development time of cuspate forelands. Lastly, a linear relationship between the size of cuspate

  20. Microclimate Data Improve Predictions of Insect Abundance Models Based on Calibrated Spatiotemporal Temperatures

    PubMed Central

    Rebaudo, François; Faye, Emile; Dangles, Olivier

    2016-01-01

    A large body of literature has recently recognized the role of microclimates in controlling the physiology and ecology of species, yet the relevance of fine-scale climatic data for modeling species performance and distribution remains a matter of debate. Using a 6-year monitoring of three potato moth species, major crop pests in the tropical Andes, we asked whether the spatiotemporal resolution of temperature data affect the predictions of models of moth performance and distribution. For this, we used three different climatic data sets: (i) the WorldClim dataset (global dataset), (ii) air temperature recorded using data loggers (weather station dataset), and (iii) air crop canopy temperature (microclimate dataset). We developed a statistical procedure to calibrate all datasets to monthly and yearly variation in temperatures, while keeping both spatial and temporal variances (air monthly temperature at 1 km² for the WorldClim dataset, air hourly temperature for the weather station, and air minute temperature over 250 m radius disks for the microclimate dataset). Then, we computed pest performances based on these three datasets. Results for temperature ranging from 9 to 11°C revealed discrepancies in the simulation outputs in both survival and development rates depending on the spatiotemporal resolution of the temperature dataset. Temperature and simulated pest performances were then combined into multiple linear regression models to compare predicted vs. field data. We used an additional set of study sites to test the ability of the results of our model to be extrapolated over larger scales. Results showed that the model implemented with microclimatic data best predicted observed pest abundances for our study sites, but was less accurate than the global dataset model when performed at larger scales. Our simulations therefore stress the importance to consider different temperature datasets depending on the issue to be solved in order to accurately predict species

  1. Multilocus Variable Number of Tandem Repeat Analysis Reveals Multiple Introductions in Spain of Xanthomonas arboricola pv. pruni, the Causal Agent of Bacterial Spot Disease of Stone Fruits and Almond.

    PubMed

    López-Soriano, Pablo; Boyer, Karine; Cesbron, Sophie; Morente, María Clara; Peñalver, Javier; Palacio-Bielsa, Ana; Vernière, Christian; López, María M; Pruvost, Olivier

    Xanthomonas arboricola pv. pruni is the causal agent of the bacterial spot disease of stone fruits, almond and some ornamental Prunus species. In Spain it was first detected in 2002 and since then, several outbreaks have occurred in different regions affecting mainly Japanese plum, peach and almond, both in commercial orchards and nurseries. As the origin of the introduction(s) was unknown, we have assessed the genetic diversity of 239 X. arboricola pv. pruni strains collected from 11 Spanish provinces from 2002 to 2013 and 25 reference strains from international collections. We have developed an optimized multilocus variable number of tandem repeat analysis (MLVA) scheme targeting 18 microsatellites and five minisatellites. A high discriminatory power was achieved since almost 50% of the Spanish strains were distinguishable, confirming the usefulness of this genotyping technique at small spatio-temporal scales. Spanish strains grouped in 18 genetic clusters (conservatively delineated so that each cluster contained haplotype networks linked by up to quadruple-locus variations). Furthermore, pairwise comparisons among populations from different provinces showed a strong genetic differentiation. Our results suggest multiple introductions of this pathogen in Spain and redistribution through contaminated nursery propagative plant material.

  2. Multilocus Variable Number of Tandem Repeat Analysis Reveals Multiple Introductions in Spain of Xanthomonas arboricola pv. pruni, the Causal Agent of Bacterial Spot Disease of Stone Fruits and Almond

    PubMed Central

    López-Soriano, Pablo; Boyer, Karine; Cesbron, Sophie; Morente, María Clara; Peñalver, Javier; Palacio-Bielsa, Ana; Vernière, Christian; López, María M.; Pruvost, Olivier

    2016-01-01

    Xanthomonas arboricola pv. pruni is the causal agent of the bacterial spot disease of stone fruits, almond and some ornamental Prunus species. In Spain it was first detected in 2002 and since then, several outbreaks have occurred in different regions affecting mainly Japanese plum, peach and almond, both in commercial orchards and nurseries. As the origin of the introduction(s) was unknown, we have assessed the genetic diversity of 239 X. arboricola pv. pruni strains collected from 11 Spanish provinces from 2002 to 2013 and 25 reference strains from international collections. We have developed an optimized multilocus variable number of tandem repeat analysis (MLVA) scheme targeting 18 microsatellites and five minisatellites. A high discriminatory power was achieved since almost 50% of the Spanish strains were distinguishable, confirming the usefulness of this genotyping technique at small spatio-temporal scales. Spanish strains grouped in 18 genetic clusters (conservatively delineated so that each cluster contained haplotype networks linked by up to quadruple-locus variations). Furthermore, pairwise comparisons among populations from different provinces showed a strong genetic differentiation. Our results suggest multiple introductions of this pathogen in Spain and redistribution through contaminated nursery propagative plant material. PMID:27669415

  3. The spatiotemporal order of signaling events unveils the logic of development signaling

    PubMed Central

    Zhu, Hao; Owen, Markus R.; Mao, Yanlan

    2016-01-01

    Motivation: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like. Results: We have developed a computational model for Drosophila eye development with innovated methods to reveal how interactions among multiple pathways control the dynamically generated hexagonal array of R8 cells. We obtained two novel findings. First, the coupling between the long-range inductive signals produced by the proneural Hh signaling and the short-range restrictive signals produced by the antineural Notch and EGFR signaling is essential for generating accurately spaced R8s. Second, the spatiotemporal orders of key signaling events reveal a robust pattern of lateral inhibition conducted by Ato-coordinated Notch and EGFR signaling to collectively determine R8 patterning. This pattern, stipulating the orders of signaling and comparable to the protocols of communication, may help decipher the well-appreciated but poorly defined logic of developmental signaling. Availability and implementation: The model is available upon request. Contact: hao.zhu@ymail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153573

  4. Experimentally observed route to spatiotemporal chaos in an extended one-dimensional array of convective oscillators.

    PubMed

    Miranda, M A; Burguete, J

    2009-04-01

    We report experimental evidence of the route to spatiotemporal chaos in a large one-dimensional array of hotspots in a thermoconvective system. As the driving force is increased, a stationary cellular pattern becomes unstable toward a mixed pattern of irregular clusters which consist of time-dependent localized patterns of variable spatiotemporal coherence. These irregular clusters coexist with the basic cellular pattern. The Fourier spectra corresponding to this synchronization transition reveal the weak coupling of a resonant triad. This pattern saturates with the formation of a unique domain of high spatiotemporal coherence. As we further increase the driving force, a supercritical bifurcation to a spatiotemporal beating regime takes place. The new pattern is characterized by the presence of two stationary clusters with a characteristic zig-zag geometry. The Fourier analysis reveals a stronger coupling than the previous mixed pattern and enables us to find out that this beating phenomenon is produced by the splitting of the fundamental spatiotemporal frequencies in a narrow band. Both secondary instabilities are phaselike synchronization transitions with global and absolute character. Far beyond this threshold, a new instability takes place when the system is not able to sustain the spatial frequency splitting, although the temporal beating remains inside these domains. These experimental results may support the understanding of other systems in nature undergoing similar clustering processes.

  5. Experimentally observed route to spatiotemporal chaos in an extended one-dimensional array of convective oscillators

    NASA Astrophysics Data System (ADS)

    Miranda, M. A.; Burguete, J.

    2009-04-01

    We report experimental evidence of the route to spatiotemporal chaos in a large one-dimensional array of hotspots in a thermoconvective system. As the driving force is increased, a stationary cellular pattern becomes unstable toward a mixed pattern of irregular clusters which consist of time-dependent localized patterns of variable spatiotemporal coherence. These irregular clusters coexist with the basic cellular pattern. The Fourier spectra corresponding to this synchronization transition reveal the weak coupling of a resonant triad. This pattern saturates with the formation of a unique domain of high spatiotemporal coherence. As we further increase the driving force, a supercritical bifurcation to a spatiotemporal beating regime takes place. The new pattern is characterized by the presence of two stationary clusters with a characteristic zig-zag geometry. The Fourier analysis reveals a stronger coupling than the previous mixed pattern and enables us to find out that this beating phenomenon is produced by the splitting of the fundamental spatiotemporal frequencies in a narrow band. Both secondary instabilities are phaselike synchronization transitions with global and absolute character. Far beyond this threshold, a new instability takes place when the system is not able to sustain the spatial frequency splitting, although the temporal beating remains inside these domains. These experimental results may support the understanding of other systems in nature undergoing similar clustering processes.

  6. Analytical study of spatiotemporal chaos control by applying local injections

    PubMed

    Gang; Jinghua; Jihua; Xiangming; Yugui; Hu

    2000-09-01

    Spatiotemporal chaos control by applying local feedback injections is investigated analytically. The influence of gradient force on the controllability is investigated. It is shown that as the gradient force of the system is larger than a critical value, local control can reach very high efficiency to drive the turbulent system of infinite size to a regular target state by using a single control signal. The complex Ginzburg-Landau equation is used as a model to confirm the above analysis, and a four-wave-mixing mode is revealed to determine the dynamical behavior of the controlled system at the onset of instability.

  7. Spatiotemporal signal processing for blind separation of multichannel signals

    NASA Astrophysics Data System (ADS)

    Tugnait, Jitendra K.

    1996-06-01

    This paper is concerned with the problem of blind separation of independent signals (sources) from their linear convolutive mixtures. The problem consists of recovering the sources up to shaping filters from the observations of multiple-input multiple-output (MIMO) system output. The various signals are assumed to be linear but not necessarily i.i.d. (independent and identically distributed). The problem is cast into the framework of spatio-temporal equalization and estimation of the matrix impulse response function of MIMO channels (systems). An iterative, Godard cost based approach is considered for spatio-temporal equalization and MIMO impulse response estimation. Stationary points of the cost function are investigated and it is shown that all stable local minima correspond to desirable minima when doubly infinite equalizers are used. Analysis is also provided for the case when finite-length equalizers exist. The various input sequences are extracted and cancelled one-by-one. The matrix impulse response is then obtained by cross-correlating the extracted inputs with the observed outputs. Identifiability conditions are analyzed. Computer simulation examples are presented to illustrate the proposed approach.

  8. An Intelligent Polar Cyberinfrastrucuture to Support Spatiotemporal Decision Making

    NASA Astrophysics Data System (ADS)

    Song, M.; Li, W.; Zhou, X.

    2014-12-01

    In the era of big data, polar sciences have already faced an urgent demand of utilizing intelligent approaches to support precise and effective spatiotemporal decision-making. Service-oriented cyberinfrastructure has advantages of seamlessly integrating distributed computing resources, and aggregating a variety of geospatial data derived from Earth observation network. This paper focuses on building a smart service-oriented cyberinfrastructure to support intelligent question answering related to polar datasets. The innovation of this polar cyberinfrastructure includes: (1) a problem-solving environment that parses geospatial question in natural language, builds geoprocessing rules, composites atomic processing services and executes the entire workflow; (2) a self-adaptive spatiotemporal filter that is capable of refining query constraints through semantic analysis; (3) a dynamic visualization strategy to support results animation and statistics in multiple spatial reference systems; and (4) a user-friendly online portal to support collaborative decision-making. By means of this polar cyberinfrastructure, we intend to facilitate integration of distributed and heterogeneous Arctic datasets and comprehensive analysis of multiple environmental elements (e.g. snow, ice, permafrost) to provide a better understanding of the environmental variation in circumpolar regions.

  9. Cell Population Tracking and Lineage Construction with Spatiotemporal Context 1

    PubMed Central

    Li, Kang; Chen, Mei; Kanade, Takeo; Miller, Eric D.; Weiss, Lee E.; Campbell, Phil G.

    2008-01-01

    Automated visual-tracking of cell populations in vitro using phase contrast time-lapse microscopy enables quantitative, systematic and high-throughput measurements of cell behaviors. These measurements include the spatiotemporal quantification of cell migration, mitosis, apoptosis, and the construction of cell lineages. The combination of low signal-to-noise ratio of phase contrast microscopy images, high and varying densities of the cell cultures, topological complexities of cell shapes, and wide range of cell behaviors pose many challenges to existing tracking techniques. This paper presents a fully-automated multi-target tracking system that can efficiently cope with these challenges while simultaneously tracking and analyzing thousands of cells observed using time-lapse phase contrast microscopy. The system combines bottom-up and top-down image analysis by integrating multiple collaborative modules, which exploit a fast geometric active contour tracker in conjunction with adaptive interacting multiple models (IMM) motion filtering and spatiotemporal trajectory optimization. The system, which was tested using a variety of cell populations, achieved tracking accuracy in the range of 86.9%–92.5%. PMID:18656418

  10. Cross-species characterization of the promoter region of the cystic fibrosis transmembrane conductance regulator gene reveals multiple levels of regulation.

    PubMed Central

    Vuillaumier, S; Dixmeras, I; Messaï, H; Lapouméroulie, C; Lallemand, D; Gekas, J; Chehab, F F; Perret, C; Elion, J; Denamur, E

    1997-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) gene is highly conserved within vertebrate species. Its pattern of expression in vivo seems to be tightly regulated both developmentally and in a tissue-specific manner, but shows differences with species. To identify transcriptional regulatory elements in the CFTR promoter region, we have used a combined approach based both on the analysis of the chromatin structure in vivo in rat tissues and on evolutionary clues (i.e. phylogenetic footprinting). In CFTR-expressing tissues, 15 DNase I-hypersensitive sites were identified within a 36 kb region encompassing exon 1. Eleven of them are clustered in a 3.5 kb region that exhibits eleven phylogenetic footprints observed when comparing sequences from eight mammalian species representing four orders (Primates, Artiodactylia, Lagomorpha and Rodentia). Comparison of the two sets of data allows the identification of two types of regulatory elements. Some are conserved between species, such as a non-consensus cAMP response element (CRE) and a PMA-responsive element (TRE) located respectively at positions -0.1 and -1.3 kb relative to ATG. Some are species-specific elements such as a 300 bp purine.pyrimidine (Pu.Py) stretch that is present only in rodents. Analysis of protein/DNA interactions in vitro with rat tissue protein extracts on the conserved elements revealed that the TRE site binds a specific heterodimeric complex composed of Fra-2, Jun D and a protein immunologically related to Jun/CRE-binding protein in the duodenum, whereas the CRE-like site binds ATF-1 ubiquitously. Functional analysis in Caco-2 cells showed that the CRE-like site supports a high basal transcriptional activity but is not able by itself to induce a response to cAMP, whereas the TRE site acts as a weak transactivator stimulated by PMA. Lastly, we found that the rodent-specific Pu.Py stretch confers nuclease S1 hypersensitivity under conditions of acidic pH and supercoiling. This

  11. Parametric study of diffusion-enhancement networks for spatiotemporal grouping in real-time artificial vision

    NASA Astrophysics Data System (ADS)

    Cunningham, Robert K.; Waxman, Allen M.

    1991-06-01

    This is the first Annual Technical Summary of the MIT Lincoln Laboratory effort into the parametric study of diffusion-enhancement networks for spatiotemporal grouping in real-time artificial vision. Spatiotemporal grouping phenomena are examined in the context of static and time-varying imagery. Dynamics that exhibit static feature grouping on multiple scales as a function of time and long-range apparent motion between time-varying inputs are developed for a biologically plausible diffusion-enhancement bilayer. The architecture consists of a diffusion and a contrast-enhancement layer coupled by feedforward and feedback connections: input is provided by a separate feature extracting layer. The model is cast as an analog circuit that is realizable in VLSI, the parameters of which are selected to satisfy a psychophysical database on apparent motion. Specific topics include: neural networks, astrocyte glial networks, diffusion enhancement, long-range apparent motion, spatiotemporal grouping dynamics, and interference suppression.

  12. Spatiotemporally controlled single cell sonoporation

    PubMed Central

    Fan, Zhenzhen; Liu, Haiyan; Mayer, Michael; Deng, Cheri X.

    2012-01-01

    This paper presents unique approaches to enable control and quantification of ultrasound-mediated cell membrane disruption, or sonoporation, at the single-cell level. Ultrasound excitation of microbubbles that were targeted to the plasma membrane of HEK-293 cells generated spatially and temporally controlled membrane disruption with high repeatability. Using whole-cell patch clamp recording combined with fluorescence microscopy, we obtained time-resolved measurements of single-cell sonoporation and quantified the size and resealing rate of pores. We measured the intracellular diffusion coefficient of cytoplasmic RNA/DNA from sonoporation-induced transport of an intercalating fluorescent dye into and within single cells. We achieved spatiotemporally controlled delivery with subcellular precision and calcium signaling in targeted cells by selective excitation of microbubbles. Finally, we utilized sonoporation to deliver calcein, a membrane-impermeant substrate of multidrug resistance protein-1 (MRP1), into HEK-MRP1 cells, which overexpress MRP1, and monitored the calcein efflux by MRP1. This approach made it possible to measure the efflux rate in individual cells and to compare it directly to the efflux rate in parental control cells that do not express MRP1. PMID:23012425

  13. Spatiotemporal recurrences of sandpile avalanches

    NASA Astrophysics Data System (ADS)

    Tarun, Anjali B.; Paguirigan, Antonino A.; Batac, Rene C.

    2015-10-01

    We study the space and time properties of avalanches in a continuous sandpile model by constructing a temporally directed network linking together the recurrent avalanche events based on their spatial separation. We use two different criteria for network construction: a later event is connected to a previous one if it is either nearest or farthest from it among all the later events. With this, we observe scale-free regimes emerge as characterized by the following power-law exponents: (a) α = 1.7 for the avalanche size distributions; (b) βF = 2.1 in the in-degree distribution of farthest recurrences; (c) δ = 1 for the separation distances; and (d) γ = 1 for the temporal separations of recurrences. Our results agree with earlier observations that describe the sandpile avalanches as repulsive events, i.e. the next avalanche is more likely to be physically separated from an earlier one. These observations, which are not captured by usual interoccurrence statistics and by random connection mechanisms, suggest an underlying spatiotemporal organization in the sandpile that makes it useful for modeling real-world systems.

  14. Object correspondence across brief occlusion is established on the basis of both spatiotemporal and surface feature cues.

    PubMed

    Hollingworth, Andrew; Franconeri, Steven L

    2009-11-01

    The correspondence problem is a classic issue in vision and cognition. Frequent perceptual disruptions, such as saccades and brief occlusion, create gaps in perceptual input. How does the visual system establish correspondence between objects visible before and after the disruption? Current theories hold that object correspondence is established solely on the basis of an object's spatiotemporal properties and that an object's surface feature properties (such as color or shape) are not consulted in correspondence operations. In five experiments, we tested the relative contributions of spatiotemporal and surface feature properties to establishing object correspondence across brief occlusion. Correspondence operations were strongly influenced both by the consistency of an object's spatiotemporal properties across occlusion and by the consistency of an object's surface feature properties across occlusion. These data argue against the claim that spatiotemporal cues dominate the computation of object correspondence. Instead, the visual system consults multiple sources of relevant information to establish continuity across perceptual disruption.

  15. Spatio-temporal Hotelling observer for signal detection from image sequences

    PubMed Central

    Caucci, Luca; Barrett, Harrison H.; Rodríguez, Jeffrey J.

    2010-01-01

    Detection of signals in noisy images is necessary in many applications, including astronomy and medical imaging. The optimal linear observer for performing a detection task, called the Hotelling observer in the medical literature, can be regarded as a generalization of the familiar prewhitening matched filter. Performance on the detection task is limited by randomness in the image data, which stems from randomness in the object, randomness in the imaging system, and randomness in the detector outputs due to photon and readout noise, and the Hotelling observer accounts for all of these effects in an optimal way. If multiple temporal frames of images are acquired, the resulting data set is a spatio-temporal random process, and the Hotelling observer becomes a spatio-temporal linear operator. This paper discusses the theory of the spatio-temporal Hotelling observer and estimation of the required spatio-temporal covariance matrices. It also presents a parallel implementation of the observer on a cluster of Sony PLAYSTATION 3 gaming consoles. As an example, we consider the use of the spatio-temporal Hotelling observer for exoplanet detection. PMID:19550494

  16. Spatio-temporal Hotelling observer for signal detection from image sequences.

    PubMed

    Caucci, Luca; Barrett, Harrison H; Rodriguez, Jeffrey J

    2009-06-22

    Detection of signals in noisy images is necessary in many applications, including astronomy and medical imaging. The optimal linear observer for performing a detection task, called the Hotelling observer in the medical literature, can be regarded as a generalization of the familiar prewhitening matched filter. Performance on the detection task is limited by randomness in the image data, which stems from randomness in the object, randomness in the imaging system, and randomness in the detector outputs due to photon and readout noise, and the Hotelling observer accounts for all of these effects in an optimal way. If multiple temporal frames of images are acquired, the resulting data set is a spatio-temporal random process, and the Hotelling observer becomes a spatio-temporal linear operator. This paper discusses the theory of the spatio-temporal Hotelling observer and estimation of the required spatio-temporal covariance matrices. It also presents a parallel implementation of the observer on a cluster of Sony PLAYSTATION 3 gaming consoles. As an example, we consider the use of the spatio-temporal Hotelling observer for exoplanet detection.

  17. Spatiotemporal localization and categorization of human actions in unsegmented image sequences.

    PubMed

    Oikonomopoulos, Antonios; Patras, Ioannis; Pantic, Maja

    2011-04-01

    In this paper we address the problem of localization and recognition of human activities in unsegmented image sequences. The main contribution of the proposed method is the use of an implicit representation of the spatiotemporal shape of the activity which relies on the spatiotemporal localization of characteristic ensembles of feature descriptors. Evidence for the spatiotemporal localization of the activity is accumulated in a probabilistic spatiotemporal voting scheme. The local nature of the proposed voting framework allows us to deal with multiple activities taking place in the same scene, as well as with activities in the presence of clutter and occlusion. We use boosting in order to select characteristic ensembles per class. This leads to a set of class specific codebooks where each codeword is an ensemble of features. During training, we store the spatial positions of the codeword ensembles with respect to a set of reference points, as well as their temporal positions with respect to the start and end of the action instance. During testing, each activated codeword ensemble casts votes concerning the spatiotemporal position and extend of the action, using the information that was stored during training. Mean Shift mode estimation in the voting space provides the most probable hypotheses concerning the localization of the subjects at each frame, as well as the extend of the activities depicted in the image sequences. We present classification and localization results for a number of publicly available datasets, and for a number of sequences where there is a significant amount of clutter and occlusion.

  18. Spatio-temporal variability in ventricular fibrillation

    NASA Astrophysics Data System (ADS)

    Hastings, Harold M.; Evans, Steven J.; Fenton, Flavio H.; Garfinkel, Alan

    2001-03-01

    It is widely believed that reentrant ventricular tachycardia arises when a spiral wave of activation takes over and drives the ventricle at a rate significantly faster than sinus rhythm, and that ventricular fibrillation (VF), a spatio-temporally disorganized form of cardiac activity leading to sudden cardiac death, arises when this spiral breaks down into multiple offspring. Many authors have found that VF displays significant spatial and temporal organization. The purpose of this research is to quantify time scales and temporal and spatial variability in VF. Surface electrograms were obtained from a stable canine model of VF (cf. Nwasokwa and Bodenheimer, Am. J. Physiol. 253, H643 (1987)). These electrograms were analyzed to identify activation times to an accuracy of 1 ms (cf. Garfinkel et al., J. Clin. Invest. 99, 305 (1997)), yielded eighteen usable series, each containing over 1024 intervactivation intervals, two or three from widely spaced sites per episode of VF, 7 total episodes in 4 animals. Spatial and long-term (60 - 120 sec) temporal variability were analyzed and compared by ANOVA techniques (Evans et al., Proc. Royal Soc. B265, 2167 (1998)). In 6 of 7 episodes, spatial variability among sites was statistically more significant than variability between the first and second halves of each series. More recently, Fourier analysis of these series found three distinct scaling regions, with power law dynamics in each and break points of ca. 1 sec and 4 sec. Finally, there was significant variability in the fraction of "short" interactivation intervals (lasting < 60 of 125 ms) among sites. Together these results suggest variability in physiological properties among sites and consequent variability in spiral wave dynamics among sites.

  19. Three-dimensional spatiotemporal focusing of holographic patterns

    NASA Astrophysics Data System (ADS)

    Hernandez, Oscar; Papagiakoumou, Eirini; Tanese, Dimitrii; Fidelin, Kevin; Wyart, Claire; Emiliani, Valentina

    2016-06-01

    Two-photon excitation with temporally focused pulses can be combined with phase-modulation approaches, such as computer-generated holography and generalized phase contrast, to efficiently distribute light into two-dimensional, axially confined, user-defined shapes. Adding lens-phase modulations to 2D-phase holograms enables remote axial pattern displacement as well as simultaneous pattern generation in multiple distinct planes. However, the axial confinement linearly degrades with lateral shape area in previous reports where axially shifted holographic shapes were not temporally focused. Here we report an optical system using two spatial light modulators to independently control transverse- and axial-target light distribution. This approach enables simultaneous axial translation of single or multiple spatiotemporally focused patterns across the sample volume while achieving the axial confinement of temporal focusing. We use the system's capability to photoconvert tens of Kaede-expressing neurons with single-cell resolution in live zebrafish larvae.

  20. Three-dimensional spatiotemporal focusing of holographic patterns

    PubMed Central

    Hernandez, Oscar; Papagiakoumou, Eirini; Tanese, Dimitrii; Fidelin, Kevin; Wyart, Claire; Emiliani, Valentina

    2016-01-01

    Two-photon excitation with temporally focused pulses can be combined with phase-modulation approaches, such as computer-generated holography and generalized phase contrast, to efficiently distribute light into two-dimensional, axially confined, user-defined shapes. Adding lens-phase modulations to 2D-phase holograms enables remote axial pattern displacement as well as simultaneous pattern generation in multiple distinct planes. However, the axial confinement linearly degrades with lateral shape area in previous reports where axially shifted holographic shapes were not temporally focused. Here we report an optical system using two spatial light modulators to independently control transverse- and axial-target light distribution. This approach enables simultaneous axial translation of single or multiple spatiotemporally focused patterns across the sample volume while achieving the axial confinement of temporal focusing. We use the system's capability to photoconvert tens of Kaede-expressing neurons with single-cell resolution in live zebrafish larvae. PMID:27306044

  1. Spatiotemporal Analysis of a Glycolytic Activity Gradient Linked to Mouse Embryo Mesoderm Development.

    PubMed

    Bulusu, Vinay; Prior, Nicole; Snaebjornsson, Marteinn T; Kuehne, Andreas; Sonnen, Katharina F; Kress, Jana; Stein, Frank; Schultz, Carsten; Sauer, Uwe; Aulehla, Alexander

    2017-02-27

    How metabolism is rewired during embryonic development is still largely unknown, as it remains a major technical challenge to resolve metabolic activities or metabolite levels with spatiotemporal resolution. Here, we investigated metabolic changes during development of organogenesis-stage mouse embryos, focusing on the presomitic mesoderm (PSM). We measured glycolytic labeling kinetics from (13)C-glucose tracing experiments and detected elevated glycolysis in the posterior, more undifferentiated PSM. We found evidence that the spatial metabolic differences are functionally relevant during PSM development. To enable real-time quantification of a glycolytic metabolite with spatiotemporal resolution, we generated a pyruvate FRET-sensor reporter mouse line. We revealed dynamic changes in cytosolic pyruvate levels as cells transit toward a more anterior PSM state. Combined, our approach identifies a gradient of glycolytic activity across the PSM, and we provide evidence that these spatiotemporal metabolic changes are intrinsically linked to PSM development and differentiation.

  2. Spatiotemporal Dynamics of a Network of Coupled Time-Delay Digital Tanlock Loops

    NASA Astrophysics Data System (ADS)

    Paul, Bishwajit; Banerjee, Tanmoy; Sarkar, B. C.

    The time-delay digital tanlock loop (TDTLs) is an important class of phase-locked loop that is widely used in electronic communication systems. Although nonlinear dynamics of an isolated TDTL has been studied in the past but the collective behavior of TDTLs in a network is an important topic of research and deserves special attention as in practical communication systems separate entities are rarely isolated. In this paper, we carry out the detailed analysis and numerical simulations to explore the spatiotemporal dynamics of a network of a one-dimensional ring of coupled TDTLs with nearest neighbor coupling. The equation representing the network is derived and we carry out analytical calculations using the circulant matrix formalism to obtain the stability criteria. An extensive numerical simulation reveals that with the variation of gain parameter and coupling strength the network shows a variety of spatiotemporal dynamics such as frozen random pattern, pattern selection, spatiotemporal intermittency and fully developed spatiotemporal chaos. We map the distinct dynamical regions of the system in two-parameter space. Finally, we quantify the spatiotemporal dynamics by using quantitative measures like Lyapunov exponent and the average quadratic deviation of the full network.

  3. Bayesian spatio-temporal analysis and geospatial risk factors of human monocytic ehrlichiosis.

    PubMed

    Raghavan, Ram K; Neises, Daniel; Goodin, Douglas G; Andresen, Daniel A; Ganta, Roman R

    2014-01-01

    Variations in spatio-temporal patterns of Human Monocytic Ehrlichiosis (HME) infection in the state of Kansas, USA were examined and the relationship between HME relative risk and various environmental, climatic and socio-economic variables were evaluated. HME data used in the study was reported to the Kansas Department of Health and Environment between years 2005-2012, and geospatial variables representing the physical environment [National Land cover/Land use, NASA Moderate Resolution Imaging Spectroradiometer (MODIS)], climate [NASA MODIS, Prediction of Worldwide Renewable Energy (POWER)], and socio-economic conditions (US Census Bureau) were derived from publicly available sources. Following univariate screening of candidate variables using logistic regressions, two Bayesian hierarchical models were fit; a partial spatio-temporal model with random effects and a spatio-temporal interaction term, and a second model that included additional covariate terms. The best fitting model revealed that spatio-temporal autocorrelation in Kansas increased steadily from 2005-2012, and identified poverty status, relative humidity, and an interactive factor, 'diurnal temperature range x mixed forest area' as significant county-level risk factors for HME. The identification of significant spatio-temporal pattern and new risk factors are important in the context of HME prevention, for future research in the areas of ecology and evolution of HME, and as well as climate change impacts on tick-borne diseases.

  4. Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyce cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol.

    PubMed

    Wang, Xin; Li, Bing-Zhi; Ding, Ming-Zhu; Zhang, Wei-Wen; Yuan, Ying-Jin

    2013-03-01

    During hydrolysis of lignocellulosic biomass, a broad range of inhibitors are generated, which interfere with yeast growth and bioethanol production. In order to improve the strain tolerance to multiple inhibitors--acetic acid, furfural, and phenol (three representative lignocellulose-derived inhibitors) and uncover the underlying tolerant mechanism, an adaptation experiment was performed in which the industrial Saccharomyces cerevisiae was cultivated repeatedly in a medium containing multiple inhibitors. The adaptation occurred quickly, accompanied with distinct increase in growth rate, glucose utilization rate, furfural metabolism rate, and ethanol yield, only after the first transfer. A similar rapid adaptation was also observed for the lab strains of BY4742 and BY4743. The metabolomic analysis was employed to investigate the responses of the industrial S. cereviaise to three inhibitors during the adaptation. The results showed that higher levels of 2-furoic acid, 2, 3-butanediol, intermediates in glycolytic pathway, and amino acids derived from glycolysis, were discovered in the adapted strains, suggesting that enhanced metabolic activity in these pathways may relate to resistance against inhibitors. Additionally, through single-gene knockouts, several genes related to alanine metabolism, GABA shunt, and glycerol metabolism were verified to be crucial for the resistance to multiple inhibitors. This study provides new insights into the tolerance mechanism against multiple inhibitors, and guides for the improvement of tolerant ethanologenic yeast strains for lignocellulose-bioethanol fermentation.

  5. Neural method of spatiotemporal filter design

    NASA Astrophysics Data System (ADS)

    Szostakowski, Jaroslaw

    1997-10-01

    There is a lot of applications in medical imaging, computer vision, and the communications, where the video processing is critical. Although many techniques have been successfully developed for the filtering of the still-images, significantly fewer techniques have been proposed for the filtering of noisy image sequences. In this paper the novel approach to spatio- temporal filtering design is proposed. The multilayer perceptrons and functional-link nets are used for the 3D filtering. The spatio-temporal patterns are creating from real motion video images. The neural networks learn these patterns. The perceptrons with different number of layers and neurons in each layer are tested. Also, the different input functions in functional- link net are searched. The practical examples of the filtering are shown and compared with traditional (non-neural) spatio-temporal methods. The results are very interesting and the neural spatio-temporal filters seems to be very efficient tool for video noise reduction.

  6. Spatiotemporal dynamics of HIV infection

    NASA Astrophysics Data System (ADS)

    Strain, Matthew Carl

    during the primary or chronic stages of HIV infection. The nonlinear clearance of HIV DNA therefore predicts lifelong virus production, even in treated patients. Collectively, these results demonstrate that important features of the spatiotemporal dynamics of HIV infection both in vitro and in vivo are best explained with explicit spatial models.

  7. Spatiotemporal trends of mercury in walleye and largemouth bass from the Laurentian Great Lakes region.

    PubMed

    Monson, Bruce A; Staples, David F; Bhavsar, Satyendra P; Holsen, Thomas M; Schrank, Candy S; Moses, Sara K; McGoldrick, Daryl J; Backus, Sean M; Williams, Kathryn A

    2011-10-01

    The risk of mercury (Hg) exposure to humans and wildlife from fish consumption has driven extensive mercury analysis throughout the Great Lakes Region since the 1970s. This study compiled fish-Hg data from multiple sources in the region and assessed spatiotemporal trends of Hg concentrations in two representative top predator fish species. Walleye (Sander vitreus) and largemouth bass (Micropterus salmoides) were chosen for the trend analysis because they had more Hg records (63,872) than other fish species that had been sampled from waters throughout the region. Waterbody types were inland lakes (70%), the Great Lakes, impoundments, and rivers. The compiled datasets were analyzed with a mixed effects statistical model having random effects of station, year, and fish length; and fixed effects of year, tissue type, fish length, habitat, and season. The results showed a generally declining temporal trend in fish-Hg for the region (1970-2009), with spatial trends of increasing Hg concentration from south to north and from west to east across the region. Nonlinearity was evident in the general downward trends of Ontario walleye, with a shift to an upward trend beginning in the 1990s. Only ongoing monitoring can reveal if this upward shift is an oscillation in a long-term decline, a statistical anomaly, or a sustained declining temporal trend in regional fish-Hg concentrations.

  8. Spatiotemporal Wave Front Shaping in a Microwave Cavity

    NASA Astrophysics Data System (ADS)

    del Hougne, Philipp; Lemoult, Fabrice; Fink, Mathias; Lerosey, Geoffroy

    2016-09-01

    Controlling waves in complex media has become a major topic of interest, notably through the concepts of time reversal and wave front shaping. Recently, it was shown that spatial light modulators can counterintuitively focus waves both in space and time through multiple scattering media when illuminated with optical pulses. In this Letter, we transpose the concept to a microwave cavity using flat arrays of electronically tunable resonators. We prove that maximizing the Green's function between two antennas at a chosen time yields diffraction limited spatiotemporal focusing. Then, changing the photons' dwell time inside the cavity, we modify the relative distribution of the spatial and temporal degrees of freedom (DOF), and we demonstrate that it has no impact on the field enhancement: wave front shaping makes use of all available DOF, irrespective of their spatial or temporal nature. Our results prove that wave front shaping using simple electronically reconfigurable arrays of reflectors is a viable approach to the spatiotemporal control of microwaves, with potential applications in medical imaging, therapy, telecommunications, radar, or sensing. They also offer new fundamental insights regarding the coupling of spatial and temporal DOF in complex media.

  9. A unified framework for gesture recognition and spatiotemporal gesture segmentation.

    PubMed

    Alon, Jonathan; Athitsos, Vassilis; Yuan, Quan; Sclaroff, Stan

    2009-09-01

    Within the context of hand gesture recognition, spatiotemporal gesture segmentation is the task of determining, in a video sequence, where the gesturing hand is located and when the gesture starts and ends. Existing gesture recognition methods typically assume either known spatial segmentation or known temporal segmentation, or both. This paper introduces a unified framework for simultaneously performing spatial segmentation, temporal segmentation, and recognition. In the proposed framework, information flows both bottom-up and top-down. A gesture can be recognized even when the hand location is highly ambiguous and when information about when the gesture begins and ends is unavailable. Thus, the method can be applied to continuous image streams where gestures are performed in front of moving, cluttered backgrounds. The proposed method consists of three novel contributions: a spatiotemporal matching algorithm that can accommodate multiple candidate hand detections in every frame, a classifier-based pruning framework that enables accurate and early rejection of poor matches to gesture models, and a subgesture reasoning algorithm that learns which gesture models can falsely match parts of other longer gestures. The performance of the approach is evaluated on two challenging applications: recognition of hand-signed digits gestured by users wearing short-sleeved shirts, in front of a cluttered background, and retrieval of occurrences of signs of interest in a video database containing continuous, unsegmented signing in American Sign Language (ASL).

  10. Integrating GIS and ABM to Explore Spatiotemporal Dynamics

    NASA Astrophysics Data System (ADS)

    Sun, M.; Jiang, Y.; Yang, C.

    2013-12-01

    Agent-based modeling as a methodology for the bottom-up exploration with the account of adaptive behavior and heterogeneity of system components can help discover the development and pattern of the complex social and environmental system. However, ABM is a computationally intensive process especially when the number of system components becomes large and the agent-agent/agent-environmental interaction is modeled very complex. Most of traditional ABM frameworks developed based on CPU do not have a satisfying computing capacity. To address the problem and as the emergence of advanced techniques, GPU computing with CUDA can provide powerful parallel structure to enable the complex simulation of spatiotemporal dynamics. In this study, we first develop a GPU-based ABM system. Secondly, in order to visualize the dynamics generated from the movement of agent and the change of agent/environmental attributes during the simulation, we integrate GIS into the ABM system. Advanced geovisualization technologies can be utilized for representing the spatiotemporal change events, such as proper 2D/3D maps with state-of-the-art symbols, space-time cube and multiple layers each of which presents pattern in one time-stamp, etc. Thirdly, visual analytics which include interactive tools (e.g. grouping, filtering, linking, etc.) is included in our ABM-GIS system to help users conduct real-time data exploration during the progress of simulation. Analysis like flow analysis and spatial cluster analysis can be integrated according to the geographical problem we want to explore.

  11. Chimera states in spatiotemporal systems: Theory and Applications

    NASA Astrophysics Data System (ADS)

    Yao, Nan; Zheng, Zhigang

    2016-03-01

    In this paper, we propose a retrospective and summary on recent studies of chimera states. Chimera states demonstrate striking inhomogeneous spatiotemporal patterns emerging in homogeneous systems through unexpected spontaneous symmetry breaking, where the consequent spatiotemporal patterns are composed of both coherence and incoherence domains, respectively characterized by the synchronized and desynchronized motions of oscillators. Since the discovery of chimera states by Kuramoto and others, this striking collective behavior has attracted a great deal of research interest in the community of physics and related interdisciplinary fields from both theoretical and experimental viewpoints. In recent works exploring chimera states, rich phenomena such as the spiral wave chimera, multiple cluster chimera, amplitude chimera were observed from various types of model systems. Theoretical framework by means of self-consistency approach and Ott-Antonsen approach were proposed for further understanding to this symmetry-breaking-induced behavior. The stability and robustness of chimera states were also discussed. More importantly, experiments ranging from optical, chemical to mechanical designs successfully approve the existence of chimera states.

  12. Collaborative simulation method with spatiotemporal synchronization process control

    NASA Astrophysics Data System (ADS)

    Zou, Yisheng; Ding, Guofu; Zhang, Weihua; Zhang, Jian; Qin, Shengfeng; Tan, John Kian

    2016-10-01

    When designing a complex mechatronics system, such as high speed trains, it is relatively difficult to effectively simulate the entire system's dynamic behaviors because it involves multi-disciplinary subsystems. Currently,a most practical approach for multi-disciplinary simulation is interface based coupling simulation method, but it faces a twofold challenge: spatial and time unsynchronizations among multi-directional coupling simulation of subsystems. A new collaborative simulation method with spatiotemporal synchronization process control is proposed for coupling simulating a given complex mechatronics system across multiple subsystems on different platforms. The method consists of 1) a coupler-based coupling mechanisms to define the interfacing and interaction mechanisms among subsystems, and 2) a simulation process control algorithm to realize the coupling simulation in a spatiotemporal synchronized manner. The test results from a case study show that the proposed method 1) can certainly be used to simulate the sub-systems interactions under different simulation conditions in an engineering system, and 2) effectively supports multi-directional coupling simulation among multi-disciplinary subsystems. This method has been successfully applied in China high speed train design and development processes, demonstrating that it can be applied in a wide range of engineering systems design and simulation with improved efficiency and effectiveness.

  13. Using spatiotemporal statistical models to estimate animal abundance and infer ecological dynamics from survey counts

    USGS Publications Warehouse

    Conn, Paul B.; Johnson, Devin S.; Ver Hoef, Jay M.; Hooten, Mevin B.; London, Joshua M.; Boveng, Peter L.

    2015-01-01

    Ecologists often fit models to survey data to estimate and explain variation in animal abundance. Such models typically require that animal density remains constant across the landscape where sampling is being conducted, a potentially problematic assumption for animals inhabiting dynamic landscapes or otherwise exhibiting considerable spatiotemporal variation in density. We review several concepts from the burgeoning literature on spatiotemporal statistical models, including the nature of the temporal structure (i.e., descriptive or dynamical) and strategies for dimension reduction to promote computational tractability. We also review several features as they specifically relate to abundance estimation, including boundary conditions, population closure, choice of link function, and extrapolation of predicted relationships to unsampled areas. We then compare a suite of novel and existing spatiotemporal hierarchical models for animal count data that permit animal density to vary over space and time, including formulations motivated by resource selection and allowing for closed populations. We gauge the relative performance (bias, precision, computational demands) of alternative spatiotemporal models when confronted with simulated and real data sets from dynamic animal populations. For the latter, we analyze spotted seal (Phoca largha) counts from an aerial survey of the Bering Sea where the quantity and quality of suitable habitat (sea ice) changed dramatically while surveys were being conducted. Simulation analyses suggested that multiple types of spatiotemporal models provide reasonable inference (low positive bias, high precision) about animal abundance, but have potential for overestimating precision. Analysis of spotted seal data indicated that several model formulations, including those based on a log-Gaussian Cox process, had a tendency to overestimate abundance. By contrast, a model that included a population closure assumption and a scale prior on total

  14. Measuring ultracomplex supercontinuum pulses and spatio-temporal distortions

    NASA Astrophysics Data System (ADS)

    Gu, Xun

    This thesis contains two components of research: studies of supercontinuum pulses generated in the novel microstructure fiber, and research on spatio-temporal coupling in ultrafast laser beams. One of the most exciting developments in optics in recent years has been the invention of the microstructure optical fiber. By controlling the structural parameters of these novel fibers in design and manufacturing, their dispersion profile can be freely tailored, opening up a huge application base. One particularly interesting effect in the microstructure fiber is the generation of ultrabroadband supercontinuum with only nJ-level Ti:sapphire oscillator pulse pump. This supercontinuum is arguably the most complicated ultrafast pulse ever generated, with its huge time-bandwidth product (>1000 from a 16-cm-long fiber). Although many applications have been demonstrated or envisioned with this continuum, its generation is a very complicated process that is poorly understood, and the characteristics of the continuum pulses are not clearly known. In this work, we make a full-intensity-and-phase measurement of the continuum pulses using cross-correlation frequency-resolved optical gating (XFROG). The results reveal surprising unstable fine spectral structure in the continuum pulses, which is confirmed by single-shot measurements. Our study on the coherence of the continuum, on the other hand, shows that the spectral phase of the supercontinuum is fairly stable. Numerical simulations are carried out whose results are in good agreement with experiments. The second component of this thesis is the study of spatio-temporal coupling in ultrafast beams. We propose two definitions of spatial chirp, point out their respective physical meanings, and derive their relationship. On the common perception of the equivalence between pulse-front tilt and angular dispersion, we show that the equivalence only holds for plane waves. We establish a generalized theory of ultrafast laser beams with first

  15. Spatiotemporal Dynamics of the Wind Velocity from Minisodar Measurement Data

    NASA Astrophysics Data System (ADS)

    Simakhin, V. A.; Cherepanov, O. S.; Shamanaeva, L. G.

    2016-04-01

    The spatiotemporal dynamics of the three wind velocity components in the atmospheric boundary layer is analyzed on the basis of Doppler minisodar measurements. The data were processed and analyzed with the help of robust nonparametric methods based on the weighted maximum likelihood method and classical methods. Distribution laws were obtained for each wind velocity component. There are outliers in the distribution functions; both right and left asymmetry of the distributions are observed. For the x- and ycomponents, the width of the distribution increases as the observation altitude is increased, but the maximum of the distribution function decreases, which is in agreement with the data available in the literature. For the zcomponents the width of the distribution remains practically constant, but the value of the maximum also decreases with altitude. Analysis of the hourly semidiurnal dynamics showed that all three components have maxima in the morning and evening hours. For the y- and z-components the maxima in the evening hours are more strongly expressed than in the morning hours. For the x- and y-components the horizontal wind shear is closely tracked in the evening hours. It is shown that adaptive estimates on the efficiency significantly exceed the classical parametric estimates and allow one to analyze the spatiotemporal dynamics of the wind velocity, and reveal jets and detect wind shears.

  16. Mining Spatiotemporal Patterns of the Elder's Daily Movement

    NASA Astrophysics Data System (ADS)

    Chen, C. R.; Chen, C. F.; Liu, M. E.; Tsai, S. J.; Son, N. T.; Kinh, L. V.

    2016-06-01

    With rapid developments in wearable device technology, a vast amount of spatiotemporal data, such as people's movement and physical activities, are generated. Information derived from the data reveals important knowledge that can contribute a long-term care and psychological assessment of the elders' living condition especially in long-term care institutions. This study aims to develop a method to investigate the spatial-temporal movement patterns of the elders with their outdoor trajectory information. To achieve the goal, GPS based location data of the elderly subjects from long-term care institutions are collected and analysed with geographic information system (GIS). A GIS statistical model is developed to mine the elderly subjects' spatiotemporal patterns with the location data and represent their daily movement pattern at particular time. The proposed method first finds the meaningful trajectory and extracts the frequent patterns from the time-stamp location data. Then, a density-based clustering method is used to identify the major moving range and the gather/stay hotspot in both spatial and temporal dimensions. The preliminary results indicate that the major moving area of the elderly people encompasses their dorm and has a short moving distance who often stay in the same site. Subjects' outdoor appearance are corresponded to their life routine. The results can be useful for understanding elders' social network construction, risky area identification and medical care monitoring.

  17. Measurement of spatio-temporal transport in live cells

    NASA Astrophysics Data System (ADS)

    Wang, Ru; Wang, Zhuo; Millet, Larry; Gillette, Martha U.; Popescu, Gabriel

    2010-03-01

    The live cell is a highly dynamical system with complicated biophysical and biochemical processes taking place at diverse spatiotemporal scales. Though it is well known that microtubules and actin filaments play important roles in intracellular transport, their dynamic behavior is not entirely understood. We propose a unified approach to studying transport in live cells. We used Spatial Light Interference Microscopy, a quantitative phase imaging method developed in our laboratory, to extract cell mass distributions over broad spatiotemporal scales. The dispersion relations for this transport dynamics, i.e. frequency bandwidth vs. spatial frequencies, reveal deterministic mass transport at large spatial scales (w˜q) and diffusive transport at small spatial scales (w˜q̂2). At submicron scales, we observed a w˜q̂3 behavior, which indicates whip-like movements of protein filaments. Further control experiments where both the microtubule and actin polymerization were blocked suggests that essentially actin governs the long spatial scales behavior and microtubules the short scales. This label-free method enables us to access different components of cell dynamics and quantify diffusion coefficients and speed of motor proteins.

  18. Placing invasive species management in a spatiotemporal context.

    PubMed

    Baker, Christopher M; Bode, Michael

    2016-04-01

    Invasive species are a worldwide issue, both ecologically and economically. A large body of work focuses on various aspects of invasive species control, including how to allocate control efforts to eradicate an invasive population as cost effectively as possible: There are a diverse range of invasive species management problems, and past mathematical analyses generally focus on isolated examples, making it hard to identify and understand parallels between the different contexts. In this study, we use a single spatiotemporal model to tackle the problem of allocating control effort for invasive species when suppressing an island invasive species, and for long-term spatial suppression projects. Using feral cat suppression as an illustrative example, we identify the optimal resource allocation for island and mainland suppression projects. Our results demonstrate how using a single model to solve different problems reveals similar characteristics of the solutions in different scenarios. As well as illustrating the insights offered by linking problems through a spatiotemporal model, we also derive novel and practically applicable results for our case studies. For temporal suppression projects on islands, we find that lengthy projects are more cost effective and that rapid control projects are only economically cost effective when population growth rates are high or diminishing returns on control effort are low. When suppressing invasive species around conservation assets (e.g., national parks or exclusion fences), we find that the size of buffer zones should depend on the ratio of the species growth and spread rate.

  19. Mining spatiotemporal patterns of urban dwellers from taxi trajectory data

    NASA Astrophysics Data System (ADS)

    Mao, Feng; Ji, Minhe; Liu, Ting

    2016-06-01

    With the widespread adoption of locationaware technology, obtaining long-sequence, massive and high-accuracy spatiotemporal trajectory data of individuals has become increasingly popular in various geographic studies. Trajectory data of taxis, one of the most widely used inner-city travel modes, contain rich information about both road network traffic and travel behavior of passengers. Such data can be used to study the microscopic activity patterns of individuals as well as the macro system of urban spatial structures. This paper focuses on trajectories obtained from GPS-enabled taxis and their applications for mining urban commuting patterns. A novel approach is proposed to discover spatiotemporal patterns of household travel from the taxi trajectory dataset with a large number of point locations. The approach involves three critical steps: spatial clustering of taxi origin-destination (OD) based on urban traffic grids to discover potentially meaningful places, identifying threshold values from statistics of the OD clusters to extract urban jobs-housing structures, and visualization of analytic results to understand the spatial distribution and temporal trends of the revealed urban structures and implied household commuting behavior. A case study with a taxi trajectory dataset in Shanghai, China is presented to demonstrate and evaluate the proposed method.

  20. Spatiotemporal Characteristics of Freezing of Gait in Patients After Hypoxic-Ischemic Brain Injury

    PubMed Central

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Yong Wook

    2016-01-01

    Abstract The objective of this study was to investigate spatiotemporal characteristics with gait variability in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI). Eleven patients showing FOG after HIBI and 15 normal controls were consecutively enrolled. We performed gait analysis using a computerized gait system (VICON MX-T10 Motion Analysis System) and compared spatiotemporal characteristics and gait variability in both groups. Additionally, we performed correlation analysis to identify the gait parameters associated with severity of freezing, which we measured based on unified Parkinson disease Rating Scale subscore. Spatiotemporal characteristic of FOG patients showed increased stance time and double support phase and decreased swing time, single support phase, stride length, step length, and gait velocity compared with normal controls (P < 0.05). Besides baseline spatiotemporal characteristics, step time asymmetry and step length asymmetry were significantly increased in HIBI patients with FOG (P < 0.05). The coefficient of variation, which reflects the variability of each parameter, demonstrated increased cadence, stride time, swing time, single support phase, stride length, step length, and gait velocity variability in HIBI patients with FOG compared with normal controls (P < 0.05). Correlation analysis between FOG severity and spatiotemporal parameters revealed gait velocity, step length, and single support phase to be spatiotemporal parameters related to FOG severity (P < 0.05). Our findings suggest that bilateral gait coordination deterioration plays a considerable role for pathophysiology of FOG in HIBI patients. Additional studies with a larger number of subjects are needed to further investigate the neural mechanism of FOG after HIBI. PMID:27175696

  1. Spatiotemporal chaos in Easter Island ecology.

    PubMed

    Sprott, J C

    2012-10-01

    This paper demonstrates that a recently proposed spatiotemporal model for the ecology of Easter Island admits periodic and chaotic attractors, not previously reported. Such behavior may more realistically depict the population dynamics of general ecosystems and illustrates the power of simple models to produce the kind of complex behavior that is ubiquitous in such systems.

  2. Analysis of spatiotemporal signals of complex systems

    NASA Astrophysics Data System (ADS)

    Uhl, C.; Friedrich, R.; Haken, H.

    1995-05-01

    We present a method of analyzing spatiotemporal signals emerging from nonequilibrium self-organizing systems that are close to instability. The algorithm aims at an identification of spatial modes and corresponding order-parameter equations. We discuss and demonstrate the method by examples of simulated codimension I and II instabilities, including a numerically integrated partial differential equation leading to ``blinking states.''

  3. A Hierarchical Bayesian Approach for Learning Sparse Spatio-Temporal Decomposition of Multichannel EEG

    PubMed Central

    Wu, Wei; Chen, Zhe; Gao, Shangkai; Brown, Emery N.

    2011-01-01

    Multichannel electroencephalography (EEG) offers a non-invasive tool to explore spatio-temporal dynamics of brain activity. With EEG recordings consisting of multiple trials, traditional signal processing approaches that ignore inter-trial variability in the data may fail to accurately estimate the underlying spatio-temporal brain patterns. Moreover, precise characterization of such inter-trial variability per se can be of high scientific value in establishing the relationship between brain activity and behavior. In this paper, a statistical modeling framework is introduced for learning spatiotemporal decomposition of multiple-trial EEG data recorded under two contrasting experimental conditions. By modeling the variance of source signals as random variables varying across trials, the proposed two-stage hierarchical Bayesian model is able to capture inter-trial amplitude variability in the data in a sparse way where a parsimonious representation of the data can be obtained. A variational Bayesian (VB) algorithm is developed for statistical inference of the hierarchical model. The efficacy of the proposed modeling framework is validated with the analysis of both synthetic and real EEG data. In the simulation study we show that even at low signal-to-noise ratios our approach is able to recover with high precision the underlying spatiotemporal patterns and the evolution of source amplitude across trials; on two brain-computer interface (BCI) data sets we show that our VB algorithm can extract physiologically meaningful spatio-temporal patterns and make more accurate predictions than other two widely used algorithms: the common spatial patterns (CSP) algorithm and the Infomax algorithm for independent component analysis (ICA). The results demonstrate that our statistical modeling framework can serve as a powerful tool for extracting brain patterns, characterizing trial-to-trial brain dynamics, and decoding brain states by exploiting useful structures in the data. PMID

  4. Task-relevant information is prioritized in spatiotemporal contextual cueing.

    PubMed

    Higuchi, Yoko; Ueda, Yoshiyuki; Ogawa, Hirokazu; Saiki, Jun

    2016-11-01

    Implicit learning of visual contexts facilitates search performance-a phenomenon known as contextual cueing; however, little is known about contextual cueing under situations in which multidimensional regularities exist simultaneously. In everyday vision, different information, such as object identity and location, appears simultaneously and interacts with each other. We tested the hypothesis that, in contextual cueing, when multiple regularities are present, the regularities that are most relevant to our behavioral goals would be prioritized. Previous studies of contextual cueing have commonly used the visual search paradigm. However, this paradigm is not suitable for directing participants' attention to a particular regularity. Therefore, we developed a new paradigm, the "spatiotemporal contextual cueing paradigm," and manipulated task-relevant and task-irrelevant regularities. In four experiments, we demonstrated that task-relevant regularities were more responsible for search facilitation than task-irrelevant regularities. This finding suggests our visual behavior is focused on regularities that are relevant to our current goal.

  5. Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides

    PubMed Central

    Egan, Jan B.; Shi, Chang-Xin; Tembe, Waibhav; Christoforides, Alexis; Kurdoglu, Ahmet; Sinari, Shripad; Middha, Sumit; Asmann, Yan; Schmidt, Jessica; Braggio, Esteban; Keats, Jonathan J.; Fonseca, Rafael; Bergsagel, P. Leif; Craig, David W.; Carpten, John D.

    2012-01-01

    The longitudinal evolution of a myeloma genome from diagnosis to plasma cell leukemia has not previously been reported. We used whole-genome sequencing (WGS) on 4 purified tumor samples and patient germline DNA drawn over a 5-year period in a t(4;14) multiple myeloma patient. Tumor samples were acquired at diagnosis, first relapse, second relapse, and end-stage secondary plasma cell leukemia (sPCL). In addition to the t(4;14), all tumor time points also shared 10 common single-nucleotide variants (SNVs) on WGS comprising shared initiating events. Interestingly, we observed genomic sequence variants that waxed and waned with time in progressive tumors, suggesting the presence of multiple independent, yet related, clones at diagnosis that rose and fell in dominance. Five newly acquired SNVs, including truncating mutations of RB1 and ZKSCAN3, were observed only in the final sPCL sample suggesting leukemic transformation events. This longitudinal WGS characterization of the natural history of a high-risk myeloma patient demonstrated tumor heterogeneity at diagnosis with shifting dominance of tumor clones over time and has also identified potential mutations contributing to myelomagenesis as well as transformation from myeloma to overt extramedullary disease such as sPCL. PMID:22529291

  6. Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy.

    PubMed

    McGorum, Bruce C; Pirie, R Scott; Eaton, Samantha L; Keen, John A; Cumyn, Elizabeth M; Arnott, Danielle M; Chen, Wenzhang; Lamont, Douglas J; Graham, Laura C; Llavero Hurtado, Maica; Pemberton, Alan; Wishart, Thomas M

    2015-11-01

    Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of ∼2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell

  7. Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy*

    PubMed Central

    McGorum, Bruce C.; Pirie, R. Scott; Eaton, Samantha L.; Keen, John A.; Cumyn, Elizabeth M.; Arnott, Danielle M.; Chen, Wenzhang; Lamont, Douglas J.; Graham, Laura C.; Llavero Hurtado, Maica; Pemberton, Alan; Wishart, Thomas M.

    2015-01-01

    Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of ∼2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell

  8. Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex

    PubMed Central

    Piché, Marilyse; Thomas, Sébastien

    2015-01-01

    The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. PMID:26289469

  9. The influence of spatiotemporal conditions and personality on survival in reintroductions-evolutionary implications.

    PubMed

    Haage, Marianne; Maran, Tiit; Bergvall, Ulrika Alm; Elmhagen, Bodil; Angerbjörn, Anders

    2017-01-01

    Personality exists in non-human animals and can impact fitness. There is, however, a shortage of empirical studies in certain areas within the field, and fundamental evolutionary theory on personality remains largely untested. For example, little is known on how variation in personality is maintained over evolutionary time. Theory suggests that fluctuating selection pressures due to spatiotemporal variation in conditions, e.g. food availability, is a possible mechanism and a few studies have shown that the success of different personality types varies with spatiotemporal conditions. However, it remains unknown whether different mechanisms can maintain personality within a species. Here we use a reintroduction programme for the critically endangered European mink (Mustela lutreola) to test whether multiple personality trait domains (boldness, exploration and sociability) affected survival in two different years and islands. This was done through pre-release personality tests and post-release radio-tracking monitoring. Survival was positively correlated with boldness, whereas the relationship with exploration was either negative or positive depending on year/island. The results show a complex relationship between personality and survival and suggest that exploration can be maintained over evolutionary time via spatiotemporal variation in conditions. However, in contrast to exploration, boldness did not vary spatiotemporally and sociability had no impact on survival. This indicates that different personality trait domains might be maintained by different mechanisms. To date, personality has been studied primarily within behavioural sciences, but through empirical findings we highlight the importance of personality also in ecology and conservation biology.

  10. Compositional and Microstructural Evolution of Olivine Under Multiple-Cycle Pulsed Laser Irradiation as Revealed by FIB/Field-Emission TEM

    NASA Technical Reports Server (NTRS)

    Christoffersen, R.; Loeffler, M. J.; Dukes, C. A.; Keller, L. P.; Baragiola, R. A.

    2016-01-01

    The use of pulsed laser irradiation to simulate the short duration, high-energy conditions characteristic of micrometeorite impacts is now an established approach in experimental space weathering studies. The laser generates both melt and vapor deposits that contain nanophase metallic Fe (npFe(sup 0)) grains with size distributions and optical properties similar to those in natural impact-generated melt and vapor deposits. There remains uncertainty, however, about how well lasers simulate the mechanical work and internal (thermal) energy partitioning that occurs in actual impacts. We are currently engaged in making a direct comparison between the products of laser irradiation and experimental/natural hypervelocity impacts. An initial step reported here is to use analytical SEM and TEM is to attain a better understanding of how the microstructure and composition of laser deposits evolve over multiple cycles of pulsed laser irradiation.

  11. DNA-based identifications reveal multiple introductions of the vegetable leafminer Liriomyza sativae (Diptera: Agromyzidae) into the Torres Strait Islands and Papua New Guinea.

    PubMed

    Blacket, M J; Rice, A D; Semeraro, L; Malipatil, M B

    2015-10-01

    Leafmining flies (Diptera: Agromyzidae) can be serious economic pests of horticultural crops. Some genera such as Liriomyza are particularly problematic with numerous species, some of which are highly polyphagous (wide host range), which can only be confidently identified morphologically from adult males. In our study, DNA barcoding was employed to establish new locality records of the vegetable leafminer fly, Liriomyza sativae, from the islands of Torres Strait (Queensland, Australia) and the central highlands of Papua New Guinea (PNG). These records represent significant range extensions of this highly invasive plant pest. Specimens of immature leafminers (from leaf mines) were collected over a 5-year period during routine plant health surveys in ethanol or on FTA® filter paper cards, both methods proved effective at preserving and transporting insect DNA under tropical conditions, with FTA cards possessing some additional logistical benefits. Specimens were identified through sequencing two sections of the cytochrome oxidase I gene and the utility of each was assessed for the identification of species and intra-specific genetic lineages. Our study indicates that multiple haplotypes of L. sativae occur in PNG, while a different haplotype is present in the Torres Strait, with genetic regionalization between these areas apart from a single possible instance - one haplotype 'S.7' appears to be common between these two regions - interestingly this has also been the most common haplotype detected in previous studies of invasive L. sativae populations. The DNA barcoding methods employed here not only identified multiple introductions of L. sativae, but also appear generally applicable to the identification of other agromyzid leafminers (Phytomyzinae and Agromyzinae) and should decrease the likelihood of potentially co-amplifying internal hymenopteran parasitoids. Currently, L. sativae is still not recorded from the Australian mainland; however, further sampling of

  12. Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis

    PubMed Central

    Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Namaki, Saeed

    2016-01-01

    Background The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. Methods Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MS vs. control) and PBMCs (relapse vs. remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression. Results The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapse vs. remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS vs. control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse vs. remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways. Discussion This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets. PMID:28028462

  13. Studies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis

    PubMed Central

    Shevchouk, Olesya T.; Ball, Gregory F.; Cornil, Charlotte A.

    2017-01-01

    In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β-estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers. PMID:28141859

  14. Engineering of a conditional allele reveals multiple roles of XRN2 in Caenorhabditis elegans development and substrate specificity in microRNA turnover.

    PubMed

    Miki, Takashi S; Rüegger, Stefan; Gaidatzis, Dimos; Stadler, Michael B; Großhans, Helge

    2014-04-01

    Although XRN2 proteins are highly conserved eukaryotic 5'→3' exonucleases, little is known about their function in animals. Here, we characterize Caenorhabditis elegans XRN2, which we find to be a broadly and constitutively expressed nuclear protein. An xrn-2 null mutation or loss of XRN2 catalytic activity causes a molting defect and early larval arrest. However, by generating a conditionally mutant xrn-2ts strain de novo through an approach that may be also applicable to other genes of interest, we reveal further functions in fertility, during embryogenesis and during additional larval stages. Consistent with the known role of XRN2 in controlling microRNA (miRNA) levels, we can demonstrate that loss of XRN2 activity stabilizes some rapidly decaying miRNAs. Surprisingly, however, other miRNAs continue to decay rapidly in xrn-2ts animals. Thus, XRN2 has unanticipated miRNA specificity in vivo, and its diverse developmental functions may relate to distinct substrates. Finally, our global analysis of miRNA stability during larval stage 1 reveals that miRNA passenger strands (miR*s) are substantially less stable than guide strands (miRs), supporting the notion that the former are mostly byproducts of biogenesis rather than a less abundant functional species.

  15. Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits.

    PubMed

    Marcelletti, Simone; Scortichini, Marco

    2015-01-01

    The European hazelnut (Corylus avellana) is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches.

  16. Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits

    PubMed Central

    Marcelletti, Simone; Scortichini, Marco

    2015-01-01

    The European hazelnut (Corylus avellana) is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches. PMID:26147218

  17. Spatiotemporal analysis of prepyriform, visual, auditory, and somesthetic surface EEGs in trained rabbits.

    PubMed

    Barrie, J M; Freeman, W J; Lenhart, M D

    1996-07-01

    1. Spatial ensemble averages were computed for 64 traces of electroencephalograms (EEGs) simultaneously recorded from 8 x 8 arrays over the epidural surfaces of the prepyriform cortex (PPC) and visual, somatic, and auditory cortices. They revealed a common waveform across each array. Examination of the spatial amplitude modulation (AM) of the waveform revealed classifiable spatial pattern in short time segments. The AM patterns varied within trials after presentation of identical conditioned stimuli, and also between trials with differing stimuli. 2. PPC EEGs revealed strong correlates with the respiratory rhythm; neocortical EEGs did not. 3. Time ensemble averaging of the PPC EEG attenuated the oscillatory bursts, indicating that olfactory gamma oscillations (20-80 Hz) were not phase-locked to the times of stimulus delivery but instead to inhalations. Time ensemble averages of neocortical recordings across trials revealed average evoked potentials starting 30-50 ms after the arrival of the stimulus. 4. Average temporal fast Fourier transform (FFT) power spectral densities (PSDs) from pre- and poststimulus PPC EEG segments revealed a peak of gamma activity in olfactory bursts. 5. The logarithm of the average temporal FFT PSDs from pre- and poststimulus neocortical EEG segments, when plotted against log frequency, revealed 1/f-type spectra in both pre- and poststimulus segments for negative/aversive conditioned stimuli (CS-) and positive/rewarding conditioned stimuli (CS+). The alpha'- and beta'-coefficients from the regression of Eq. 2 onto the average PSDs were significantly different between pre- and poststimulus segments, owing to the evoked potentials, but not between CS- and CS+ stimulus segments. 6. Spatiotemporal patterns were invariant over all frequency bins in the 1/f domain (20-100 Hz). Spatiotemporal patterns in the 2- to 20-Hz domain progressively differed from the invariant patterns with decreasing frequency. 7. In the spatial frequency domain, the

  18. Spatio-Temporal Metabolite Profiling of the Barley Germination Process by MALDI MS Imaging

    PubMed Central

    Gorzolka, Karin; Kölling, Jan; Nattkemper, Tim W.; Niehaus, Karsten

    2016-01-01

    MALDI mass spectrometry imaging was performed to localize metabolites during the first seven days of the barley germination. Up to 100 mass signals were detected of which 85 signals were identified as 48 different metabolites with highly tissue-specific localizations. Oligosaccharides were observed in the endosperm and in parts of the developed embryo. Lipids in the endosperm co-localized in dependency on their fatty acid compositions with changes in the distributions of diacyl phosphatidylcholines during germination. 26 potentially antifungal hordatines were detected in the embryo with tissue-specific localizations of their glycosylated, hydroxylated, and O-methylated derivates. In order to reveal spatio-temporal patterns in local metabolite compositions, multiple MSI data sets from a time series were analyzed in one batch. This requires a new preprocessing strategy to achieve comparability between data sets as well as a new strategy for unsupervised clustering. The resulting spatial segmentation for each time point sample is visualized in an interactive cluster map and enables simultaneous interactive exploration of all time points. Using this new analysis approach and visualization tool germination-dependent developments of metabolite patterns with single MS position accuracy were discovered. This is the first study that presents metabolite profiling of a cereals’ germination process over time by MALDI MSI with the identification of a large number of peaks of agronomically and industrially important compounds such as oligosaccharides, lipids and antifungal agents. Their detailed localization as well as the MS cluster analyses for on-tissue metabolite profile mapping revealed important information for the understanding of the germination process, which is of high scientific interest. PMID:26938880

  19. Integrative analysis of miRNA and mRNA paired expression profiling of primary fibroblast derived from diabetic foot ulcers reveals multiple impaired cellular functions.

    PubMed

    Liang, Liang; Stone, Rivka C; Stojadinovic, Olivera; Ramirez, Horacio; Pastar, Irena; Maione, Anna G; Smith, Avi; Yanez, Vanessa; Veves, Aristides; Kirsner, Robert S; Garlick, Jonathan A; Tomic-Canic, Marjana

    2016-11-01

    Diabetic foot ulcers (DFUs) are one of the major complications of diabetes. Its molecular pathology remains poorly understood, impeding the development of effective treatments. Although it has been established that multiple cell types, including fibroblasts, keratinocytes, macrophages, and endothelial cells, all contribute to inhibition of healing, less is known regarding contributions of individual cell type. Thus, we generated primary fibroblasts from nonhealing DFUs and evaluated their cellular and molecular properties in comparison to nondiabetic foot fibroblasts (NFFs). Specifically, we analyzed both micro-RNA and mRNA expression profiles of primary DFU fibroblasts. Paired genomic analyses identified a total of 331 reciprocal miRNA-mRNA pairs including 21 miRNAs (FC > 2.0) along with 239 predicted target genes (FC > 1.5) that are significantly and differentially expressed. Of these, we focused on three miRNAs (miR-21-5p, miR-34a-5p, miR-145-5p) that were induced in DFU fibroblasts as most differentially regulated. The involvement of these microRNAs in wound healing was investigated by testing the expression of their downstream targets as well as by quantifying cellular behaviors in prospectively collected and generated cell lines from 15 patients (seven DFUF and eight NFF samples). We found large number of downstream targets of miR-21-5p, miR-34a-5p, miR-145-5p to be coordinately regulated in mRNA profiles, which was confirmed by quantitative real-time PCR. Pathway analysis on paired miRNA-mRNA profiles predicted inhibition of cell movement and cell proliferation, as well as activation of cell differentiation and senescence in DFU fibroblasts, which was confirmed by cellular assays. We concluded that induction of miR-21-5p, miR-34a-5p, miR-145-5p in DFU dermal fibroblasts plays an important role in impairing multiple cellular functions, thus contributing to overall inhibition of healing in DFUs.

  20. Spatiotemporal dynamics of underwater conical shock wave focusing

    NASA Astrophysics Data System (ADS)

    Hoffer, P.; Lukes, P.; Akiyama, H.; Hosseini, H.

    2016-12-01

    The paper presents an experimental study on spatiotemporal dynamics of conical shock waves focusing in water. A multichannel pulsed electrohydraulic discharge source with a cylindrical ceramic-coated electrode was used. Time-resolved visualizations revealed that cylindrical pressure waves were focused to produce conical shock wave reflection over the axis of symmetry in water. Positive and negative pressures of 372 MPa and -17 MPa at the focus with 0.48 mm lateral and 22 mm axial extension (-6 dB) were measured by a fiber-optic probe hydrophone. The results clearly show the propagation process leading to the high-intensity underwater shock wave. Such strong and sharp shock wave focusing offers better localization for extracorporeal lithotripsy or other non-invasive medical shock wave procedures.

  1. Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression.

    PubMed

    Ma, L; Merenmies, J; Parada, L F

    2000-09-01

    Neural development relies on stringent regulation of key genes that mediate specialized function. TrkA is primarily expressed in neural crest-derived sensory and sympathetic neurons where it transmits critical survival information. We have identified a 457 base pair sequence upstream of the murine first TrkA coding exon that is conserved in human and in chick, and is sufficient for expression in the correct cells with appropriate timing. Mutation analysis of consensus transcription factor binding domains within the minimal enhancer reveals a complex positive regulation that includes sites required for global expression and sites that are specifically required for DRG, trigeminal or sympathetic expression. These results provide a foundation for identification of the transcriptional machinery that specifies neurotrophin receptor expression.

  2. Genome-wide comparison and taxonomic relatedness of multiple Xylella fastidiosa strains reveal the occurrence of three subspecies and a new Xylella species.

    PubMed

    Marcelletti, Simone; Scortichini, Marco

    2016-10-01

    A total of 21 Xylella fastidiosa strains were assessed by comparing their genomes to infer their taxonomic relationships. The whole-genome-based average nucleotide identity and tetranucleotide frequency correlation coefficient analyses were performed. In addition, a consensus tree based on comparisons of 956 core gene families, and a genome-wide phylogenetic tree and a Neighbor-net network were constructed with 820,088 nucleotides (i.e., approximately 30-33 % of the entire X. fastidiosa genome). All approaches revealed the occurrence of three well-demarcated genetic clusters that represent X. fastidiosa subspecies fastidiosa, multiplex and pauca, with the latter appeared to diverge. We suggest that the proposed but never formally described subspecies 'sandyi' and 'morus' are instead members of the subspecies fastidiosa. These analyses support the view that the Xylella strain isolated from Pyrus pyrifolia in Taiwan is likely to be a new species. A widely used multilocus sequence typing analysis yielded conflicting results.

  3. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions

    PubMed Central

    Lipinski, Marta M.; Hoffman, Greg; Ng, Aylwin; Zhou, Wen; Py, Bénédicte F.; Hsu, Emily; Liu, Xuxin; Eisenberg, Jason; Liu, Jun; Blenis, John; Xavier, Ramnik J.; Yuan, Junying

    2010-01-01

    Summary Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions up regulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3 and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner. PMID:20627085

  4. High-throughput sequencing of TCR repertoires in multiple sclerosis reveals intrathecal enrichment of EBV-reactive CD8+ T cells.

    PubMed

    Lossius, Andreas; Johansen, Jorunn N; Vartdal, Frode; Robins, Harlan; Jūratė Šaltytė, Benth; Holmøy, Trygve; Olweus, Johanna

    2014-11-01

    Epstein-Barr virus (EBV) has long been suggested as a pathogen in multiple sclerosis (MS). Here, we used high-throughput sequencing to determine the diversity, compartmentalization, persistence, and EBV-reactivity of the T-cell receptor (TCR) repertoires in MS. TCR-β genes were sequenced in paired samples of cerebrospinal fluid (CSF) and blood from patients with MS and controls with other inflammatory neurological diseases. The TCR repertoires were highly diverse in both compartments and patient groups. Expanded T-cell clones, represented by TCR-β sequences >0.1%, were of different identity in CSF and blood of MS patients, and persisted for more than a year. Reference TCR-β libraries generated from peripheral blood T cells reactive against autologous EBV-transformed B cells were highly enriched for public EBV-specific sequences and were used to quantify EBV-reactive TCR-β sequences in CSF. TCR-β sequences of EBV-reactive CD8+ T cells, including several public EBV-specific sequences, were intrathecally enriched in MS patients only, whereas those of EBV-reactive CD4+ T cells were also enriched in CSF of controls. These data provide evidence for a clonally diverse, yet compartmentalized and persistent, intrathecal T-cell response in MS. The presented strategy links TCR sequence to intrathecal T-cell specificity, demonstrating enrichment of EBV-reactive CD8+ T cells in MS.

  5. The Glycan Role in the Glycopeptide Immunogenicity Revealed by Atomistic Simulations and Spectroscopic Experiments on the Multiple Sclerosis Biomarker CSF114(Glc)

    NASA Astrophysics Data System (ADS)

    Bruno, Agostino; Scrima, Mario; Novellino, Ettore; D'Errico, Gerardino; D'Ursi, Anna Maria; Limongelli, Vittorio

    2015-03-01

    Glycoproteins are often recognized as not-self molecules by antibodies triggering the onset of severe autoimmune diseases such as Multiple Sclerosis (MS). Thus, the development of antigen-mimicking biomarkers represents an attractive strategy for an early diagnosis of the disease. An example is the synthetic glycopeptide CSF114(Glc), which was designed and tested as MS biomarker and whose clinical application was limited by its reduced ability to detect autoantibodies in MS patients. In the attempt to improve the efficacy of CSF114(Glc), we have characterized all the events leading to the final binding of the biomarker to the autoantibody using atomistic simulations, ESR and NMR experiments. The glycosydic moiety plays a primary role in the whole process. In particular, in an environment mimicking that used in the clinical tests the glycopeptide assumes a α-helix structure that is functional for the interaction with the antibody. In this conformation CSF114(Glc) binds the monoclonal antibody mAb8-18C5 similarly to the myelin oligodendrocyte glycoprotein MOG, which is a known MS auto-antigen, thus explaining its diagnostic activity. Our study offers new molecular bases to design more effective biomarkers and provides a most valid protocol to investigate other systems where the environment effect is determinant for the biological activity.

  6. Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

    NASA Astrophysics Data System (ADS)

    Imitola, Jaime; Côté, Daniel; Rasmussen, Stine; Xie, X. Sunney; Liu, Yingru; Chitnis, Tanuja; Sidman, Richard L.; Lin, Charles. P.; Khoury, Samia J.

    2011-02-01

    Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over time of demyelination and neurodegeneration in brain slices with high spatial resolution and signal-to-noise ratio. Local areas of severe loss of lipid signal indicative of demyelination and loss of the reflectance signal from axons were seen in the corpus callosum and spinal cord of EAE animals. Even in myelinated areas of EAE mice, the intensity of myelin lipid signals is significantly reduced. Using heterozygous knock-in mice in which green fluorescent protein replaces the CX3CR1 coding sequence that labels central nervous system microglia, we find areas of activated microglia colocalized with areas of altered reflectance and CARS signals reflecting axonal injury and demyelination. Our data demonstrate the use of multimodal CARS microscopy for characterization of demyelinating and neurodegenerative pathology in a mouse model of multiple sclerosis, and further confirm the critical role of microglia in chronic inflammatory neurodegeneration.

  7. Dynamic Analysis of the Lactococcus lactis Transcriptome in Cheeses Made from Milk Concentrated by Ultrafiltration Reveals Multiple Strategies of Adaptation to Stresses ▿

    PubMed Central

    Cretenet, Marina; Laroute, Valérie; Ulvé, Vincent; Jeanson, Sophie; Nouaille, Sébastien; Even, Sergine; Piot, Michel; Girbal, Laurence; Le Loir, Yves; Loubière, Pascal; Lortal, Sylvie; Cocaign-Bousquet, Muriel

    2011-01-01

    Lactococcus lactis is used extensively for the production of various cheeses. At every stage of cheese fabrication, L. lactis has to face several stress-generating conditions that result from its own modification of the environment as well as externally imposed conditions. We present here the first in situ global gene expression profile of L. lactis in cheeses made from milk concentrated by ultrafiltration (UF-cheeses), a key economical cheese model. The transcriptomic response of L. lactis was analyzed directly in a cheese matrix, starting from as early as 2 h and continuing for 7 days. The growth of L. lactis stopped after 24 h, but metabolic activity was maintained for 7 days. Conservation of its viability relied on an efficient proteolytic activity measured by an increasing, quantified number of free amino acids in the absence of cell lysis. Extensive downregulation of genes under CodY repression was found at day 7. L. lactis developed multiple strategies of adaptation to stressful modifications of the cheese matrix. In particular, expression of genes involved in acidic- and oxidative-stress responses was induced. L. lactis underwent unexpected carbon limitation characterized by an upregulation of genes involved in carbon starvation, principally due to the release of the CcpA control. We report for the first time that in spite of only moderately stressful conditions, lactococci phage is repressed under UF-cheese conditions. PMID:21075879

  8. Collision of extensive exocrine and neuroendocrine neoplasms in multiple endocrine neoplasia type 1 revealed by cytogenetic analysis of loss of heterozygosity: a case report.

    PubMed

    Moriyoshi, Koki; Minamiguchi, Sachiko; Miyagawa-Hayashino, Aya; Fujimoto, Masakazu; Kawaguchi, Michiya; Haga, Hironori

    2013-09-01

    The combination of exocrine and neuroendocrine neoplasms is rarely found in the pancreas. These combined lesions vary from a clonal tumor with mixed differentiation to the incidental co-existence of two or more independent tumors, but the differential diagnosis is sometimes difficult. Here we report a case of multiple endocrine neoplasia type 1 (MEN1) with extensive ductal and neuroendocrine neoplastic changes. These two types of tumors admixed markedly in some parts, which made it difficult to determine the pathological diagnosis based on histological findings. Cytogenetic analysis showed that loss of heterozygosity (LOH) of the MEN1 locus exists in neuroendocrine but not in exocrine neoplasms, indicating that independent mechanisms of tumorigenesis may occur in these two types of tumors. This case shows the usefulness of cytogenetic analysis for the diagnosis of combined tumors of the pancreas. Extensive exocrine neoplastic change, including pancreatic intraepithelial neoplasia (PanIN) in virtually all pancreatic ducts and a focus of intraductal papillary mucinous neoplasm (IPMN) with focal invasion, was a distinguishing feature of the present case. The possible association of ductal tumorigenesis and a MEN1 background is discussed.

  9. THE INFRARED EYE OF THE WIDE-FIELD CAMERA 3 ON THE HUBBLE SPACE TELESCOPE REVEALS MULTIPLE MAIN SEQUENCES OF VERY LOW MASS STARS IN NGC 2808

    SciTech Connect

    Milone, A. P.; Aparicio, A.; Monelli, M. E-mail: aparicio@iac.es; and others

    2012-08-01

    We use images taken with the infrared channel of the Wide Field Camera 3 on the Hubble Space Telescope to study the multiple main sequences (MSs) of NGC 2808. Below the turnoff, the red, the middle, and the blue MS, previously detected from visual-band photometry, are visible over an interval of about 3.5 F160W magnitudes. The three MSs merge together at the level of the MS bend. At fainter magnitudes, the MS again splits into two components containing {approx}65% and {approx}35% of stars, with the most-populated MS being the bluest one. Theoretical isochrones suggest that the latter is connected to the red MS discovered in the optical color-magnitude diagram (CMD) and hence corresponds to the first stellar generation, having primordial helium and enhanced carbon and oxygen abundances. The less-populated MS in the faint part of the near-IR CMD is helium-rich and poor in carbon and oxygen, and it can be associated with the middle and the blue MS of the optical CMD. The finding that the photometric signature of abundance anti-correlation is also present in fully convective MS stars reinforces the inference that they have a primordial origin.

  10. Assignment of Chinook salmon (Oncorhynchus tshawytscha) linkage groups to specific chromosomes reveals a karyotype with multiple rearrangements of the chromosome arms of rainbow trout (Oncorhynchus mykiss).

    PubMed

    Phillips, Ruth B; Park, Linda K; Naish, Kerry A

    2013-12-09

    The Chinook salmon genetic linkage groups have been assigned to specific chromosomes using fluorescence in situ hybridization with bacterial artificial chromosome probes containing genetic markers mapped to each linkage group in Chinook salmon and rainbow trout. Comparison of the Chinook salmon chromosome map with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in these species, corresponding to entire chromosome arms in the rainbow trout as expected. In almost every case, the markers were found at approximately the same location on the chromosome arm in each species, suggesting conservation of marker order on the chromosome arms of the two species in most cases. Although theoretically a few centric fissions could convert the karyotype of rainbow trout (2N = 58-64) into that of Chinook salmon (2N = 68) or vice versa, our data suggest that chromosome arms underwent multiple centric fissions and subsequent new centric fusions to form the current karyotypes. The morphology of only approximately one-third of the chromosome pairs have been conserved between the two species.

  11. Succinyl-proteome profiling of a high taxol containing hybrid Taxus species (Taxus × media) revealed involvement of succinylation in multiple metabolic pathways

    PubMed Central

    Shen, Chenjia; Xue, Jie; Sun, Tao; Guo, Hong; Zhang, Lei; Meng, Yijun; Wang, Huizhong

    2016-01-01

    Protein lysine succinylation, a ubiquitous protein post-translational modification among eukaryotic and prokaryotic cells, represents a vital regulator of various metabolic processes. However, little is known about its functions and cellular distribution in Taxus × media, which is a hybrid Taxus species containing a high content of taxol. In this study, LC-MS/MS was used to identify peptides enriched by immune-purification with high-efficiency succinyl-lysine antibody. A total of 193 succinylated proteins and 325 succinylation sites were identified. The bioinformatics analysis indicated that these succinylated proteins were involved in a wide range of cellular functions from metabolism to protein binding and showed diverse subcellular localizations. Furthermore, our findings suggested that lysine succinylation in Taxus × media involved a diverse array of metabolic processes and protein–protein interactions. Many enzymes involved in multiple metabolic pathways, such as glycolysis, pyruvate metabolism, the tricarboxylic acid cycle and carbon fixation, were identified as substrates for lysine succinylation, suggesting the presence of a common mechanism underlying the participation of succinylation in metabolic regulation. These results provide the first comprehensive view of the succinylome of Taxus × media and may catalyze future biological investigation of succinylation. PMID:26902839

  12. Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

    PubMed Central

    Imitola, Jaime; Côté, Daniel; Rasmussen, Stine; Xie, X. Sunney; Liu, Yingru; Chitnis, Tanuja; Sidman, Richard L.; Lin, Charles. P.; Khoury, Samia J.

    2011-01-01

    Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over time of demyelination and neurodegeneration in brain slices with high spatial resolution and signal-to-noise ratio. Local areas of severe loss of lipid signal indicative of demyelination and loss of the reflectance signal from axons were seen in the corpus callosum and spinal cord of EAE animals. Even in myelinated areas of EAE mice, the intensity of myelin lipid signals is significantly reduced. Using heterozygous knock-in mice in which green fluorescent protein replaces the CX3CR1 coding sequence that labels central nervous system microglia, we find areas of activated microglia colocalized with areas of altered reflectance and CARS signals reflecting axonal injury and demyelination. Our data demonstrate the use of multimodal CARS microscopy for characterization of demyelinating and neurodegenerative pathology in a mouse model of multiple sclerosis, and further confirm the critical role of microglia in chronic inflammatory neurodegeneration. PMID:21361672

  13. How Diverse Is the Genus Wolbachia? Multiple-Gene Sequencing Reveals a Putatively New Wolbachia Supergroup Recovered from Spider Mites (Acari: Tetranychidae)▿ †

    PubMed Central

    Ros, Vera I. D.; Fleming, Vicki M.; Feil, Edward J.; Breeuwer, Johannes A. J.

    2009-01-01

    At least 20% of all arthropods and some nematode species are infected with intracellular bacteria of the genus Wolbachia. This highly diverse genus has been subdivided into eight “supergroups” (A to H) on the basis of nucleotide sequence data. Here, we report the discovery of a new Wolbachia supergroup recovered from the spider mite species Bryobia species V (Acari: Tetranychidae), based on the sequences of three protein-coding genes (ftsZ, gltA, and groEL) and the 16S rRNA gene. Other tetranychid mites possess supergroup B Wolbachia strains. The discovery of another Wolbachia supergroup expands the known diversity of Wolbachia and emphasizes the high variability of the genus. Our data also clarify the existing supergroup structure and highlight the use of multiple gene sequences for robust phylogenetic analysis. In addition to previous reports of recombination between the arthropod-infecting supergroups A and B, we provide evidence for recombination between the nematode-infecting supergroups C and D. Robust delineation of supergroups is essential for understanding the origin and spread of this common reproductive parasite and for unraveling mechanisms of host adaptation and manipulation across a wide range of hosts. PMID:19098217

  14. Phenotypic, Genomic and Functional Characterization Reveals No Differences between CD138++ and CD138low Subpopulations in Multiple Myeloma Cell Lines

    PubMed Central

    Paíno, Teresa; Sarasquete, María E.; Paiva, Bruno; Krzeminski, Patryk; San-Segundo, Laura; Corchete, Luis A.; Redondo, Alba; Garayoa, Mercedes; García-Sanz, Ramón; Gutiérrez, Norma C.; Ocio, Enrique M.; San-Miguel, Jesús F.

    2014-01-01

    Despite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described three decades ago, the phenotype of MM-CSC is still controversial, especially with respect to the expression of syndecan-1 (CD138). Here, we demonstrate the presence of two subpopulations - CD138++ (95–99%) and CD138low (1–5%) - in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are phenotypically interconvertible. Overall, our results differ from previously published data in MM cell lines which attribute a B-cell phenotype to MM-CSC. Future characterization of clonal plasma cell subpopulations in MM patients' samples will guarantee the discovery of more reliable markers able to discriminate true clonogenic myeloma cells. PMID:24658332

  15. Multiple markers pyrosequencing reveals highly diverse and host-specific fungal communities on the mangrove trees Avicennia marina and Rhizophora stylosa.

    PubMed

    Arfi, Yonathan; Buée, Marc; Marchand, Cyril; Levasseur, Anthony; Record, Eric

    2012-02-01

    Fungi are important actors in ecological processes and trophic webs in mangroves. Although saprophytic fungi occurring in the intertidal part of mangrove have been well studied, little is known about the diversity and structure of the fungal communities in this ecosystem or about the importance of functional groups like pathogens and mutualists. Using tag-encoded 454 pyrosequencing of the ITS1, ITS2, nu-ssu-V5 and nu-ssu-V7 regions, we studied and compared the fungal communities found on the marine and aerial parts of Avicennia marina and Rhizophora stylosa trees in a mangrove in New Caledonia. A total of 209,544 reads were analysed, corresponding to several thousand molecular operational taxonomic units (OTU). There is a marked zonation in the species distribution, with most of the OTU being found specifically in one of the microhabitat studied. Ascomycetes are the dominant phylum (82%), Basidiomycetes are very rare (3%), and 15% of the sequences correspond to unknown taxa. Our results indicate that host specificity is a key factor in the distribution of the highly diverse fungal communities, in both the aerial and intertidal parts of the trees. This study also validates the usefulness of multiple markers in tag-encoded pyrosequencing to consolidate and refine the assessment of the taxonomic diversity.

  16. The Glycan Role in the Glycopeptide Immunogenicity Revealed by Atomistic Simulations and Spectroscopic Experiments on the Multiple Sclerosis Biomarker CSF114(Glc)

    PubMed Central

    Bruno, Agostino; Scrima, Mario; Novellino, Ettore; D'Errico, Gerardino; D'Ursi, Anna Maria; Limongelli, Vittorio

    2015-01-01

    Glycoproteins are often recognized as not-self molecules by antibodies triggering the onset of severe autoimmune diseases such as Multiple Sclerosis (MS). Thus, the development of antigen-mimicking biomarkers represents an attractive strategy for an early diagnosis of the disease. An example is the synthetic glycopeptide CSF114(Glc), which was designed and tested as MS biomarker and whose clinical application was limited by its reduced ability to detect autoantibodies in MS patients. In the attempt to improve the efficacy of CSF114(Glc), we have characterized all the events leading to the final binding of the biomarker to the autoantibody using atomistic simulations, ESR and NMR experiments. The glycosydic moiety plays a primary role in the whole process. In particular, in an environment mimicking that used in the clinical tests the glycopeptide assumes a α-helix structure that is functional for the interaction with the antibody. In this conformation CSF114(Glc) binds the monoclonal antibody mAb8-18C5 similarly to the myelin oligodendrocyte glycoprotein MOG, which is a known MS auto-antigen, thus explaining its diagnostic activity. Our study offers new molecular bases to design more effective biomarkers and provides a most valid protocol to investigate other systems where the environment effect is determinant for the biological activity. PMID:25776265

  17. Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics

    PubMed Central

    Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.

    2013-01-01

    The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100

  18. Genetic, Physiological, and Gene Expression Analyses Reveal That Multiple QTL Enhance Yield of Rice Mega-Variety IR64 under Drought

    PubMed Central

    Swamy B. P., Mallikarjuna; Ahmed, Helal Uddin; Henry, Amelia; Mauleon, Ramil; Dixit, Shalabh; Vikram, Prashant; Tilatto, Ram; Verulkar, Satish B.; Perraju, Puvvada; Mandal, Nimai P.; Variar, Mukund; S., Robin; Chandrababu, Ranganath; Singh, Onkar N.; Dwivedi, Jawaharlal L.; Das, Sankar Prasad; Mishra, Krishna K.; Yadaw, Ram B.; Aditya, Tamal Lata; Karmakar, Biswajit; Satoh, Kouji; Moumeni, Ali; Kikuchi, Shoshi; Leung, Hei; Kumar, Arvind

    2013-01-01

    Background Rice (Oryza sativa L.) is a highly drought sensitive crop, and most semi dwarf rice varieties suffer severe yield losses from reproductive stage drought stress. The genetic complexity of drought tolerance has deterred the identification of agronomically relevant quantitative trait loci (QTL) that can be deployed to improve rice yield under drought in rice. Convergent evidence from physiological characterization, genetic mapping, and multi-location field evaluation was used to address this challenge. Methodology/Principal Findings Two pairs of backcross inbred lines (BILs) from a cross between drought-tolerant donor Aday Sel and high-yielding but drought-susceptible rice variety IR64 were produced. From six BC4F3 mapping populations produced by crossing the +QTL BILs with the −QTL BILs and IR64, four major-effect QTL - one each on chromosomes 2, 4, 9, and 10 - were identified. Meta-analysis of transcriptome data from the +QTL/−QTL BILs identified differentially expressed genes (DEGs) significantly associated with QTL on chromosomes 2, 4, 9, and 10. Physiological characterization of BILs showed increased water uptake ability under drought. The enrichment of DEGs associated with root traits points to differential regulation of root development and function as contributing to drought tolerance in these BILs. BC4F3-derived lines with the QTL conferred yield advantages of 528 to 1875 kg ha−1 over IR64 under reproductive-stage drought stress in the targeted ecosystems of South Asia. Conclusions/Significance Given the importance of rice in daily food consumption and the popularity of IR64, the BC4F3 lines with multiple QTL could provide higher livelihood security to farmers in drought-prone environments. Candidate genes were shortlisted for further characterization to confirm their role in drought tolerance. Differential yield advantages of different combinations of the four QTL reported here indicate that future research should include optimizing QTL

  19. Deep sequencing of the ancestral tobacco species Nicotiana tomentosiformis reveals multiple T-DNA inserts and a complex evolutionary history of natural transformation in the genus Nicotiana.

    PubMed

    Chen, Ke; Dorlhac de Borne, François; Szegedi, Ernö; Otten, Léon

    2014-11-01

    Nicotiana species carry cellular T-DNA sequences (cT-DNAs), acquired by Agrobacterium-mediated transformation. We characterized the cT-DNA sequences of the ancestral Nicotiana tabacum species Nicotiana tomentosiformis by deep sequencing. N. tomentosiformis contains four cT-DNA inserts derived from different Agrobacterium strains. Each has an incomplete inverted-repeat structure. TA is similar to part of the Agrobacterium rhizogenes 1724 mikimopine-type T-DNA, but has unusual orf14 and mis genes. TB carries a 1724 mikimopine-type orf14-mis fragment and a mannopine-agropine synthesis region (mas2-mas1-ags). The mas2' gene codes for an active enzyme. TC is similar to the left part of the A. rhizogenes A4 T-DNA, but also carries octopine synthase-like (ocl) and c-like genes normally found in A. tumefaciens. TD shows a complex rearrangement of T-DNA fragments similar to the right end of the A4 TL-DNA, and including an orf14-like gene and a gene with unknown function, orf511. The TA, TB, TC and TD insertion sites were identified by alignment with N. tabacum and Nicotiana sylvestris sequences. The divergence values for the TA, TB, TC and TD repeats provide an estimate for their relative introduction times. A large deletion has occurred in the central part of the N. tabacum cv. Basma/Xanthi TA region, and another deletion removed the complete TC region in N. tabacum. Nicotiana otophora lacks TA, TB and TD, but contains TC and another cT-DNA, TE. This analysis, together with that of Nicotiana glauca and other Nicotiana species, indicates multiple sequential insertions of cT-DNAs during the evolution of the genus Nicotiana.

  20. Secretome Analysis Identifies Novel Signal Peptide Peptidase-Like 3 (SPPL3) Substrates and Reveals a Role of SPPL3 in Multiple Golgi Glycosylation Pathways*

    PubMed Central

    Kuhn, Peer-Hendrik; Voss, Matthias; Haug-Kröper, Martina; Schröder, Bernd; Schepers, Ute; Bräse, Stefan; Haass, Christian; Lichtenthaler, Stefan F.; Fluhrer, Regina

    2015-01-01

    Signal peptide peptidase-like 3 (SPPL3) is a Golgi-resident intramembrane-cleaving protease that is highly conserved among multicellular eukaryotes pointing to pivotal physiological functions in the Golgi network which are only beginning to emerge. Recently, SPPL3 was shown to control protein N-glycosylation, when the key branching enzyme N-acetylglucosaminyltransferase V (GnT-V) and other medial/trans Golgi glycosyltransferases were identified as first physiological SPPL3 substrates. SPPL3-mediated endoproteolysis releases the catalytic ectodomains of these enzymes from their type II membrane anchors. Protein glycosylation is a multistep process involving numerous type II membrane-bound enzymes, but it remains unclear whether only few of them are SPPL3 substrates or whether SPPL3 cleaves many of them and thereby controls protein glycosylation at multiple levels. Therefore, to systematically identify SPPL3 substrates we used Sppl3-deficient and SPPL3-overexpression cell culture models and analyzed them for changes in secreted membrane protein ectodomains using the proteomics “secretome protein enrichment with click sugars (SPECS)” method. SPECS analysis identified numerous additional new SPPL3 candidate glycoprotein substrates, several of which were biochemically validated as SPPL3 substrates. All novel SPPL3 substrates adopt a type II topology. The majority localizes to the Golgi network and is implicated in Golgi functions. Importantly, most of the novel SPPL3 substrates catalyze the modification of N-linked glycans. Others contribute to O-glycan and in particular glycosaminoglycan biosynthesis, suggesting that SPPL3 function is not restricted to N-glycosylation, but also functions in other forms of protein glycosylation. Hence, SPPL3 emerges as a crucial player of Golgi function and the newly identified SPPL3 substrates will be instrumental to investigate the molecular mechanisms underlying the physiological function of SPPL3 in the Golgi network and in vivo

  1. Spatiotemporal video segmentation based on graphical models.

    PubMed

    Wang, Yang; Loe, Kia-Fock; Tan, Tele; Wu, Jian-Kang

    2005-07-01

    This paper proposes a probabilistic framework for spatiotemporal segmentation of video sequences. Motion information, boundary information from intensity segmentation, and spatial connectivity of segmentation are unified in the video segmentation process by means of graphical models. A Bayesian network is presented to model interactions among the motion vector field, the intensity segmentation field, and the video segmentation field. The notion of the Markov random field is used to encourage the formation of continuous regions. Given consecutive frames, the conditional joint probability density of the three fields is maximized in an iterative way. To effectively utilize boundary information from the intensity segmentation, distance transformation is employed in local objective functions. Experimental results show that the method is robust and generates spatiotemporally coherent segmentation results. Moreover, the proposed video segmentation approach can be viewed as the compromise of previous motion based approaches and region merging approaches.

  2. What Is Spatio-Temporal Data Warehousing?

    NASA Astrophysics Data System (ADS)

    Vaisman, Alejandro; Zimányi, Esteban

    In the last years, extending OLAP (On-Line Analytical Processing) systems with spatial and temporal features has attracted the attention of the GIS (Geographic Information Systems) and database communities. However, there is no a commonly agreed definition of what is a spatio-temporal data warehouse and what functionality such a data warehouse should support. Further, the solutions proposed in the literature vary considerably in the kind of data that can be represented as well as the kind of queries that can be expressed. In this paper we present a conceptual framework for defining spatio-temporal data warehouses using an extensible data type system. We also define a taxonomy of different classes of queries of increasing expressive power, and show how to express such queries using an extension of the tuple relational calculus with aggregated functions.

  3. Nonlinear Analysis of Spatiotemporal Heart Data

    NASA Astrophysics Data System (ADS)

    Simonotto, Jennifer; Spano, Mark; Ditto, William; Kavanagh, Katherine; Harrison, Robert G.

    2002-03-01

    Studying the nonlinear dynamics of ventricular fibrillation (VF) and ventricular tachycardia (VT) is necessary for the development of better models of and treatments for VF/VT. Through the use of voltage sensitive dyes and new high speed video cameras, we can now obtain optical mapping data that exhibit signal to noise ratios high enough to tackle (in 2D) the acquisition and analysis of spatiotemporal dynamics of VF/VT. It is now possible to effectively apply conventional statistical analyses (spatial correlation, coherence, signal decomposition), as well as techniques based upon wavefront motion (phase maps, propagation velocity vectors, waveform dynamics) of the electrical waves under study. Yet it is unclear if these measures alone will suffice to describe the complexity of the system. Thus we combine statistical and optical analysis with nonlinear analysis (entropy measures, symbolic dynamics, unstable periodic orbits (UPO) statistics) in order to extract the most information of the spatiotemporal behavior of VF/VT.

  4. Comprehensive SNP scan of DNA repair and DNA damage response genes reveal multiple susceptibility loci conferring risk to tobacco associated leukoplakia and oral cancer.

    PubMed

    Mondal, Pinaki; Datta, Sayantan; Maiti, Guru Prasad; Baral, Aradhita; Jha, Ganga Nath; Panda, Chinmay Kumar; Chowdhury, Shantanu; Ghosh, Saurabh; Roy, Bidyut; Roychoudhury, Susanta

    2013-01-01

    Polymorphic variants of DNA repair and damage response genes play major role in carcinogenesis. These variants are suspected as predisposition factors to Oral Squamous Cell Carcinoma (OSCC). For identification of susceptible variants affecting OSCC development in Indian population, the "maximally informative" method of SNP selection from HapMap data to non-HapMap populations was applied. Three hundred twenty-five SNPs from 11 key genes involved in double strand break repair, mismatch repair and DNA damage response pathways were genotyped on a total of 373 OSCC, 253 leukoplakia and 535 unrelated control individuals. The significantly associated SNPs were validated in an additional cohort of 144 OSCC patients and 160 controls. The rs12515548 of MSH3 showed significant association with OSCC both in the discovery and validation phases (discovery P-value: 1.43E-05, replication P-value: 4.84E-03). Two SNPs (rs12360870 of MRE11A, P-value: 2.37E-07 and rs7003908 of PRKDC, P-value: 7.99E-05) were found to be significantly associated only with leukoplakia. Stratification of subjects based on amount of tobacco consumption identified SNPs that were associated with either high or low tobacco exposed group. The study reveals a synergism between associated SNPs and lifestyle factors in predisposition to OSCC and leukoplakia.

  5. Phylogeographic Analysis of Haplogroup E3b (E-M215) Y Chromosomes Reveals Multiple Migratory Events Within and Out Of Africa

    PubMed Central

    Cruciani, Fulvio; La Fratta, Roberta; Santolamazza, Piero; Sellitto, Daniele; Pascone, Roberto; Moral, Pedro; Watson, Elizabeth; Guida, Valentina; Colomb, Eliane Beraud; Zaharova, Boriana; Lavinha, João; Vona, Giuseppe; Aman, Rashid; Calì, Francesco; Akar, Nejat; Richards, Martin; Torroni, Antonio; Novelletto, Andrea; Scozzari, Rosaria

    2004-01-01

    We explored the phylogeography of human Y-chromosomal haplogroup E3b by analyzing 3,401 individuals from five continents. Our data refine the phylogeny of the entire haplogroup, which appears as a collection of lineages with very different evolutionary histories, and reveal signatures of several distinct processes of migrations and/or recurrent gene flow that occurred in Africa and western Eurasia over the past 25,000 years. In Europe, the overall frequency pattern of haplogroup E-M78 does not support the hypothesis of a uniform spread of people from a single parental Near Eastern population. The distribution of E-M81 chromosomes in Africa closely matches the present area of distribution of Berber-speaking populations on the continent, suggesting a close haplogroup–ethnic group parallelism. E-M34 chromosomes were more likely introduced in Ethiopia from the Near East. In conclusion, the present study shows that earlier work based on fewer Y-chromosome markers led to rather simple historical interpretations and highlights the fact that many population-genetic analyses are not robust to a poorly resolved phylogeny. PMID:15042509

  6. Lead isotopes in lichen transplants around a Cu smelter in Russia determined by MC-ICP-MS reveal transient records of multiple sources.

    PubMed

    Spiro, B; Weiss, D J; Purvis, O W; Mikhailova, I; Williamson, B J; Coles, B J; Udachin, V

    2004-12-15

    Transplants of the lichen Hypogymnia physodes, which is relatively tolerant to SO2 and heavy metals, were deployed for 3 months over a 60 km long SW-NE transect centered on a highly polluting Cu smelter and its adjoining town of Karabash, southern Urals, Russia. The abundance of 206Pb, 207Pb, 208Pb, and 204Pb were determined by MC-ICP-MS. The measurement of 204Pb revealed critical features, which would otherwise remain concealed: (i) The precise isotope ratios referenced to 204Pb allowed several different sources to be resolved even within the small area covered: (a) the obvious pollutant source of the Karabash Cu smelter; (b) two dispersed sources, likely to include soil with lower and different contributions of thorogenic and uranogenic lead; and (c) one anthropogenic source with higher contribution of 235U derived Pb. (ii) In part of the transect, the Pb isotope composition changed while the Pb concentrations remained the same. This indicates that the Pb content of the transplantation material from the background site was largely replaced and that the transplants provide a transient record reflecting a continuous accumulation and loss of environmental Pb, probably mainly in the form of extracellular particles. Overall, the method of lichen transplantation coupled with Pb isotope ratio determinations proved effective in assessing the usefulness of lichens in biomonitoring and in resolving different sources of atmospheric deposition.

  7. Behavioural mapping of a pelagic seabird: combining multiple sensors and a hidden Markov model reveals the distribution of at-sea behaviour

    PubMed Central

    Dean, Ben; Freeman, Robin; Kirk, Holly; Leonard, Kerry; Phillips, Richard A.; Perrins, Chris M.; Guilford, Tim

    2013-01-01

    The use of miniature data loggers is rapidly increasing our understanding of the movements and habitat preferences of pelagic seabirds. However, objectively interpreting behavioural information from the large volumes of highly detailed data collected by such devices can be challenging. We combined three biologging technologies—global positioning system (GPS), saltwater immersion and time–depth recorders—to build a detailed picture of the at-sea behaviour of the Manx shearwater (Puffinus puffinus) during the breeding season. We used a hidden Markov model to explore discrete states within the combined GPS and immersion data, and found that behaviour could be organized into three principal activities representing (i) sustained direct flight, (ii) sitting on the sea surface, and (iii) foraging, comprising tortuous flight interspersed with periods of immersion. The additional logger data verified that the foraging activity corresponded well to the occurrence of diving. Applying this approach to a large tracking dataset revealed that birds from two different colonies foraged in local waters that were exclusive, but overlapped in one key area: the Irish Sea Front (ISF). We show that the allocation of time to each activity differed between colonies, with birds breeding furthest from the ISF spending the greatest proportion of time engaged in direct flight and the smallest proportion of time engaged in foraging activity. This type of analysis has considerable potential for application in future biologging studies and in other taxa. PMID:23034356

  8. 19F NMR Reveals Multiple Conformations at the Dimer Interface of the Non-Structural Protein 1 Effector Domain from Influenza A Virus

    PubMed Central

    Ma, Li-Chung; Swapna, G. V. T.; Leonard, Paul G.; Ladbury, John E.; Krug, Robert M.; Montelione, Gaetano T.

    2014-01-01

    SUMMARY Non-structural protein 1 of influenza A virus, NS1A, is a conserved virulence factor comprised of an N-terminal double-stranded RNA (dsRNA)-binding domain (RBD) and a multifunctional C-terminal effector domain (ED), each of which can independently form symmetric homodimers. Here we apply 19F NMR to NS1A from influenza A/Udorn/307/1972 virus (H3N2) labeled with 5-fluorotryptophan (5-F-Trp), and demonstrate that the 19F signal of Trp187 is a sensitive, direct monitor of the ED helix-helix dimer interface. 19F relaxation dispersion data reveal the presence of conformational dynamics within this functionally important protein-protein interface, whose rate is over three orders of magnitude faster than the kinetics of ED dimerization. 19F NMR also affords direct spectroscopic evidence that Trp187, which mediates intermolecular ED:ED interactions required for cooperative dsRNA binding, is solvent exposed in full-length NS1Aat concentrations below aggregation. These results have important implications for the diverse roles of this NS1A epitope during influenza virus infection. PMID:24582435

  9. X chromosome exome sequencing reveals a novel ALG13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings.

    PubMed

    Bissar-Tadmouri, Nesrine; Donahue, Whithey L; Al-Gazali, Lihadh; Nelson, Stanley F; Bayrak-Toydemir, Pinar; Kantarci, Sibel

    2014-01-01

    X-linked intellectual disability (XLID) is a heterogeneous condition associated with mutations in >100 genes, accounting for over 10% of all cases of intellectual impairment. The majority of XLID cases show nonsyndromic forms (NSXLID), in which intellectual disability is the sole clinically consistent manifestation. Here we performed X chromosome exome (X-exome) sequencing to identify the causative mutation in an NSXLID family with four affected male siblings and five unaffected female siblings. The X-exome sequencing at 88× coverage in one affected male sibling revealed a novel missense mutation (p.Tyr1074Cys) in the asparagine-linked glycosylation 13 homolog (ALG13) gene. Segregation analysis by Sanger sequencing showed that the all affected siblings were hemizygous and the mother was heterozygous for the mutation. Recently, a de novo missense mutation in ALG13 has been reported in a patient with X-linked congenital disorders of glycosylation type I. Our study reports the first case of NSXLID caused by a mutation in ALG13 involved in protein N-glycosylation.

  10. Whole-genome bisulfite sequencing maps from multiple human tissues reveal novel CpG islands associated with tissue-specific regulation

    PubMed Central

    Mendizabal, Isabel; Yi, Soojin V.

    2016-01-01

    CpG islands (CGIs) are one of the most widely studied regulatory features of the human genome, with critical roles in development and disease. Despite such significance and the original epigenetic definition, currently used CGI sets are typically predicted from DNA sequence characteristics. Although CGIs are deeply implicated in practical analyses of DNA methylation, recent studies have shown that such computational annotations suffer from inaccuracies. Here we used whole-genome bisulfite sequencing from 10 diverse human tissues to identify a comprehensive, experimentally obtained, single-base resolution CGI catalog. In addition to the unparalleled annotation precision, our method is free from potential bias due to arbitrary sequence features or probe affinity differences. In addition to clarifying substantial false positives in the widely used University of California Santa Cruz (UCSC) annotations, our study identifies numerous novel epigenetic loci. In particular, we reveal significant impact of transposable elements on the epigenetic regulatory landscape of the human genome and demonstrate ubiquitous presence of transcription initiation at CGIs, including alternative promoters in gene bodies and non-coding RNAs in intergenic regions. Moreover, coordinated DNA methylation and chromatin modifications mark tissue-specific enhancers at novel CGIs. Enrichment of specific transcription factor binding from ChIP-seq supports mechanistic roles of CGIs on the regulation of tissue-specific transcription. The new CGI catalog provides a comprehensive and integrated list of genomic hotspots of epigenetic regulation. PMID:26512062

  11. Multi locus analysis of Pristionchus pacificus on La Réunion Island reveals an evolutionary history shaped by multiple introductions, constrained dispersal events and rare out-crossing.

    PubMed

    Morgan, Katy; McGaughran, Angela; Villate, Laure; Herrmann, Matthias; Witte, Hanh; Bartelmes, Gabi; Rochat, Jacques; Sommer, Ralf J

    2012-01-01

    Pristionchus pacificus, recently established as a model organism in evolutionary biology, is a cosmopolitan nematode that has a necromenic association with scarab beetles. The diverse array of host beetle species and habitat types occupied by P. pacificus make it a good model for investigating local adaptation to novel environments. Presence of P. pacificus on La Réunion Island, a young volcanic island with a dynamic geological history and a wide variety of ecozones, facilitates such investigation in an island biogeographic setting. Microsatellite data from 20 markers and 223 strains and mitochondrial sequence data from 272 strains reveal rich genetic diversity among La Réunion P. pacificus isolates, shaped by differentially timed introductions from diverse sources and in association with different beetle species. Distinctions between volcanic zones and between arid western and wet eastern climatic zones have likely limited westward dispersal of recently colonized lineages and maintained a genetic distinction between eastern and western clades. The highly selfing lifestyle of P. pacificus contributes to the strong fine-scale population structure detected, with each beetle host harbouring strongly differentiated assemblages of strains. Periodic out-crossing generates admixture between genetically diverse lineages, creating a diverse array of allelic combinations likely to increase the evolutionary potential of the species and facilitate adaptation to local environments and beetle hosts.

  12. Toward Full Spatiotemporal Control on the Nanoscale

    NASA Astrophysics Data System (ADS)

    Durach, Maxim; Rusina, Anastasia; Stockman, Mark I.; Nelson, Keith

    2007-10-01

    We introduce an approach to implement full coherent control on nanometer length scales. It is based on spatio-temporal modulation of the surface plasmon polariton (SPP) fields at the thick edge of a nanowedge. The SPP wavepackets propagating toward the sharp edge of this nanowedge are compressed and adiabatically concentrated at a nanofocus, forming an ultrashort pulse of local fields. The one-dimensional spatial profile and temporal waveform of this pulse are completely coherently controlled.

  13. Toward full spatiotemporal control on the nanoscale.

    PubMed

    Durach, Maxim; Rusina, Anastasia; Stockman, Mark I; Nelson, Keith

    2007-10-01

    We introduce an approach to implement full coherent control on nanometer length scales. It is based on spatiotemporal modulation of the surface plasmon polariton (SPP) fields at the thick edge of a nanowedge. The SPP wavepackets propagating toward the sharp edge of this nanowedge are compressed and adiabatically concentrated at a nanofocus, forming an ultrashort pulse of local fields. The profile of the focused waveform as a function of time and one spatial dimension is completely coherently controlled.

  14. Spatiotemporal Patterns and Predictability of Cyberattacks

    PubMed Central

    Chen, Yu-Zhong; Huang, Zi-Gang; Xu, Shouhuai; Lai, Ying-Cheng

    2015-01-01

    A relatively unexplored issue in cybersecurity science and engineering is whether there exist intrinsic patterns of cyberattacks. Conventional wisdom favors absence of such patterns due to the overwhelming complexity of the modern cyberspace. Surprisingly, through a detailed analysis of an extensive data set that records the time-dependent frequencies of attacks over a relatively wide range of consecutive IP addresses, we successfully uncover intrinsic spatiotemporal patterns underlying cyberattacks, where the term “spatio” refers to the IP address space. In particular, we focus on analyzing macroscopic properties of the attack traffic flows and identify two main patterns with distinct spatiotemporal characteristics: deterministic and stochastic. Strikingly, there are very few sets of major attackers committing almost all the attacks, since their attack “fingerprints” and target selection scheme can be unequivocally identified according to the very limited number of unique spatiotemporal characteristics, each of which only exists on a consecutive IP region and differs significantly from the others. We utilize a number of quantitative measures, including the flux-fluctuation law, the Markov state transition probability matrix, and predictability measures, to characterize the attack patterns in a comprehensive manner. A general finding is that the attack patterns possess high degrees of predictability, potentially paving the way to anticipating and, consequently, mitigating or even preventing large-scale cyberattacks using macroscopic approaches. PMID:25992837

  15. Complexity of Neutralizing Antibodies against Multiple Dengue Virus Serotypes after Heterotypic Immunization and Secondary Infection Revealed by In-Depth Analysis of Cross-Reactive Antibodies

    PubMed Central

    Tsai, Wen-Yang; Durbin, Anna; Tsai, Jih-Jin; Hsieh, Szu-Chia; Whitehead, Stephen

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV) cause the most important and rapidly emerging arboviral diseases in humans. The recent phase 2b and 3 studies of a tetravalent dengue vaccine reported a moderate efficacy despite the presence of neutralizing antibodies, highlighting the need for a better understanding of neutralizing antibodies in polyclonal human sera. Certain type-specific (TS) antibodies were recently discovered to account for the monotypic neutralizing activity and protection after primary DENV infection. The nature of neutralizing antibodies after secondary DENV infection remains largely unknown. In this study, we examined sera from 10 vaccinees with well-documented exposure to first and second DENV serotypes through heterotypic immunization with live-attenuated vaccines. Higher serum IgG avidities to both exposed and nonexposed serotypes were found after secondary immunization than after primary immunization. Using a two-step depletion protocol to remove different anti-envelope antibodies, including group-reactive (GR) and complex-reactive (CR) antibodies separately, we found GR and CR antibodies together contributed to more than 50% of neutralizing activities against multiple serotypes after secondary immunization. Similar findings were demonstrated in patients after secondary infection. Anti-envelope antibodies recognizing previously exposed serotypes consisted of a large proportion of GR antibodies, CR antibodies, and a small proportion of TS antibodies, whereas those recognizing nonexposed serotypes consisted of GR and CR antibodies. These findings have implications for sequential heterotypic immunization or primary immunization of DENV-primed individuals as alternative strategies for DENV vaccination. The complexity of neutralizing antibodies after secondary infection provides new insights into the difficulty of their application as surrogates of protection. IMPORTANCE The four serotypes of dengue virus (DENV) are the leading cause of

  16. A 30 Myr record of retrograde metamorphism and multiple generations of monazite and garnet in western MA revealed by coordinated LASS and EPMA

    NASA Astrophysics Data System (ADS)

    Peterman, E. M.; Burton, Z. F. M.; Rubel, J. N.; Snoeyenbos, D. R.; Kylander-Clark, A. R.

    2014-12-01

    Garnet-kyanite-cordierite pelitic schists with relict phosphatic garnets thought to record ultrahigh-pressure metamorphism (e.g., Snoeyenbos and Koziol, 2008) crop out along the western margin of the Goshen Dome in western Massachusetts. These schists contain monazite inclusions within Grt, Ky, Crd, Bt, Pl, Qz, and Chl. Compositional maps via EPMA-WDS show overgrowths on each monazite grain, indicating that each grain records multiple metamorphic events. We analyzed monazite in situ using laser-ablation split-stream (LASS) ICPMS to correlate the geochemical and age domains and to reconstruct the polyphase metamorphic history. We used WDS compositional maps of Y and Th, and ICPMS Gd/Yb ratios and U/Pb ages to define the timing of major garnet growth and breakdown processes, and melting and/or fluid-rich metamorphism. For example, decreasing Gd/Yb and high Y concentrations are consistent with garnet breakdown; highly variable Gd/Yb indicate melting and/or fluid-rich metamorphism (e.g., Stearns et al., 2013). The following cumulative histories are interpreted from two samples (B and G). In both samples, decreasing Gd/Yb in monazite suggest garnet breakdown from c. 398 to 387 Ma. Data from sample B (n = 644 analyses) indicate two additional phases of garnet growth: 382 to 377 Ma and 375 to 369 Ma (see figure). Data from sample G (n = 231 analyses) also indicate two additional phases of garnet growth: 387 to 381 Ma and 379 to 369 Ma. The final garnet growth event affecting both samples is marked by the most variable Gd/Yb ratios in monazite from all petrographic contexts and is consistent with melting or a fluid-rich metamorphic event. These data are most consistent with metamorphism during emplacement to crustal levels in the early Acadian, and a substantial overprint during the regional thermal maximum. This complex record can only be unraveled by collecting geochronologic and geochemical data in situ to preserve the petrographic context of each grain, thus

  17. Spatiotemporal dynamics and optical vortices in a photorefractive phase-conjugate resonator

    NASA Technical Reports Server (NTRS)

    Liu, Siuying Raymond; Indebetouw, Guy

    1992-01-01

    A truncated modal expansion approach is used to study the spatiotemporal dynamics of a phase-conjugate resonator as a function of Bragg detuning. The numerical results reveal a rich variety of behaviors. Emphasis is given to the spatial distribution of optical vortices, their trajectories and their relationship to the beam's spatial coherence. The limitations of the model are discussed and experimental results are presented for comparison with the model's predictions and assessment of its soundness.

  18. Analysis of integrated multiple 'omics' datasets reveals the mechanisms of initiation and determination in the formation of tuberous roots in Rehmannia glutinosa.

    PubMed

    Li, Mingjie; Yang, Yanhui; Li, Xinyu; Gu, Li; Wang, Fengji; Feng, Fajie; Tian, Yunhe; Wang, Fengqing; Wang, Xiaoran; Lin, Wenxiong; Chen, Xinjian; Zhang, Zhongyi

    2015-09-01

    All tuberous roots in Rehmannia glutinosa originate from the expansion of fibrous roots (FRs), but not all FRs can successfully transform into tuberous roots. This study identified differentially expressed genes and proteins associated with the expansion of FRs, by comparing the tuberous root at expansion stages (initiated tuberous root, ITRs) and FRs at the seedling stage (initiated FRs, IFRs). The role of miRNAs in the expansion of FRs was also explored using the sRNA transcriptome and degradome to identify miRNAs and their target genes that were differentially expressed between ITRs and FRs at the mature stage (unexpanded FRs, UFRs, which are unable to expand into ITRs). A total of 6032 genes and 450 proteins were differentially expressed between ITRs and IFRs. Integrated analyses of these data revealed several genes and proteins involved in light signalling, hormone response, and signal transduction that might participate in the induction of tuberous root formation. Several genes related to cell division and cell wall metabolism were involved in initiating the expansion of IFRs. Of 135 miRNAs differentially expressed between ITRs and UFRs, there were 27 miRNAs whose targets were specifically identified in the degradome. Analysis of target genes showed that several miRNAs specifically expressed in UFRs were involved in the degradation of key genes required for the formation of tuberous roots. As far as could be ascertained, this is the first time that the miRNAs that control the transition of FRs to tuberous roots in R. glutinosa have been identified. This comprehensive analysis of 'omics' data sheds new light on the mechanisms involved in the regulation of tuberous roots formation.

  19. Downregulation of Cinnamoyl-Coenzyme A Reductase in Poplar: Multiple-Level Phenotyping Reveals Effects on Cell Wall Polymer Metabolism and Structure[W

    PubMed Central

    Leplé, Jean-Charles; Dauwe, Rebecca; Morreel, Kris; Storme, Véronique; Lapierre, Catherine; Pollet, Brigitte; Naumann, Annette; Kang, Kyu-Young; Kim, Hoon; Ruel, Katia; Lefèbvre, Andrée; Joseleau, Jean-Paul; Grima-Pettenati, Jacqueline; De Rycke, Riet; Andersson-Gunnerås, Sara; Erban, Alexander; Fehrle, Ines; Petit-Conil, Michel; Kopka, Joachim; Polle, Andrea; Messens, Eric; Sundberg, Björn; Mansfield, Shawn D.; Ralph, John; Pilate, Gilles; Boerjan, Wout

    2007-01-01

    Cinnamoyl-CoA reductase (CCR) catalyzes the penultimate step in monolignol biosynthesis. We show that downregulation of CCR in transgenic poplar (Populus tremula × Populus alba) was associated with up to 50% reduced lignin content and an orange-brown, often patchy, coloration of the outer xylem. Thioacidolysis, nuclear magnetic resonance (NMR), immunocytochemistry of lignin epitopes, and oligolignol profiling indicated that lignin was relatively more reduced in syringyl than in guaiacyl units. The cohesion of the walls was affected, particularly at sites that are generally richer in syringyl units in wild-type poplar. Ferulic acid was incorporated into the lignin via ether bonds, as evidenced independently by thioacidolysis and by NMR. A synthetic lignin incorporating ferulic acid had a red-brown coloration, suggesting that the xylem coloration was due to the presence of ferulic acid during lignification. Elevated ferulic acid levels were also observed in the form of esters. Transcript and metabolite profiling were used as comprehensive phenotyping tools to investigate how CCR downregulation impacted metabolism and the biosynthesis of other cell wall polymers. Both methods suggested reduced biosynthesis and increased breakdown or remodeling of noncellulosic cell wall polymers, which was further supported by Fourier transform infrared spectroscopy and wet chemistry analysis. The reduced levels of lignin and hemicellulose were associated with an increased proportion of cellulose. Furthermore, the transcript and metabolite profiling data pointed toward a stress response induced by the altered cell wall structure. Finally, chemical pulping of wood derived from 5-year-old, field-grown transgenic lines revealed improved pulping characteristics, but growth was affected in all transgenic lines tested. PMID:18024569

  20. A comparative transcriptome analysis reveals expression profiles conserved across three Eimeria spp. of domestic fowl and associated with multiple developmental stages.

    PubMed

    Novaes, Jeniffer; Rangel, Luiz Thibério L D; Ferro, Milene; Abe, Ricardo Y; Manha, Alessandra P S; de Mello, Joana C M; Varuzza, Leonardo; Durham, Alan M; Madeira, Alda Maria B N; Gruber, Arthur

    2012-01-01

    Coccidiosis of the domestic fowl is a worldwide disease caused by seven species of protozoan parasites of the genus Eimeria. The genome of the model species, Eimeria tenella, presents a complexity of 55-60MB distributed in 14 chromosomes. Relatively few studies have been undertaken to unravel the complexity of the transcriptome of Eimeria parasites. We report here the generation of more than 45,000 open reading frame expressed sequence tag (ORESTES) cDNA reads of E. tenella, Eimeria maxima and Eimeria acervulina, covering several developmental stages: unsporulated oocysts, sporoblastic oocysts, sporulated oocysts, sporozoites and second generation merozoites. All reads were assembled to constitute gene indices and submitted to a comprehensive functional annotation pipeline. In the case of E. tenella, we also incorporated publicly available ESTs to generate an integrated body of information. Orthology analyses have identified genes conserved across different apicomplexan parasites, as well as genes restricted to the genus Eimeria. Digital expression profiles obtained from ORESTES/EST countings, submitted to clustering analyses, revealed a high conservation pattern across the three Eimeria spp. Distance trees showed that unsporulated and sporoblastic oocysts constitute a distinct clade in all species, with sporulated oocysts forming a more external branch. This latter stage also shows a close relationship with sporozoites, whereas first and second generation merozoites are more closely related to each other than to sporozoites. The profiles were unambiguously associated with the distinct developmental stages and strongly correlated with the order of the stages in the parasite life cycle. Finally, we present The Eimeria Transcript Database (http://www.coccidia.icb.usp.br/eimeriatdb), a website that provides open access to all sequencing data, annotation and comparative analysis. We expect this repository to represent a useful resource to the Eimeria scientific

  1. Extensive sampling of polar bears (Ursus maritimus) in the Northwest Passage (Canadian Arctic Archipelago) reveals population differentiation across multiple spatial and temporal scales.

    PubMed

    Campagna, Leonardo; Van Coeverden de Groot, Peter J; Saunders, Brenda L; Atkinson, Stephen N; Weber, Diana S; Dyck, Markus G; Boag, Peter T; Lougheed, Stephen C

    2013-09-01

    As global warming accelerates the melting of Arctic sea ice, polar bears (Ursus maritimus) must adapt to a rapidly changing landscape. This process will necessarily alter the species distribution together with population dynamics and structure. Detailed knowledge of these changes is crucial to delineating conservation priorities. Here, we sampled 361 polar bears from across the center of the Canadian Arctic Archipelago spanning the Gulf of Boothia (GB) and M'Clintock Channel (MC). We use DNA microsatellites and mitochondrial control region sequences to quantify genetic differentiation, estimate gene flow, and infer population history. Two populations, roughly coincident with GB and MC, are significantly differentiated at both nuclear (F ST = 0.01) and mitochondrial (ΦST = 0.47; F ST = 0.29) loci, allowing Bayesian clustering analyses to assign individuals to either group. Our data imply that the causes of the mitochondrial and nuclear genetic patterns differ. Analysis of mtDNA reveals the matrilineal structure dates at least to the Holocene, and is common to individuals throughout the species' range. These mtDNA differences probably reflect both genetic drift and historical colonization dynamics. In contrast, the differentiation inferred from microsatellites is only on the scale of hundreds of years, possibly reflecting contemporary impediments to gene flow. Taken together, our data suggest that gene flow is insufficient to homogenize the GB and MC populations and support the designation of GB and MC as separate polar bear conservation units. Our study also provide a striking example of how nuclear DNA and mtDNA capture different aspects of a species demographic history.

  2. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development

    PubMed Central

    Beauchemin, Kyle J.; Wells, Julie M.; Kho, Alvin T.; Philip, Vivek M.; Kamir, Daniela; Kohane, Isaac S.

    2016-01-01

    To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS). Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular) defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO) archive (GSE74243). Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http

  3. Multiple actions of φ-LITX-Lw1a on ryanodine receptors reveal a functional link between scorpion DDH and ICK toxins

    PubMed Central

    Smith, Jennifer J.; Vetter, Irina; Lewis, Richard J.; Peigneur, Steve; Tytgat, Jan; Lam, Alexander; Gallant, Esther M.; Beard, Nicole A.; Alewood, Paul F.; Dulhunty, Angela F.

    2013-01-01

    We recently reported the isolation of a scorpion toxin named U1-liotoxin-Lw1a (U1-LITX-Lw1a) that adopts an unusual 3D fold termed the disulfide-directed hairpin (DDH) motif, which is the proposed evolutionary structural precursor of the three-disulfide-containing inhibitor cystine knot (ICK) motif found widely in animals and plants. Here we reveal that U1-LITX-Lw1a targets and activates the mammalian ryanodine receptor intracellular calcium release channel (RyR) with high (fM) potency and provides a functional link between DDH and ICK scorpion toxins. Moreover, U1-LITX-Lw1a, now described as φ-liotoxin-Lw1a (φ-LITX-Lw1a), has a similar mode of action on RyRs as scorpion calcines, although with significantly greater potency, inducing full channel openings at lower (fM) toxin concentrations whereas at higher pM concentrations increasing the frequency and duration of channel openings to a submaximal state. In addition, we show that the C-terminal residue of φ-LITX-Lw1a is crucial for the increase in full receptor openings but not for the increase in receptor subconductance opening, thereby supporting the two-binding-site hypothesis of scorpion toxins on RyRs. φ-LITX-Lw1a has potential both as a pharmacological tool and as a lead molecule for the treatment of human diseases that involve RyRs, such as malignant hyperthermia and polymorphic ventricular tachycardia. PMID:23671114

  4. BioenergyKDF: Enabling Spatiotemporal Data Synthesis and Research Collaboration

    SciTech Connect

    Myers, Aaron T; Movva, Sunil; Karthik, Rajasekar; Bhaduri, Budhendra L; White, Devin A; Thomas, Neil; Chase, Adrian S Z

    2014-01-01

    The Bioenergy Knowledge Discovery Framework (BioenergyKDF) is a scalable, web-based collaborative environment for scientists working on bioenergy related research in which the connections between data, literature, and models can be explored and more clearly understood. The fully-operational and deployed system, built on multiple open source libraries and architectures, stores contributions from the community of practice and makes them easy to find, but that is just its base functionality. The BioenergyKDF provides a national spatiotemporal decision support capability that enables data sharing, analysis, modeling, and visualization as well as fosters the development and management of the U.S. bioenergy infrastructure, which is an essential component of the national energy infrastructure. The BioenergyKDF is built on a flexible, customizable platform that can be extended to support the requirements of any user community especially those that work with spatiotemporal data. While there are several community data-sharing software platforms available, some developed and distributed by national governments, none of them have the full suite of capabilities available in BioenergyKDF. For example, this component-based platform and database independent architecture allows it to be quickly deployed to existing infrastructure and to connect to existing data repositories (spatial or otherwise). As new data, analysis, and features are added; the BioenergyKDF will help lead research and support decisions concerning bioenergy into the future, but will also enable the development and growth of additional communities of practice both inside and outside of the Department of Energy. These communities will be able to leverage the substantial investment the agency has made in the KDF platform to quickly stand up systems that are customized to their data and research needs.

  5. Revealing Rembrandt

    PubMed Central

    Parker, Andrew J.

    2014-01-01

    The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI). Our results emphasized the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt's portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings. PMID:24795552

  6. Land-use controls on sources and fate of nitrate in shallow groundwater of an agricultural area revealed by multiple environmental tracers

    NASA Astrophysics Data System (ADS)

    Koh, Dong-Chan; Mayer, Bernhard; Lee, Kwang-Sik; Ko, Kyung-Seok,

    2010-10-01

    nitrification; these samples were also characterized by low DO and NO 3-N concentrations and elevated Cl and Mn concentrations indicating anthropogenic contamination and denitrification in the aquifer. These conditions were observed primarily in aquifers on floodplains. Statistical comparison between land-use groups revealed that Cl/Br ratios were more diagnostic for the impact of different land-use types on groundwater quality than stable isotope compositions of nitrate. This indicates that the former is an additional efficient tracer for the effect of land use on groundwater quality in agricultural areas. We conclude that the combination of groundwater age dating together with the use of chemical and isotopic parameters is a highly effective but yet underutilized approach for elucidating the sources and the fate of nitrate in aquifers in Asia.

  7. Land-use controls on sources and fate of nitrate in shallow groundwater of an agricultural area revealed by multiple environmental tracers.

    PubMed

    Koh, Dong-Chan; Mayer, Bernhard; Lee, Kwang-Sik; Ko, Kyung-Seok

    2010-10-21

    by chemolithoautotrophic nitrification; these samples were also characterized by low DO and NO₃-N concentrations and elevated Cl and Mn concentrations indicating anthropogenic contamination and denitrification in the aquifer. These conditions were observed primarily in aquifers on floodplains. Statistical comparison between land-use groups revealed that Cl/Br ratios were more diagnostic for the impact of different land-use types on groundwater quality than stable isotope compositions of nitrate. This indicates that the former is an additional efficient tracer for the effect of land use on groundwater quality in agricultural areas. We conclude that the combination of groundwater age dating together with the use of chemical and isotopic parameters is a highly effective but yet underutilized approach for elucidating the sources and the fate of nitrate in aquifers in Asia.

  8. Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures.

    PubMed

    Wagner, Fabien B; Eskandar, Emad N; Cosgrove, G Rees; Madsen, Joseph R; Blum, Andrew S; Potter, N Stevenson; Hochberg, Leigh R; Cash, Sydney S; Truccolo, Wilson

    2015-11-15

    Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4×4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~2-3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25-60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA

  9. Spatiotemporal Behavior and Nonlinear Dynamics in a Phase Conjugate Resonator

    NASA Astrophysics Data System (ADS)

    Liu, Siuying Raymond

    The work described in this dissertation can be divided into two parts. The first part is an investigation of the transient behavior and stability property of a phase conjugate resonator (PCR) below threshold. The second part is an experimental and theoretical study of the PCR's spatiotemporal dynamics above threshold. The time-dependent coupled wave equations for four-wave mixing (FWM) in a photorefractive crystal, with two distinct interaction regions caused by feedback from an ordinary mirror, was used to model the transient dynamics of a PCR below threshold. Analytical expressions of the steady state cavity's fields for the case of nondepleted pumps and an absorption free medium were derived and used to determine the self-oscillation conditions. The solutions, through simple frequency domain transformation techniques, were used to define the PCR's transfer function and analyse its stability. Taking into account pump depletion and medium absorption, the transient buildup and decay times of the cavity's fields as well as the specularly reflected and phase conjugate reflected intensities were numerically calculated as functions of a number of system parameters such as the coupling parameter and the pump and probe ratios. Experiments were carried out above threshold to study the spatiotemporal dynamics of the PCR as a function of the Bragg detuning achieved by misaligning one of the two pump beams and of the degree of transverse confinement controlled by varying the resonator's Fresnel number. The temporal aspects of the beam's complexity were studied by local intensity time series, power spectra, and reconstructed pseudo phase portraits. The transverse dynamics and the spatiotemporal instabilities were also described by modeling the three dimensional coupled wave equations in photorefractive FWM, using a truncated modal expansion approach. Numerical solutions of the model revealed the presence and motion of optical vortices in the wavefront. Simulations using the

  10. Microscale Spatiotemporal Dynamics during Neocortical Propagation of Human Focal Seizures

    PubMed Central

    Wagner, Fabien B.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.; Truccolo, Wilson

    2015-01-01

    Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4 × 4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) A newly developed stage segmentation method, applied to local field potentials (LFPs) and multi-unit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~ 2–3Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25–60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the

  11. Internally Recurring Hippocampal Sequences as a Population Template of Spatiotemporal Information

    PubMed Central

    Villette, Vincent; Malvache, Arnaud; Tressard, Thomas; Dupuy, Nathalie; Cossart, Rosa

    2015-01-01

    Summary The hippocampus is essential for spatiotemporal cognition. Sequences of neuronal activation provide a substrate for this fundamental function. At the behavioral timescale, these sequences have been shown to occur either in the presence of successive external landmarks or through internal mechanisms within an episodic memory task. In both cases, activity is externally constrained by the organization of the task and by the size of the environment explored. Therefore, it remains unknown whether hippocampal activity can self-organize into a default mode in the absence of any external memory demand or spatiotemporal boundary. Here we show that, in the presence of self-motion cues, a population code integrating distance naturally emerges in the hippocampus in the form of recurring sequences. These internal dynamics clamp spontaneous travel since run distance distributes into integer multiples of the span of these sequences. These sequences may thus guide navigation when external landmarks are reduced. PMID:26494280

  12. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

    PubMed Central

    Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

    2016-01-01

    Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

  13. Spatio-temporal dependencies between hospital beds, physicians and health expenditure using visual variables and data classification in statistical table

    NASA Astrophysics Data System (ADS)

    Medyńska-Gulij, Beata; Cybulski, Paweł

    2016-06-01

    This paper analyses the use of table visual variables of statistical data of hospital beds as an important tool for revealing spatio-temporal dependencies. It is argued that some of conclusions from the data about public health and public expenditure on health have a spatio-temporal reference. Different from previous studies, this article adopts combination of cartographic pragmatics and spatial visualization with previous conclusions made in public health literature. While the significant conclusions about health care and economic factors has been highlighted in research papers, this article is the first to apply visual analysis to statistical table together with maps which is called previsualisation.

  14. Super-resolved Parallel MRI by Spatiotemporal Encoding

    PubMed Central

    Schmidt, Rita; Baishya, Bikash; Ben-Eliezer, Noam; Seginer, Amir; Frydman, Lucio

    2016-01-01

    Recent studies described an alternative “ultrafast” scanning method based on spatiotemporal (SPEN) principles. SPEN demonstrates numerous potential advantages over EPI-based alternatives, at no additional expense in experimental complexity. An important aspect that SPEN still needs to achieve for providing a competitive acquisition alternative entails exploiting parallel imaging algorithms, without compromising its proven capabilities. The present work introduces a combination of multi-band frequency-swept pulses simultaneously encoding multiple, partial fields-of-view; together with a new algorithm merging a Super-Resolved SPEN image reconstruction and SENSE multiple-receiving methods. The ensuing approach enables one to reduce both the excitation and acquisition times of ultrafast SPEN acquisitions by the customary acceleration factor R, without compromises in either the ensuing spatial resolution, SAR deposition, or the capability to operate in multi-slice mode. The performance of these new single-shot imaging sequences and their ancillary algorithms were explored on phantoms and human volunteers at 3T. The gains of the parallelized approach were particularly evident when dealing with heterogeneous systems subject to major T2/T2* effects, as is the case upon single-scan imaging near tissue/air interfaces. PMID:24120293

  15. Controlling spatiotemporal chaos in active dissipative-dispersive nonlinear systems

    NASA Astrophysics Data System (ADS)

    Gomes, S. N.; Pradas, M.; Kalliadasis, S.; Papageorgiou, D. T.; Pavliotis, G. A.

    2015-08-01

    We present an alternative methodology for the stabilization and control of infinite-dimensional dynamical systems exhibiting low-dimensional spatiotemporal chaos. We show that with an appropriate choice of time-dependent controls we are able to stabilize and/or control all stable or unstable solutions, including steady solutions, traveling waves (single and multipulse ones or bound states), and spatiotemporal chaos. We exemplify our methodology with the generalized Kuramoto-Sivashinsky equation, a paradigmatic model of spatiotemporal chaos, which is known to exhibit a rich spectrum of wave forms and wave transitions and a rich variety of spatiotemporal structures.

  16. SPATIO-TEMPORAL COMPLEXITY OF THE AORTIC SINUS VORTEX.

    PubMed

    Moore, Brandon; Dasi, Lakshmi Prasad

    2014-06-01

    The aortic sinus vortex is a classical flow structure of significant importance to aortic valve dynamics and the initiation and progression of calific aortic valve disease. We characterize the spatio-temporal characteristics of aortic sinus voxtex dynamics in relation to the viscosity of blood analog solution as well as heart rate. High resolution time-resolved (2KHz) particle image velocimetry was conducted to capture 2D particle streak videos and 2D instantaneous velocity and streamlines along the sinus midplane using a physiological but rigid aorta model fitted with a porcine bioprosthetic heart valve. Blood analog fluids used include a water-glycerin mixture and saline to elucidate the sensitivity of vortex dynamics to viscosity. Experiments were conducted to record 10 heart beats for each combination of blood analog and heart rate condition. Results show that the topological characteristics of the velocity field vary in time-scales as revealed using time bin averaged vectors and corresponding instantaneous streamlines. There exist small time-scale vortices and a large time-scale main vortex. A key flow structure observed is the counter vortex at the upstream end of the sinus adjacent to the base (lower half) of the leaflet. The spatio-temporal complexity of vortex dynamics is shown to be profoundly influenced by strong leaflet flutter during systole with a peak frequency of 200Hz and peak amplitude of 4 mm observed in the saline case. While fluid viscosity influences the length and time-scales as well as the introduction of leaflet flutter, heart rate influences the formation of counter vortex at the upstream end of the sinus. Higher heart rates are shown to reduce the strength of the counter vortex that can greatly influence the directionality and strength of shear stresses along the base of the leaflet. This study demonstrates the impact of heart rate and blood analog viscosity on aortic sinus hemodynamics.

  17. Spatiotemporal Analysis of the 2014 Ebola Epidemic in West Africa

    PubMed Central

    Backer, Jantien A.; Wallinga, Jacco

    2016-01-01

    In 2014–2016, Guinea, Sierra Leone and Liberia in West Africa experienced the largest and longest Ebola epidemic since the discovery of the virus in 1976. During the epidemic, incidence data were collected and published at increasing resolution. To monitor the epidemic as it spread within and between districts, we develop an analysis method that exploits the full spatiotemporal resolution of the data by combining a local model for time-varying effective reproduction numbers with a gravity-type model for spatial dispersion of the infection. We test this method in simulations and apply it to the weekly incidences of confirmed and probable cases per district up to June 2015, as reported by the World Health Organization. Our results indicate that, of the newly infected cases, only a small percentage, between 4% and 10%, migrates to another district, and a minority of these migrants, between 0% and 23%, leave their country. The epidemics in the three countries are found to be similar in estimated effective reproduction numbers, and in the probability of importing infection into a district. The countries might have played different roles in cross-border transmissions, although a sensitivity analysis suggests that this could also be related to underreporting. The spatiotemporal analysis method can exploit available longitudinal incidence data at different geographical locations to monitor local epidemics, determine the extent of spatial spread, reveal the contribution of local and imported cases, and identify sources of introductions in uninfected areas. With good quality data on incidence, this data-driven method can help to effectively control emerging infections. PMID:27930675

  18. Spatio-temporal activity of lightnings over Greece

    NASA Astrophysics Data System (ADS)

    Nastos, P. T.; Matsangouras, I. T.; Chronis, T. G.

    2012-04-01

    Extreme precipitation events are always associated with convective weather conditions driving to intense lightning activity: Cloud to Ground (CG), Ground to Cloud (GC) and Cloud to Cloud (CC). Thus, the study of lightnings, which typically occur during thunderstorms, gives evidence of the spatio-temporal variability of intense precipitation. Lightning is a natural phenomenon in the atmosphere, being a major cause of storm related with deaths and main trigger of forest fires during dry season. Lightning affects the many electrochemical systems of the body causing nerve damage, memory loss, personality change, and emotional problems. Besides, among the various nitrogen oxides sources, the contribution from lightning likely represents the largest uncertainty. An operational lightning detection network (LDN) has been established since 2007 by HNMS, consisting of eight time-of-arrival sensors (TOA), spatially distributed across Greek territory. In this study, the spatial and temporal variability of recorded lightnings (CG, GC and CC) are analyzed over Greece, during the period from January 14, 2008 to December 31, 2009, for the first time. The data for retrieving the location and time-of-occurrence of lightning were acquired from Hellenic National Meteorological Service (HNMS). In addition to the analysis of spatio-temporal activity over Greece, the HNMS-LDN characteristics are also presented. The results of the performed analysis reveal the specific geographical sub-regions associated with lightnings incidence. Lightning activity occurs mainly during the autumn season, followed by summer and spring. Higher frequencies of flashes appear over Ionian and Aegean Sea than over land during winter period against continental mountainous regions during summer period.

  19. Spatiotemporal conceptual platform for querying archaeological information systems

    NASA Astrophysics Data System (ADS)

    Partsinevelos, Panagiotis; Sartzetaki, Mary; Sarris, Apostolos

    2015-04-01

    Spatial and temporal distribution of archaeological sites has been shown to associate with several attributes including marine, water, mineral and food resources, climate conditions, geomorphological features, etc. In this study, archeological settlement attributes are evaluated under various associations in order to provide a specialized query platform in a geographic information system (GIS). Towards this end, a spatial database is designed to include a series of archaeological findings for a secluded geographic area of Crete in Greece. The key categories of the geodatabase include the archaeological type (palace, burial site, village, etc.), temporal information of the habitation/usage period (pre Minoan, Minoan, Byzantine, etc.), and the extracted geographical attributes of the sites (distance to sea, altitude, resources, etc.). Most of the related spatial attributes are extracted with readily available GIS tools. Additionally, a series of conceptual data attributes are estimated, including: Temporal relation of an era to a future one in terms of alteration of the archaeological type, topologic relations of various types and attributes, spatial proximity relations between various types. These complex spatiotemporal relational measures reveal new attributes towards better understanding of site selection for prehistoric and/or historic cultures, yet their potential combinations can become numerous. Therefore, after the quantification of the above mentioned attributes, they are classified as of their importance for archaeological site location modeling. Under this new classification scheme, the user may select a geographic area of interest and extract only the important attributes for a specific archaeological type. These extracted attributes may then be queried against the entire spatial database and provide a location map of possible new archaeological sites. This novel type of querying is robust since the user does not have to type a standard SQL query but

  20. Direct comparison between genomic constitution and flavonoid contents in Allium multiple alien addition lines reveals chromosomal locations of genes related to biosynthesis from dihydrokaempferol to quercetin glucosides in scaly leaf of shallot (Allium cepa L.).

    PubMed

    Masuzaki, S; Shigyo, M; Yamauchi, N

    2006-02-01

    The extrachromosome 5A of shallot (Allium cepa L., genomes AA) has an important role in flavonoid biosynthesis in the scaly leaf of Allium fistulosum-shallot monosomic addition lines (FF+nA). This study deals with the production and biochemical characterisation of A. fistulosum-shallot multiple alien addition lines carrying at least 5A to determine the chromosomal locations of genes for quercetin formation. The multiple alien additions were selected from the crossing between allotriploid FFA (female symbol) and A. fistulosum (male symbol). The 113 plants obtained from this cross were analysed by a chromosome 5A-specific PGI isozyme marker of shallot. Thirty plants were preliminarily selected for an alien addition carrying 5A. The chromosome numbers of the 30 plants varied from 18 to 23. The other extrachromosomes in 19 plants were completely identified by using seven other chromosome markers of shallot. High-performance liquid chromatography analyses of the 19 multiple additions were conducted to identify the flavonoid compounds produced in the scaly leaves. Direct comparisons between the chromosomal constitution and the flavonoid contents of the multiple alien additions revealed that a flavonoid 3'-hydroxylase (F3'H) gene for the synthesis of quercetin from kaempferol was located on 7A and that an anonymous gene involved in the glucosidation of quercetin was on 3A or 4A. As a result of supplemental SCAR analyses by using genomic DNAs from two complete sets of A. fistulosum-shallot monosomic additions, we have assigned F3'H to 7A and flavonol synthase to 4A.

  1. Role of bioactive 3D hybrid fibrous scaffolds on mechanical behavior and spatiotemporal osteoblast gene expression.

    PubMed

    Allo, Bedilu A; Lin, Shigang; Mequanint, Kibret; Rizkalla, Amin S

    2013-08-14

    Three-dimensional (3D) bioactive organic-inorganic (O/I) hybrid fibrous scaffolds are attractive extracellular matrix (ECM) surrogates for bone tissue engineering. With the aim of regulating osteoblast gene expression in 3D, a new class of hybrid fibrous scaffolds with two distinct fiber diameters (260 and 600 nm) and excellent physico-mechanical properties were fabricated from tertiary (SiO2-CaO-P2O5) bioactive glass (BG) and poly (ε-caprolactone) (PCL) by in situ sol-gel and electrospinning process. The PCL/BG hybrid fibrous scaffolds exhibited accelerated wetting properties, enhanced pore sizes and porosity, and superior mechanical properties that were dependent on fiber diameter. Contrary to control PCL fibrous scaffolds that were devoid of bonelike apatite particles, incubating PCL/BG hybrid fibrous scaffolds in simulated body fluid (SBF) revealed bonelike apatite deposition. Osteoblast cells cultured on PCL/BG hybrid fibrous scaffolds spread with multiple attachments and actively proliferated suggesting that the low temperature in situ sol-gel and electrospinning process did not have a detrimental effect. Targeted bone-associated gene expressions by rat calvarial osteoblasts seeded on these hybrid scaffolds demonstrated remarkable spatiotemporal gene activation. Transcriptional-level gene expressions for alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin (OCN) were significantly higher on the hybrid fibrous scaffolds (p < 0.001) that were largely dependent on fiber diameter compared. Taken together, our results suggest that PCL/BG fibrous scaffolds may accelerate bone formation by providing a favorable microenvironment.

  2. Transition effects characterization on spatiotemporal images

    NASA Astrophysics Data System (ADS)

    Ruiloba, Rosa I.; Joly, Philippe

    2000-10-01

    This article presents the results of a study on spatio-temporal images to evaluate their performances for video-to-shots segmentation purposes. Some shots segmentation methods involve spatio-temporal images that are computed by a projection of successive video frames over the X or Y-axis. On these projections, transition effects and motion are supposed to have different characteristics. Whereas cuts can be easily recognized, the main problem remains in determining a measure that discriminates motions from gradual transition effects. In this article, the quality of transition detections based on line similarity of spatio-temporal images is studied. The probability functions of several measures are estimated to determine which one produce the lowest detection error rate. These distributions are computed on four classes of events: intra shot sequences without motion, sequences with cuts, sequences with fades and sequences with motion. A line matching is performed, based on correlation estimations between projection lines. To separate these classes, we estimate first the density probability functions of the correlation between consecutive lines for each class. For different line segment sizes, the experimental results prove that the class separation can not be clearly produced. To take into account the evolution of the correlation and because we try to detect some particular types of boundaries, we then consider ratios between statistic moments. There are computed over a subset of correlation values. The results show that used measures, based on the matching of projection lines, can not discriminate between motion and fade. Only a subset of motions will be differentiated from gradual transitions. Therefore previous measures should be combined with methods that produce complementary results. Such a method could be a similar measure based on correlation between spatial-shifted segments.

  3. Spatial and Spatiotemporal Data Mining: Recent Advances

    SciTech Connect

    Shekhar, Shashi; Vatsavai, Raju; Celik, Mete

    2008-01-01

    Explosive growth in geospatial data and the emergence of new spatial technologies emphasize the need for automated discovery of spatial knowledge. Spatial data mining is the process of discovering interesting and previously unknown, but potentially useful patterns from large spatial databases. The complexity of spatial data and intrinsic spatial relationships limits the usefulness of conventional data mining techniques for extracting spatial patterns. In this chapter we explore the emerging field of spatial data mining, focusing on four major topics: prediction and classification, outlier detection, co-location mining, and clustering. Spatiotemporal data mining is also briefly discussed.

  4. Spatiotemporal evolution of bacterial biofilm colonies

    NASA Astrophysics Data System (ADS)

    Wilking, James; Koehler, Stephan; Sinha, Naveen; Seminara, Agnese; Brenner, Michael; Weitz, David

    2014-03-01

    Many bacteria on earth live in surface-attached communities known as biofilms. Gene expression in a biofilm is typically varied, resulting in a variety of phenotypes within a single film. These phenotypes play a critical role in biofilm physiology and development. We use time-resolved, wide-field fluorescence microscopy to image triple-labeled fluorescent Bacillus Subtilis colonies grown on agar to determine in a non-invasive fashion the evolving phenotypes. We infer their transition rates from the resulting spatiotemporal maps of gene expression. Moreover, we correlate these transition rates with local measurements of nutrient concentration to determine the influence of extracellular signals on gene expression.

  5. Spatiotemporal rogue events in femtosecond filamentation

    SciTech Connect

    Majus, D.; Jukna, V.; Valiulis, G.; Dubietis, A.; Faccio, D.

    2011-02-15

    We present experimental and numerical investigations of optical extreme (rogue) event statistics recorded in the regime of femtosecond pulse filamentation in water. In the spectral domain, the extreme events manifest themselves as either large or small extremes of the spectral intensity, justified by right- or left-tailed statistical distributions, respectively. In the time domain, the observed extreme events are associated with pulse splitting and energy redistribution in space and therefore are exquisitely linked to three-dimensional, spatiotemporal dynamics and formation of the X waves.

  6. Analyzing spatial clustering and the spatiotemporal nature and trends of HIV/AIDS prevalence using GIS: the case of Malawi, 1994-2010

    PubMed Central

    2014-01-01

    Background Although local spatiotemporal analysis can improve understanding of geographic variation of the HIV epidemic, its drivers, and the search for targeted interventions, it is limited in sub-Saharan Africa. Despite recent declines, Malawi’s estimated 10.0% HIV prevalence (2011) remained among the highest globally. Using data on pregnant women in Malawi, this study 1) examines spatiotemporal trends in HIV prevalence 1994-2010, and 2) for 2010, identifies and maps the spatial variation/clustering of factors associated with HIV prevalence at district level. Methods Inverse distance weighting was used within ArcGIS Geographic Information Systems (GIS) software to generate continuous surfaces of HIV prevalence from point data (1994, 1996, 1999, 2001, 2003, 2005, 2007, and 2010) obtained from surveillance antenatal clinics. From the surfaces prevalence estimates were extracted at district level and the results mapped nationally. Spatial dependency (autocorrelation) and clustering of HIV prevalence were also analyzed. Correlation and multiple regression analyses were used to identify factors associated with HIV prevalence for 2010 and their spatial variation/clustering mapped and compared to HIV clustering. Results Analysis revealed wide spatial variation in HIV prevalence at regional, urban/rural, district and sub-district levels. However, prevalence was spatially leveling out within and across ‘sub-epidemics’ while declining significantly after 1999. Prevalence exhibited statistically significant spatial dependence nationally following initial (1995-1999) localized, patchy low/high patterns as the epidemic spread rapidly. Locally, HIV “hotspots” clustered among eleven southern districts/cities while a “coldspot” captured configurations of six central region districts. Preliminary multiple regression of 2010 HIV prevalence produced a model with four significant explanatory factors (adjusted R2 = 0.688): mean distance to main roads, mean travel time

  7. Transient spatiotemporal chaos in the Morris-Lecar neuronal ring network

    NASA Astrophysics Data System (ADS)

    Keplinger, Keegan; Wackerbauer, Renate

    2014-03-01

    Transient behavior is thought to play an integral role in brain functionality. Numerical simulations of the firing activity of diffusively coupled, excitable Morris-Lecar neurons reveal transient spatiotemporal chaos in the parameter regime below the saddle-node on invariant circle bifurcation point. The neighborhood of the chaotic saddle is reached through perturbations of the rest state, in which few initially active neurons at an effective spatial distance can initiate spatiotemporal chaos. The system escapes from the neighborhood of the chaotic saddle to either the rest state or to a state of pulse propagation. The lifetime of the chaotic transients is manipulated in a statistical sense through a singular application of a synchronous perturbation to a group of neurons.

  8. Synchronization and spatiotemporal patterns in coupled phase oscillators on a weighted planar network

    NASA Astrophysics Data System (ADS)

    Kagawa, Yuki; Takamatsu, Atsuko

    2009-04-01

    To reveal the relation between network structures found in two-dimensional biological systems, such as protoplasmic tube networks in the plasmodium of true slime mold, and spatiotemporal oscillation patterns emerged on the networks, we constructed coupled phase oscillators on weighted planar networks and investigated their dynamics. Results showed that the distribution of edge weights in the networks strongly affects (i) the propensity for global synchronization and (ii) emerging ratios of oscillation patterns, such as traveling and concentric waves, even if the total weight is fixed. In-phase locking, traveling wave, and concentric wave patterns were, respectively, observed most frequently in uniformly weighted, center weighted treelike, and periphery weighted ring-shaped networks. Controlling the global spatiotemporal patterns with the weight distribution given by the local weighting (coupling) rules might be useful in biological network systems including the plasmodial networks and neural networks in the brain.

  9. Transient spatiotemporal chaos in the Morris-Lecar neuronal ring network

    SciTech Connect

    Keplinger, Keegan Wackerbauer, Renate

    2014-03-15

    Transient behavior is thought to play an integral role in brain functionality. Numerical simulations of the firing activity of diffusively coupled, excitable Morris-Lecar neurons reveal transient spatiotemporal chaos in the parameter regime below the saddle-node on invariant circle bifurcation point. The neighborhood of the chaotic saddle is reached through perturbations of the rest state, in which few initially active neurons at an effective spatial distance can initiate spatiotemporal chaos. The system escapes from the neighborhood of the chaotic saddle to either the rest state or to a state of pulse propagation. The lifetime of the chaotic transients is manipulated in a statistical sense through a singular application of a synchronous perturbation to a group of neurons.

  10. Revealing the multiple structures of serine

    PubMed Central

    Blanco, Susana; Sanz, M. Eugenia; López, Juan C.; Alonso, José L.

    2007-01-01

    We explored the conformational landscape of the proteinogenic amino acid serine [CH2OHCH(NH2)COOH] in the gas phase. Solid serine was vaporized by laser ablation, expanded in a supersonic jet, and characterized by Fourier transform microwave spectroscopy. In the isolation conditions of the jet there have been discovered up to seven different neutral (non-zwitterionic) structures of serine, which are conclusively identified by the comparison between the experimental values of the rotational and quadrupole coupling constants with those predicted by ab initio calculations. These seven forms can serve as a basis to represent the shape of serine in the gas phase. From the postexpansion abundances we derived the conformational stability trend, which is controlled by the subtle network of intramolecular hydrogen bonds formed between the polar groups in the amino acid backbone and the hydroxy side chain. It is proposed that conformational cooling perturbs the equilibrium conformational distribution; thus, some of the lower-energy forms are “missing” in the supersonic expansion. PMID:18077350

  11. Spatio-temporal patterns of stream methane and carbon dioxide emissions in a hemiboreal catchment in Southwest Sweden

    NASA Astrophysics Data System (ADS)

    Natchimuthu, Sivakiruthika; Wallin, Marcus B.; Klemedtsson, Leif; Bastviken, David

    2017-01-01

    Global stream and river greenhouse gas emissions seem to be as large as the oceanic C uptake. However, stream and river emissions are uncertain until both spatial and temporal variability have been quantified. Here we investigated in detail the stream CH4 and CO2 emissions within a hemiboreal catchment in Southwest Sweden primarily covered by coniferous forest. Gas transfer velocities (k600), CH4 and CO2 concentrations were measured with multiple methods. Our data supported modelling approaches accounting for various stream slopes, water velocities and discharge. The results revealed large but partially predictable spatio-temporal variabilities in k600, dissolved gas concentrations, and emissions. The variability in CO2 emission was best explained by the variability in k, while dissolved CH4 concentrations explained most of the variability in CH4 emission, having implications for future measurements. There were disproportionately large emissions from high slope stream reaches including waterfalls, and from high discharge events. In the catchment, stream reaches with low slope and time periods of moderate discharge dominated (90% of area and 69% of time). Measurements in these stream areas and time periods only accounted for <36% of the total estimated emissions. Hence, not accounting for local or episodic high emissions can lead to substantially underestimated emissions.

  12. Spatio-temporal patterns of stream methane and carbon dioxide emissions in a hemiboreal catchment in Southwest Sweden.

    PubMed

    Natchimuthu, Sivakiruthika; Wallin, Marcus B; Klemedtsson, Leif; Bastviken, David

    2017-01-03

    Global stream and river greenhouse gas emissions seem to be as large as the oceanic C uptake. However, stream and river emissions are uncertain until both spatial and temporal variability have been quantified. Here we investigated in detail the stream CH4 and CO2 emissions within a hemiboreal catchment in Southwest Sweden primarily covered by coniferous forest. Gas transfer velocities (k600), CH4 and CO2 concentrations were measured with multiple methods. Our data supported modelling approaches accounting for various stream slopes, water velocities and discharge. The results revealed large but partially predictable spatio-temporal variabilities in k600, dissolved gas concentrations, and emissions. The variability in CO2 emission was best explained by the variability in k, while dissolved CH4 concentrations explained most of the variability in CH4 emission, having implications for future measurements. There were disproportionately large emissions from high slope stream reaches including waterfalls, and from high discharge events. In the catchment, stream reaches with low slope and time periods of moderate discharge dominated (90% of area and 69% of time). Measurements in these stream areas and time periods only accounted for <36% of the total estimated emissions. Hence, not accounting for local or episodic high emissions can lead to substantially underestimated emissions.

  13. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons

    PubMed Central

    Appel, Elena; Weissmann, Sarit; Salzberg, Yehuda; Orlovsky, Kira; Negreanu, Varda; Tsoory, Michael; Raanan, Calanit; Feldmesser, Ester; Bernstein, Yael; Wolstein, Orit; Levanon, Ditsa; Groner, Yoram

    2016-01-01

    The Runx3 transcription factor is essential for development and diversification of the dorsal root ganglia (DRGs) TrkC sensory neurons. In Runx3-deficient mice, developing TrkC neurons fail to extend central and peripheral afferents, leading to cell death and disruption of the stretch reflex circuit, resulting in severe limb ataxia. Despite its central role, the mechanisms underlying the spatiotemporal expression specificities of Runx3 in TrkC neurons were largely unknown. Here we first defined the genomic transcription unit encompassing regulatory elements (REs) that mediate the tissue-specific expression of Runx3. Using transgenic mice expressing BAC reporters spanning the Runx3 locus, we discovered three REs—dubbed R1, R2, and R3—that cross-talk with promoter-2 (P2) to drive TrkC neuron-specific Runx3 transcription. Deletion of single or multiple elements either in the BAC transgenics or by CRISPR/Cas9-mediated endogenous ablation established the REs’ ability to promote and/or repress Runx3 expression in developing sensory neurons. Our analysis reveals that an intricate combinatorial interplay among the three REs governs Runx3 expression in distinct subtypes of TrkC neurons while concomitantly extinguishing its expression in non-TrkC neurons. These findings provide insights into the mechanism regulating cell type-specific expression and subtype diversification of TrkC neurons in developing DRGs. PMID:28007784

  14. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons.

    PubMed

    Appel, Elena; Weissmann, Sarit; Salzberg, Yehuda; Orlovsky, Kira; Negreanu, Varda; Tsoory, Michael; Raanan, Calanit; Feldmesser, Ester; Bernstein, Yael; Wolstein, Orit; Levanon, Ditsa; Groner, Yoram

    2016-12-01

    The Runx3 transcription factor is essential for development and diversification of the dorsal root ganglia (DRGs) TrkC sensory neurons. In Runx3-deficient mice, developing TrkC neurons fail to extend central and peripheral afferents, leading to cell death and disruption of the stretch reflex circuit, resulting in severe limb ataxia. Despite its central role, the mechanisms underlying the spatiotemporal expression specificities of Runx3 in TrkC neurons were largely unknown. Here we first defined the genomic transcription unit encompassing regulatory elements (REs) that mediate the tissue-specific expression of Runx3. Using transgenic mice expressing BAC reporters spanning the Runx3 locus, we discovered three REs-dubbed R1, R2, and R3-that cross-talk with promoter-2 (P2) to drive TrkC neuron-specific Runx3 transcription. Deletion of single or multiple elements either in the BAC transgenics or by CRISPR/Cas9-mediated endogenous ablation established the REs' ability to promote and/or repress Runx3 expression in developing sensory neurons. Our analysis reveals that an intricate combinatorial interplay among the three REs governs Runx3 expression in distinct subtypes of TrkC neurons while concomitantly extinguishing its expression in non-TrkC neurons. These findings provide insights into the mechanism regulating cell type-specific expression and subtype diversification of TrkC neurons in developing DRGs.

  15. Spatio-temporal patterns of stream methane and carbon dioxide emissions in a hemiboreal catchment in Southwest Sweden

    PubMed Central

    Natchimuthu, Sivakiruthika; Wallin, Marcus B.; Klemedtsson, Leif; Bastviken, David

    2017-01-01

    Global stream and river greenhouse gas emissions seem to be as large as the oceanic C uptake. However, stream and river emissions are uncertain until both spatial and temporal variability have been quantified. Here we investigated in detail the stream CH4 and CO2 emissions within a hemiboreal catchment in Southwest Sweden primarily covered by coniferous forest. Gas transfer velocities (k600), CH4 and CO2 concentrations were measured with multiple methods. Our data supported modelling approaches accounting for various stream slopes, water velocities and discharge. The results revealed large but partially predictable spatio-temporal variabilities in k600, dissolved gas concentrations, and emissions. The variability in CO2 emission was best explained by the variability in k, while dissolved CH4 concentrations explained most of the variability in CH4 emission, having implications for future measurements. There were disproportionately large emissions from high slope stream reaches including waterfalls, and from high discharge events. In the catchment, stream reaches with low slope and time periods of moderate discharge dominated (90% of area and 69% of time). Measurements in these stream areas and time periods only accounted for <36% of the total estimated emissions. Hence, not accounting for local or episodic high emissions can lead to substantially underestimated emissions. PMID:28045092

  16. Spatiotemporal Data Mining, Analysis, and Visualization of Human Activity Data

    ERIC Educational Resources Information Center

    Li, Xun

    2012-01-01

    This dissertation addresses the research challenge of developing efficient new methods for discovering useful patterns and knowledge in large volumes of electronically collected spatiotemporal activity data. I propose to analyze three types of such spatiotemporal activity data in a methodological framework that integrates spatial analysis, data…

  17. Faster P300 Classifier Training Using Spatiotemporal Beamforming.

    PubMed

    Wittevrongel, Benjamin; Van Hulle, Marc M

    2016-05-01

    The linearly-constrained minimum-variance (LCMV) beamformer is traditionally used as a spatial filter for source localization, but here we consider its spatiotemporal extension for P300 classification. We compare two variants and show that the spatiotemporal LCMV beamformer is at par with state-of-the-art P300 classifiers, but several orders of magnitude faster in training the classifier.

  18. Spatiotemporal characteristics of electrocortical brain activity during mental calculation.

    PubMed

    Vansteensel, Mariska J; Bleichner, Martin G; Freudenburg, Zac V; Hermes, Dora; Aarnoutse, Erik J; Leijten, Frans S S; Ferrier, Cyrille H; Jansma, Johan Martijn; Ramsey, Nick F

    2014-12-01

    Mental calculation is a complex mental procedure involving a frontoparietal network of brain regions. Functional MRI (fMRI) studies have revealed interesting characteristics of these regions, but the precise function of some areas remains elusive. In the present study, we used electrocorticographic (ECoG) recordings to chronometrically assess the neuronal processes during mental arithmetic. A calculation task was performed during presurgical 3T fMRI scanning and subsequent ECoG monitoring. Mental calculation induced an increase in fMRI blood oxygen level dependent signal in prefrontal, parietal and lower temporo-occipital regions. The group-fMRI result was subsequently used to cluster the implanted electrodes into anatomically defined regions of interest (ROIs). We observed remarkable differences in high frequency power profiles between ROIs, some of which were closely associated with stimulus presentation and others with the response. Upon stimulus presentation, occipital areas were the first to respond, followed by parietal and frontal areas, and finally by motor areas. Notably, we demonstrate that the fMRI activation in the middle frontal gyrus/precentral gyrus is associated with two subfunctions during mental calculation. This finding reveals the significance of the temporal dynamics of neural ensembles within regions with an apparent uniform function. In conclusion, our results shed more light on the spatiotemporal aspects of brain activation during a mental calculation task, and demonstrate that the use of fMRI data to cluster ECoG electrodes is a useful approach for ECoG group analysis.

  19. Spatiotemporal-atlas-based dynamic speech imaging

    NASA Astrophysics Data System (ADS)

    Fu, Maojing; Woo, Jonghye; Liang, Zhi-Pei; Sutton, Bradley P.

    2016-03-01

    Dynamic magnetic resonance imaging (DS-MRI) has been recognized as a promising method for visualizing articulatory motion of speech in scientific research and clinical applications. However, characterization of the gestural and acoustical properties of the vocal tract remains a challenging task for DS-MRI because it requires: 1) reconstructing high-quality spatiotemporal images by incorporating stronger prior knowledge; and 2) quantitatively interpreting the reconstructed images that contain great motion variability. This work presents a novel imaging method that simultaneously meets both requirements by integrating a spatiotemporal atlas into a Partial Separability (PS) model-based imaging framework. Through the use of an atlas-driven sparsity constraint, this method is capable of capturing high-quality articulatory dynamics at an imaging speed of 102 frames per second and a spatial resolution of 2.2 × 2.2 mm2. Moreover, the proposed method enables quantitative characterization of variability of speech motion, compared to the generic motion pattern across all subjects, through the spatial residual components.

  20. The emergence of nonuniform spatiotemporal fractionation schemes within the standard BED model

    SciTech Connect

    Unkelbach, Jan Papp, Dávid

    2015-05-15

    Purpose: Nonuniform spatiotemporal radiotherapy fractionation schemes, i.e., delivering distinct dose distributions in different fractions can potentially improve the therapeutic ratio. This is possible if the dose distributions are designed such that similar doses are delivered to normal tissues (exploit the fractionation effect) while hypofractionating subregions of the tumor. In this paper, the authors develop methodology for treatment planning with nonuniform fractions and demonstrate this concept in the context of intensity-modulated proton therapy (IMPT). Methods: Treatment planning is performed by simultaneously optimizing (possibly distinct) IMPT dose distributions for multiple fractions. This is achieved using objective and constraint functions evaluated for the cumulative biologically equivalent dose (BED) delivered at the end of treatment. BED based treatment planning formulations lead to nonconvex optimization problems, such that local gradient based algorithms require adequate starting positions to find good local optima. To that end, the authors develop a combinatorial algorithm to initialize the pencil beam intensities. Results: The concept of nonuniform spatiotemporal fractionation schemes is demonstrated for a spinal metastasis patient treated in two fractions using stereotactic body radiation therapy. The patient is treated with posterior oblique beams with the kidneys being located in the entrance region of the beam. It is shown that a nonuniform fractionation scheme that hypofractionates the central part of the tumor allows for a skin and kidney BED reduction of approximately 10%–20%. Conclusions: Nonuniform spatiotemporal fractionation schemes represent a novel approach to exploit fractionation effects that deserves further exploration for selected disease sites.

  1. Supporting Research using Satellite Data: A Framework for Spatiotemporal Queries in SciDB

    NASA Astrophysics Data System (ADS)

    Ho, S. S.; Krcal, L.

    2015-12-01

    Natural phenomena such as haze, hurricane, and blizzard that evolve over time usually do not have well-defined boundaries. Their features may be captured by multiple satellites. To process and extract information from the large-scale satellite data, one needs a data-intensive architecture for distributed storage and computation resources. Such architecture allows end users such as scientists to effectively run their computation tasks with sharing computational resources and intermediate results, but without data replication. The satellite data is most conveniently represented using arrays, exploiting its multidimensional nature. For our investigation, we use the open-source distributed, array-based SciDB as a platform for our spatiotemporal framework. SciDB conforms with the data-intensive architecture, providing a highly effectively computational and data storage platform. Moreover, it provides standard extension points, i.e., user defined data types, operators and functions. Our current work focuses on more sophisticated indices including cartesian-coordinate indices, hierarchical triangular mesh and hybrid indices with data statistics and indexing. Furthermore, we introduce a spatiotemporal framework that allows us to generate and maintain indices according to given criteria and perform spatial and temporal operators and predicates. This framework overcomes weaknesses in SciDB where standard underlying array operations are less effective. We will demonst