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  1. Spatiotemporal Evolution of Calophaca (Fabaceae) Reveals Multiple Dispersals in Central Asian Mountains

    PubMed Central

    Zhang, Ming-Li; Wen, Zhi-Bin; Fritsch, Peter W.; Sanderson, Stewart C.

    2015-01-01

    Background The Central Asian flora plays a significant role in Eurasia and the Northern Hemisphere. Calophaca, a member of this flora, includes eight currently recognized species, and is centered in Central Asia, with some taxa extending into adjacent areas. A phylogenetic analysis of the genus utilizing nuclear ribosomal ITS and plastid trnS-trnG and rbcL sequences was carried out in order to confirm its taxonomic status and reconstruct its evolutionary history. Methodology/Principal Finding We employed BEAST Bayesian inference for dating, and S-DIVA and BBM for ancestral area reconstruction, to study its spatiotemporal evolution. Our results show that Calophacais monophyletic and nested within Caragana. The divergence time of Calophaca is estimated at ca. 8.0 Ma, most likely driven by global cooling and aridification, influenced by rapid uplift of the Qinghai Tibet Plateau margins. Conclusions/Significance According to ancestral area reconstructions, the genus most likely originated in the Pamir Mountains, a global biodiversity hotspot and hypothesized Tertiary refugium of many Central Asian plant lineages. Dispersals from this location are inferred to the western Tianshan Mountains, then northward to the Tarbagatai Range, eastward to East Asia, and westward to the Caucasus, Russia, and Europe. The spatiotemporal evolution of Calophaca provides a case contributing to an understanding of the flora and biodiversity of the Central Asian mountains and adjacent regions. PMID:25849146

  2. 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. PMID:26426798

  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. Spatio-temporal registration of multiple trajectories.

    PubMed

    Padoy, Nicolas; Hager, Gregory D

    2011-01-01

    A growing number of medical datasets now contain both a spatial and a temporal dimension. Trajectories, from tools or body features, are thus becoming increasingly important for their analysis. In this paper, we are interested in recovering the spatial and temporal differences between trajectories coming from different datasets. In particular, we address the case of surgical gestures, where trajectories contain both spatial transformations and speed differences in the execution. We first define the spatio-temporal registration problem between multiple trajectories. We then propose an optimization method to jointly recover both the rigid spatial motions and the non-linear time warpings. The optimization generates also a generic trajectory template, in which spatial and temporal differences have been factored out. This approach can be potentially used to register and compare gestures side-by-side for training sessions, to build gesture trajectory models for automation by a robot, or to register the trajectories of natural or artificial markers which follow similar motions. We demonstrate its usefulness with synthetic and real experiments. In particular, we register and analyze complex surgical gestures performed by tele-manipulation using the da Vinci robot. PMID:22003611

  5. Phylodynamics of DENV-1 reveals the spatiotemporal co-circulation of two distinct lineages in 2013 and multiple introductions of dengue virus in Goiás, Brazil.

    PubMed

    Cunha, Marielton Dos Passos; Guimarães, Vanessa Neiva; Souza, Menira; de Paula Cardoso, Divina das Dôres; de Almeida, Tâmera Nunes Vieira; de Oliveira, Thaís Santana; Fiaccadori, Fabíola Souza

    2016-09-01

    Dengue virus type 1 (DENV-1) was the first serotype introduced in Brazil, during in the 1980s. Since then, this virus has spread in the Brazilian territory, causing several outbreaks. In 2013 the highest number of dengue cases was notified, when compared to the previous years in Brazil, and the state of Goiás reported over 160 thousand cases. In this study, we aimed to present the Phylodynamics of DENV-1 isolates from the state of Goiás, Brazil, during 2013 outbreak, based on the envelope gene (E) sequences. Phylogenetic analysis revealed that Brazilian DENV-1 isolates are grouped together with viruses from genotype V in two distinct lineages (lineage I and lineage II) reflecting co-circulation. Phylogeographic analyses showed that these lineages were introduced in different moments in Goiás, Brazil, using distinct routes, likely originated from the Caribbean. Lineage I was first introduced coming from Rio de Janeiro (2007-2012), followed by the introduction from Argentina (2010-2013). Lineage II was introduced in a single moment from Rio de Janeiro and this clade has existed since 2007-2010. The different viral introduction events demonstrate the viral dispersion process with neighboring regions, which is essential for the maintenance of outbreaks and introduction of new emerging viruses. In conclusion, obtained data reveals the importance of continuous molecular surveillance of this virus in different regions, providing a better understanding of DENV-1 circulation, considering the evolutionary and virus spread patterns. PMID:27223633

  6. 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. PMID:24483663

  7. Spatiotemporal Rogue Events in Optical Multiple Filamentation

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    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.

  8. 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

  9. Motion coordination of multiple autonomous vehicles in a spatiotemporal flowfield

    NASA Astrophysics Data System (ADS)

    Peterson, Cameron Kai

    The long-term goal of this research is to provide theoretically justified control strategies to operate autonomous vehicles in spatiotemporal flowfields. The specific objective of this dissertation is to use estimation and nonlinear control techniques to generate decentralized control algorithms that enable motion coordination for multiple autonomous vehicles while operating in a time-varying flowfield. A cooperating team of vehicles can benefit from sharing data and tasking responsibilities. Many existing control algorithms promote collaboration of autonomous vehicles. However, these algorithms often fail to account for the degradation of control performance caused by flowfields. This dissertation presents decentralized multivehicle coordination algorithms designed for operation in a spatially or temporally varying flowfield. Each vehicle is represented using a Newtonian particle traveling in a plane at constant speed relative to the flow and subject to a steering control. Initially, we assume the flowfield is known and describe algorithms that stabilize a circular formation in a time-varying spatially nonuniform flow of moderate intensity. These algorithms are extended by relaxing the assumption that the flow is known: the vehicles dynamically estimate the flow and use that estimate in the control. We propose a distributed estimation and control algorithm comprising a consensus filter to share information gleaned from noisy position measurements, and an information filter to reconstruct a spatially varying flowfield. The theoretical results are illustrated with numerical simulations of circular formation control and validated in outdoor unmanned aerial vehicle (UAV) flight tests.

  10. Multiple dipole modeling of spatio-temporal MEG (magnetoencephalogram) data

    SciTech Connect

    Mosher, J.C. . Systems Engineering and Development Div. University of Southern California, Los Angeles, CA . Signal and Image Processing Inst.); Lewis, P.S. ); Leahy, R. . Signal and Image Processing Inst.); Singh, M. (University of Southern Californi

    1990-01-01

    An array of SQUID biomagentometers may be used to measure the spatio-temporal neuromagnetic field produced by the brain in response to a given sensory stimulus. A popular model for the neural activity that produces these fields is a set of current dipoles. We present here a common linear algebraic framework for three common spatio-temporal dipole models: moving and rotating dipoles, rotating dipoles with fixed location, and dipoles with fixed orientation and location. Our intent here is not to argue the merits of one model over another, but rather show how each model may be solved efficiently, and within the same framework as the others. In all cases, we assume that the location, orientation, and magnitude of the dipoles are unknown. We present the parameter estimation problem for these three models in a common framework, and show how, in each case, the problem may be decomposed into the estimation of the dipole locations using nonlinear minimization followed by linear estimation of the associated moment time series. Numerically efficient means of calculating the cost function are presented, and problems of model order selection and missing moments are also investigated. The methods described are demonstrated in a simulated application to a three dipole problem. 21 refs., 2 figs., 1 tab.

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

    PubMed

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

    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

  12. 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

  13. 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

  14. Power law in random multiplicative processes with spatio-temporal correlated multipliers

    NASA Astrophysics Data System (ADS)

    Morita, Satoru

    2016-02-01

    It is well known that random multiplicative processes generate power-law probability distributions. We study how the spatio-temporal correlation of the multipliers influences the power-law exponent. We investigate two sources of the time correlation: the local environment and the global environment. In addition, we introduce two simple models through which we analytically and numerically show that the local and global environments yield different trends in the power-law exponent.

  15. Spatiotemporal SNP analysis reveals pronounced biocomplexity at the northern range margin of Atlantic cod Gadus morhua

    PubMed Central

    Therkildsen, Nina Overgaard; Hemmer-Hansen, Jakob; Hedeholm, Rasmus Berg; Wisz, Mary S; Pampoulie, Christophe; Meldrup, Dorte; Bonanomi, Sara; Retzel, Anja; Olsen, Steffen Malskær; Nielsen, Einar Eg

    2013-01-01

    Accurate prediction of species distribution shifts in the face of climate change requires a sound understanding of population diversity and local adaptations. Previous modeling has suggested that global warming will lead to increased abundance of Atlantic cod (Gadus morhua) in the ocean around Greenland, but the dynamics of earlier abundance fluctuations are not well understood. We applied a retrospective spatiotemporal population genomics approach to examine the temporal stability of cod population structure in this region and to search for signatures of divergent selection over a 78-year period spanning major demographic changes. Analyzing >900 gene-associated single nucleotide polymorphisms in 847 individuals, we identified four genetically distinct groups that exhibited varying spatial distributions with considerable overlap and mixture. The genetic composition had remained stable over decades at some spawning grounds, whereas complete population replacement was evident at others. Observations of elevated differentiation in certain genomic regions are consistent with adaptive divergence between the groups, indicating that they may respond differently to environmental variation. Significantly increased temporal changes at a subset of loci also suggest that adaptation may be ongoing. These findings illustrate the power of spatiotemporal population genomics for revealing biocomplexity in both space and time and for informing future fisheries management and conservation efforts. PMID:23789034

  16. The Plasmodium berghei translocon of exported proteins reveals spatiotemporal dynamics of tubular extensions.

    PubMed

    Matz, Joachim M; Goosmann, Christian; Brinkmann, Volker; Grützke, Josephine; Ingmundson, Alyssa; Matuschewski, Kai; Kooij, Taco W A

    2015-01-01

    The erythrocyte is an extraordinary host cell for intracellular pathogens and requires extensive remodelling to become permissive for infection. Malaria parasites modify their host red blood cells through protein export to acquire nutrients and evade immune responses. Endogenous fluorescent tagging of three signature proteins of the Plasmodium berghei translocon of exported proteins (PTEX), heat shock protein 101, exported protein 2 (EXP2), and PTEX88, revealed motile, tubular extensions of the parasitophorous vacuole that protrude from the parasite far into the red blood cell. EXP2 displays a more prominent presence at the periphery of the parasite, consistent with its proposed role in pore formation. The tubular compartment is most prominent during trophozoite growth. Distinct spatiotemporal expression of individual PTEX components during sporogony and liver-stage development indicates additional functions and tight regulation of the PTEX translocon during parasite life cycle progression. Together, live cell imaging and correlative light and electron microscopy permitted previously unrecognized spatiotemporal and subcellular resolution of PTEX-containing tubules in murine malaria parasites. These findings further refine current models for Plasmodium-induced erythrocyte makeover. PMID:26219962

  17. The Plasmodium berghei translocon of exported proteins reveals spatiotemporal dynamics of tubular extensions

    PubMed Central

    Matz, Joachim M.; Goosmann, Christian; Brinkmann, Volker; Grützke, Josephine; Ingmundson, Alyssa; Matuschewski, Kai; Kooij, Taco W. A.

    2015-01-01

    The erythrocyte is an extraordinary host cell for intracellular pathogens and requires extensive remodelling to become permissive for infection. Malaria parasites modify their host red blood cells through protein export to acquire nutrients and evade immune responses. Endogenous fluorescent tagging of three signature proteins of the Plasmodium berghei translocon of exported proteins (PTEX), heat shock protein 101, exported protein 2 (EXP2), and PTEX88, revealed motile, tubular extensions of the parasitophorous vacuole that protrude from the parasite far into the red blood cell. EXP2 displays a more prominent presence at the periphery of the parasite, consistent with its proposed role in pore formation. The tubular compartment is most prominent during trophozoite growth. Distinct spatiotemporal expression of individual PTEX components during sporogony and liver-stage development indicates additional functions and tight regulation of the PTEX translocon during parasite life cycle progression. Together, live cell imaging and correlative light and electron microscopy permitted previously unrecognized spatiotemporal and subcellular resolution of PTEX-containing tubules in murine malaria parasites. These findings further refine current models for Plasmodium-induced erythrocyte makeover. PMID:26219962

  18. 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.

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

    PubMed

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

    2016-06-24

    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. PMID:27391722

  20. The spatiotemporal organization of cerebellar network activity resolved by two-photon imaging of multiple single neurons

    PubMed Central

    Gandolfi, Daniela; Pozzi, Paolo; Tognolina, Marialuisa; Chirico, Giuseppe; Mapelli, Jonathan; D'Angelo, Egidio

    2014-01-01

    In order to investigate the spatiotemporal organization of neuronal activity in local microcircuits, techniques allowing the simultaneous recording from multiple single neurons are required. To this end, we implemented an advanced spatial-light modulator two-photon microscope (SLM-2PM). A critical issue for cerebellar theory is the organization of granular layer activity in the cerebellum, which has been predicted by single-cell recordings and computational models. With SLM-2PM, calcium signals could be recorded from different network elements in acute cerebellar slices including granule cells (GrCs), Purkinje cells (PCs) and molecular layer interneurons. By combining WCRs with SLM-2PM, the spike/calcium relationship in GrCs and PCs could be extrapolated toward the detection of single spikes. The SLM-2PM technique made it possible to monitor activity of over tens to hundreds neurons simultaneously. GrC activity depended on the number of spikes in the input mossy fiber bursts. PC and molecular layer interneuron activity paralleled that in the underlying GrC population revealing the spread of activity through the cerebellar cortical network. Moreover, circuit activity was increased by the GABA-A receptor blocker, gabazine, and reduced by the AMPA and NMDA receptor blockers, NBQX and APV. The SLM-2PM analysis of spatiotemporal patterns lent experimental support to the time-window and center-surround organizing principles of the granular layer. PMID:24782707

  1. 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.

  2. 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. PMID:23695686

  3. Examination of spatiotemporal gait parameters during the 6-min walk in individuals with multiple sclerosis.

    PubMed

    Socie, Michael J; Motl, Robert W; Sosnoff, Jacob J

    2014-12-01

    This investigation examined spatiotemporal parameters of gait during the 6-min walk (6MW) in individuals with multiple sclerosis (MS) and in healthy controls. Eighteen individuals with MS [divided into those who were independently ambulatory (n=10) and those who were ambulatory with assistance (n=8)] and 10 healthy controls performed a 6MW while recording spatiotemporal gait parameters using a pressure-sensitive walkway. Parameters recorded were walking velocity, cadence, step length and width, step time, percent of the gait cycle in double support, and variability of step length and width, step time, and double support. The ambulatory with assistance MS group had a significantly greater reduction in walking velocity (P=0.000) over the course of the 6MW, which coincided with a significantly greater increase in step time and double support (P=0.029) than in the other groups. Only the ambulatory with assistance MS group showed an increase in step-time variability and double-support variability during the 6MW (P's<0.05). The novel results indicate that the reduction in velocity over prolonged walking occurs through a greater change in the temporal parameters of gait in persons with MS who require assistance while walking. In addition, the increase in gait variability in the individuals with MS who require assistance while walking indicates that the control over walking further deteriorates over the course of the 6MW. PMID:25117855

  4. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.

    PubMed

    Bindea, Gabriela; Mlecnik, Bernhard; Tosolini, Marie; Kirilovsky, Amos; Waldner, Maximilian; Obenauf, Anna C; Angell, Helen; Fredriksen, Tessa; Lafontaine, Lucie; Berger, Anne; Bruneval, Patrick; Fridman, Wolf Herman; Becker, Christoph; Pagès, Franck; Speicher, Michael R; Trajanoski, Zlatko; Galon, Jérôme

    2013-10-17

    The complex interactions between tumors and their microenvironment remain to be elucidated. Combining large-scale approaches, we examined the spatio-temporal dynamics of 28 different immune cell types (immunome) infiltrating tumors. We found that the immune infiltrate composition changed at each tumor stage and that particular cells had a major impact on survival. Densities of T follicular helper (Tfh) cells and innate cells increased, whereas most T cell densities decreased along with tumor progression. The number of B cells, which are key players in the core immune network and are associated with prolonged survival, increased at a late stage and showed a dual effect on recurrence and tumor progression. The immune control relevance was demonstrated in three endoscopic orthotopic colon-cancer mouse models. Genomic instability of the chemokine CXCL13 was a mechanism associated with Tfh and B cell infiltration. CXCL13 and IL21 were pivotal factors for the Tfh/B cell axis correlating with survival. This integrative study reveals the immune landscape in human colorectal cancer and the major hallmarks of the microenvironment associated with tumor progression and recurrence. PMID:24138885

  5. 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.

  6. 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

  7. Spatiotemporal Molecular Analysis of Cyanobacteria Blooms Reveals Microcystis-Aphanizomenon Interactions

    PubMed Central

    Miller, Todd R.; Beversdorf, Lucas; Chaston, Sheena D.; McMahon, Katherine D.

    2013-01-01

    Spatial and temporal variability in cyanobacterial community composition (CCC) within and between eutrophic lakes is not well-described using culture independent molecular methods. We analyzed CCC across twelve locations in four eutrophic lakes and within-lake locations in the Yahara Watershed, WI, on a weekly basis, for 5 months. Taxa were discriminated by length of MspI-digested cpcB/A intergenic spacer gene sequences and identified by comparison to a PCR-based clone library. CCC across all stations was spatially segregated by depth of sampling locations (ANOSIM R = 0.23, p < 0.001). Accordingly, CCC was correlated with thermal stratification, nitrate and soluble reactive phosphorus (SRP, R = 0.2-0.3). Spatial variability in CCC and temporal trends in taxa abundances were rarely correlative between sampling locations in the same lake indicating significant within lake spatiotemporal heterogeneity. Across all stations, a total of 37 bloom events were observed based on distinct increases in phycocyanin. Out of 97 taxa, a single Microcystis, and two different Aphanizomenon taxa were the dominant cyanobacteria detected during bloom events. The Microcystis and Aphanizomenon taxa rarely bloomed together and were significantly anti-correlated with each other at 9 of 12 stations with Pearson R values of -0.6 to -0.9 (p < 0.001). Of all environmental variables measured, nutrients, especially nitrate were significantly greater during periods of Aphanizomenon dominance while the nitrate+nitrite:SRP ratio was lower. This study shows significant spatial variability in CCC within and between lakes structured by depth of the sampling location. Furthermore, our study reveals specific genotypes involved in bloom formation. More in-depth characterization of these genotypes should lead to a better understanding of factors promoting bloom events in these lakes and more reliable bloom prediction models. PMID:24086400

  8. Resonant control of stochastic spatiotemporal dynamics in a tunnel diode by multiple time-delayed feedback.

    PubMed

    Majer, Niels; Schöll, Eckehard

    2009-01-01

    We study the control of noise-induced spatiotemporal current density patterns in a semiconductor nanostructure (double-barrier resonant tunneling diode) by multiple time-delayed feedback. We find much more pronounced resonant features of noise-induced oscillations compared to single time feedback, rendering the system more sensitive to variations in the delay time tau . The coherence of noise-induced oscillations measured by the correlation time exhibits sharp resonances as a function of tau , and can be strongly increased by optimal choices of tau . Similarly, the peaks in the power spectral density are sharpened. We provide analytical insight into the control mechanism by relating the correlation times and mean frequencies of noise-induced breathing oscillations to the stability properties of the deterministic stationary current density filaments under the influence of the control loop. Moreover, we demonstrate that the use of multiple time delays enlarges the regime in which the deterministic dynamical properties of the system are not changed by delay-induced bifurcations. PMID:19257003

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

    PubMed

    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

  10. 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

  11. 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. PMID:26901477

  12. 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.

  13. Primary motor and sensory cortical areas communicate via spatiotemporally coordinated networks at multiple frequencies.

    PubMed

    Arce-McShane, Fritzie I; Ross, Callum F; Takahashi, Kazutaka; Sessle, Barry J; Hatsopoulos, Nicholas G

    2016-05-01

    Skilled movements rely on sensory information to shape optimal motor responses, for which the sensory and motor cortical areas are critical. How these areas interact to mediate sensorimotor integration is largely unknown. Here, we measure intercortical coherence between the orofacial motor (MIo) and somatosensory (SIo) areas of cortex as monkeys learn to generate tongue-protrusive force. We report that coherence between MIo and SIo is reciprocal and that neuroplastic changes in coherence gradually emerge over a few days. These functional networks of coherent spiking and local field potentials exhibit frequency-specific spatiotemporal properties. During force generation, theta coherence (2-6 Hz) is prominent and exhibited by numerous paired signals; before or after force generation, coherence is evident in alpha (6-13 Hz), beta (15-30 Hz), and gamma (30-50 Hz) bands, but the functional networks are smaller and weaker. Unlike coherence in the higher frequency bands, the distribution of the phase at peak theta coherence is bimodal with peaks near 0° and ±180°, suggesting that communication between somatosensory and motor areas is coordinated temporally by the phase of theta coherence. Time-sensitive sensorimotor integration and plasticity may rely on coherence of local and large-scale functional networks for cortical processes to operate at multiple temporal and spatial scales. PMID:27091982

  14. Dynamical systems with multiple long-delayed feedbacks: Multiscale analysis and spatiotemporal equivalence.

    PubMed

    Yanchuk, Serhiy; Giacomelli, Giovanni

    2015-10-01

    Dynamical systems with multiple, hierarchically long-delayed feedback are introduced and studied extending our previous work [Yanchuk and Giacomelli, Phys. Rev. Lett. 112, 174103 (2014)]. Focusing on the phenomenological model of a Stuart-Landau oscillator with two feedbacks, we show the multiscale properties of its dynamics and demonstrate them by means of a space-time representation. For sufficiently long delays, we derive a normal form describing the system close to the destabilization. The space and temporal variables, which are involved in the space-time representation, correspond to suitable time scales of the original system. The physical meaning of the results, together with the interpretation of the description at different scales, is presented and discussed. In particular, it is shown how this representation uncovers hidden multiscale patterns such as spirals or spatiotemporal chaos. The effect of the delay size and the features of the transition between small and large delays is also analyzed. Finally, we comment on the application of the method and on its extension to an arbitrary, but finite, number of delayed feedback terms. PMID:26565300

  15. 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.

  16. Biomaterial constructs for delivery of multiple therapeutic genes: a spatiotemporal evaluation of efficacy using molecular beacons.

    PubMed

    Alexander, Jennifer C; Browne, Shane; Pandit, Abhay; Rochev, Yury

    2013-01-01

    Gene therapy is emerging as a potential therapeutic approach for cardiovascular pathogenesis. An appropriate therapy may require multiple genes to enhance therapeutic outcome by modulating inflammatory response and angiogenesis in a controlled and time-dependent manner. Thus, the aim of this research was to assess the spatiotemporal efficacy of a dual-gene therapy model based on 3D collagen scaffolds loaded with the therapeutic genes interleukin 10 (IL-10), a potent anti-inflammatory cytokine, and endothelial nitric oxide synthase (eNOS), a promoter of angiogenesis. A collagen-based scaffold loaded with plasmid IL-10 polyplexes and plasmid eNOS polyplexes encapsulated into microspheres was used to transfect HUVECs and HMSCs cells.The therapeutic efficacy of the system was monitored at 2, 7 and 14 days for eNOS and IL-10 mRNA expression using RT-PCR and live cell imaging molecular beacon technology. The dual gene releasing collagen-based scaffold provided both sustained and delayed release of functional polyplexes in vitro over a 14 day period which was corroborated with variation in expression levels seen using RT-PCR and MB imaging. Maximum fold increases in IL-10 mRNA and eNOS mRNA expression levels occurred at day 7 in HMSCs and HUVECs. However, IL-10 mRNA expression levels seemed dependent on frequency of media changes and/or ease of transfection of the cell type. It was demonstrated that molecular beacons are able to monitor changes in mRNA levels at various time points, in the presence of a 3D scaffolding gene carrier system and the results complemented those of RT-PCR. PMID:23755278

  17. Phenology Data Products to Support Assessment and Forecasting of Phenology on Multiple Spatiotemporal Scales

    NASA Astrophysics Data System (ADS)

    Gerst, K.; Enquist, C.; Rosemartin, A.; Denny, E. G.; Marsh, L.; Moore, D. J.; Weltzin, J. F.

    2014-12-01

    The USA National Phenology Network (USA-NPN; www.usanpn.org) serves science and society by promoting a broad understanding of plant and animal phenology and the relationships among phenological patterns and environmental change. The National Phenology Database maintained by USA-NPN now has over 3.7 million records for plants and animals for the period 1954-2014, with the majority of these observations collected since 2008 as part of a broad, national contributory science strategy. These data have been used in a number of science, conservation and resource management applications, including national assessments of historical and potential future trends in phenology, regional assessments of spatio-temporal variation in organismal activity, and local monitoring for invasive species detection. Customizable data downloads are freely available, and data are accompanied by FGDC-compliant metadata, data-use and data-attribution policies, vetted and documented methodologies and protocols, and version control. While users are free to develop custom algorithms for data cleaning, winnowing and summarization prior to analysis, the National Coordinating Office of USA-NPN is developing a suite of standard data products to facilitate use and application by a diverse set of data users. This presentation provides a progress report on data product development, including: (1) Quality controlled raw phenophase status data; (2) Derived phenometrics (e.g. onset, duration) at multiple scales; (3) Data visualization tools; (4) Tools to support assessment of species interactions and overlap; (5) Species responsiveness to environmental drivers; (6) Spatially gridded phenoclimatological products; and (7) Algorithms for modeling and forecasting future phenological responses. The prioritization of these data products is a direct response to stakeholder needs related to informing management and policy decisions. We anticipate that these products will contribute to broad understanding of plant

  18. STED-FLCS: An Advanced Tool to Reveal Spatiotemporal Heterogeneity of Molecular Membrane Dynamics

    PubMed Central

    2015-01-01

    Heterogeneous diffusion dynamics of molecules play an important role in many cellular signaling events, such as of lipids in plasma membrane bioactivity. However, these dynamics can often only be visualized by single-molecule and super-resolution optical microscopy techniques. Using fluorescence lifetime correlation spectroscopy (FLCS, an extension of fluorescence correlation spectroscopy, FCS) on a super-resolution stimulated emission depletion (STED) microscope, we here extend previous observations of nanoscale lipid dynamics in the plasma membrane of living mammalian cells. STED-FLCS allows an improved determination of spatiotemporal heterogeneity in molecular diffusion and interaction dynamics via a novel gated detection scheme, as demonstrated by a comparison between STED-FLCS and previous conventional STED-FCS recordings on fluorescent phosphoglycerolipid and sphingolipid analogues in the plasma membrane of live mammalian cells. The STED-FLCS data indicate that biophysical and biochemical parameters such as the affinity for molecular complexes strongly change over space and time within a few seconds. Drug treatment for cholesterol depletion or actin cytoskeleton depolymerization not only results in the already previously observed decreased affinity for molecular interactions but also in a slight reduction of the spatiotemporal heterogeneity. STED-FLCS specifically demonstrates a significant improvement over previous gated STED-FCS experiments and with its improved spatial and temporal resolution is a novel tool for investigating how heterogeneities of the cellular plasma membrane may regulate biofunctionality. PMID:26235350

  19. Quail-duck chimeras reveal spatiotemporal plasticity in molecular and histogenic programs of cranial feather development.

    PubMed

    Eames, B Frank; Schneider, Richard A

    2005-04-01

    The avian feather complex represents a vivid example of how a developmental module composed of highly integrated molecular and histogenic programs can become rapidly elaborated during the course of evolution. Mechanisms that facilitate this evolutionary diversification may involve the maintenance of plasticity in developmental processes that underlie feather morphogenesis. Feathers arise as discrete buds of mesenchyme and epithelium, which are two embryonic tissues that respectively form dermis and epidermis of the integument. Epithelial-mesenchymal signaling interactions generate feather buds that are neatly arrayed in space and time. The dermis provides spatiotemporal patterning information to the epidermis but precise cellular and molecular mechanisms for generating species-specific differences in feather pattern remain obscure. In the present study, we exploit the quail-duck chimeric system to test the extent to which the dermis regulates the expression of genes required for feather development. Quail and duck have distinct feather patterns and divergent growth rates, and we exchange pre-migratory neural crest cells destined to form the craniofacial dermis between them. We find that donor dermis induces host epidermis to form feather buds according to the spatial pattern and timetable of the donor species by altering the expression of members and targets of the Bone Morphogenetic Protein, Sonic Hedgehog and Delta/Notch pathways. Overall, we demonstrate that there is a great deal of spatiotemporal plasticity inherent in the molecular and histogenic programs of feather development, a property that may have played a generative and regulatory role throughout the evolution of birds. PMID:15728671

  20. Quail-duck chimeras reveal spatiotemporal plasticity in molecular and histogenic programs of cranial feather development

    PubMed Central

    Eames, B. Frank; Schneider, Richard A.

    2010-01-01

    Summary The avian feather complex represents a vivid example of how a developmental module composed of highly integrated molecular and histogenic programs can become rapidly elaborated during the course of evolution. Mechanisms that facilitate this evolutionary diversification may involve the maintenance of plasticity in developmental processes that underlie feather morphogenesis. Feathers arise as discrete buds of mesenchyme and epithelium, which are two embryonic tissues that respectively form dermis and epidermis of the integument. Epithelial-mesenchymal signaling interactions generate feather buds that are neatly arrayed in space and time. The dermis provides spatiotemporal patterning information to the epidermis but precise cellular and molecular mechanisms for generating species-specific differences in feather pattern remain obscure. In the present study, we exploit the quail-duck chimeric system to test the extent to which the dermis regulates the expression of genes required for feather development. Quail and duck have distinct feather patterns and divergent growth rates, and we exchange premigratory neural crest cells destined to form the craniofacial dermis between them. We find that donor dermis induces host epidermis to form feather buds according to the spatial pattern and timetable of the donor species by altering the expression of members and targets of the Bone Morphogenetic Protein, Sonic Hedgehog and Delta/Notch pathways. Overall, we demonstrate that there is a great deal of spatiotemporal plasticity inherent in the molecular and histogenic programs of feather development, a property that may have played a generative and regulatory role throughout the evolution of birds. PMID:15728671

  1. STED-FLCS: An Advanced Tool to Reveal Spatiotemporal Heterogeneity of Molecular Membrane Dynamics.

    PubMed

    Vicidomini, Giuseppe; Ta, Haisen; Honigmann, Alf; Mueller, Veronika; Clausen, Mathias P; Waithe, Dominic; Galiani, Silvia; Sezgin, Erdinc; Diaspro, Alberto; Hell, Stefan W; Eggeling, Christian

    2015-09-01

    Heterogeneous diffusion dynamics of molecules play an important role in many cellular signaling events, such as of lipids in plasma membrane bioactivity. However, these dynamics can often only be visualized by single-molecule and super-resolution optical microscopy techniques. Using fluorescence lifetime correlation spectroscopy (FLCS, an extension of fluorescence correlation spectroscopy, FCS) on a super-resolution stimulated emission depletion (STED) microscope, we here extend previous observations of nanoscale lipid dynamics in the plasma membrane of living mammalian cells. STED-FLCS allows an improved determination of spatiotemporal heterogeneity in molecular diffusion and interaction dynamics via a novel gated detection scheme, as demonstrated by a comparison between STED-FLCS and previous conventional STED-FCS recordings on fluorescent phosphoglycerolipid and sphingolipid analogues in the plasma membrane of live mammalian cells. The STED-FLCS data indicate that biophysical and biochemical parameters such as the affinity for molecular complexes strongly change over space and time within a few seconds. Drug treatment for cholesterol depletion or actin cytoskeleton depolymerization not only results in the already previously observed decreased affinity for molecular interactions but also in a slight reduction of the spatiotemporal heterogeneity. STED-FLCS specifically demonstrates a significant improvement over previous gated STED-FCS experiments and with its improved spatial and temporal resolution is a novel tool for investigating how heterogeneities of the cellular plasma membrane may regulate biofunctionality. PMID:26235350

  2. Spatio-temporal activity patterns of odor-induced synchronized potentials revealed by voltage-sensitive dye imaging and intracellular recording in the antennal lobe of the cockroach.

    PubMed

    Watanabe, Hidehiro; Ai, Hiroyuki; Yokohari, Fumio

    2012-01-01

    In animals, odor qualities are represented as both spatial activity patterns of glomeruli and temporal patterns of synchronized oscillatory signals in the primary olfactory centers. By optical imaging of a voltage-sensitive dye (VSD) and intracellular recording from secondary olfactory interneurons, we examined possible neural correlates of the spatial and temporal odor representations in the primary olfactory center, the antennal lobe (AL), of the cockroach Periplaneta americana. Voltage-sensitive dye imaging revealed that all used odorants induced odor-specific temporal patterns of depolarizing potentials in specific combinations of anterior glomeruli of the AL. The depolarizing potentials evoked by different odorants were temporally synchronized across glomeruli and were termed "synchronized potentials." These observations suggest that odor qualities are represented by spatio-temporal activity patterns of the synchronized potentials across glomeruli. We also performed intracellular recordings and stainings from secondary olfactory interneurons, namely projection neurons and local interneurons. We analyzed the temporal structures of enanthic acid-induced action potentials of secondary olfactory interneurons using simultaneous paired intracellular recording from two given neurons. Our results indicated that the multiple local interneurons synchronously fired in response to the olfactory stimulus. In addition, all stained enanthic acid-responsive projection neurons exhibited dendritic arborizations within the glomeruli where the synchronized potentials were evoked. Since multiple local interneurons are known to synapse to a projection neuron in each glomerulus in the cockroach AL, converging inputs from local interneurons to the projection neurons appear to contribute the odorant specific spatio-temporal activity patterns of the synchronized potentials. PMID:22848191

  3. Fine spatiotemporal activity in contracting myometrium revealed by motion-corrected calcium imaging

    PubMed Central

    Loftus, Fiona C; Shmygol, Anatoly; Richardson, Magnus J E

    2014-01-01

    Successful childbirth depends on the occurrence of precisely coordinated uterine contractions during labour. Calcium indicator fluorescence imaging is one of the main techniques for investigating the mechanisms governing this physiological process and its pathologies. The effective spatiotemporal resolution of calcium signals is, however, limited by the motion of contracting tissue: structures of interest in the order of microns can move over a hundred times their width during a contraction. The simultaneous changes in local intensity and tissue configuration make motion tracking a non-trivial problem in image analysis and confound many of the standard techniques. This paper presents a method that tracks local motion throughout the tissue and allows for the almost complete removal of motion artefacts. This provides a stabilized calcium signal down to a pixel resolution, which, for the data examined, is in the order of a few microns. As a byproduct of image stabilization, a complete kinematic description of the contraction–relaxation cycle is also obtained. This contains novel information about the mechanical response of the tissue, such as the identification of a characteristic length scale, in the order of 40–50 μm, below which tissue motion is homogeneous. Applied to our data, we illustrate that the method allows for analyses of calcium dynamics in contracting myometrium in unprecedented spatiotemporal detail. Additionally, we use the kinematics of tissue motion to compare calcium signals at the subcellular level and local contractile motion. The computer code used is provided in a freely modifiable form and has potential applicability to in vivo calcium imaging of neural tissue, as well as other smooth muscle tissue. PMID:25085893

  4. Metabarcoding reveals environmental factors influencing spatio-temporal variation in pelagic micro-eukaryotes.

    PubMed

    Brannock, Pamela M; Ortmann, Alice C; Moss, Anthony G; Halanych, Kenneth M

    2016-08-01

    Marine environments harbour a vast diversity of micro-eukaryotic organisms (protists and other small eukaryotes) that play important roles in structuring marine ecosystems. However, micro-eukaryote diversity is not well understood. Likewise, knowledge is limited regarding micro-eukaryote spatial and seasonal distribution, especially over long temporal scales. Given the importance of this group for mobilizing energy from lower trophic levels near the base of the food chain to larger organisms, assessing community stability, diversity and resilience is important to understand ecosystem health. Herein, we use a metabarcoding approach to examine pelagic micro-eukaryote communities over a 2.5-year time series. Bimonthly surface sampling (July 2009 to December 2011) was conducted at four locations within Mobile Bay (Bay) and along the Alabama continental shelf (Shelf). Alpha-diversity only showed significant differences in Shelf sites, with the greatest differences observed between summer and winter. Beta-diversity showed significant differences in community composition in relation to season and the Bay was dominated by diatoms, while the Shelf was characterized by dinoflagellates and copepods. The northern Gulf of Mexico is heavily influenced by the Mobile River Basin, which brings low-salinity nutrient-rich water mostly during winter and spring. Community composition was correlated with salinity, temperature and dissolved silicate. However, species interactions (e.g. predation and parasitism) may also contribute to the observed variation, especially on the Shelf, which warrants further exploration. Metabarcoding revealed clear patterns in surface pelagic micro-eukaryote communities that were consistent over multiple years, demonstrating how these techniques could be greatly beneficial to ecological monitoring and management over temporal scales. PMID:27238767

  5. 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…

  6. Superresolution fluorescence mapping of single-nanoparticle catalysts reveals spatiotemporal variations in surface reactivity

    PubMed Central

    Zhang, Yuwei; Lucas, J. Matthew; Song, Ping; Beberwyck, Brandon; Fu, Qiang; Xu, Weilin; Alivisatos, A. Paul

    2015-01-01

    For the practical application of nanocatalysts, it is desirable to understand the spatiotemporal fluctuations of nanocatalytic activity at the single-nanoparticle level. Here we use time-lapsed superresolution mapping of single-molecule catalysis events on individual nanoparticles to observe time-varying changes in the spatial distribution of catalysis events on Sb-doped TiO2 nanorods and Au triangle nanoplates. Compared with the active sites on well-defined surface facets, the defects of the nanoparticle catalysts possess higher intrinsic reactivity but lower stability. Corners and ends are more reactive but also less stable than flat surfaces. Averaged over time, the most stable sites dominate the total apparent activity of single nanocatalysts. However, the active sites with higher intrinsic activity but lower stability show activity at earlier time points before deactivating. Unexpectedly, some active sites are found to recover their activity (“self-healing”) after deactivation, which is probably due to desorption of the adsorbate. Our superresolution measurement of different types of active catalytic sites, over both space and time, leads to a more comprehensive understanding of reactivity patterns and may enable the design of new and more productive heterogeneous catalysts. PMID:26150516

  7. Superresolution fluorescence mapping of single-nanoparticle catalysts reveals spatiotemporal variations in surface reactivity.

    PubMed

    Zhang, Yuwei; Lucas, J Matthew; Song, Ping; Beberwyck, Brandon; Fu, Qiang; Xu, Weilin; Alivisatos, A Paul

    2015-07-21

    For the practical application of nanocatalysts, it is desirable to understand the spatiotemporal fluctuations of nanocatalytic activity at the single-nanoparticle level. Here we use time-lapsed superresolution mapping of single-molecule catalysis events on individual nanoparticles to observe time-varying changes in the spatial distribution of catalysis events on Sb-doped TiO2 nanorods and Au triangle nanoplates. Compared with the active sites on well-defined surface facets, the defects of the nanoparticle catalysts possess higher intrinsic reactivity but lower stability. Corners and ends are more reactive but also less stable than flat surfaces. Averaged over time, the most stable sites dominate the total apparent activity of single nanocatalysts. However, the active sites with higher intrinsic activity but lower stability show activity at earlier time points before deactivating. Unexpectedly, some active sites are found to recover their activity ("self-healing") after deactivation, which is probably due to desorption of the adsorbate. Our superresolution measurement of different types of active catalytic sites, over both space and time, leads to a more comprehensive understanding of reactivity patterns and may enable the design of new and more productive heterogeneous catalysts. PMID:26150516

  8. Stable Isotope Analysis of Precipitation Samples Obtained via Crowdsourcing Reveals the Spatiotemporal Evolution of Superstorm Sandy

    PubMed Central

    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 O, 160‰ for 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. PMID:24618882

  9. Spatiotemporal fusion of multiple-satellite aerosol optical depth (AOD) products using Bayesian maximum entropy method

    NASA Astrophysics Data System (ADS)

    Tang, Qingxin; Bo, Yanchen; Zhu, Yuxin

    2016-04-01

    Merging multisensor aerosol optical depth (AOD) products is an effective way to produce more spatiotemporally complete and accurate AOD products. A spatiotemporal statistical data fusion framework based on a Bayesian maximum entropy (BME) method was developed for merging satellite AOD products in East Asia. The advantages of the presented merging framework are that it not only utilizes the spatiotemporal autocorrelations but also explicitly incorporates the uncertainties of the AOD products being merged. The satellite AOD products used for merging are the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 5.1 Level-2 AOD products (MOD04_L2) and the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Deep Blue Level 2 AOD products (SWDB_L2). The results show that the average completeness of the merged AOD data is 95.2%,which is significantly superior to the completeness of MOD04_L2 (22.9%) and SWDB_L2 (20.2%). By comparing the merged AOD to the Aerosol Robotic Network AOD records, the results show that the correlation coefficient (0.75), root-mean-square error (0.29), and mean bias (0.068) of the merged AOD are close to those (the correlation coefficient (0.82), root-mean-square error (0.19), and mean bias (0.059)) of the MODIS AOD. In the regions where both MODIS and SeaWiFS have valid observations, the accuracy of the merged AOD is higher than those of MODIS and SeaWiFS AODs. Even in regions where both MODIS and SeaWiFS AODs are missing, the accuracy of the merged AOD is also close to the accuracy of the regions where both MODIS and SeaWiFS have valid observations.

  10. 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.

  11. Optical test-benches for multiple source wavefront propagation and spatiotemporal point-spread function emulation.

    PubMed

    Weddell, Stephen J; Lambert, Andrew J

    2014-12-10

    Precise measurement of aberrations within an optical system is essential to mitigate combined effects of user-generated aberrations for the study of anisoplanatic imaging using optical test benches. The optical system point spread function (PSF) is first defined, and methods to minimize the effects of the optical system are discussed. User-derived aberrations, in the form of low-order Zernike ensembles, are introduced using a liquid crystal spatial light modulator (LC-SLM), and dynamic phase maps are used to study the spatiotemporal PSF. A versatile optical test bench is described, where the Shack Hartmann and curvature wavefront sensors are used to emulate the effects of wavefront propagation over time from two independent sources. PMID:25608061

  12. 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. PMID:26982028

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

    PubMed

    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

  14. 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

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

    PubMed Central

    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 multiple object tracking task during functional magnetic resonance (fMRI) imaging. Participants actively tracked a target among six distracters or passively viewed the animations. Neural activation in girls with Turner syndrome during object tracking overlapped with but was dissimilar to the canonical frontoparietal network evident in typically developing controls and included greater limbic activity. Task performance and atypical functional activation indicate anomalous development of cortical and subcortical temporal and spatial processing circuits in girls with Turner syndrome. PMID:20441384

  16. Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer.

    PubMed

    Hashimshony, Tamar; Feder, Martin; Levin, Michal; Hall, Brian K; Yanai, Itai

    2015-03-12

    The concept of germ layers has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years (refs 1 - 3). Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve. The origin of the ectoderm and endoderm germ layers, however, remains unclear, with models supporting the antecedence of each as well as a simultaneous origin. Here we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer both to evolve and to develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is also observed in the expression of endoderm orthologues during the embryology of the frog Xenopus tropicalis, the sea anemone Nematostella vectensis and the sponge Amphimedon queenslandica. Querying the phylogenetic ages of specifically expressed genes reveals that the endoderm comprises older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, whereas the ectoderm originated as a secondary germ layer freed from ancestral feeding functions. PMID:25487147

  17. Spatiotemporal transcriptomics reveals the evolutionary history of the endoderm germ layer

    PubMed Central

    Hashimshony, Tamar; Feder, Martin; Levin, Michal; Hall, Brian K.; Yanai, Itai

    2014-01-01

    The germ layer concept has been one of the foremost organizing principles in developmental biology, classification, systematics and evolution for 150 years1-3. Of the three germ layers, the mesoderm is found in bilaterian animals but is absent in species in the phyla Cnidaria and Ctenophora, which has been taken as evidence that the mesoderm was the final germ layer to evolve1,4,5. The origin of the ectoderm and endoderm germ layers, however, remains unclear with models supporting the antecedence of each as well as a simultaneous origin4,6-9. Here, we determine the temporal and spatial components of gene expression spanning embryonic development for all Caenorhabditis elegans genes and use it to determine the evolutionary ages of the germ layers. The gene expression program of the mesoderm is induced after those of the ectoderm and endoderm, thus making it the last germ layer to both evolve and develop. Strikingly, the C. elegans endoderm and ectoderm expression programs do not co-induce; rather the endoderm activates earlier, and this is observed also in the expression of endoderm orthologs during the embryology of Xenopus tropicalis, Nematostella vectensis, and the sponge Amphimedon queenslandica. Querying for the phylogenetic ages of specifically expressed genes revealed that the endoderm is comprised of older genes. Taken together, we propose that the endoderm program dates back to the origin of multicellularity, while the ectoderm originated as a secondary germ layer freed from ancestral feeding functions. PMID:25487147

  18. 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.

  19. Novel approaches in Extended Principal Components Analysis to compare spatio-temporal patterns among multiple image time series

    NASA Astrophysics Data System (ADS)

    Neeti, N.; Eastman, R.

    2012-12-01

    Extended Principal Components Analysis (EPCA) aims to examine the patterns of variability shared among multiple image time series. Conventionally, this is done by virtually extending the spatial dimension of the time series by spatially concatenating the different time series and then performing S-mode PCA. In S-mode analysis, samples in space are the statistical variables and samples in time are the statistical observations. This paper introduces the concept of temporal concatenation of multiple image time series to perform EPCA. EPCA can also be done with T-mode orientation in which samples in time are the statistical variables and samples in space are the statistical observations. This leads to a total of four orientations in which EPCA can be carried out. This research explores these four orientations and their implications in investigating spatio-temporal relationships among multiple time series. This research demonstrates that EPCA carried out with temporal concatenation of the multiple time series with T-mode (tT) is able to identify similar spatial patterns among multiple time series. The conventional S-mode EPCA with spatial concatenation (sS) identifies similar temporal patterns among multiple time series. The other two modes, namely T-mode with spatial concatenation (sT) and S-mode with temporal concatenation (tS), are able to identify patterns which share consistent temporal phase relationships and consistent spatial phase relationships with each other, respectively. In a case study using three sets of precipitation time series data from GPCP, CMAP and NCEP-DOE, the results show that examination of all four modes provides an effective basis comparison of the series.

  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. [Meningococcal Septicemia Revealing Multiple Myeloma: A Case Report].

    PubMed

    Arakawa, Risturo; Mori, Nobuaki; Kagawa, Narito; Higuchi, Akiko; Tanaka, Masashi; Aoki, Yasuko; Seki, Shiko; Suzuki, Ryo

    2016-05-01

    Meningococcal infection is among the most devastating diseases. It is rarely seen in Japan. However, several environmental and host factors have been associated with increased risks of Neisseria meningitidis infection. We present a case of invasive N. meningitidis infection that revealed the presence of multiple myeloma. A 55-year-old Japanese man was admitted with fever and altered consciousness. He was sent to the intensive care unit for septic shock and disseminated intravascular coagulation. In addition to standard septic shock and multiple organ failure treatment, polymyxin-B immobilized column direct hemoperfusion was performed. His blood culture was positive for N. meningitidis. The patient gradually improved and was discharged on day 35. We evaluated the risk factors for the development of meningococcal infection. A laboratory examination showed that the patient was negative for human immunodeficiency virus antibody and had a normal total complement function. However, his serum immunoglobulin G level was high, and serum and urine protein electrophoresis detected a monoclonal gammopathy. A bone marrow examination led to the diagnosis of multiple myeloma. Because N. meningitidis bacteria spreads between individuals in close contact through the exchange of oral secretions, droplet precautions and antimicrobial chemoprophylaxis (ciprofloxacin, 500 mg) were implemented to prevent the spread of the meningococcal infection. Sporadic meningococcal infection warrants an evaluation for immunodeficiency and the prevention of secondary infection. PMID:27529971

  2. The Influence of Weather and Lemmings on Spatiotemporal Variation in the Abundance of Multiple Avian Guilds in the Arctic

    PubMed Central

    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

  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. 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

    2016-08-01

    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. PMID:27426513

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

    PubMed

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

    2015-01-01

    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

  7. Multiple interacting brain areas underlie successful spatiotemporal memory retrieval in humans.

    PubMed

    Schedlbauer, Amber M; Copara, Milagros S; Watrous, Andrew J; Ekstrom, Arne D

    2014-01-01

    Emerging evidence suggests that our memories for recent events depend on a dynamic interplay between multiple cortical brain regions, although previous research has also emphasized a primary role for the hippocampus in episodic memory. One challenge in determining the relative importance of interactions between multiple brain regions versus a specific brain region is a lack of analytic approaches to address this issue. Participants underwent neuroimaging while retrieving the spatial and temporal details of a recently experienced virtual reality environment; we then employed graph theory to analyze functional connectivity patterns across multiple lobes. Dense, large-scale increases in connectivity during successful memory retrieval typified network topology, with individual participant performance correlating positively with overall network density. Within this dense network, the hippocampus, prefrontal cortex, precuneus, and visual cortex served as "hubs" of high connectivity. Spatial and temporal retrieval were characterized by distinct but overlapping "subnetworks" with higher connectivity within posterior and anterior brain areas, respectively. Together, these findings provide new insight into the neural basis of episodic memory, suggesting that the interactions of multiple hubs characterize successful memory retrieval. Furthermore, distinct subnetworks represent components of spatial versus temporal retrieval, with the hippocampus acting as a hub integrating information between these two subnetworks. PMID:25234342

  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. PMID:26459123

  9. Spatiotemporal patterns of evapotranspiration in response to multiple environmental factors simulated by the Community Land Model

    SciTech Connect

    Shi, Xiaoying; Mao, Jiafu; Thornton, Peter E; Huang, Maoyi; Hoffman, Forrest

    2013-01-01

    In this study, spatial and temporal patterns of evapotranspiration (ET) over the period of 1982-2008 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 derived from the FLUXNET network of eddy covariance towers using the model tree ensembles (MTE) approach. We find that climate trends and variability dominate 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 functions as the dominant factor controlling ET changes over North America, South America and Asia regions. Compared to the effect of climate change and CO2 concentration, the roles of other factors such as nitrogen deposition, land use change and aerosol deposition are less pronounced and regionally dependent. For example, the aerosol deposition contribution is the third-most important factor for trends of ET over Europe, while it has the smallest impact on ET trend 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 and land cover change, in addition to climate, could have significant impact on future projections of water resources and water cycle dynamics at global and regional scales.

  10. 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…

  11. Spatiotemporal model evaluation across Europe: A methodology based on expert knowledge, multiple datasets, physiography, flow signatures and performance metrics

    NASA Astrophysics Data System (ADS)

    Donnelly, Chantal; Andersson, Jafet; Arheimer, Berit; Gustafsson, David; Hundecha, Yeshewatesfa; Pechlivanidis, Ilias

    2015-04-01

    The hydrological model E-HYPE is spatially distributed with an average subbasin size of 200 km2 for continental Europe. The third version of the model (E-HYPE v3.0) has recently been released, building on experience in setting up multi-basin models at the large scale using open data from readily available sources. A methodology adopting a stepwise calibration of the model is used to optimize model performance to multiple datasets including (a) satellite estimates of potential evapotranspiration and ice cover, (b) in situ snow depth measurements, and (c) 116++ discharge stations representing a variety of catchment sizes, hydro-climatologies, physiographies and anthropogenic influences across Europe. Furthermore, the model is evaluated against an independent validation set of 750 discharge stations. This assists on determining how well the model represents the spatiotemporal variation in flow signatures including low, mean and high flows, flashiness, coefficient of variation and various scales of temporal variation (daily, seasonal and interannual). Assuming that the stations sufficiently represent the variation in catchment scales, hydro-climatology and physiography across Europe, the spread in performance of the validation stations may be assumed to represent the uncertainty in predicting an ungauged basin. This assumption will be further explored. Model evaluation using a large database of discharge data has the added value of informing on spatial errors, which can then be related to erroneous/uncertain input data (e.g. presence of undercatch in gridded precipitation databases), insufficient processes descriptions (e.g. groundwater recharge for a region), and limited knowledge on anthropogenic processes (e.g. extractions, regulation). This has then fed back into development of improved input data sets for precipitation, improved model process descriptions for irrigation and regulation and a new model module for deep aquifer interchange. E-HYPEv3.0 performs well

  12. 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…

  13. 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. PMID:27313049

  14. Phylogenetic analysis reveals multiple introductions of Cynodon species in Australia.

    PubMed

    Jewell, M; Frère, C H; Harris-Shultz, K; Anderson, W F; Godwin, I D; Lambrides, C J

    2012-11-01

    The distinction between native and introduced flora within isolated land masses presents unique challenges. The geological and colonisation history of Australia, the world's largest island, makes it a valuable system for studying species endemism, introduction, and phylogeny. Using this strategy we investigated Australian cosmopolitan grasses belonging to the genus Cynodon. While it is believed that seven species of Cynodon are present in Australia, no genetic analyses have investigated the origin, diversity and phylogenetic history of Cynodon within Australia. To address this gap, 147 samples (92 from across Australia and 55 representing global distribution) were sequenced for a total of 3336bp of chloroplast DNA spanning six genes. Data showed the presence of at least six putatively introduced Cynodon species (C. transvaalensis, C. incompletus, C. hirsutus, C. radiatus, C. plectostachyus and C. dactylon) in Australia and suggested multiple recent introductions. C. plectostachyus, a species often confused with C. nlemfuensis, was not previously considered to be present in Australia. Most significantly, we identified two common haplotypes that formed a monophyletic clade diverging from previously identified Cynodon species. We hypothesise that these two haplotypes may represent a previously undescribed species of Cynodon. We provide further evidence that two Australian native species, Brachyachne tenella and B. convergens belong in the genus Cynodon and, therefore, argue for the taxonomic revision of the genus Cynodon. PMID:22797088

  15. A unified approach for revealing multiple balance recovery strategies.

    PubMed

    Cheng, Kuangyou B; Yeh, Chih-Kuo

    2015-12-01

    In human balance recovery, different strategies have been proposed with generally overlooked knee motions but extensive focus on the ankle, hip, and step strategies. It is not well understood whether maintaining balance is regulated at the lower "muscular-articular" level of coordinating segment joints or at a higher level of controlling whole body dynamics. Whether balance control is to minimize joint degrees of freedom (DOF) or utilize all the available DOF also remains unclear. This study aimed to use a realistic musculoskeletal human model to identify multiple balance recovery strategies with a single optimization criterion. Movements were driven by neural excitations (which activated muscle force generation) and were assumed to be symmetric. Balance recoveries were simulated with forward-inclined straight body postures as the initial conditions. When the position of the toes was fixed, balance was regained with virtually straight knees and mixed ankle/hip strategies. Under a severely perturbed condition, use of the forward hop strategy after releasing the fixed-toes constraint indicated spontaneous recruitment or suppression of DOF, which mimicked functions of optimally computed CNS commands in humans. The results also indicated that increase/decrease in the number of DOF depends on the imposed perturbation intensity and movement constraints. PMID:26519905

  16. Multiple System Atrophy. Using Clinical Pharmacology to Reveal Pathophysiology

    PubMed Central

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-01-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson’s disease (PD) have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, with near normal plasma norepinephrine in MSA but very low levels in PAF, and in neurophysiological testing. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. E.g., the ganglionic blocker trimethaphan reduce residual sympathetic tone and lower blood pressure in MSA but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction, are counteracted by the increase in brain norepinephrine which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

  17. Multiple system atrophy: using clinical pharmacology to reveal pathophysiology.

    PubMed

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-02-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson disease have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, as well as in neurophysiological testing, with near normal plasma norephrine in MSA but very low levels in PAF. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. For example, the ganglionic blocker trimethaphan reduces residual sympathetic tone and lowers blood pressure in MSA, but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects, the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction are counteracted by the increase in brain norepinephrine, which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers, only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

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

    PubMed

    Simeone, Marco Cosimo; 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

  19. 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

  20. 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. PMID:26021467

  1. 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.

  2. Interactome Analysis Reveals Ezrin Can Adopt Multiple Conformational States*

    PubMed Central

    Viswanatha, Raghuvir; Wayt, Jessica; Ohouo, Patrice Y.; Smolka, Marcus B.; Bretscher, Anthony

    2013-01-01

    Ezrin, a member of the ezrin-radixin-moesin family (ERM), is an essential regulator of the structure of microvilli on the apical aspect of epithelial cells. Ezrin provides a linkage between membrane-associated proteins and F-actin, oscillating between active/open and inactive/closed states, and is regulated in part by phosphorylation of a C-terminal threonine. In the open state, ezrin can bind a number of ligands, but in the closed state the ligand-binding sites are inaccessible. In vitro analysis has proposed that there may be a third hyperactivated form of ezrin. To gain a better understanding of ezrin, we conducted an unbiased proteomic analysis of ezrin-binding proteins in an epithelial cell line, Jeg-3. We refined our list of interactors by comparing the interactomes using quantitative mass spectrometry between wild-type ezrin, closed ezrin, open ezrin, and hyperactivated ezrin. The analysis reveals several novel interactors confirmed by their localization to microvilli, as well as a significant class of proteins that bind closed ezrin. Taken together, the data indicate that ezrin can exist in three different conformational states, and different ligands “perceive” ezrin conformational states differently. PMID:24151071

  3. 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

  4. A Unified Spatiotemporal Modeling Approach for Predicting Concentrations of Multiple Air Pollutants in the Multi-Ethnic Study of Atherosclerosis and Air Pollution

    PubMed Central

    Olives, Casey; Kim, Sun-Young; Sheppard, Lianne; Sampson, Paul D.; Szpiro, Adam A.; Oron, Assaf P.; Lindström, Johan; Vedal, Sverre; Kaufman, Joel D.

    2014-01-01

    Background: Cohort studies of the relationship between air pollution exposure and chronic health effects require predictions of exposure over long periods of time. Objectives: We developed a unified modeling approach for predicting fine particulate matter, nitrogen dioxide, oxides of nitrogen, and black carbon (as measured by light absorption coefficient) in six U.S. metropolitan regions from 1999 through early 2012 as part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Methods: We obtained monitoring data from regulatory networks and supplemented those data with study-specific measurements collected from MESA Air community locations and participants’ homes. In each region, we applied a spatiotemporal model that included a long-term spatial mean, time trends with spatially varying coefficients, and a spatiotemporal residual. The mean structure was derived from a large set of geographic covariates that was reduced using partial least-squares regression. We estimated time trends from observed time series and used spatial smoothing methods to borrow strength between observations. Results: Prediction accuracy was high for most models, with cross-validation R2 (R2CV) > 0.80 at regulatory and fixed sites for most regions and pollutants. At home sites, overall R2CV ranged from 0.45 to 0.92, and temporally adjusted R2CV ranged from 0.23 to 0.92. Conclusions: This novel spatiotemporal modeling approach provides accurate fine-scale predictions in multiple regions for four pollutants. We have generated participant-specific predictions for MESA Air to investigate health effects of long-term air pollution exposures. These successes highlight modeling advances that can be adopted more widely in modern cohort studies. Citation: Keller JP, Olives C, Kim SY, Sheppard L, Sampson PD, Szpiro AA, Oron AP, Lindström J, Vedal S, Kaufman JD. 2015. A unified spatiotemporal modeling approach for predicting concentrations of multiple air pollutants in the Multi

  5. 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

  6. Monitoring and identification of spatiotemporal landscape changes in multiple remote sensing images by using a stratified conditional Latin hypercube sampling approach and geostatistical simulation.

    PubMed

    Lin, Yu-Pin; Chu, Hone-Jay; Huang, Yu-Long; Tang, Chia-Hsi; Rouhani, Shahrokh

    2011-06-01

    This study develops a stratified conditional Latin hypercube sampling (scLHS) approach for multiple, remotely sensed, normalized difference vegetation index (NDVI) images. The objective is to sample, monitor, and delineate spatiotemporal landscape changes, including spatial heterogeneity and variability, in a given area. The scLHS approach, which is based on the variance quadtree technique (VQT) and the conditional Latin hypercube sampling (cLHS) method, selects samples in order to delineate landscape changes from multiple NDVI images. The images are then mapped for calibration and validation by using sequential Gaussian simulation (SGS) with the scLHS selected samples. Spatial statistical results indicate that in terms of their statistical distribution, spatial distribution, and spatial variation, the statistics and variograms of the scLHS samples resemble those of multiple NDVI images more closely than those of cLHS and VQT samples. Moreover, the accuracy of simulated NDVI images based on SGS with scLHS samples is significantly better than that of simulated NDVI images based on SGS with cLHS samples and VQT samples, respectively. However, the proposed approach efficiently monitors the spatial characteristics of landscape changes, including the statistics, spatial variability, and heterogeneity of NDVI images. In addition, SGS with the scLHS samples effectively reproduces spatial patterns and landscape changes in multiple NDVI images. PMID:20711861

  7. Bioluminescent imaging of Ca2+ activity reveals spatiotemporal dynamics in glial networks of dark-adapted mouse retina

    PubMed Central

    Agulhon, Cendra; Platel, Jean-Claude; Kolomiets, Bogdan; Forster, Valérie; Picaud, Serge; Brocard, Jacques; Faure, Philippe; Brulet, Philippe

    2007-01-01

    Glial Ca2+ excitability plays a key role in reciprocal neuron–glia communication. In the retina, neuron–glia signalling is expected to be maximal in the dark, but the glial Ca2+ signal characteristics under such conditions have not been evaluated. To address this question, we used bioluminescence imaging to monitor spontaneous Ca2+ changes under dark conditions selectively in Müller cells, the principal retinal glial cells. By combining this imaging approach with network analysis, we demonstrate that activity in Müller cells is organized in networks of coactive cells, involving 2–16 cells located distantly and/or in clusters. We also report that spontaneous activity of small networks (2–6 Müller cells) repeat over time, sometimes in the same sequential order, revealing specific temporal dynamics. In addition, we show that networks of coactive glial cells are inhibited by TTX, indicating that ganglion and/or amacrine neuronal cells probably regulate Müller cell network properties. These results represent the first demonstration that spontaneous activity in adult Müller cells is patterned into correlated networks that display repeated sequences of coactivations over time. Furthermore, our bioluminescence technique provides a novel tool to study the dynamic characteristics of glial Ca2+ events in the retina under dark conditions, which should greatly facilitate future investigations of retinal dark-adaptive processes. PMID:17627996

  8. 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. PMID:26394866

  9. Unsupervised spatio-temporal detection of brain functional activation based on hidden Markov multiple event sequence models

    NASA Astrophysics Data System (ADS)

    Faisan, Sylvain; Thoraval, Laurent; Armspach, Jean-Paul; Heitz, Fabrice; Foucher, Jack

    2005-04-01

    This paper presents a novel, completely unsupervised fMRI brain mapping approach that addresses the three problems of hemodynamic response function (HRF) shape variability, neural event timing, and fMRI response linearity. To make it robust, the method takes into account spatial and temporal information directly into the core of the activation detection process. In practice, activation detection is formulated in terms of temporal alignment between the sequence of hemodynamic response onsets (HROs) detected in the fMRI signal at υ and in the spatial neighbourhood of υ, and the sequence of "off-on" transitions observed in the input blocked stimulation paradigm (when considering epoch-related fMRI data), or the sequence of stimuli of the event-based paradigm (when considering event-related fMRI data). This multiple event sequence alignment problem, which comes under multisensor data fusion, is solved within the probabilistic framework of hidden Markov multiple event sequence models (HMMESMs), a special class of hidden Markov models. Results obtained on real and synthetic data compete with those obtained with the popular statistical parametric mapping (SPM) approach, but without necessitating any prior definition of the expected activation patterns, the HMMESM mapping approach being completely unsupervised.

  10. 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.

  11. A probabilistic framework for the spatio-temporal segmentation of multiple sclerosis lesions in MR images of the brain

    NASA Astrophysics Data System (ADS)

    Greenspan, Hayit; Mayer, Arnaldo; Shahar, Allon

    2003-05-01

    In this paper we describe the application of a novel statistical image-sequence (video) modeling scheme to sequences of multiple sclerosis (MS) images taken over time. A unique key feature of the proposed framework is the analysis of the image-sequence input as a single entity as opposed to a sequence of separate frames. The extracted space-time regions allow for the detection and identification of disease events and processes, such as the appearance and progression of lesions. According to the proposed methodology, coherent space-time regions in the feature space, and corresponding coherent segments in the video content are extracted by unsupervised clustering via Gaussian mixture modeling (GMM). The parameters of the GMM are determined via the maximum likelihood principle and the Expectation-Maximization (EM) algorithm. The clustering of the image sequence yields a collection of regions (blobs) in a four-dimensional feature space (including intensity, position (x,y), and time). Regions corresponding to MS lesions are automatically identified based on criteria regarding the mean intensity and the size variability over time. The proposed methodology was applied to a registered sequence of 24 T2-weighted MR images acquired from an MS patient over a period of approximately a year. Examples of preliminary qualitative results are shown.

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

    PubMed

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

    2016-08-01

    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

  13. 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

  14. 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

  15. 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.

  16. Master stability analysis in transient spatiotemporal chaos.

    PubMed

    Wackerbauer, Renate

    2007-11-01

    The asymptotic stability of spatiotemporal chaos is difficult to determine, since transient spatiotemporal chaos may be extremely long lived. A master stability analysis reveals that the asymptotic state of transient spatiotemporal chaos in the Gray-Scott system and in the Bär-Eiswirth system is characterized by negative transverse Lyapunov exponents on the attractor of the invariant synchronization manifold. The average lifetime of transient spatiotemporal chaos depends on the number of transverse directions that are unstable along a typical excitation cycle. PMID:18233739

  17. 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

  18. Worldwide phylogeography of wild boar reveals multiple centers of pig domestication.

    PubMed

    Larson, Greger; Dobney, Keith; Albarella, Umberto; Fang, Meiying; Matisoo-Smith, Elizabeth; Robins, Judith; Lowden, Stewart; Finlayson, Heather; Brand, Tina; Willerslev, Eske; Rowley-Conwy, Peter; Andersson, Leif; Cooper, Alan

    2005-03-11

    Mitochondrial DNA (mtDNA) sequences from 686 wild and domestic pig specimens place the origin of wild boar in island Southeast Asia (ISEA), where they dispersed across Eurasia. Previous morphological and genetic evidence suggested pig domestication took place in a limited number of locations (principally the Near East and Far East). In contrast, new genetic data reveal multiple centers of domestication across Eurasia and that European, rather than Near Eastern, wild boar are the principal source of modern European domestic pigs. PMID:15761152

  19. Thromboelastography, thrombin generation test and thrombodynamics reveal hypercoagulability in patients with multiple myeloma.

    PubMed

    Gracheva, Marina A; Urnova, Evdokiya S; Sinauridze, Elena I; Tarandovskiy, Ivan D; Orel, Elena B; Poletaev, Alexander V; Mendeleeva, Larisa P; Ataullakhanov, Fazoil I; Balandina, Anna N

    2015-01-01

    Patients with multiple myeloma (MM) are at increased risk of venous thromboembolism. Therefore, adequate laboratory control of hemostasis and subsequent adjustments of anticoagulant therapy are necessary. We studied hemostasis changes using thromboelastography (TEG), thrombin generation test (TGT) and thrombodynamics (TD) in primary MM patients (PMMpt, n=25) and patients in remission (RMMpt, n=34) during blood stem cell (BSC) mobilization. TD and TEG reveal hypercoagulability in PMMpt (*p<0.05) in relation to healthy volunteers. There was no difference in any of the tests between PMMpt and RMMpt. We detected no heparin effect in 22% of patients one day after the onset of the prophylactic heparin treatment (500 IU/h) during BSC mobilization; tests shifted toward the hypercoagulability in 75% of patients one day after cyclophosphamide (4 g/m2) chemotherapy. Global hemostasis tests were in good agreement with each other, revealed hypercoagulability and heparin "resistance" in patients with MM and may be useful for therapy individualization. PMID:25907422

  20. 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

  1. 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

  2. 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.

  3. Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity

    PubMed Central

    2014-01-01

    Background Mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably Mycobacterium tuberculosis. Considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (PG) remodelling to determine the potential of exploiting this area of bacterial metabolism for the discovery of new drug targets. Results We conducted an in silico analysis of 19 mycobacterial species/clinical strains for the presence of genes encoding resuscitation promoting factors (Rpfs), penicillin binding proteins, endopeptidases, L,D-transpeptidases and N-acetylmuramoyl-L-alanine amidases. Our analysis reveals extensive genetic multiplicity, allowing for classification of mycobacterial species into three main categories, primarily based on their rpf gene complement. These include the M. tuberculosis Complex (MTBC), other pathogenic mycobacteria and environmental species. The complement of these genes within the MTBC and other mycobacterial pathogens is highly conserved. In contrast, environmental strains display significant genetic expansion in most of these gene families. Mycobacterium leprae retains more than one functional gene from each enzyme family, underscoring the importance of genetic multiplicity for PG remodelling. Notably, the highest degree of conservation is observed for N-acetylmuramoyl-L-alanine amidases suggesting that these enzymes are essential for growth and survival. Conclusion PG remodelling enzymes in a range of mycobacterial species are associated with extensive genetic multiplicity, suggesting functional diversification within these families of enzymes to allow organisms to adapt. PMID:24661741

  4. Massive parallel IGHV gene sequencing reveals a germinal center pathway in origins of human multiple myeloma

    PubMed Central

    Bryant, Dean; Seckinger, Anja; Hose, Dirk; Zojer, Niklas; Sahota, Surinder S.

    2015-01-01

    Human multiple myeloma (MM) is characterized by accumulation of malignant terminally differentiated plasma cells (PCs) in the bone marrow (BM), raising the question when during maturation neoplastic transformation begins. Immunoglobulin IGHV genes carry imprints of clonal tumor history, delineating somatic hypermutation (SHM) events that generally occur in the germinal center (GC). Here, we examine MM-derived IGHV genes using massive parallel deep sequencing, comparing them with profiles in normal BM PCs. In 4/4 presentation IgG MM, monoclonal tumor-derived IGHV sequences revealed significant evidence for intraclonal variation (ICV) in mutation patterns. IGHV sequences of 2/2 normal PC IgG populations revealed dominant oligoclonal expansions, each expansion also displaying mutational ICV. Clonal expansions in MM and in normal BM PCs reveal common IGHV features. In such MM, the data fit a model of tumor origins in which neoplastic transformation is initiated in a GC B-cell committed to terminal differentiation but still targeted by on-going SHM. Strikingly, the data parallel IGHV clonal sequences in some monoclonal gammopathy of undetermined significance (MGUS) known to display on-going SHM imprints. Since MGUS generally precedes MM, these data suggest origins of MGUS and MM with IGHV gene mutational ICV from the same GC B-cell, arising via a distinctive pathway. PMID:25929340

  5. Phylogenetic analyses of the subgenus Mollienesia (Poecilia, Poeciliidae, Teleostei) reveal taxonomic inconsistencies, cryptic biodiversity, and spatio-temporal aspects of diversification in Middle America.

    PubMed

    Palacios, Maura; Voelker, Gary; Arias Rodriguez, Lenin; Mateos, Mariana; Tobler, Michael

    2016-10-01

    The subgenus Mollienesia is a diverse group of freshwater fishes, including species that have served as important models across multiple biological disciplines. Nonetheless, the taxonomic history of this group has been conflictive and convoluted, in part because the evolutionary relationships have not been rigorously resolved. We conducted a comprehensive molecular phylogenetic analysis of the subgenus Mollienesia to identify taxonomic discrepancies and potentially identify undescribed species, estimate ancestral areas of origin and estimate dates of divergence, as well as explore biogeographical patterns. Our findings confirm the presence of three main clades composed of the P. latipinna, P. sphenops, and P. mexicana species complexes. Unlike previously hypothesized morphology-based analyses, species found on the Caribbean Islands are not part of Mollienesia, but are more closely related to species of the subgenus Limia. Our study also revealed several taxonomic inconsistencies and distinct lineages in the P. mexicana species complex that may represent undescribed species. The diversity in the subgenus Mollienesia is a result of dynamic geologic activity leading to vicariant events, dispersal across geologic blocks, and ecological speciation. PMID:27472959

  6. Hearing Without Listening: Functional Connectivity Reveals the Engagement of Multiple Nonauditory Networks During Basic Sound Processing

    PubMed Central

    Melcher, Jennifer R.

    2011-01-01

    Abstract The present functional magnetic resonance imaging (fMRI) study presents data challenging the traditional view that sound is processed almost exclusively in the classical auditory pathway unless imbued with behavioral significance. In a first experiment, subjects were presented with broadband noise in on/off fashion as they performed an unrelated visual task. A conventional analysis assuming predictable sound-evoked responses demonstrated a typical activation pattern that was confined to classical auditory centers. In contrast, spatial independent component analysis (sICA) disclosed multiple networks of acoustically responsive brain centers. One network comprised classical auditory centers, but four others included nominally “nonauditory” areas: cingulo-insular cortex, mediotemporal limbic lobe, basal ganglia, and posterior orbitofrontal cortex, respectively. Functional connectivity analyses confirmed the sICA results by demonstrating coordinated activity between the involved brain structures. In a second experiment, fMRI data obtained from unstimulated (i.e., resting) subjects revealed largely similar networks. Together, these two experiments suggest the existence of a coordinated system of multiple acoustically responsive intrinsic brain networks, comprising classical auditory centers but also other brain areas. Our results suggest that nonauditory centers play a role in sound processing at a very basic level, even when the sound is not intertwined with behaviors requiring the well-known functionality of these regions. PMID:22433051

  7. Mechanically Untying a Protein Slipknot: Multiple Pathways Revealed by Force Spectroscopy and Steered Molecular Dynamics Simulations

    PubMed Central

    He, Chengzhi; Genchev, Georgi Z.; Lu, Hui; Li, Hongbin

    2013-01-01

    Protein structure is highly diverse when considering a wide range of protein types, helping to give rise to the multitude of functions that proteins perform. In particular, certain proteins are known to adopt a knotted or slipknotted fold. How such proteins undergo mechanical unfolding was investigated utilizing a combination of single molecule atomic force microscopy (AFM), protein engineering and steered molecular dynamics (SMD) simulations to show the mechanical unfolding mechanism of the slipknotted protein AFV3-109. Our results reveal that the mechancial unfolding of AFV3-109 can proceed via multiple parallel unfolding pathways that all cause the protein slipknot to untie, and the polypeptide chain to completely extend. These distinct unfolding pathways proceed either via a two-state or three-state unfolding process involving the formation of a well-defined, stable intermediate state. SMD simulations predict the same contour length increments for different unfolding pathways as single molecule AFM results, thus provding a plausible molecular mechanism for the mechanical unfolding of AFV3-109. These SMD simulations also reveal that two-state unfolding is initiated from both the N- and C-termini, while three-state unfolding is initiated only from the C-terminus. In both pathways, the protein slipknot was untied during unfolding, and no tightened slipknot conformation observed. Detailed analysis revealed that interactions between key structural elements lock the knotting loop in place, preventing it from shrinking and the formation of a tightened slipknot conformation. Our results demonstrate the bifurcation of the mechancial unfolding pathway of AFV3-109, and point to the generality of a kinetic partitioning mechanism for protein folding/unfolding. PMID:22626004

  8. 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. PMID:25098164

  9. 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

  10. Multiple Differential Networks Strategy Reveals Carboplatin and Melphalan-Induced Dynamic Module Changes in Retinoblastoma.

    PubMed

    Chen, Cui; Ma, Feng-Wei; Du, Cui-Yun; Wang, Ping

    2016-01-01

    BACKGROUND Retinoblastoma (RB) is the most common malignant tumor of the eye in childhood. The objective of this paper was to investigate carboplatin (CAR)- and melphalan (MEL)-induced dynamic module changes in RB based on multiple (M) differential networks, and to generate systems-level insights into RB progression. MATERIAL AND METHODS To achieve this goal, we constructed M-differential co-expression networks (DCNs), assigned a weight to each edge, and identified seed genes in M DCNs by ranking genes based on their topological features. Starting with seed genes, a module search was performed to explore candidate modules in CAR and MEL condition. M-DMs were detected according to significance evaluations of M-modules, which originated from refinement of candidate modules. Further, we revealed dynamic changes in M-DM activity and connectivity on the basis of significance of Module Connectivity Dynamic Score (MCDS). RESULTS In the present study, M=2, a total of 21 seed genes were obtained. By assessing module search, refinement, and evaluation, we gained 18 2-DMs. Moreover, 3 significant 2-DMs (Module 1, Module 2, and Module 3) with dynamic changes across CAR and MEL condition were determined, and we denoted them as dynamic modules. Module 1 had 27 nodes of which 6 were seed genes and 56 edges. Module 2 was composed of 28 nodes and 54 edges. A total of 28 nodes interacted with 45 edges presented in Module 3. CONCLUSIONS We have identified 3 dynamic modules with changes induced by CAR and MEL in RB, which might give insights in revealing molecular mechanism for RB therapy. PMID:27144687

  11. 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

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

    PubMed Central

    2015-01-01

    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. PMID:26538210

  13. Transcriptomic Profile Reveals Gender-Specific Molecular Mechanisms Driving Multiple Sclerosis Progression

    PubMed Central

    Irizar, Haritz; Muñoz-Culla, Maider; Sepúlveda, Lucia; Sáenz-Cuesta, Matías; Prada, Álvaro; Castillo-Triviño, Tamara; Zamora-López, Gorka; de Munain, Adolfo López; Olascoaga, Javier; Otaegui, David

    2014-01-01

    Background Although the most common clinical presentation of multiple sclerosis (MS) is the so called Relapsing-Remitting MS (RRMS), the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMS patients. Results The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 patients in remission and relapse and 25 healthy subjects has revealed 174 genes altered in both remission and relapse, a high proportion of them showing what we have called “mirror pattern”: they are upregulated in remission and downregulated in relapse or vice versa. The coexpression analysis of these genes has shown that they are organized in three female-specific and one male-specific modules. Conclusions The interpretation of the modules of the coexpression network suggests that Epstein-Barr virus (EBV) reactivation of B cells happens in MS relapses; however, qPCR expression data of the viral genes supports that hypothesis only in female patients, reinforcing the notion that different molecular processes drive disease progression in females and males. Besides, we propose that the “primed” state showed by neutrophils in women is an endogenous control mechanism triggered to keep EBV reactivation under control through vitamin B12 physiology. Finally, our results also point towards an important sex-specific role of non-coding RNA in MS. PMID:24587374

  14. Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia.

    PubMed

    Hubscher, C H; Reed, W R; Kaddumi, E G; Armstrong, J E; Johnson, R D

    2010-04-01

    The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45-60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs. PMID:20142271

  15. Relationships between spatio-temporal environmental and genetic variation reveal an important influence of exogenous selection in a pupfish hybrid zone.

    PubMed

    Carson, Evan W; Tobler, Michael; Minckley, W L; Ainsworth, Ryan J; Dowling, Thomas E

    2012-03-01

    The importance of exogenous selection in a natural hybrid zone between the pupfishes Cyprinodon atrorus and Cyprinodon bifasciatus was tested via spatio-temporal analyses of environmental and genetic change over winter, spring and summer for three consecutive years. A critical influence of exogenous selection on hybrid zone regulation was demonstrated by a significant relationship between environmental (salinity and temperature) and genetic (three diagnostic nuDNA loci) variation over space and time (seasons) in the Rio Churince system, Cuatro Ciénegas, Mexico. At sites environmentally more similar to parental habitats, the genetic composition of hybrids was stable and similar to the resident parental species, whereas complex admixtures of parental and hybrid genotypic classes characterized intermediate environments, as did the greatest change in allelic and genotypic frequencies across seasons. Within hybrids across the entire Rio Churince system, seasonal changes in allelic and genotypic frequencies were consistent with results from previous reciprocal transplant experiments, which showed C. bifasciatus to suffer high mortality (75%) when exposed to the habitat of C. atrorus in winter (extreme temperature lows and variability) and summer (abrupt salinity change and extreme temperature highs and variability). Although unconfirmed, the distributional limits of C. atrorus and C. atrorus-like hybrids appear to be governed by similar constraints (predation or competition). The argument favouring evolutionary significance of hybridization in animals is bolstered by the results of this study, which links the importance of exogenous selection in a contemporary hybrid zone between C. atrorus and C. bifasciatus to previous demonstration of the long-term evolutionary significance of environmental variation and introgression on the phenotypic diversification Cuatro Ciénegas Cyprinodon. PMID:22269008

  16. 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

  17. 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

  18. 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.

  19. Functional TCR retrieval from single antigen-specific human T cells reveals multiple novel epitopes.

    PubMed

    Simon, Petra; Omokoko, Tana A; Breitkreuz, Andrea; Hebich, Lisa; Kreiter, Sebastian; Attig, Sebastian; Konur, Abdo; Britten, Cedrik M; Paret, Claudia; Dhaene, Karl; Türeci, Özlem; Sahin, Ugur

    2014-12-01

    The determination of the epitope specificity of disease-associated T-cell responses is relevant for the development of biomarkers and targeted immunotherapies against cancer, autoimmune, and infectious diseases. The lack of known T-cell epitopes and corresponding T-cell receptors (TCR) for novel antigens hinders the efficient development and monitoring of new therapies. We developed an integrated approach for the systematic retrieval and functional characterization of TCRs from single antigen-reactive T cells that includes the identification of epitope specificity. This is accomplished through the rapid cloning of full-length TCR-α and TCR-β chains directly from single antigen-specific CD8(+) or CD4(+) T lymphocytes. The functional validation of cloned TCRs is conducted using in vitro-transcribed RNA transfer for expression of TCRs in T cells and HLA molecules in antigen-presenting cells. This method avoids the work and bias associated with repetitive cycles of in vitro T-cell stimulation, and enables fast characterization of antigen-specific T-cell responses. We applied this strategy to viral and tumor-associated antigens (TAA), resulting in the retrieval of 56 unique functional antigen-specific TCRs from human CD8(+) and CD4(+) T cells (13 specific for CMV-pp65, 16 specific for the well-known TAA NY-ESO-1, and 27 for the novel TAA TPTE), which are directed against 39 different epitopes. The proof-of-concept studies with TAAs NY-ESO-1 and TPTE revealed multiple novel TCR specificities. Our approach enables the rational development of immunotherapy strategies by providing antigen-specific TCRs and immunogenic epitopes. PMID:25245536

  20. Multiple sampling and discriminatory fingerprinting reveals clonally complex and compartmentalized infections by M. bovis in cattle.

    PubMed

    Navarro, Yurena; Romero, Beatriz; Copano, María Francisca; Bouza, Emilio; Domínguez, Lucas; de Juan, Lucía; García-de-Viedma, Darío

    2015-01-30

    The combination of new genotyping tools and a more exhaustive sampling policy in the analysis of infection by Mycobacterium tuberculosis has shown that infection by this pathogen is more complex than initially expected. Mixed infections, coexistence of clonal variants from a parental strain, and compartmentalized infections are all different modalities of this clonal complexity. Until recently, genotyping of Mycobacterium bovis in animal populations was based on spoligotyping and analysis of a single isolate per infection; therefore, clonal complexity is probably underdetected. We used multiple sampling combined with highly discriminatory MIRU-VNTR to study compartmentalized infections by M. bovis in a low-tuberculosis prevalence setting. We spoligotyped the M. bovis isolates from two or more anatomic locations sampled from 55 animals on 39 independent farms. Compartmentalized infections, with two different strains infecting independent lymph nodes in the same animal, were found in six cases (10.9%). MIRU-VNTR analysis confirmed that the compartmentalization was strict and that only one strain was present in each infected node. MIRU-VNTR analysis of additional infected animals on one of the farms confirmed that the compartmentalized infection was a consequence of superinfection, since the two strains were independently infecting other animals. This same analysis revealed the emergence of a microevolved clonal variant in one of the lymph nodes of the compartmentalized animal. Clonal complexity must also be taken into consideration in M. bovis infection, even in low-prevalence settings, and analyses must be adapted to detect it and increase the accuracy of molecular epidemiology studies. PMID:25439651

  1. 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

  2. Two-hybrid analysis reveals multiple direct interactions for thrombospondin 1.

    PubMed

    Aho, S; Uitto, J

    1998-10-01

    The yeast two-hybrid system was used to reveal the interactions between proteins residing within the cutaneous basement membrane zone and other gene products expressed in cultured human keratinocytes. The proteins of interest included type VII collagen, the predominant component of anchoring fibrils, and laminin 5, a component of anchoring filaments. Although the two-hybrid system was not able to verify a direct interaction between the type VII collagen NC1 domain and the short arm of Lam(beta)3, the type VII collagen NC1 domain (tVII/NC1) and the laminin 5 beta3 chain globular domain VI (lam5/beta3) cDNAs, when used as baits, detected four overlapping cDNA clones encoding thrombospondin 1 (TSP1). The overlapping region of these cDNAs encodes amino acids 400-459, a segment included within a 70 kDa chymotryptic fragment known to bind type V collagen, laminin-1 and other matrix components. The type VII collagen NC1/TSP1 interaction was confirmed by exchanging the vectors, and the interacting domain was mapped by testing a set of both 5' and 3' deletion constructs. The central region of TSP1, when used as a bait in two-hybrid system, showed strong binding to the fibronectin (FN) type III-like repeats 4-7 of type VII collagen NC1 domain. The TSP1 bait also interacted with laminin 5 beta3 chain domain V/III, and the TSP1/laminin 5 beta3 chain interaction was verified by a GST-fusion protein interaction assay. The transcripts encoding TSP1, TSP2, Lam(beta)3 and type VII collagen were abundant in cultured foreskin keratinocytes, and the expression of TSP1 and TSP2 in a wide variety of adult and fetal tissues was confirmed by PCR analysis of multiple tissue cDNA panels. Furthermore, TSP1 type I repeats showed self interaction, and recognized a clone for extracellular matrix protein fibrillin-2. In addition, clones encoding angiogenesis related protein Jagged1 and a platelet enzyme phospholipase scramblase were identified. Thus, the results indicate several previously

  3. 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

  4. New meta-analysis tools reveal common transciptional regulatory basis for multiple determinants of behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    : A fundamental problem in meta-analysis is how to systematically combine information from multiple statistical tests to rigorously evaluate a single overarching hypothesis. This occurs in systems biology when attempting to map genomic attributes to complex phenotypes such as ...

  5. 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. PMID:27241629

  6. 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.

  7. 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. PMID:25867455

  8. 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

  9. 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. PMID:26682988

  10. Structural Alterations from Multiple Displacement Amplification of a Human Genome Revealed by Mate-Pair Sequencing

    PubMed Central

    Jiao, Xiang; Rosenlund, Magnus; Hooper, Sean D.; Tellgren-Roth, Christian; He, Liqun; Fu, Yutao; Mangion, Jonathan; Sjöblom, Tobias

    2011-01-01

    Comprehensive identification of the acquired mutations that cause common cancers will require genomic analyses of large sets of tumor samples. Typically, the tissue material available from tumor specimens is limited, which creates a demand for accurate template amplification. We therefore evaluated whether phi29-mediated whole genome amplification introduces false positive structural mutations by massive mate-pair sequencing of a normal human genome before and after such amplification. Multiple displacement amplification led to a decrease in clone coverage and an increase by two orders of magnitude in the prevalence of inversions, but did not increase the prevalence of translocations. While multiple strand displacement amplification may find uses in translocation analyses, it is likely that alternative amplification strategies need to be developed to meet the demands of cancer genomics. PMID:21799804

  11. Simulations reveal adverse hemodynamics in patients with multiple systemic to pulmonary shunts.

    PubMed

    Esmaily-Moghadam, Mahdi; Murtuza, Bari; Hsia, Tain-Yen; Marsden, Alison

    2015-03-01

    For newborns diagnosed with pulmonary atresia or severe pulmonary stenosis leading to insufficient pulmonary blood flow, cyanosis can be mitigated with placement of a modified Blalock-Taussig shunt (MBTS) between the innominate and pulmonary arteries. In some clinical scenarios, patients receive two systemic-to-pulmonary connections, either by leaving the patent ductus arteriosus (PDA) open or by adding an additional central shunt (CS) in conjunction with the MBTS. This practice has been motivated by the thinking that an additional source of pulmonary blood flow could beneficially increase pulmonary flow and provide the security of an alternate pathway in case of thrombosis. However, there have been clinical reports of premature shunt occlusion when more than one shunt is employed, leading to speculation that multiple shunts may in fact lead to unfavorable hemodynamics and increased mortality. In this study, we hypothesize that multiple shunts may lead to undesirable flow competition, resulting in increased residence time (RT) and elevated risk of thrombosis, as well as pulmonary overcirculation. Computational fluid dynamics-based multiscale simulations were performed to compare a range of shunt configurations and systematically quantify flow competition, pulmonary circulation, and other clinically relevant parameters. In total, 23 cases were evaluated by systematically changing the PDA/CS diameter, pulmonary vascular resistance (PVR), and MBTS position and compared by quantifying oxygen delivery (OD) to the systemic and coronary beds, wall shear stress (WSS), oscillatory shear index (OSI), WSS gradient (WSSG), and RT in the pulmonary artery (PA), and MBTS. Results showed that smaller PDA/CS diameters can lead to flow conditions consistent with increased thrombus formation due to flow competition in the PA, and larger PDA/CS diameters can lead to insufficient OD due to pulmonary hyperfusion. In the worst case scenario, it was found that multiple shunts can lead to

  12. 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

  13. Immunologic profiles of multiple sclerosis treatments reveal shared early B cell alterations

    PubMed Central

    Dooley, James; Pauwels, Ine; Franckaert, Dean; Smets, Ide; Garcia-Perez, Josselyn E.; Hilven, Kelly; Danso-Abeam, Dina; Terbeek, Joanne; Nguyen, Anh T.L.; De Muynck, Louis; Decallonne, Brigitte; Dubois, Bénédicte

    2016-01-01

    Objective: We undertook a systems immunology approach of the adaptive immune system in multiple sclerosis (MS), overcoming tradeoffs between scale and level of detail, in order to identify the immunologic signature of MS and the changes wrought by current immunomodulatory treatments. Methods: We developed a comprehensive flow cytometry platform measuring 38 immunologic cell types in the peripheral blood of 245 individuals in a routine clinical setting. These include patients with MS, untreated or receiving any of 4 current immunomodulatory treatments (interferon-β, glatiramer acetate, natalizumab, or fingolimod), patients with autoimmune thyroid disease, and healthy controls. Results: An increase in memory CD8+ T cells and B cells was observed in untreated patients with MS. Interferon-β and fingolimod induce significant changes upon multiple aspects of the peripheral immune system, with an unexpectedly prominent alteration of B cells. Overall, both treatments push the immune system in different directions, with only 2 significant effects shared across these treatments—an increase in transitional B cells and a decrease in class-switched B cells. We further identified heightened B cell-activating factor (BAFF) levels as regulating this shared B cell pathway. Conclusions: A systems immunology approach established different immunologic profiles induced by current immunomodulatory MS treatments, offering perspectives for personalized medicine. Pathways shared between the immunologic architecture of existing efficacious treatments identify targets for future treatment design. PMID:27231713

  14. 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.

  15. 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

    2015-01-01

    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. PMID:26437396

  16. Analysis of multiple compound-protein interactions reveals novel bioactive molecules.

    PubMed

    Yabuuchi, Hiroaki; Niijima, Satoshi; Takematsu, Hiromu; Ida, Tomomi; Hirokawa, Takatsugu; Hara, Takafumi; Ogawa, Teppei; Minowa, Yohsuke; Tsujimoto, Gozoh; Okuno, Yasushi

    2011-03-01

    The discovery of novel bioactive molecules advances our systems-level understanding of biological processes and is crucial for innovation in drug development. For this purpose, the emerging field of chemical genomics is currently focused on accumulating large assay data sets describing compound-protein interactions (CPIs). Although new target proteins for known drugs have recently been identified through mining of CPI databases, using these resources to identify novel ligands remains unexplored. Herein, we demonstrate that machine learning of multiple CPIs can not only assess drug polypharmacology but can also efficiently identify novel bioactive scaffold-hopping compounds. Through a machine-learning technique that uses multiple CPIs, we have successfully identified novel lead compounds for two pharmaceutically important protein families, G-protein-coupled receptors and protein kinases. These novel compounds were not identified by existing computational ligand-screening methods in comparative studies. The results of this study indicate that data derived from chemical genomics can be highly useful for exploring chemical space, and this systems biology perspective could accelerate drug discovery processes. PMID:21364574

  17. Transcriptome Analysis Reveals Crosstalk of Responsive Genes to Multiple Abiotic Stresses in Cotton (Gossypium hirsutum L.)

    PubMed Central

    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 (1μM ABA), cold (4°C), drought (200mM mannitol), salinity (200mM 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 abiotic

  18. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients

    PubMed Central

    Vazquez-Marrufo, Manuel; Gonzalez-Rosa, Javier J; Vaquero, Encarnacion; Duque, Pablo; Borges, Monica; Gomez, Carlos; Izquierdo, Guillermo

    2008-01-01

    Background A possible method of finding physiological markers of multiple sclerosis (MS) is the application of EEG quantification (QEEG) of brain activity when the subject is stressed by the demands of a cognitive task. In particular, modulations of the spectral content that take place in the EEG of patients with multiple sclerosis remitting-relapsing (RRMS) and benign multiple sclerosis (BMS) during a visuo-spatial task need to be observed. Methods The sample consisted of 19 patients with RRMS, 10 with BMS, and 21 control subjects. All patients were free of medication and had not relapsed within the last month. The power spectral density (PSD) of different EEG bands was calculated by Fast-Fourier-Transformation (FFT), those analysed being delta, theta, alpha, beta and gamma. Z-transformation was performed to observe individual profiles in each experimental group for spectral modulations. Lastly, correlation analyses was performed between QEEG values and other variables from participants in the study (age, EDSS, years of evolution and cognitive performance). Results Nearly half (42%) the RRMS patients showed a statistically significant increase of two or more standard deviations (SD) compared to the control mean value for the beta-2 and gamma bands (F = 2.074, p = 0.004). These alterations were localized to the anterior regions of the right hemisphere, and bilaterally to the posterior areas of the scalp. None of the BMS patients or control subjects had values outside the range of ± 2 SD. There were no significant correlations between these values and the other variables analysed (age, EDSS, years of evolution or behavioural performance). Conclusion During the attentional processing, changes in the high EEG spectrum (beta-2 and gamma) in MS patients exhibit physiological alterations that are not normally detected by spontaneous EEG analysis. The different spectral pattern between pathological and controls groups could represent specific changes for the RRMS

  19. Disruption of neurofascin localization reveals early changes preceding demyelination and remyelination in multiple sclerosis.

    PubMed

    Howell, O W; Palser, A; Polito, A; Melrose, S; Zonta, B; Scheiermann, C; Vora, A J; Brophy, P J; Reynolds, R

    2006-12-01

    Saltatory conduction in the nervous system is enabled through the intimate association between the leading edge of the myelin sheath and the axonal membrane to demarcate the node of Ranvier. The 186 kDa neuron specific isoform of the adhesion molecule neurofascin (Nfasc186) is required for the clustering of voltage gated Na+ channels at the node, whilst the 155 kDa glial specific isoform (Nfasc155) is required for the assembly of correct paranodal junctions. In order to understand the relationship between these vital structures and how they are affected in multiple sclerosis we have examined the expression of Nfasc155 and Nfasc186 in areas of inflammation, demyelination and remyelination from post-mortem brains. Fourteen cases of neuropathologically confirmed multiple sclerosis (8 female and 6 male; post-mortem delay 7-24 h; age 37-77 years; and disease duration 15-40 years), comprising 20 tissue blocks with 32 demyelinating or remyelinating lesions, were used in this study. A significant early alteration in Nfasc155+ paranodal structures occurs within and adjacent to actively demyelinating white matter lesions that are associated with damaged axons. Shaker-type Kv1.2 channels, normally located distally to the paranode, overlapped with the disrupted Nfasc155+ structures. In the absence of Nfasc155, Kv1.2 channels abutted normally clustered Nfasc186+ nodes, indicating that complete disruption of the paranodal structure and movement of Kv1.2 channels precede alterations at the node itself. Within areas of partial remyelination, a number of atypical triple-Nfasc155+ structures were noted that may represent transient oligodendrocyte-axonal contacts during the process of myelin repair or aberrant interactions. Within shadow plaques discretely clustered Na+v, Nfasc186+ and Nfasc155+ domains indicated the restoration of normal nodal architecture. The alterations in oligodendrocyte Nfasc155 expression that accompany inflammation and demyelination suggest an ongoing

  20. 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. PMID:26301598

  1. Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities.

    PubMed

    Shay, G; Hazlehurst, L; Lynch, C C

    2016-01-01

    Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents such as bortezomib and lenalidomide have significantly improved overall survival, the disease is currently incurable with the emergence of drug resistance limiting the efficacy of chemotherapeutic strategies. Failure to cure the disease is in part due to the underlying genetic heterogeneity of the cancer. Myeloma progression is critically dependent on the surrounding microenvironment. Defining the interactions between myeloma cells and the more genetically stable hematopoietic and mesenchymal components of the bone microenvironment is critical for the development of new therapeutic targets. In this review, we discuss recent advances in our understanding of how microenvironmental elements contribute to myeloma progression and, therapeutically, how those elements can or are currently being targeted in a bid to eradicate the disease. PMID:26423531

  2. Functional multiplicity of motor molecules revealed by a simple kinetic analysis.

    PubMed Central

    Lark, E; Omoto, C K; Schumaker, M F

    1994-01-01

    We present a simple analytical solution for a kinetic model of motor molecule function with multiple arms. This model has a rate of motion proportional to the probability that all arms in a complex are detached from the cytoskeleton and, therefore, we refer to it as obligate cooperativity. The model has the form: v = Vmax/(1 + q/S)n, where Vmax is the maximum velocity, the product nq is the effective Michaelis constant at high [ATP], and n is the number of arms. Values of n = 2 and n = 1 give good fits to the heavy meromyosin and myosin S1 sliding velocity data, respectively, consistent with the number of active sites. Despite the complexity of the eukaryotic axoneme, beat frequency data from Chlamydomonas wild-type and oda mutants are also fit by this model. PMID:7811925

  3. 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

    2014-01-01

    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. PMID:25523484

  4. Transport characteristics of a single C60-molecule junction revealed by multiple Andreev reflections

    NASA Astrophysics Data System (ADS)

    Hiraoka, Ryoichi; Arafune, Ryuichi; Tsukahara, Noriyuki; Kawai, Maki; Takagi, Noriaki

    2014-12-01

    We have determined the number of transport channels and the value of the transmission coefficients of a single molecular junction by measuring the multiple Andreev reflections (MARs) with a scanning tunneling microscope (STM). By precisely positioning a Nb STM tip to a single C60 molecule on Pb(111), a single molecular junction was fabricated in which the C60 molecule connects with the two superconducting electrodes. From the subharmonic gap structures arising from MARs in the current-voltage characteristics together with the tunneling spectrum of the C60 molecule, we found that unoccupied molecular orbitals of C60 extending to the Fermi level provide three electronic transport channels in the molecular junction. We also found that the transmission coefficients depend on the contact geometry of the molecule. These results demonstrate that the combination of the STM imaging with the MARs measurement provides an effective path for investigating the electronic transport properties through a single molecule sandwiched by two superconducting electrodes.

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

    PubMed Central

    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

    2014-01-01

    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. PMID:25523484

  6. Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co-occurrence of multiple events.

    PubMed

    Armour, Christine M; Smith, Amanda; Hartley, Taila; Chardon, Jodi Warman; Sawyer, Sarah; Schwartzentruber, Jeremy; Hennekam, Raoul; Majewski, Jacek; Bulman, Dennis E; Suri, Mohnish; Boycott, Kym M

    2016-07-01

    In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and "low-normal" intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the SACS gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the TRPS1, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A TBL1XR1 mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that "Fitzsimmons syndrome" is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome-wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. © 2016 Wiley Periodicals, Inc. PMID:27133561

  7. 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. PMID:26487699

  8. Multiple Fermi pockets revealed by Shubnikov-de Haas oscillations in WTe2

    NASA Astrophysics Data System (ADS)

    Xiang, Fei-Xiang; Veldhorst, Menno; Dou, Shi-Xue; Wang, Xiao-Lin

    2015-11-01

    The recently discovered non-saturating and parabolic magnetoresistance and the pressure-induced superconductivity at low temperature in WTe2 imply its rich electronic structure and possible practical applications. Here we use magnetotransport measurements to investigate the electronic structure of WTe2 single crystals. A non-saturating and parabolic magnetoresistance is observed from low temperature to high temperature up to 200 K with magnetic fields up to 8 T. Shubnikov-de Haas (SdH) oscillations with beating patterns are observed, the fast Fourier transform of which reveals three oscillation frequencies, corresponding to three pairs of Fermi pockets with comparable effective masses, m* ∼ 0.31~me . By fitting the Hall resistivity, we infer that they can be attributed to one pair of electron pockets and two pairs of hole pockets, together with nearly perfect compensation of the electron-hole carrier concentration. These magnetotransport measurements reveal the complex electronic structure in WTe2, explaining the non-saturating magnetoresistance.

  9. Multiple knockout mouse models reveal lincRNAs are required for life and brain development

    PubMed Central

    Sauvageau, Martin; Goff, Loyal A; Lodato, Simona; Bonev, Boyan; Groff, Abigail F; Gerhardinger, Chiara; Sanchez-Gomez, Diana B; Hacisuleyman, Ezgi; Li, Eric; Spence, Matthew; Liapis, Stephen C; Mallard, William; Morse, Michael; Swerdel, Mavis R; D’Ecclessis, Michael F; Moore, Jennifer C; Lai, Venus; Gong, Guochun; Yancopoulos, George D; Frendewey, David; Kellis, Manolis; Hart, Ronald P; Valenzuela, David M; Arlotta, Paola; Rinn, John L

    2013-01-01

    Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc–Brn1b and linc–Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr−/− neonates, whereas linc–Brn1b−/− mutants displayed distinct abnormalities in the generation of upper layer II–IV neurons in the neocortex. This study demonstrates that lncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of lncRNA molecules. DOI: http://dx.doi.org/10.7554/eLife.01749.001 PMID:24381249

  10. Molecular phylogenetics reveal multiple tertiary vicariance origins of the African rain forest trees

    PubMed Central

    Couvreur, Thomas LP; Chatrou, Lars W; Sosef, Marc SM; Richardson, James E

    2008-01-01

    Background Tropical rain forests are the most diverse terrestrial ecosystems on the planet. How this diversity evolved remains largely unexplained. In Africa, rain forests are situated in two geographically isolated regions: the West-Central Guineo-Congolian region and the coastal and montane regions of East Africa. These regions have strong floristic affinities with each other, suggesting a former connection via an Eocene pan-African rain forest. High levels of endemism observed in both regions have been hypothesized to be the result of either 1) a single break-up followed by a long isolation or 2) multiple fragmentation and reconnection since the Oligocene. To test these hypotheses the evolutionary history of endemic taxa within a rain forest restricted African lineage of the plant family Annonaceae was studied. Molecular phylogenies and divergence dates were estimated using a Bayesian relaxed uncorrelated molecular clock assumption accounting for both calibration and phylogenetic uncertainties. Results Our results provide strong evidence that East African endemic lineages of Annonaceae have multiple origins dated to significantly different times spanning the Oligocene and Miocene epochs. Moreover, these successive origins (c. 33, 16 and 8 million years – Myr) coincide with known periods of aridification and geological activity in Africa that would have recurrently isolated the Guineo-Congolian rain forest from the East African one. All East African taxa were found to have diversified prior to Pleistocene times. Conclusion Molecular phylogenetic dating analyses of this large pan-African clade of Annonaceae unravels an interesting pattern of diversification for rain forest restricted trees co-occurring in West/Central and East African rain forests. Our results suggest that repeated reconnections between the West/Central and East African rain forest blocks allowed for biotic exchange while the break-ups induced speciation via vicariance, enhancing the levels of

  11. 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

  12. Cutting Edge: Il-1 Receptor-Associated Kinase 4 Structures Reveal Novel Features And Multiple Conformations

    SciTech Connect

    Kuglstatter, A.; Villasenor, A.G.; Shaw, D.; Lee, S.W.; Tsing, S.; Niu, L.; Song, K.W.; Barnett, J.W.; Browner, M.F.

    2007-07-09

    L-1R-associated kinase (IRAK)4 plays a central role in innate and adaptive immunity, and is a crucial component in IL-1/TLR signaling. We have determined the crystal structures of the apo and ligand-bound forms of human IRAK4 kinase domain. These structures reveal several features that provide opportunities for the design of selective IRAK4 inhibitors. The N-terminal lobe of the IRAK4 kinase domain is structurally distinctive due to a loop insertion after an extended N-terminal helix. The gatekeeper residue is a tyrosine, a unique feature of the IRAK family. The IRAK4 structures also provide insights into the regulation of its activity. In the apo structure, two conformations coexist, differing in the relative orientation of the two kinase lobes and the position of helix C. In the presence of an ATP analog only one conformation is observed, indicating that this is the active conformation.

  13. 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

    2007-10-01

    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. PMID:17913879

  14. 2-D Convection and Electrodynamic Features of Substorms Revealed by Multiple Radar Observations (Invited)

    NASA Astrophysics Data System (ADS)

    Zou, S.

    2010-12-01

    Substorms are one of the fundamental elements of geomagnetic activity, which involve complex magnetosphere-ionosphere coupling processes. In this work, we aim to better understand the evolution of high latitude ionospheric convection and the relevant current systems associated with substorms, with emphasis on these features near the nightside Harang reversal region. Three different types of radars, including the Super Dual Auroral Radar Network (SuperDARN) coherent-scatter radars, the new advanced modular incoherent-scatter radar at Poker Flat (PFISR), and the Sondrestrom ISR, have been utilized. Observations from these radars, together with those from complementary instruments, including satellites and other ground-based instruments, have enabled fundamental new understanding of the ionospheric electrodynamic properties associated with substorms. In this presentation, I focus on electrodynamics near the nightside Harang reversal region. Observations from the SuperDARN and the PFISR radars revealed that auroral activity at substorm onset is located near the center of the Harang reversal, which represents a key feature of magnetospheric and ionospheric convection and is part of the Region 2 system. The observations also show nightside convection flows exhibit repeatable, distinct variations at different locations relative to the substorm-related auroral activity. Taking advantage of the simultaneous flow and ionization measurements from PFISR, a current closure relation has been found between the Region 2 and the substorm field-aligned current systems. By synthesizing these observations, a 2-D comprehensive view of the nightside ionospheric electrodynamical features, including electrical equipotentials, flows and FACs, and their evolution associated with substorms has been constructed, which has revealed a strong coupling between the substorm and the Region 2 current systems. This study sheds new light on substorm-related magnetosphere-ionosphere coupling and

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

    PubMed

    Stewart, Philip E; 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

  16. Biomusic: a novel technology for revealing the personhood of people with profound multiple disabilities.

    PubMed

    Blain-Moraes, Stefanie; Chesser, Stephanie; Kingsnorth, Shauna; McKeever, Patricia; Biddiss, Elaine

    2013-06-01

    It is often difficult for family members and caregivers to interact with persons with profound multiple disabilities (PMD) because of the severely compromised communicative repertoire of this population. The resulting communication challenges may limit the ability of others to perceive personhood in individuals with PMD. This preliminary study investigated the effects of music generated in real time from physiological signals (biomusic) on caregiver perceptions of their interactions with persons with PMD. Caregivers (n = 10; parents and clinical staff) engaged in four, 10-min interactions with a person with PMD (n = 3; diagnoses = traumatic brain injury, pervasive developmental disorder, hypoxic brain injury), whose biomusic was projected throughout. Caregivers participated in two open-ended, semi-structured interviews to explore the effect of biomusic on these interactions. Most caregiver responses to biomusic were very positive, and many reported that biomusic caused an improvement in their interaction with and perceptions of the person with PMD. By providing audible evidence of the changing physiological state of persons with PMD, biomusic may enhance the perceived personhood of these individuals and enrich interactions with their family members and caregivers. PMID:23484489

  17. VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis

    PubMed Central

    Serres, Sébastien; Mardiguian, Silvy; Campbell, Sandra J.; McAteer, Martina A.; Akhtar, Asim; Krapitchev, Alexandre; Choudhury, Robin P.; Anthony, Daniel C.; Sibson, Nicola R.

    2012-01-01

    Diagnosis of multiple sclerosis (MS) currently requires lesion identification by gadolinium (Gd)-enhanced or T2-weighted magnetic resonance imaging (MRI). However, these methods only identify late-stage pathology associated with blood-brain barrier breakdown. There is a growing belief that more widespread, but currently undetectable, pathology is present in the MS brain. We have previously demonstrated that an anti-VCAM-1 antibody conjugated to microparticles of iron oxide (VCAM-MPIO) enables in vivo detection of VCAM-1 by MRI. Here, in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we have shown that presymptomatic lesions can be quantified using VCAM-MPIO when they are undetectable by Gd-enhancing MRI. Moreover, in symptomatic animals VCAM-MPIO binding was present in all regions showing Gd-DTPA enhancement and also in areas of no Gd-DTPA enhancement, which were confirmed histologically to be regions of leukocyte infiltration. VCAM-MPIO binding correlated significantly with increasing disability. Negligible MPIO-induced contrast was found in either EAE animals injected with an equivalent nontargeted contrast agent (IgG-MPIO) or in control animals injected with the VCAM-MPIO. These findings describe a highly sensitive molecular imaging tool that may enable detection of currently invisible pathology in MS, thus accelerating diagnosis, guiding treatment, and enabling quantitative disease assessment. PMID:21908714

  18. VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis.

    PubMed

    Serres, Sébastien; Mardiguian, Silvy; Campbell, Sandra J; McAteer, Martina A; Akhtar, Asim; Krapitchev, Alexandre; Choudhury, Robin P; Anthony, Daniel C; Sibson, Nicola R

    2011-12-01

    Diagnosis of multiple sclerosis (MS) currently requires lesion identification by gadolinium (Gd)-enhanced or T(2)-weighted magnetic resonance imaging (MRI). However, these methods only identify late-stage pathology associated with blood-brain barrier breakdown. There is a growing belief that more widespread, but currently undetectable, pathology is present in the MS brain. We have previously demonstrated that an anti-VCAM-1 antibody conjugated to microparticles of iron oxide (VCAM-MPIO) enables in vivo detection of VCAM-1 by MRI. Here, in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we have shown that presymptomatic lesions can be quantified using VCAM-MPIO when they are undetectable by Gd-enhancing MRI. Moreover, in symptomatic animals VCAM-MPIO binding was present in all regions showing Gd-DTPA enhancement and also in areas of no Gd-DTPA enhancement, which were confirmed histologically to be regions of leukocyte infiltration. VCAM-MPIO binding correlated significantly with increasing disability. Negligible MPIO-induced contrast was found in either EAE animals injected with an equivalent nontargeted contrast agent (IgG-MPIO) or in control animals injected with the VCAM-MPIO. These findings describe a highly sensitive molecular imaging tool that may enable detection of currently invisible pathology in MS, thus accelerating diagnosis, guiding treatment, and enabling quantitative disease assessment. PMID:21908714

  19. 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

  20. Phylogenetic and molecular epidemiological studies reveal evidence of multiple past recombination events between infectious laryngotracheitis viruses.

    PubMed

    Lee, Sang-Won; Devlin, Joanne M; Markham, John F; Noormohammadi, Amir H; Browning, Glenn F; Ficorilli, Nino P; Hartley, Carol A; Markham, Philip F

    2013-01-01

    In contrast to the RNA viruses, the genome of large DNA viruses such as herpesviruses have been considered to be relatively stable. Intra-specific recombination has been proposed as an important, but underestimated, driving force in herpesvirus evolution. Recently, two distinct field strains of infectious laryngotracheitis virus (ILTV) have been shown to have arisen from independent recombination events between different commercial ILTV vaccines. In this study we sequenced the genomes of additional ILTV strains and also utilized other recently updated complete genome sequences of ILTV to confirm the existence of a number of ILTV recombinants in nature. Multiple recombination events were detected in the unique long and repeat regions of the genome, but not in the unique short region. Most recombinants contained a pair of crossover points between two distinct lineages of ILTV, corresponding to the European origin and the Australian origin vaccine strains of ILTV. These results suggest that there are two distinct genotypic lineages of ILTV and that these commonly recombine in the field. PMID:23383306

  1. Phylogenetic and Molecular Epidemiological Studies Reveal Evidence of Multiple Past Recombination Events between Infectious Laryngotracheitis Viruses

    PubMed Central

    Lee, Sang-Won; Devlin, Joanne M.; Markham, John F.; Noormohammadi, Amir H.; Browning, Glenn F.; Ficorilli, Nino P.; Hartley, Carol A.; Markham, Philip F.

    2013-01-01

    In contrast to the RNA viruses, the genome of large DNA viruses such as herpesviruses have been considered to be relatively stable. Intra-specific recombination has been proposed as an important, but underestimated, driving force in herpesvirus evolution. Recently, two distinct field strains of infectious laryngotracheitis virus (ILTV) have been shown to have arisen from independent recombination events between different commercial ILTV vaccines. In this study we sequenced the genomes of additional ILTV strains and also utilized other recently updated complete genome sequences of ILTV to confirm the existence of a number of ILTV recombinants in nature. Multiple recombination events were detected in the unique long and repeat regions of the genome, but not in the unique short region. Most recombinants contained a pair of crossover points between two distinct lineages of ILTV, corresponding to the European origin and the Australian origin vaccine strains of ILTV. These results suggest that there are two distinct genotypic lineages of ILTV and that these commonly recombine in the field. PMID:23383306

  2. Multiple origins of deep-sea Asellota (Crustacea: Isopoda) from shallow waters revealed by molecular data

    PubMed Central

    Raupach, Michael J.; Mayer, Christoph; Malyutina, Marina; Wägele, Johann-Wolfgang

    2008-01-01

    The Asellota are a highly variable group of Isopoda with many species in freshwater and marine shallow-water environments. However, in the deep sea, they show their most impressive radiation with a broad range of astonishing morphological adaptations and bizarre body forms. Nevertheless, the evolution and phylogeny of the deep-sea Asellota are poorly known because of difficulties in scoring morphological characters. In this study, the molecular phylogeny of the Asellota is evaluated for 15 marine shallow-water species and 101 deep-sea species, using complete 18S and partial 28S rDNA gene sequences. Our molecular data support the monophyly of most deep-sea families and give evidence for a multiple colonization of the deep sea by at least four major lineages of asellote isopods. According to our molecular data, one of these lineages indicates an impressive radiation in the deep sea. Furthermore, the present study rejects the monophyly of the family Janiridae, a group of plesiomorphic shallow-water Asellota, and several shallow-water and deep-sea genera (Acanthaspidia, Ianthopsis, Haploniscus, Echinozone, Eurycope, Munnopsurus and Syneurycope). PMID:19033145

  3. 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. PMID:22392996

  4. 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

  5. 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

  6. Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS.

    PubMed

    Wang, Qian; Yang, Can; Gelernter, Joel; Zhao, Hongyu

    2015-11-01

    Although some existing epidemiological observations and molecular experiments suggested that brain disorders in the realm of psychiatry may be influenced by immune dysregulation, the degree of genetic overlap between psychiatric disorders and immune disorders has not been well established. We investigated this issue by integrative analysis of genome-wide association studies of 18 complex human traits/diseases (five psychiatric disorders, seven immune disorders, and others) and multiple genome-wide annotation resources (central nervous system genes, immune-related expression-quantitative trait loci (eQTL) and DNase I hypertensive sites from 98 cell lines). We detected pleiotropy in 24 of the 35 psychiatric-immune disorder pairs. The strongest pleiotropy was observed for schizophrenia-rheumatoid arthritis with MHC region included in the analysis (p = 3.9 x 10(-285), and schizophrenia-Crohn's disease with MHC region excluded (p = 1.1 x 10(-36). Significant enrichment (> 1.4 fold) of immune-related eQTL was observed in four psychiatric disorders. Genomic regions responsible for pleiotropy between psychiatric disorders and immune disorders were detected. The MHC region on chromosome 6 appears to be the most important with other regions, such as cytoband 1p13.2, also playing significant roles in pleiotropy. We also found that most alleles shared between schizophrenia and Crohn's disease have the same effect direction, with similar trend found for other disorder pairs, such as bipolar-Crohn's disease. Our results offer a novel bird's-eye view of the genetic relationship and demonstrate strong evidence for pervasive pleiotropy between psychiatric disorders and immune disorders. Our findings might open new routes for prevention and treatment strategies for these disorders based on a new appreciation of the importance of immunological mechanisms in mediating risk of many psychiatric diseases. PMID:26340901

  7. Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

    PubMed Central

    Zhang, Xu; Bai, Xiaotao; Wang, Jun; Wang, Ailan; Milne, Richard

    2014-01-01

    Background During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual. Methodology/Principal Findings In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively. Conclusions These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation. PMID:24587023

  8. DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways

    PubMed Central

    Nardone, S; Sharan Sams, D; Reuveni, E; Getselter, D; Oron, O; Karpuj, M; Elliott, E

    2014-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by dysfunction in social interaction, communication and stereotypic behavior. Genetic and environmental factors have been implicated in the development of ASD, but the molecular mechanisms underlying their interaction are not clear. Epigenetic modifications have been suggested as molecular mechanism that can mediate the interaction between the environment and the genome to produce adaptive or maladaptive behaviors. Here, using the Illumina 450 K methylation array we have determined the existence of many dysregulated CpGs in two cortical regions, Brodmann area 10 (BA10) and Brodmann area 24 (BA24), of individuals who had ASD. In BA10 we found a very significant enrichment for genomic areas responsible for immune functions among the hypomethylated CpGs, whereas genes related to synaptic membrane were enriched among hypermethylated CpGs. By comparing our methylome data with previously published transcriptome data, and by performing real-time PCR on selected genes that were dysregulated in our study, we show that hypomethylated genes are often overexpressed, and that there is an inverse correlation between gene expression and DNA methylation within the individuals. Among these genes there were C1Q, C3, ITGB2 (C3R), TNF-α, IRF8 and SPI1, which have recently been implicated in synaptic pruning and microglial cell specification. Finally, we determined the epigenetic dysregulation of the gene HDAC4, and we confirm that the locus encompassing C11orf21/TSPAN32 has multiple hypomethylated CpGs in the autistic brain, as previously demonstrated. Our data suggest a possible role for epigenetic processes in the etiology of ASD. PMID:25180572

  9. 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

  10. Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression.

    PubMed

    Pervouchine, Dmitri D; Djebali, Sarah; Breschi, Alessandra; Davis, Carrie A; Barja, Pablo Prieto; Dobin, Alex; Tanzer, Andrea; Lagarde, Julien; Zaleski, Chris; See, Lei-Hoon; Fastuca, Meagan; Drenkow, Jorg; Wang, Huaien; Bussotti, Giovanni; Pei, Baikang; Balasubramanian, Suganthi; Monlong, Jean; Harmanci, Arif; Gerstein, Mark; Beer, Michael A; Notredame, Cedric; Guigó, Roderic; Gingeras, Thomas R

    2015-01-01

    Mice have been a long-standing model for human biology and disease. Here we characterize, by RNA sequencing, the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles in human cell lines reveals substantial conservation of transcriptional programmes, and uncovers a distinct class of genes with levels of expression that have been constrained early in vertebrate evolution. This core set of genes captures a substantial fraction of the transcriptional output of mammalian cells, and participates in basic functional and structural housekeeping processes common to all cell types. Perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer. Evolutionary constraint in gene expression levels is not reflected in the conservation of the genomic sequences, but is associated with conserved epigenetic marking, as well as with characteristic post-transcriptional regulatory programme, in which sub-cellular localization and alternative splicing play comparatively large roles. PMID:25582907

  11. 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.

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

    PubMed

    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

  13. The similarity structure of distributed neural responses reveals the multiple representations of letters

    PubMed Central

    Rothlein, David; Rapp, Brenda

    2014-01-01

    Most cognitive theories of reading and spelling posit modality-specific representations of letter shapes, spoken letter names, and motor plans as well as abstract, amodal letter representations that serve to unify the various modality-specific formats. However, fundamental questions remain regarding the very existence of abstract letter representations, the neuro-topography of the different types of letter representations, and the degree of cortical selectivity for orthographic information. We directly test quantitative models of the similarity/dissimilarity structure of distributed neural representations of letters using Multivariate Pattern Analysis-Representational Similarity Analysis (MVPA-RSA) searchlight methods to analyze the BOLD response recorded from single letter viewing. These analyses reveal a left hemisphere ventral temporal region selectively tuned to abstract letter representations as well as substrates tuned to modality-specific (visual, phonological and motoric) representations of letters. The approaches applied in this research address various shortcoming of previous studies that have investigated these questions and, therefore, the findings we report serve to advance our understanding of the nature and format of the representations that occur within the various sub- regions of the large-scale networks used in reading and spelling. PMID:24321558

  14. Dengue virus surveillance in Singapore reveals high viral diversity through multiple introductions and in situ evolution.

    PubMed

    Lee, Kim-Sung; Lo, Sharon; Tan, Sharon Siok-Yin; Chua, Rachel; Tan, Li-Kiang; Xu, Helen; Ng, Lee-Ching

    2012-01-01

    Dengue fever, a vector-borne disease, has caused tremendous burden to countries in the tropics and sub tropics. Over the past 20 years, dengue epidemics have become more widespread, severe and frequent. This study aims to understand the dynamics of dengue viruses in cosmopolitan Singapore. Envelope protein gene sequences of all four dengue serotypes (DENV-1-DENV-4) obtained from human sera in Singapore (2008-2010) revealed that constant viral introductions and in situ evolution contribute to viral diversity in Singapore and play important roles in shaping the epidemiology of dengue in the island state. The diversity of dengue viruses reported here could be a reflection of the on-going dengue situation in the region given Singapore's location in a dengue hyperendemic region and its role as the regional hub for travels and trade. Though cosmopolitan genotype of DENV-2 has remained as the predominant strain circulating in Singapore, we uncovered evidence of in situ evolution which could possibly result in viruses with improved fitness. While we have previously shown that a switch in the predominant dengue serotype could serve as a warning for an impending outbreak, our current data shows that a replacement of a predominant viral clade, even in the absence of a switch in predominant serotype, could signal a possible increase in dengue transmission. The circulating dengue viruses in Singapore are highly diverse, a situation which could offer ample opportunities for selection of strains of higher fitness, thus increasing the risk of outbreaks despite a low Aedes population. PMID:22036707

  15. 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

  16. Timing of posterior parahippocampal gyrus activity reveals multiple scene processing stages.

    PubMed

    Bastin, Julien; Committeri, Giorgia; Kahane, Philippe; Galati, Gaspare; Minotti, Lorella; Lachaux, Jean-Philippe; Berthoz, Alain

    2013-06-01

    Posterior parahippocampal gyrus (PPHG) is strongly involved during scene recognition and spatial cognition. How PPHG electrophysiological activity could underlie these functions, and whether they share similar timing mechanisms is unknown. We addressed this question in two intracerebral experiments which revealed that PPHG neural activity dissociated an early stimulus-driven effect (>200 and <500 ms) and a late task-related effect (>600 and <800 ms). Strongest PPHG gamma band (50-150 Hz) activities were found early when subjects passively viewed scenes (scene selectivity effect) and lately when they had to estimate the position of an object relative to the environment (allocentric effect). Based on single trial analyses, we were able to predict when patients viewed scenes (compared to other visual categories) and when they performed allocentric judgments (compared to other spatial judgments). The anatomical location corresponding to the strongest effects was in the depth of the collateral sulcus. Our findings directly affect current theories of visual scene processing and spatial orientation by providing new timing constraints and by demonstrating the existence of separable information processing stages in the functionally defined parahippocampal place area. PMID:22287281

  17. 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. PMID:17609171

  18. Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary constraint in gene expression

    PubMed Central

    Pervouchine, Dmitri D.; Djebali, Sarah; Breschi, Alessandra; Davis, Carrie A.; Barja, Pablo Prieto; Dobin, Alex; Tanzer, Andrea; Lagarde, Julien; Zaleski, Chris; See, Lei-Hoon; Fastuca, Meagan; Drenkow, Jorg; Wang, Huaien; Bussotti, Giovanni; Pei, Baikang; Balasubramanian, Suganthi; Monlong, Jean; Harmanci, Arif; Gerstein, Mark; Beer, Michael A.; Notredame, Cedric; Guigó, Roderic; Gingeras, Thomas R.

    2015-01-01

    Mice have been a long-standing model for human biology and disease. Here we characterize, by RNA sequencing, the transcriptional profiles of a large and heterogeneous collection of mouse tissues, augmenting the mouse transcriptome with thousands of novel transcript candidates. Comparison with transcriptome profiles in human cell lines reveals substantial conservation of transcriptional programmes, and uncovers a distinct class of genes with levels of expression that have been constrained early in vertebrate evolution. This core set of genes captures a substantial fraction of the transcriptional output of mammalian cells, and participates in basic functional and structural housekeeping processes common to all cell types. Perturbation of these constrained genes is associated with significant phenotypes including embryonic lethality and cancer. Evolutionary constraint in gene expression levels is not reflected in the conservation of the genomic sequences, but is associated with conserved epigenetic marking, as well as with characteristic post-transcriptional regulatory programme, in which sub-cellular localization and alternative splicing play comparatively large roles. PMID:25582907

  19. Subterranean termite phylogeography reveals multiple postglacial colonization events in southwestern Europe.

    PubMed

    Lefebvre, Thomas; Vargo, Edward L; Zimmermann, Marie; Dupont, Simon; Kutnik, Magdalena; Bagnères, Anne-Geneviève

    2016-08-01

    A long-standing goal of evolutionary biology is to understand how paleoclimatic and geological events shape the geographical distribution and genetic structure within and among species. Using a diverse set of markers (cuticular hydrocarbons, mitochondrial and nuclear gene sequences, microsatellite loci), we studied Reticulitermes grassei and R. banyulensis, two closely related termite species in southwestern Europe. We sought to clarify the current genetic structure of populations that formed following postglacial dispersal from refugia in southern Spain and characterize the gene flow between the two lineages over the last several million years. Each marker type separately provided a fragmented picture of the evolutionary history at different timescales. Chemical analyses of cuticular hydrocarbons and phylogenetic analyses of mitochondrial and nuclear genes showed clear separation between the species, suggesting they diverged following vicariance events in the Late Miocene. However, the presence of intermediate chemical profiles and mtDNA introgression in some Spanish colonies suggests ongoing gene flow. The current genetic structure of Iberian populations is consistent with alternating isolation and dispersal events during Quaternary glacial periods. Analyses of population genetic structure revealed postglacial colonization routes from southern Spain to France, where populations underwent strong genetic bottlenecks after traversing the Pyrenees resulting in parapatric speciation. PMID:27547371

  20. Multiple CaMKII Binding Modes to the Actin Cytoskeleton Revealed by Single-Molecule Imaging.

    PubMed

    Khan, Shahid; Conte, Ianina; Carter, Tom; Bayer, K Ulrich; Molloy, Justin E

    2016-07-26

    Localization of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to dendritic spine synapses is determined in part by the actin cytoskeleton. We determined binding of GFP-tagged CaMKII to tag-RFP-labeled actin cytoskeleton within live cells using total internal reflection fluorescence microscopy and single-molecule tracking. Stepwise photobleaching showed that CaMKII formed oligomeric complexes. Photoactivation experiments demonstrated that diffusion out of the evanescent field determined the track lifetimes. Latrunculin treatment triggered a coupled loss of actin stress fibers and the colocalized, long-lived CaMKII tracks. The CaMKIIα (α) isoform, which was previously thought to lack F-actin interactions, also showed binding, but this was threefold weaker than that observed for CaMKIIβ (β). The βE' splice variant bound more weakly than α, showing that binding by β depends critically on the interdomain linker. The mutations βT287D and αT286D, which mimic autophosphorylation states, also abolished F-actin binding. Autophosphorylation triggers autonomous CaMKII activity, but does not impair GluN2B binding, another important synaptic protein interaction of CaMKII. The CaMKII inhibitor tatCN21 or CaMKII mutations that inhibit GluN2B association by blocking binding of ATP (βK43R and αK42M) or Ca(2+)/calmodulin (βA303R) had no effect on the interaction with F-actin. These results provide the first rationale for the reduced synaptic spine localization of the αT286D mutant, indicating that transient F-actin binding contributes to the synaptic localization of the CaMKIIα isoform. The track lifetime distributions had a stretched exponential form consistent with a heterogeneously diffusing population. This heterogeneity suggests that CaMKII adopts different F-actin binding modes, which is most easily rationalized by multiple subunit contacts between the CaMKII dodecamer and the F-actin cytoskeleton that stabilize the initial weak (micromolar

  1. Multiple cysteine proteinase forms during the life cycle of Dictyostelium discoideum revealed by electrophoretic analysis.

    PubMed Central

    North, M J; Scott, K I; Lockwood, B C

    1988-01-01

    Proteinases of the cellular slime mould Dictyostelium discoideum have been analysed using electrophoresis on polyacrylamide gels containing gelatin (gelatin/PAGE). Multiple proteinase forms were apparent in vegetative myxamoebae, but the presence of individual enzyme forms depended on the manner in which the cells were grown. Axenic cells had a characteristic A-pattern of proteinases consisting of six bands, the most active enzymes having apparent Mr values of 51,000 and 45,000 (these have been named ddCP51 and ddCP45, respectively). Some of the proteinases were also present in the medium, the major extracellular form was ddCP42, a 42,000-Mr enzyme. Cells grown in association with bacteria had a distinct B-pattern with three main enzymes that had apparent Mr values of 48,000, 43,000 and 38,000. All of the A- and B-pattern proteinases were most active at acid pH in the presence of dithiothreitol and were inhibited by various agents such as trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E64), leupeptin and chymostatin, which inactivate cysteine proteinases. One of the enzymes, ddCP30, was identified as cysteine proteinase B which had been purified and characterized previously [North, M.J. & Whyte, A. (1984) J. Gen. Microbiol. 130, 123-134]. During starvation of axenic cells in shaken suspensions some of the vegetative proteinases disappeared, ddCP42 was released from the cells and one new enzyme with an apparent Mr of 48,000 appeared. Addition of cyclic AMP had little effect on these changes. When the axenically grown myxamoebae underwent development on filters, similar changes in band pattern were observed and the aggregation stage was characterized by the presence of three cysteine proteinase bands (apparent Mr values of 48,000, 45,000 and 43,000). Proteinases, especially ddCP42, were released from the cells and could be collected from the buffer-saturated pads which supported the filters. The results demonstrate that cysteine proteinases are present

  2. Global Transcription Profiling Reveals Multiple Sugar Signal Transduction Mechanisms in ArabidopsisW⃞

    PubMed Central

    Price, John; Laxmi, Ashverya; St. Martin, Steven K.; Jang, Jyan-Chyun

    2004-01-01

    Complex and interconnected signaling networks allow organisms to control cell division, growth, differentiation, or programmed cell death in response to metabolic and environmental cues. In plants, it is known that sugar and nitrogen are critical nutrient signals; however, our understanding of the molecular mechanisms underlying nutrient signal transduction is very limited. To begin unraveling complex sugar signaling networks in plants, DNA microarray analysis was used to determine the effects of glucose and inorganic nitrogen source on gene expression on a global scale in Arabidopsis thaliana. In whole seedling tissue, glucose is a more potent signal in regulating transcription than inorganic nitrogen. In fact, other than genes associated with nitrate assimilation, glucose had a greater effect in regulating nitrogen metabolic genes than nitrogen itself. Glucose also regulated a broader range of genes, including genes associated with carbohydrate metabolism, signal transduction, and metabolite transport. In addition, a large number of stress responsive genes were also induced by glucose, indicating a role of sugar in environmental responses. Cluster analysis revealed significant interaction between glucose and nitrogen in regulating gene expression because glucose can modulate the effects of nitrogen and vise versa. Intriguingly, cycloheximide treatment appeared to disrupt glucose induction more than glucose repression, suggesting that de novo protein synthesis is an intermediary event required before most glucose induction can occur. Cross talk between sugar and ethylene signaling may take place on the transcriptional level because several ethylene biosynthetic and signal transduction genes are repressed by glucose, and the repression is largely unaffected by cycloheximide. Collectively, our global expression data strongly support the idea that glucose and inorganic nitrogen act as both metabolites and signaling molecules. PMID:15273295

  3. Sequencing of LRP2 reveals multiple rare variants associated with urinary trefoil factor-3.

    PubMed

    McMahon, Gearoid M; Olden, Matthias; Garnaas, Maija; Yang, Qiong; Liu, Xuan; Hwang, Shih-Jen; Larson, Martin G; Goessling, Wolfram; Fox, Caroline S

    2014-12-01

    Novel biomarkers are being investigated to identify patients with kidney disease. We measured a panel of 13 urinary biomarkers in participants from the Offspring Cohort of the Framingham Heart Study. Using an Affymetrix chip with imputation to 2.5 M single-nucleotide polymorphisms (SNPs), we conducted a GWAS of these biomarkers (n=2640) followed by exonic sequencing and genotyping. Functional studies in zebrafish were used to investigate histologic correlation with renal function. Across all 13 biomarkers, there were 97 significant SNPs at three loci. Lead SNPs at each locus were rs6555820 (P=6.7×10(-49); minor allele frequency [MAF]=0.49) in HAVCR1 (associated with kidney injury molecule-1), rs7565788 (P=2.15×10(-16); MAF=0.22) in LRP2 (associated with trefoil factor 3 [TFF3]), and rs11048230 (P=4.77×10(-8); MAF=0.10) in an intergenic region near RASSF8 (associated with vascular endothelial growth factor). Validation in the CKDGen Consortium (n=67,093) showed that only rs7565788 at LRP2, which encodes megalin, was associated with eGFR (P=0.003). Sequencing of exons 16-72 of LRP2 in 200 unrelated individuals at extremes of urinary TFF3 levels identified 197 variants (152 rare; MAF<0.05), 31 of which (27 rare) were nonsynonymous. In aggregate testing, rare variants were associated with urinary TFF3 levels (P=0.003), and the lead GWAS signal was not explained by these variants. Knockdown of LRP2 in zebrafish did not alter the renal phenotype in static or kidney injury models. In conclusion, this study revealed common variants associated with urinary levels of TFF3, kidney injury molecule-1, and vascular endothelial growth factor and identified a cluster of rare variants independently associated with TFF3. PMID:24876117

  4. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

    PubMed Central

    Chandran, Uma R; Ma, Changqing; Dhir, Rajiv; Bisceglia, Michelle; Lyons-Weiler, Maureen; Liang, Wenjing; Michalopoulos, George; Becich, Michael; Monzon, Federico A

    2007-01-01

    Background Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Methods Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. Results The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). Conclusion We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. PMID:17430594

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

    PubMed

    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

    2016-06-28

    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

  6. ABCC transporters mediate insect resistance to multiple Bt toxins revealed by bulk segregant analysis

    PubMed Central

    2014-01-01

    Background Relatively recent evidence indicates that ABCC2 transporters play a main role in the mode of action of Bacillus thuringiensis (Bt) Cry1A-type proteins. Mapping of major Cry1A resistance genes has linked resistance to the ABCC2 locus in Heliothis virescens, Plutella xylostella, Trichoplusia ni and Bombyx mori, and mutations in this gene have been found in three of these Bt-resistant strains. Results We have used a colony of Spodoptera exigua (Xen-R) highly resistant to a Bt commercial bioinsecticide to identify regions in the S. exigua genome containing loci for major resistance genes by using bulk segregant analysis (BSA). Results reveal a region containing three genes from the ABCC family (ABBC1, ABBC2 and ABBC3) and a mutation in one of them (ABBC2) as responsible for the resistance of S. exigua to the Bt commercial product and to its key Spodoptera-active ingredients, Cry1Ca. In contrast to all previously described mutations in ABCC2 genes that directly or indirectly affect the extracellular domains of the membrane protein, the ABCC2 mutation found in S. exigua affects an intracellular domain involved in ATP binding. Functional analyses of ABBC2 and ABBC3 support the role of both proteins in the mode of action of Bt toxins in S. exigua. Partial silencing of these genes with dsRNA decreased the susceptibility of wild type larvae to both Cry1Ac and Cry1Ca. In addition, reduction of ABBC2 and ABBC3 expression negatively affected some fitness components and induced up-regulation of arylphorin and repat5, genes that respond to Bt intoxication and that are found constitutively up-regulated in the Xen-R strain. Conclusions The current results show the involvement of different members of the ABCC family in the mode of action of B. thuringiensis proteins and expand the role of the ABCC2 transporter in B. thuringiensis resistance beyond the Cry1A family of proteins to include Cry1Ca. PMID:24912445

  7. 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. PMID:26415152

  8. 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. PMID:27412274

  9. 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. PMID:23335487

  10. 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

  11. 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

  12. Genetically targeted single-channel optical recording reveals multiple Orai1 gating states and oscillations in calcium influx.

    PubMed

    Dynes, Joseph L; Amcheslavsky, Anna; Cahalan, Michael D

    2016-01-12

    Orai1 comprises the pore-forming subunit of the Ca(2+) release-activated Ca(2+) (CRAC) channel. When bound and activated by stromal interacting molecule 1 (STIM1), an endoplasmic reticulum (ER)-resident calcium sensor, Orai1 channels possess high selectivity for calcium but extremely small conductance that has precluded direct recording of single-channel currents. We have developed an approach to visualize Orai1 activity by fusing Orai1 to fluorescent, genetically encoded calcium indicators (GECIs). The GECI-Orai1 probes reveal local Ca(2+) influx at STIM1-Orai1 puncta. By whole cell recording, these fusions are fully functional as CRAC channels. When GECI-Orai1 and the CRAC-activating domain (CAD) of STIM1 were coexpressed at low levels and imaged using a total internal reflectance fluorescence microscope, cells exhibited sporadic fluorescence transients the size of diffraction-limited spots and the brightness of a few activated GECI proteins. Transients typically rose rapidly and fell into two classes according to duration: briefer "flickers" lasting only a few hundred milliseconds, and longer "pulses" lasting one to several seconds. The size, intensity, trace shape, frequency, distribution, physiological characteristics, and association with CAD binding together demonstrate that GECI-Orai1 fluorescence transients correspond to single-channel Orai1 responses. Single Orai1 channels gated by CAD, and small Orai1 puncta gated by STIM1, exhibit repetitive fluctuations in single-channel output. CAD binding supports a role in open state maintenance and reveals a second phase of CAD/STIM1 binding after channel opening. These first recordings of single-channel Orai1 currents reveal unexpected dynamics, and when paired with CAD association, support multiple single-channel states. PMID:26712003

  13. Genetically targeted single-channel optical recording reveals multiple Orai1 gating states and oscillations in calcium influx

    PubMed Central

    Dynes, Joseph L.; Amcheslavsky, Anna; Cahalan, Michael D.

    2016-01-01

    Orai1 comprises the pore-forming subunit of the Ca2+ release-activated Ca2+ (CRAC) channel. When bound and activated by stromal interacting molecule 1 (STIM1), an endoplasmic reticulum (ER)-resident calcium sensor, Orai1 channels possess high selectivity for calcium but extremely small conductance that has precluded direct recording of single-channel currents. We have developed an approach to visualize Orai1 activity by fusing Orai1 to fluorescent, genetically encoded calcium indicators (GECIs). The GECI–Orai1 probes reveal local Ca2+ influx at STIM1–Orai1 puncta. By whole cell recording, these fusions are fully functional as CRAC channels. When GECI–Orai1 and the CRAC-activating domain (CAD) of STIM1 were coexpressed at low levels and imaged using a total internal reflectance fluorescence microscope, cells exhibited sporadic fluorescence transients the size of diffraction-limited spots and the brightness of a few activated GECI proteins. Transients typically rose rapidly and fell into two classes according to duration: briefer “flickers” lasting only a few hundred milliseconds, and longer “pulses” lasting one to several seconds. The size, intensity, trace shape, frequency, distribution, physiological characteristics, and association with CAD binding together demonstrate that GECI–Orai1 fluorescence transients correspond to single-channel Orai1 responses. Single Orai1 channels gated by CAD, and small Orai1 puncta gated by STIM1, exhibit repetitive fluctuations in single-channel output. CAD binding supports a role in open state maintenance and reveals a second phase of CAD/STIM1 binding after channel opening. These first recordings of single-channel Orai1 currents reveal unexpected dynamics, and when paired with CAD association, support multiple single-channel states. PMID:26712003

  14. Spatiotemporal control of nanooptical excitations

    PubMed Central

    Aeschlimann, Martin; Bauer, Michael; Bayer, Daniela; Brixner, Tobias; Cunovic, Stefan; Dimler, Frank; Fischer, Alexander; Pfeiffer, Walter; Rohmer, Martin; Schneider, Christian; Steeb, Felix; Strüber, Christian; Voronine, Dmitri V.

    2010-01-01

    The most general investigation and exploitation of light-induced processes require simultaneous control over spatial and temporal properties of the electromagnetic field on a femtosecond time and nanometer length scale. Based on the combination of polarization pulse shaping and time-resolved two-photon photoemission electron microscopy, we demonstrate such control over nanoscale spatial and ultrafast temporal degrees of freedom of an electromagnetic excitation in the vicinity of a nanostructure. The time-resolved cross-correlation measurement of the local photoemission yield reveals the switching of the nanolocalized optical near-field distribution with a lateral resolution well below the diffraction limit and a temporal resolution on the femtosecond time scale. In addition, successful adaptive spatiotemporal control demonstrates the flexibility of the method. This flexible simultaneous control of temporal and spatial properties of nanophotonic excitations opens new possibilities to tailor and optimize the light–matter interaction in spectroscopic methods as well as in nanophotonic applications. PMID:20212153

  15. Multiple 10Be records revealing the history of cosmic-ray variations across the Iceland Basin excursion

    NASA Astrophysics Data System (ADS)

    Horiuchi, Kazuho; Kamata, Kanae; Maejima, Shun; Sasaki, Sho; Sasaki, Nobuyoshi; Yamazaki, Toshitsugu; Fujita, Shuji; Motoyama, Hideaki; Matsuzaki, Hiroyuki

    2016-04-01

    Cosmogenic 10Be is a proxy of cosmic-ray flux, and its natural records provide vital information about the past intensity variability of the geomagnetic field and solar activity. 10Be records also serve as powerful tools for global synchronization among a variety of paleoarchives and for elucidating sedimentary processes on natural remanent magnetization acquisition. However, high-resolution (multi-decadal to multi-centennial) records of 10Be are scarce, especially those older than several tens of thousands of years. Here we present multiple high-resolution 10Be records of the Iceland Basin geomagnetic excursion interval (ca. 170-200 kyr ago) obtained from sediment cores (authigenic 10Be/9Be ratio) and an ice core (atmospheric 10Be flux). Comparing sedimentary 10Be records with relative paleointensity from the same cores, we found differences in the magnetic lock-in depth, even between adjacent cores. The 10Be-proxy records from the sediment and ice cores exhibit common characteristics: an asymmetric large-scale variation, a ∼7-kyr quasi-plateau around the maximum with a characteristic mid-term depression, and multi-millennial fluctuations in cosmic-ray flux during this interval. Minimal-synchronized and stacked 10Be records show that maximum cosmic-ray flux occurred 188.5-190.0 kyr ago and was double the present flux. A wavelet analysis of the stacked curve reveals dominant 4-kyr and secondary 8-kyr periodicities, both of which can be interpreted as intrinsic geomagnetic cycles. The wavelet spectrum of the high-resolution ice-core record shows a periodicity of 1.7 kyr and somewhat intermingled multi-centennial cycles around the maxima of 10Be, which likely represent solar cycles in this period. High-resolution 10Be records from multiple paleoarchives provide both a robust proxy record of cosmic-ray flux and a valuable tool for detailed global synchronization based on cosmic-ray variations.

  16. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes.

    PubMed

    Lobel, Lior; Herskovits, Anat A

    2016-02-01

    Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY's regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

  17. Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes

    PubMed Central

    Lobel, Lior; Herskovits, Anat A.

    2016-01-01

    Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY’s regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

  18. Asymmetric spatiotemporal chaos induced by a polypoid mass in the excised larynx

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack J.

    2008-12-01

    In this paper, asymmetric spatiotemporal chaos induced by a polypoid mass simulating the laryngeal pathology of a vocal polyp is experimentally observed using high-speed imaging in an excised larynx. Spatiotemporal analysis reveals that the normal vocal folds show spatiotemporal correlation and symmetry. Normal vocal fold vibrations are dominated mainly by the first vibratory eigenmode. However, pathological vocal folds with a polypoid mass show broken symmetry and spatiotemporal irregularity. The spatial correlation is decreased. The pathological vocal folds spread vibratory energy across a large number of eigenmodes and induce asymmetric spatiotemporal chaos. High-order eigenmodes show complicated dynamics. Spatiotemporal analysis provides a valuable biomedical application for investigating the spatiotemporal chaotic dynamics of pathological vocal fold systems with a polypoid mass and may represent a valuable clinical tool for the detection of laryngeal mass lesion using high-speed imaging.

  19. Asymmetric spatiotemporal chaos induced by a polypoid mass in the excised larynx

    PubMed Central

    Zhang, Yu; Jiang, Jack J.

    2008-01-01

    In this paper, asymmetric spatiotemporal chaos induced by a polypoid mass simulating the laryngeal pathology of a vocal polyp is experimentally observed using high-speed imaging in an excised larynx. Spatiotemporal analysis reveals that the normal vocal folds show spatiotemporal correlation and symmetry. Normal vocal fold vibrations are dominated mainly by the first vibratory eigenmode. However, pathological vocal folds with a polypoid mass show broken symmetry and spatiotemporal irregularity. The spatial correlation is decreased. The pathological vocal folds spread vibratory energy across a large number of eigenmodes and induce asymmetric spatiotemporal chaos. High-order eigenmodes show complicated dynamics. Spatiotemporal analysis provides a valuable biomedical application for investigating the spatiotemporal chaotic dynamics of pathological vocal fold systems with a polypoid mass and may represent a valuable clinical tool for the detection of laryngeal mass lesion using high-speed imaging. PMID:19123612

  20. Spatiotemporal drought forecasting using nonlinear models

    NASA Astrophysics Data System (ADS)

    Vasiliades, Lampros; Loukas, Athanasios

    2010-05-01

    Spatiotemporal data mining is the extraction of unknown and implicit knowledge, structures, spatiotemporal relationships, or patterns not explicitly stored in spatiotemporal databases. As one of data mining techniques, forecasting is widely used to predict the unknown future based upon the patterns hidden in the current and past data. In order to achieve spatiotemporal forecasting, some mature analysis tools, e.g., time series and spatial statistics are extended to the spatial dimension and the temporal dimension, respectively. Drought forecasting plays an important role in the planning and management of natural resources and water resource systems in a river basin. Early and timelines forecasting of a drought event can help to take proactive measures and set out drought mitigation strategies to alleviate the impacts of drought. Despite the widespread application of nonlinear mathematical models, comparative studies on spatiotemporal drought forecasting using different models are still a huge task for modellers. This study uses a promising approach, the Gamma Test (GT), to select the input variables and the training data length, so that the trial and error workload could be greatly reduced. The GT enables to quickly evaluate and estimate the best mean squared error that can be achieved by a smooth model on any unseen data for a given selection of inputs, prior to model construction. The GT is applied to forecast droughts using monthly Standardized Precipitation Index (SPI) timeseries at multiple timescales in several precipitation stations at Pinios river basin in Thessaly region, Greece. Several nonlinear models have been developed efficiently, with the aid of the GT, for 1-month up to 12-month ahead forecasting. Several temporal and spatial statistical indices were considered for the performance evaluation of the models. The predicted results show reasonably good agreement with the actual data for short lead times, whereas the forecasting accuracy decreases with

  1. 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. PMID:23649474

  2. 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. PMID:26489467

  3. 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

  4. A novel molecule integrating therapeutic and diagnostic activities reveals multiple aspects of stem cell-based therapy.

    PubMed

    Hingtgen, Shawn D; Kasmieh, Randa; van de Water, Jeroen; Weissleder, Ralph; Shah, Khalid

    2010-04-01

    Stem cells are promising therapeutic delivery vehicles; however pre-clinical and clinical applications of stem cell-based therapy would benefit significantly from the ability to simultaneously determine therapeutic efficacy and pharmacokinetics of therapies delivered by engineered stem cells. In this study, we engineered and screened numerous fusion variants that contained therapeutic (TRAIL) and diagnostic (luciferase) domains designed to allow simultaneous investigation of multiple events in stem cell-based therapy in vivo. When various stem cell lines were engineered with the optimized molecule, SRL(O)L(2)TR, diagnostic imaging showed marked differences in the levels and duration of secretion between stem cell lines, while the therapeutic activity of the molecule showed the different secretion levels translated to significant variability in tumor cell killing. In vivo, simultaneous diagnostic and therapeutic monitoring revealed that stem cell-based delivery significantly improved pharmacokinetics and anti-tumor effectiveness of the therapy compared to intravenous or intratumoral delivery. As treatment for highly malignant brain tumor xenografts, tracking SRL(O)L(2)TR showed stable stem cell-mediated delivery significantly regressed peripheral and intracranial tumors. Together, the integrated diagnostic and therapeutic properties of SRL(O)L(2)TR answer critical questions necessary for successful utilization of stem cells as novel therapeutic vehicles. PMID:20127797

  5. 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. PMID:24872535

  6. 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. PMID:26985781

  7. Endemic or introduced? Phylogeography of Asparagopsis (Florideophyceae) in Australia reveals multiple introductions and a new mitochondrial lineage.

    PubMed

    Andreakis, Nikos; Costello, Paul; Zanolla, Marianela; Saunders, Gary W; Mata, Leonardo

    2016-02-01

    The red seaweed Asparagopsis taxiformis embodies five cryptic mitochondrial lineages (lineage 1-5) introduced worldwide as a consequence of human mediated transport and climate change. We compared globally collected mitochondrial cox2-3 intergenic spacer sequences with sequences produced from multiple Australian locations and South Korea to identify Asparagopsis lineages and to reveal cryptic introductions. We report A. taxiformis lineage 4 from Cocos (Keeling) Islands, Australia, and the highly invasive Indo-Pacific Mediterranean lineage 2 from South Korea and Lord Howe Island, Australia. Phylogeographic analysis showed a clear haplotype and geographic separation between western Australian and Great Barrier Reef (GBR) isolates belonging to the recently described lineage 5. The same lineage, however, was characterized by a substantial genetic and geographic break between the majority of Australian specimens and Asparagopsis collections from South Solitary Island, Southern GBR, Lord Howe Island, Kermadec Islands, Norfolk Island, New Caledonia and French Polynesia. The disjunct geographic distribution and sequence divergence between these two groups supports the recognition of a sixth cryptic A. taxiformis mitochondrial lineage. As climatic changes accelerate the relocation of biota and offer novel niches for colonization, periodic surveys for early detection of cryptic invasive seaweeds will be critical in determining whether eradication or effective containment of the aliens are feasible. PMID:26987096

  8. Bayesian modeling and analysis for gradients in spatiotemporal processes.

    PubMed

    Quick, Harrison; Banerjee, Sudipto; Carlin, Bradley P

    2015-09-01

    Stochastic process models are widely employed for analyzing spatiotemporal datasets in various scientific disciplines including, but not limited to, environmental monitoring, ecological systems, forestry, hydrology, meteorology, and public health. After inferring on a spatiotemporal process for a given dataset, inferential interest may turn to estimating rates of change, or gradients, over space and time. This manuscript develops fully model-based inference on spatiotemporal gradients under continuous space, continuous time settings. Our contribution is to offer, within a flexible spatiotemporal process model setting, a framework to estimate arbitrary directional gradients over space at any given timepoint, temporal derivatives at any given spatial location and, finally, mixed spatiotemporal gradients that reflect rapid change in spatial gradients over time and vice-versa. We achieve such inference without compromising on rich and flexible spatiotemporal process models and use nonseparable covariance structures. We illustrate our methodology using a simulated data example and subsequently apply it to a dataset of daily PM2.5 concentrations in California, where the spatiotemporal gradient process reveals the effects of California's unique topography on pollution and detects the aftermath of a devastating series of wildfires. PMID:25898989

  9. Bayesian Modeling and Analysis for Gradients in Spatiotemporal Processes

    PubMed Central

    Quick, Harrison; Banerjee, Sudipto; Carlin, Bradley P.

    2015-01-01

    Summary Stochastic process models are widely employed for analyzing spatiotemporal datasets in various scientific disciplines including, but not limited to, environmental monitoring, ecological systems, forestry, hydrology, meteorology and public health. After inferring on a spatiotemporal process for a given dataset, inferential interest may turn to estimating rates of change, or gradients, over space and time. This manuscript develops fully model-based inference on spatiotemporal gradients under continuous space, continuous time settings. Our contribution is to offer, within a exible spatiotemporal process model setting, a framework to estimate arbitrary directional gradients over space at any given timepoint, temporal derivatives at any given spatial location and, finally, mixed spatiotemporal gradients that reflect rapid change in spatial gradients over time and vice-versa. We achieve such inference without compromising on rich and exible spatiotemporal process models and use nonseparable covariance structures. We illustrate our methodology using a simulated data example and subsequently apply it to a dataset of daily PM2.5 concentrations in California, where the spatiotemporal gradient process reveals the effects of California’s unique topography on pollution and detects the aftermath of a devastating series of wildfires. PMID:25898989

  10. Optical textures: characterizing spatiotemporal chaos.

    PubMed

    Clerc, Marcel G; González-Cortés, Gregorio; Odent, Vincent; Wilson, Mario

    2016-07-11

    Macroscopic systems subjected to injection and dissipation of energy can exhibit complex spatiotemporal behaviors as result of dissipative self-organization. Here, we report a one- and two-dimensional pattern forming setup, which exhibits a transition from stationary patterns to spatiotemporal chaotic textures, based on a nematic liquid crystal layer with spatially modulated input beam and optical feedback. Using an adequate projection of spatiotemporal diagrams, we determine the largest Lyapunov exponent. Jointly, this exponent and Fourier transform allow us to distinguish between spatiotemporal chaos and amplitude turbulence concepts, which are usually merged. PMID:27410822

  11. Meta-analysis of genome-wide association studies reveals genetic overlap between Hodgkin lymphoma and multiple sclerosis

    PubMed Central

    Khankhanian, Pouya; Cozen, Wendy; Himmelstein, Daniel S; Madireddy, Lohith; Din, Lennox; van den Berg, Anke; Matsushita, Takuya; Glaser, Sally L; Moré, Jayaji M; Smedby, Karin E.; Baranzini, Sergio E; Mack, Thomas M; Lizée, Antoine; de Sanjosé, Silvia; Gourraud, Pierre-Antoine; Nieters, Alexandra; Hauser, Stephen L; Cocco, Pierluigi; Maynadié, Marc; Foretová, Lenka; Staines, Anthony; Delahaye-Sourdeix, Manon; Li, Dalin; Bhatia, Smita; Melbye, Mads; Onel, Kenan; Jarrett, Ruth; McKay, James D; Oksenberg, Jorge R; Hjalgrim, Henrik

    2016-01-01

    Background: Based on epidemiological commonalities, multiple sclerosis (MS) and Hodgkin lymphoma (HL), two clinically distinct conditions, have long been suspected to be aetiologically related. MS and HL occur in roughly the same age groups, both are associated with Epstein-Barr virus infection and ultraviolet (UV) light exposure, and they cluster mutually in families (though not in individuals). We speculated if in addition to sharing environmental risk factors, MS and HL were also genetically related. Using data from genome-wide association studies (GWAS) of 1816 HL patients, 9772 MS patients and 25 255 controls, we therefore investigated the genetic overlap between the two diseases. Methods: From among a common denominator of 404 K single nucleotide polymorphisms (SNPs) studied, we identified SNPs and human leukocyte antigen (HLA) alleles independently associated with both diseases. Next, we assessed the cumulative genome-wide effect of MS-associated SNPs on HL and of HL-associated SNPs on MS. To provide an interpretational frame of reference, we used data from published GWAS to create a genetic network of diseases within which we analysed proximity of HL and MS to autoimmune diseases and haematological and non-haematological malignancies. Results: SNP analyses revealed genome-wide overlap between HL and MS, most prominently in the HLA region. Polygenic HL risk scores explained 4.44% of HL risk (Nagelkerke R2), but also 2.36% of MS risk. Conversely, polygenic MS risk scores explained 8.08% of MS risk and 1.94% of HL risk. In the genetic disease network, HL was closer to autoimmune diseases than to solid cancers. Conclusions: HL displays considerable genetic overlap with MS and other autoimmune diseases. PMID:26971321

  12. Multilocus Sequence Typing of Genital Chlamydia trachomatis in Norway Reveals Multiple New Sequence Types and a Large Genetic Diversity

    PubMed Central

    Gravningen, Kirsten; Christerson, Linus; Furberg, Anne-Sofie; Simonsen, Gunnar Skov; Ödman, Kristina; Ståhlsten, Anna; Herrmann, Björn

    2012-01-01

    Background The Chlamydia trachomatis incidence rate in Finnmark, the most northern and sparsely populated county in Norway, has been twice the national average. This population based cross-sectional study among Finnmark high school students had the following aims: i) to examine distribution of multilocus sequence types (STs) of C. trachomatis in a previously unmapped area, ii) to compare chlamydia genetic diversity in Finnmark with that of two urban regions, and iii) to compare discriminatory capacity of multilocus sequence typing (MLST) with conventional ompA sequencing in a large number of chlamydia specimens. Methodology ompA sequencing and a high-resolution MLST system based on PCR amplification and DNA sequencing of five highly variable genetic regions were used. Eighty chlamydia specimens from adolescents aged 15–20 years in Finnmark were collected in five high schools (n = 60) and from routine clinical samples in the laboratory (n = 20). These were compared to routine clinical samples from adolescents in Tromsø (n = 80) and Trondheim (n = 88), capitals of North and Central Norway, respectively. Principal Findings ompA sequencing detected 11 genotypes in 248 specimens from all three areas. MLST displayed 50 STs providing a five-fold higher resolution. Two-thirds of all STs were novel. The common ompA E/Bour genotype comprised 46% and resolved into 24 different STs. MLST identified the Swedish new variant of C. trachomatis not discriminated by ompA sequencing. Simpson's discriminatory index (D) was 0.93 for MLST, while a corrected Dc was 0.97. There were no statistically significant differences in ST genetic diversity between geographic areas. Finnmark had an atypical genovar distribution with G being predominant. This was mainly due to expansion of specific STs of which the novel ST161 was unique for Finnmark. Conclusions/Significance MLST revealed multiple new STs and a larger genetic diversity in comparison to ompA sequencing and proved

  13. 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

  14. 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.

  15. 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.

  16. Dynamics of an estuarine nursery ground: the spatio-temporal relationship between the river flow and the food web of the juvenile common sole ( Solea solea, L.) as revealed by stable isotopes analysis

    NASA Astrophysics Data System (ADS)

    Kostecki, C.; Le Loc'h, F.; Roussel, J.-M.; Desroy, N.; Huteau, D.; Riera, P.; Le Bris, H.; Le Pape, O.

    2010-07-01

    Estuaries are essential fish habitats because they provide nursery grounds for a number of marine species. Previous studies in the Bay of Vilaine (part of the Bay of Biscay, France) have underlined the estuarine dependence of juvenile common sole ( Solea solea, L.) and shown that the extent of sole nursery grounds was positively influenced by the variability of the river flow. In the present study, stable carbon and nitrogen isotopes were used to describe the trophic network until the young-of-the-year sole and to compare interannual variations in the dominant trophic pathways in the sole nursery areas in this bay. Particulate organic matter (POM), sediment organic matter (SOM), microphytobenthos, benthic invertebrate sole prey and young-of-the-year common sole were collected during the summer over 4 years characterised by contrasting river discharges. POM isotopic signatures were used to identify the origins of nutrient and organic matter assimilated into the estuarine food web through benthic organisms to juvenile common sole. Interannual spatial variations were found in the POM carbon stable isotope signatures, with the importance of these variations depending on the interannual fluctuations of the river flow. Moreover, the spatio-temporal variability of this POM isotopic signature was propagated along the food webs up to juvenile sole, confirming the central role of river discharge and terrigeneous subsidy input in the estuarine benthic food web in determining the size of the sole nursery habitat.

  17. 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...

  18. Phylogeny and evoluntionary 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...

  19. 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.

  20. A hybrid spatiotemporal drought forecasting model for operational use

    NASA Astrophysics Data System (ADS)

    Vasiliades, L.; Loukas, A.

    2010-09-01

    Drought forecasting plays an important role in the planning and management of natural resources and water resource systems in a river basin. Early and timelines forecasting of a drought event can help to take proactive measures and set out drought mitigation strategies to alleviate the impacts of drought. Spatiotemporal data mining is the extraction of unknown and implicit knowledge, structures, spatiotemporal relationships, or patterns not explicitly stored in spatiotemporal databases. As one of data mining techniques, forecasting is widely used to predict the unknown future based upon the patterns hidden in the current and past data. This study develops a hybrid spatiotemporal scheme for integrated spatial and temporal forecasting. Temporal forecasting is achieved using feed-forward neural networks and the temporal forecasts are extended to the spatial dimension using a spatial recurrent neural network model. The methodology is demonstrated for an operational meteorological drought index the Standardized Precipitation Index (SPI) calculated at multiple timescales. 48 precipitation stations and 18 independent precipitation stations, located at Pinios river basin in Thessaly region, Greece, were used for the development and spatiotemporal validation of the hybrid spatiotemporal scheme. Several quantitative temporal and spatial statistical indices were considered for the performance evaluation of the models. Furthermore, qualitative statistical criteria based on contingency tables between observed and forecasted drought episodes were calculated. The results show that the lead time of forecasting for operational use depends on the SPI timescale. The hybrid spatiotemporal drought forecasting model could be operationally used for forecasting up to three months ahead for SPI short timescales (e.g. 3-6 months) up to six months ahead for large SPI timescales (e.g. 24 months). The above findings could be useful in developing a drought preparedness plan in the region.

  1. [A primary epileptogenic tuber revealed after corpus callosotomy in a patient with tuberous sclerosis complex and multiple tubers].

    PubMed

    Sato, Keisuke; Iwasaki, Masaki; Uematsu, Mitsugu; Nakasato, Nobukazu; Tominaga, Teiji

    2013-05-01

    Identification of primary epileptogenic tuber is often challenging in patients with bilateral multiple tubers in tuberous sclerosis complex. We report a 3 year old girl with tuberous sclerosis complex presenting with intractable epilepsy and multiple tubers, who was successfully treated by corpus callosotomy and subsequent resective surgery. She initially presented with West syndrome which was intractable to ACTH therapy and multiple antiepileptic medications. Her EEG was characterized by generalized and multifocal spikes, and by non-focal changes at seizure onset. Ictal single photon emission computed tomography(SPECT)showed no focal hyperperfusion. Total corpus callosotomy was performed to alleviate her drop attacks. Post-operatively, interictal spikes were completely lateralized to the right hemisphere. Since her seizures were still kept uncontrolled with medications, second pre-surgical evaluation was planned and ictal SPECT disclosed focal hyperperfusion at a tuber in the right frontal lobe. After complete resection of the right frontal tuber, she was completely seizure free on antiepileptic medications for 1 year with no additional neurological deficits. Generalized or multifocal electroencephalographic(EEG)spikes are occasionally lateralized to one hemisphere after corpus callosotomy, which may help identifying the primary epileptogenic focus. Repeat pre-surgical evaluation is important after corpus callosotomy in patients with generalized or multifocal epileptiforms in EEG. PMID:23648659

  2. Spatiotemporal three-dimensional mapping of nonlinear X waves.

    PubMed

    Trull, J; Jedrkiewicz, O; Di Trapani, P; Matijosius, A; Varanavicius, A; Valiulis, G; Danielius, R; Kucinskas, E; Piskarskas, A; Trillo, S

    2004-02-01

    The spatiotemporal intensity profile of a 100-fs wave packet at the output of a X2 crystal, tuned for mismatched second-harmonic generation, is probed via sum-frequency generation with a compressed, 20-fs pulse, revealing the appearance of an X-type wave shape. PMID:14995580

  3. Multiple region whole-exome sequencing reveals dramatically evolving intratumor genomic heterogeneity in esophageal squamous cell carcinoma

    PubMed Central

    Cao, W; Wu, W; Yan, M; Tian, F; Ma, C; Zhang, Q; Li, X; Han, P; Liu, Z; Gu, J; Biddle, F G

    2015-01-01

    Cancer is a disease of genome instability and genomic alterations; now, genomic heterogeneity is rapidly emerging as a defining feature of cancer, both within and between tumors. Motivation for our pilot study of tumor heterogeneity in esophageal squamous cell carcinoma (ESCC) is that it is not well studied, but the highest incidences of esophageal cancers are found in China and ESCC is the most common type. We profiled the mutations and changes in copy number that were identified by whole-exome sequencing and array-based comparative genomic hybridization in multiple regions within an ESCC from two patients. The average mutational heterogeneity rate was 90% in all regions of the individual tumors in each patient; most somatic point mutations were nonsynonymous substitutions, small Indels occurred in untranslated regions of genes, and copy number alterations varied among multiple regions of a tumor. Independent Sanger sequencing technology confirmed selected gene mutations with more than 88% concordance. Phylogenetic analysis of the somatic mutation frequency demonstrated that multiple, genomically heterogeneous divergent clones evolve and co-exist within a primary ESCC and metastatic subclones result from the dispersal and adaptation of an initially non-metastatic parental clone. Therefore, a single-region sampling will not reflect the evolving architecture of a genomically heterogeneous landscape of mutations in ESCC tumors and the divergent complexity of this genomic heterogeneity among patients will complicate any promise of a simple genetic or epigenetic diagnostic signature in ESCC. We conclude that any potential for informative biomarker discovery in ESCC and targeted personalized therapies will require a deeper understanding of the functional biology of the ontogeny and phylogeny of the tumor heterogeneity. PMID:26619400

  4. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease.

    PubMed

    Wilbe, Maria; Kozyrev, Sergey V; Farias, Fabiana H G; Bremer, Hanna D; Hedlund, Anna; Pielberg, Gerli R; Seppälä, Eija H; Gustafson, Ulla; Lohi, Hannes; Carlborg, Örjan; Andersson, Göran; Hansson-Hamlin, Helene; Lindblad-Toh, Kerstin

    2015-06-01

    The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients' sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANA(H)) and speckled ANA (ANA(S)) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans. PMID:26057447

  5. Multiple Changes of Gene Expression and Function Reveal Genomic and Phenotypic Complexity in SLE-like Disease

    PubMed Central

    Farias, Fabiana H. G.; Bremer, Hanna D.; Hedlund, Anna; Pielberg, Gerli R.; Seppälä, Eija H.; Gustafson, Ulla; Lohi, Hannes; Carlborg, Örjan; Andersson, Göran; Hansson-Hamlin, Helene; Lindblad-Toh, Kerstin

    2015-01-01

    The complexity of clinical manifestations commonly observed in autoimmune disorders poses a major challenge to genetic studies of such diseases. Systemic lupus erythematosus (SLE) affects humans as well as other mammals, and is characterized by the presence of antinuclear antibodies (ANA) in patients’ sera and multiple disparate clinical features. Here we present evidence that particular sub-phenotypes of canine SLE-related disease, based on homogenous (ANAH) and speckled ANA (ANAS) staining pattern, and also steroid-responsive meningitis-arteritis (SRMA) are associated with different but overlapping sets of genes. In addition to association to certain MHC alleles and haplotypes, we identified 11 genes (WFDC3, HOMER2, VRK1, PTPN3, WHAMM, BANK1, AP3B2, DAPP1, LAMTOR3, DDIT4L and PPP3CA) located on five chromosomes that contain multiple risk haplotypes correlated with gene expression and disease sub-phenotypes in an intricate manner. Intriguingly, the association of BANK1 with both human and canine SLE appears to lead to similar changes in gene expression levels in both species. Our results suggest that molecular definition may help unravel the mechanisms of different clinical features common between and specific to various autoimmune disease phenotypes in dogs and humans. PMID:26057447

  6. Multiple-omic data analysis of Klebsiella pneumoniae MGH 78578 reveals its transcriptional architecture and regulatory features

    PubMed Central

    2012-01-01

    Background The increasing number of infections caused by strains of Klebsiella pneumoniae that are resistant to multiple antibiotics has developed into a major medical problem worldwide. The development of next-generation sequencing technologies now permits rapid sequencing of many K. pneumoniae isolates, but sequence information alone does not provide important structural and operational information for its genome. Results Here we take a systems biology approach to annotate the K. pneumoniae MGH 78578 genome at the structural and operational levels. Through the acquisition and simultaneous analysis of multiple sample-matched –omics data sets from two growth conditions, we detected 2677, 1227, and 1066 binding sites for RNA polymerase, RpoD, and RpoS, respectively, 3660 RNA polymerase-guided transcript segments, and 3585 transcription start sites throughout the genome. Moreover, analysis of the transcription start site data identified 83 probable leaderless mRNAs, while analysis of unannotated transcripts suggested the presence of 119 putative open reading frames, 15 small RNAs, and 185 antisense transcripts that are not currently annotated. Conclusions These findings highlight the strengths of systems biology approaches to the refinement of sequence-based annotations, and to provide new insight into fundamental genome-level biology for this important human pathogen. PMID:23194155

  7. Atomic force microscopy measurements reveal multiple bonds between Helicobacter pylori blood group antigen binding adhesin and Lewis b ligand

    PubMed Central

    Parreira, P.; Shi, Q.; Magalhaes, A.; Reis, C. A.; Bugaytsova, J.; Borén, T.; Leckband, D.; Martins, M. C. L.

    2014-01-01

    The strength of binding between the Helicobacter pylori blood group antigen-binding adhesin (BabA) and its cognate glycan receptor, the Lewis b blood group antigen (Leb), was measured by means of atomic force microscopy. High-resolution measurements of rupture forces between single receptor–ligand pairs were performed between the purified BabA and immobilized Leb structures on self-assembled monolayers. Dynamic force spectroscopy revealed two similar but statistically different bond populations. These findings suggest that the BabA may form different adhesive attachments to the gastric mucosa in ways that enhance the efficiency and stability of bacterial adhesion. PMID:25320070

  8. Spatiotemporal dynamics of actomyosin networks.

    PubMed

    Hussain, Saman; Molloy, Justin E; Khan, Shahid M

    2013-09-17

    Rhodamine-phalloidin-labeled actin filaments were visualized gliding over a skeletal heavy meromyosin (HMM)-coated surface. Experiments at low filament densities showed that when two filaments collided, their paths were affected in a manner that depended on collision angle. Some collisions resulted in complete alignment of the filament paths; in others, the filaments crossed over one another. Filament crossover or alignment was equally probable at ∼40° contact angle. Filaments often underwent significant bending during collision and analysis of filament shape indicated an energy requirement of ∼13 kBT. Experiments were performed over a wide range of HMM surface density and actin filament bulk concentration. Actin filament gliding speed and path persistence plateaued above a critical HMM surface density, and at high (micromolar) actin filament concentrations, filament motion became dramatically aligned in a common direction. Spatiotemporal features of alignment behavior were determined by correlation analysis, supported by simulations. The thermal drift of individual filament tracks was suppressed as the population became more oriented. Spatial correlation analysis revealed that long-range alignment was due to incremental recruitment rather than fusion of locally ordered seed domains. The global alignment of filament movement, described by an "order parameter," peaked at optimal actin concentrations and myosin surface densities, in contrast to previous predictions of a critical phase transition. Either hydrodynamic coupling or exchange of filaments between the surface bound and adjacent bulk phase layers might degrade order at high actin filament concentration, and high HMM surface densities might decrease alignment probability during collisions. Our results are compatible with generation of long-range order from mechanical interaction between individual actin filaments. Furthermore, we show that randomly oriented myosin motors align relatively short

  9. 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. PMID:25922968

  10. Validation and genotyping of multiple human polymorphic inversions mediated by inverted repeats reveals a high degree of recurrence.

    PubMed

    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

    2014-03-01

    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

  11. 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.

  12. Single Molecule Analysis of Replicated DNA Reveals the Usage of Multiple KSHV Genome Regions for Latent Replication

    PubMed Central

    Verma, Subhash C.; Lu, Jie; Cai, Qiliang; Kosiyatrakul, Settapong; McDowell, Maria E.; Schildkraut, Carl L.; Robertson, Erle S.

    2011-01-01

    Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences. PMID

  13. 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

  14. Integrated whole-genome screening for Pseudomonas aeruginosa virulence genes using multiple disease models reveals that pathogenicity is host specific.

    PubMed

    Dubern, Jean-Frédéric; Cigana, Cristina; De Simone, Maura; Lazenby, James; Juhas, Mario; Schwager, Stephan; Bianconi, Irene; Döring, Gerd; Eberl, Leo; Williams, Paul; Bragonzi, Alessandra; Cámara, Miguel

    2015-11-01

    Pseudomonas aeruginosa is a multi-host opportunistic pathogen causing a wide range of diseases because of the armoury of virulence factors it produces, and it is difficult to eradicate because of its intrinsic resistance to antibiotics. Using an integrated whole-genome approach, we searched for P. aeruginosa virulence genes with multi-host relevance. We constructed a random library of 57 360 Tn5 mutants in P. aeruginosa PAO1-L and screened it in vitro for those showing pleiotropic effects in virulence phenotypes (reduced swarming, exo-protease and pyocyanin production). A set of these pleiotropic mutants were assayed for reduced toxicity in Drosophila melanogaster, Caenorhabditis elegans, human cell lines and mice. Surprisingly, the screening revealed that the virulence of the majority of P. aeruginosa mutants varied between disease models, suggesting that virulence is dependent on the disease model used and hence the host environment. Genomic analysis revealed that these virulence-related genes encoded proteins from almost all functional classes, which were conserved among P. aeruginosa strains. Thus, we provide strong evidence that although P. aeruginosa is capable of infecting a wide range of hosts, many of its virulence determinants are host specific. These findings have important implication when searching for novel anti-virulence targets to develop new treatments against P. aeruginosa. PMID:25845292

  15. 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.

  16. Activity-Based Protein Profiling of Organophosphorus and Thiocarbamate Pesticides Reveals Multiple Serine Hydrolase Targets in Mouse Brain

    PubMed Central

    NOMURA, DANIEL K.; CASIDA, JOHN E.

    2010-01-01

    Organophosphorus (OP) and thiocarbamate (TC) agrochemicals are used worldwide as insecticides, herbicides, and fungicides, but their safety assessment in terms of potential off-targets remains incomplete. In this study, we used a chemoproteomic platform, termed activity-based protein profiling, to broadly define serine hydrolase targets in mouse brain of a panel of 29 OP and TC pesticides. Among the secondary targets identified, enzymes involved in degradation of endocannabinoid signaling lipids, monoacylglycerol lipase and fatty acid amide hydrolase, were inhibited by several OP and TC pesticides. Blockade of these two enzymes led to elevations in brain endocannabinoid levels and dysregulated brain arachidonate metabolism. Other secondary targets include enzymes thought to also play important roles in the nervous system and unannotated proteins. This study reveals a multitude of secondary targets for OP and TC pesticides and underscores the utility of chemoproteomic platforms in gaining insights into biochemical pathways that are perturbed by these toxicants. PMID:21341672

  17. 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. PMID:18836711

  18. A SNP based linkage map of the turkey genome reveals multiple intrachromosomal rearrangements between the Turkey and Chicken genomes

    PubMed Central

    2010-01-01

    Background The turkey (Meleagris gallopavo) is an important agricultural species that is the second largest contributor to the world's poultry meat production. The genomic resources of turkey provide turkey breeders with tools needed for the genetic improvement of commercial breeds of turkey for economically important traits. A linkage map of turkey is essential not only for the mapping of quantitative trait loci, but also as a framework to enable the assignment of sequence contigs to specific chromosomes. Comparative genomics with chicken provides insight into mechanisms of genome evolution and helps in identifying rare genomic events such as genomic rearrangements and duplications/deletions. Results Eighteen full sib families, comprising 1008 (35 F1 and 973 F2) birds, were genotyped for 775 single nucleotide polymorphisms (SNPs). Of the 775 SNPs, 570 were informative and used to construct a linkage map in turkey. The final map contains 531 markers in 28 linkage groups. The total genetic distance covered by these linkage groups is 2,324 centimorgans (cM) with the largest linkage group (81 loci) measuring 326 cM. Average marker interval for all markers across the 28 linkage groups is 4.6 cM. Comparative mapping of turkey and chicken revealed two inter-, and 57 intrachromosomal rearrangements between these two species. Conclusion Our turkey genetic map of 531 markers reveals a genome length of 2,324 cM. Our linkage map provides an improvement of previously published maps because of the more even distribution of the markers and because the map is completely based on SNP markers enabling easier and faster genotyping assays than the microsatellitemarkers used in previous linkage maps. Turkey and chicken are shown to have a highly conserved genomic structure with a relatively low number of inter-, and intrachromosomal rearrangements. PMID:21092123

  19. 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

  20. 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. PMID:24821952

  1. 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

  2. Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

    PubMed Central

    Laine, Elodie; Carbone, Alessandra

    2015-01-01

    Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2. PMID:26690684

  3. Analysis of the outer membrane proteome and secretome of Bacteroides fragilis reveals a multiplicity of secretion mechanisms.

    PubMed

    Wilson, Marlena M; Anderson, D Eric; Bernstein, Harris D

    2015-01-01

    Bacteroides fragilis is a widely distributed member of the human gut microbiome and an opportunistic pathogen. Cell surface molecules produced by this organism likely play important roles in colonization, communication with other microbes, and pathogenicity, but the protein composition of the outer membrane (OM) and the mechanisms used to transport polypeptides into the extracellular space are poorly characterized. Here we used LC-MS/MS to analyze the OM proteome and secretome of B. fragilis NCTC 9343 grown under laboratory conditions. Of the 229 OM proteins that we identified, 108 are predicted to be lipoproteins, and 61 are predicted to be TonB-dependent transporters. Based on their proximity to genes encoding TonB-dependent transporters, many of the lipoprotein genes likely encode proteins involved in nutrient or small molecule uptake. Interestingly, protease accessibility and biotinylation experiments indicated that an unusually large fraction of the lipoproteins are cell-surface exposed. We also identified three proteins that are members of a novel family of autotransporters, multiple potential type I protein secretion systems, and proteins that appear to be components of a type VI secretion apparatus. The secretome consisted of lipoproteins and other proteins that might be substrates of the putative type I or type VI secretion systems. Our proteomic studies show that B. fragilis differs considerably from well-studied Gram-negative bacteria such as Escherichia coli in both the spectrum of OM proteins that it produces and the range of secretion strategies that it utilizes. PMID:25658944

  4. Targeted mutagenesis of intergenic regions in the Neisseria gonorrhoeae gonococcal genetic island reveals multiple regulatory mechanisms controlling type IV secretion.

    PubMed

    Ramsey, Meghan E; Bender, Tobias; Klimowicz, Amy K; Hackett, Kathleen T; Yamamoto, Ami; Jolicoeur, Adrienne; Callaghan, Melanie M; Wassarman, Karen M; van der Does, Chris; Dillard, Joseph P

    2015-09-01

    Gonococci secrete chromosomal DNA into the extracellular environment using a type IV secretion system (T4SS). The secreted DNA acts in natural transformation and initiates biofilm development. Although the DNA and its effects are detectable, structural components of the T4SS are present at very low levels, suggestive of uncharacterized regulatory control. We sought to better characterize the expression and regulation of T4SS genes and found that the four operons containing T4SS genes are transcribed at very different levels. Increasing transcription of two of the operons through targeted promoter mutagenesis did not increase DNA secretion. The stability and steady-state levels of two T4SS structural proteins were affected by a homolog of tail-specific protease. An RNA switch was also identified that regulates translation of a third T4SS operon. The switch mechanism relies on two putative stem-loop structures contained within the 5' untranslated region of the transcript, one of which occludes the ribosome binding site and start codon. Mutational analysis of these stem loops supports a model in which induction of an alternative structure relieves repression. Taken together, these results identify multiple layers of regulation, including transcriptional, translational and post-translational mechanisms controlling T4SS gene expression and DNA secretion. PMID:26076069

  5. A Comprehensive Molecular Phylogeny of Dalytyphloplanida (Platyhelminthes: Rhabdocoela) Reveals Multiple Escapes from the Marine Environment and Origins of Symbiotic Relationships

    PubMed Central

    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. PMID:23536894

  6. 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. PMID:26949943

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

    PubMed

    Santos, Rosaysela; Kawauchi, Shimako; 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

    2016-09-01

    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

  8. 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

    2015-01-01

    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

  9. 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. PMID:26900928

  10. SET7/9 Catalytic Mutants Reveal the Role of Active Site Water Molecules in Lysine Multiple Methylation

    SciTech Connect

    Del Rizzo, Paul A.; Couture, Jean-François; Dirk, Lynnette M.A.; Strunk, Bethany S.; Roiko, Marijo S.; Brunzelle, Joseph S.; Houtz, Robert L.; Trievel, Raymond C.

    2010-11-15

    SET domain lysine methyltransferases (KMTs) methylate specific lysine residues in histone and non-histone substrates. These enzymes also display product specificity by catalyzing distinct degrees of methylation of the lysine {epsilon}-amino group. To elucidate the molecular mechanism underlying this specificity, we have characterized the Y245A and Y305F mutants of the human KMT SET7/9 (also known as KMT7) that alter its product specificity from a monomethyltransferase to a di- and a trimethyltransferase, respectively. Crystal structures of these mutants in complex with peptides bearing unmodified, mono-, di-, and trimethylated lysines illustrate the roles of active site water molecules in aligning the lysine {epsilon}-amino group for methyl transfer with S-adenosylmethionine. Displacement or dissociation of these solvent molecules enlarges the diameter of the active site, accommodating the increasing size of the methylated {epsilon}-amino group during successive methyl transfer reactions. Together, these results furnish new insights into the roles of active site water molecules in modulating lysine multiple methylation by SET domain KMTs and provide the first molecular snapshots of the mono-, di-, and trimethyl transfer reactions catalyzed by these enzymes.

  11. CLAVATA1 Dominant-Negative Alleles Reveal Functional Overlap between Multiple Receptor Kinases That Regulate Meristem and Organ Development

    PubMed Central

    Diévart, Anne; Dalal, Monica; Tax, Frans E.; Lacey, Alexzandria D.; Huttly, Alison; Li, Jianming; Clark, Steven E.

    2003-01-01

    The CLAVATA1 (CLV1) receptor kinase controls stem cell number and differentiation at the Arabidopsis shoot and flower meristems. Other components of the CLV1 signaling pathway include the secreted putative ligand CLV3 and the receptor-like protein CLV2. We report evidence indicating that all intermediate and strong clv1 alleles are dominant negative and likely interfere with the activity of unknown receptor kinase(s) that have functional overlap with CLV1. clv1 dominant-negative alleles show major differences from dominant-negative alleles characterized to date in animal receptor kinase signaling systems, including the lack of a dominant-negative effect of kinase domain truncation and the ability of missense mutations in the extracellular domain to act in a dominant-negative manner. We analyzed chimeric receptor kinases by fusing CLV1 and BRASSINOSTEROID INSENSITIVE1 (BRI1) coding sequences and expressing these in clv1 null backgrounds. Constructs containing the CLV1 extracellular domain and the BRI1 kinase domain were strongly dominant negative in the regulation of meristem development. Furthermore, we show that CLV1 expressed within the pedicel can partially replace the function of the ERECTA receptor kinase. We propose the presence of multiple receptors that regulate meristem development in a functionally related manner whose interactions are driven by the extracellular domains and whose activation requires the kinase domain. PMID:12724544

  12. 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

  13. 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

  14. Transcriptome analysis of grain-filling caryopses reveals involvement of multiple regulatory pathways in chalky grain formation in rice

    PubMed Central

    2010-01-01

    Background Grain endosperm chalkiness of rice is a varietal characteristic that negatively affects not only the appearance and milling properties but also the cooking texture and palatability of cooked rice. However, grain chalkiness is a complex quantitative genetic trait and the molecular mechanisms underlying its formation are poorly understood. Results A near-isogenic line CSSL50-1 with high chalkiness was compared with its normal parental line Asominori for grain endosperm chalkiness. Physico-biochemical analyses of ripened grains showed that, compared with Asominori, CSSL50-1 contains higher levels of amylose and 8 DP (degree of polymerization) short-chain amylopectin, but lower medium length 12 DP amylopectin. Transcriptome analysis of 15 DAF (day after flowering) caryopses of the isogenic lines identified 623 differential expressed genes (P < 0.01), among which 324 genes are up-regulated and 299 down-regulated. These genes were classified into 18 major categories, with 65.3% of them belong to six major functional groups: signal transduction, cell rescue/defense, transcription, protein degradation, carbohydrate metabolism and redox homeostasis. Detailed pathway dissection demonstrated that genes involved in sucrose and starch synthesis are up-regulated, whereas those involved in non-starch polysaccharides are down regulated. Several genes involved in oxidoreductive homeostasis were found to have higher expression levels in CSSL50-1 as well, suggesting potential roles of ROS in grain chalkiness formation. Conclusion Extensive gene expression changes were detected during rice grain chalkiness formation. Over half of these differentially expressed genes are implicated in several important categories of genes, including signal transduction, transcription, carbohydrate metabolism and redox homeostasis, suggesting that chalkiness formation involves multiple metabolic and regulatory pathways. PMID:21192807

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

    PubMed

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

    2016-03-15

    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 they alter their phenotype in response to local environmental cues. Whereas 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 multimarker 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 they suggest that distinct populations play specific roles in tumor progression. PMID:26873985

  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]. PMID:27185559

  17. Elevating CLIC4 in Multiple Cell Types Reveals a TGF- Dependent Induction of a Dominant Negative Smad7 Splice Variant

    PubMed Central

    Shukla, Anjali; Yang, Yihan; Madanikia, Sara; Ho, Yan; Li, Mangmang; Sanchez, Vanesa; Cataisson, Christophe; Huang, Jing; Yuspa, Stuart H.

    2016-01-01

    CLIC4 (Chloride intracellular channel 4) belongs to a family of putative intracellular chloride channel proteins expressed ubiquitously in multiple tissues. CLIC4 is predominantly soluble and traffics between the cytoplasm and nucleus and participates in cell cycle control and differentiation. Transforming growth factor beta (TGF-β) elevates CLIC4, which enhances TGF-β signaling through CLIC4 mediated stabilization of phospho-Smad2/3. CLIC4 is essential for TGF-β induced conversion of fibroblasts to myofibroblasts and expression of matrix proteins, signaling via the p38MAPK pathway. Therefore, regulation of TGF-β signaling is a major mechanism by which CLIC4 modifies normal growth and differentiation. We now report that elevated CLIC4 alters Smad7 function, a feedback inhibitor of the TGF-β pathway. Overexpression of CLIC4 in keratinocytes, mouse embryonic fibroblasts and other mouse and human cell types increases the expression of Smad7Δ, a novel truncated form of Smad7. The alternatively spliced Smad7Δ variant is missing 94bp in exon 4 of Smad 7 and is conserved between mouse and human cells. The deletion is predicted to lack the TGF-β signaling inhibitory MH2 domain of Smad7. Treatment with exogenous TGF-β1 also enhances expression of Smad7Δ that is amplified in the presence of CLIC4. While Smad7 expression inhibits TGF-β signaling, exogenously expressed Smad7Δ does not inhibit TGF-β signaling as determined by TGF-β dependent proliferation, reporter assays and phosphorylation of Smad proteins. Instead, exogenous Smad7Δ acts as a dominant negative inhibitor of Smad7, thus increasing TGF-β signaling. This discovery adds another dimension to the myriad ways by which CLIC4 modifies TGF-β signaling. PMID:27536941

  18. Multiple rodent models and behavioral measures reveal unexpected responses to FTY720 and DMF in experimental autoimmune encephalomyelitis.

    PubMed

    de Bruin, N M W J; Schmitz, K; Schiffmann, S; Tafferner, N; Schmidt, M; Jordan, H; Häußler, A; Tegeder, I; Geisslinger, G; Parnham, M J

    2016-03-01

    Experimental autoimmune encephalomyelitis (EAE) is a widely-used rodent model for multiple sclerosis (MS), but a single model can hardly capture all features of MS. We investigated whether behavioral parameters in addition to clinical motor function scores could be used to assess treatment efficacy during score-free intervals in the relapsing-remitting EAE model in SJL/J mice. We studied the effects of the clinical reference compounds FTY720 (fingolimod, 0.5mg/kg/day) and dimethyl fumarate (DMF, 20-30 mg/kg/day) on clinical scores in several rodent EAE models in order to generate efficacy profiles. SJL/J mice with relapsing-remitting EAE were studied using behavioral tests, including rotarod, gait analysis, locomotor activity and grip strength. SJL/J mice were also examined according to Crawley's sociability and preference for social novelty test. Prophylactic treatment with FTY720 prevented clinical scores in three of the four EAE rodent models: Dark Agouti (DA) and Lewis rats and C57BL/6J mice. Neither prophylactic nor late-therapeutic treatment with FTY720 reduced clinical scores or reversed deficits in the rotarod test in SJL/J mice, but we observed effects on motor functions and sociability in the absence of clinical scores. Prophylactic treatment with FTY720 improved the gait of SJL/J mice whereas late-therapeutic treatment improved manifestations of reduced social (re)cognition or preference for social novelty. DMF was tested in three EAE models and did not improve clinical scores at the dose used. These data indicate that improvements in behavioral deficits can occur in absence of clinical scores, which indicate subtle drug effects and may have translational value for human MS. PMID:26692368

  19. Exome capture sequencing of adenoma reveals genetic alterations in multiple cellular pathways at the early stage of colorectal tumorigenesis.

    PubMed

    Zhou, Donger; Yang, Liu; Zheng, Liangtao; Ge, Weiting; Li, Dan; Zhang, Yong; Hu, Xueda; Gao, Zhibo; Xu, Jinghong; Huang, Yanqin; Hu, Hanguang; Zhang, Hang; Zhang, Hao; Liu, Mingming; Yang, Huanming; Zheng, Lei; Zheng, Shu

    2013-01-01

    Most of colorectal adenocarcinomas are believed to arise from adenomas, which are premalignant lesions. Sequencing the whole exome of the adenoma will help identifying molecular biomarkers that can predict the occurrence of adenocarcinoma more precisely and help understanding the molecular pathways underlying the initial stage of colorectal tumorigenesis. We performed the exome capture sequencing of the normal mucosa, adenoma and adenocarcinoma tissues from the same patient and sequenced the identified mutations in additional 73 adenomas and 288 adenocarcinomas. Somatic single nucleotide variations (SNVs) were identified in both the adenoma and adenocarcinoma by comparing with the normal control from the same patient. We identified 12 nonsynonymous somatic SNVs in the adenoma and 42 nonsynonymous somatic SNVs in the adenocarcinoma. Most of these mutations including OR6X1, SLC15A3, KRTHB4, RBFOX1, LAMA3, CDH20, BIRC6, NMBR, GLCCI1, EFR3A, and FTHL17 were newly reported in colorectal adenomas. Functional annotation of these mutated genes showed that multiple cellular pathways including Wnt, cell adhesion and ubiquitin mediated proteolysis pathways were altered genetically in the adenoma and that the genetic alterations in the same pathways persist in the adenocarcinoma. CDH20 and LAMA3 were mutated in the adenoma while NRXN3 and COL4A6 were mutated in the adenocarcinoma from the same patient, suggesting for the first time that genetic alterations in the cell adhesion pathway occur as early as in the adenoma. Thus, the comparison of genomic mutations between adenoma and adenocarcinoma provides us a new insight into the molecular events governing the early step of colorectal tumorigenesis. PMID:23301059

  20. 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.

  1. 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

    2015-09-01

    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.

  2. Tracking early autoimmune disease by bioluminescent imaging of NF-kappaB activation reveals pathology in multiple organ systems.

    PubMed

    Zangani, Michael; Carlsen, Harald; Kielland, Anders; Os, Audun; Hauglin, Harald; Blomhoff, Rune; Munthe, Ludvig A; Bogen, Bjarne

    2009-04-01

    It is desirable to have an early and sensitive detection marker of autoimmune disease in intact animals. Nuclear factor (NF)-kappaB is a transcription factor that is associated with inflammatory responses and immune disorders. Previously, we demonstrated that so-called idiotypic-driven T-B cell collaboration in mice doubly transgenic for paired immunoglobulin and T cell receptor transgenes resulted in a systemic autoimmune disease with systemic lupus erythematosus-like features. Here, we investigated NF-kappaB activation by including an NF-kappaB-responsive luciferase reporter transgene in this animal model. Triply transgenic mice developed bioluminescence signals from diseased organs before onset of clinical symptoms and autoantibody production, and light emissions correlated with disease progression. Signals were obtained from secondary lymphoid organs, inflamed intestines, skin lesions, and arthritic joints. Moreover, bioluminescence imaging and immunohistochemistry demonstrated that a minority of mice suffered from an autoimmune disease of the small intestine, in which light emissions correlated with antibodies against tissue transglutaminase and gliadin. Detection of luciferase by immunohistochemistry revealed NF-kappaB activation in collaborating B and T cells, as well as in macrophages. These results demonstrate that bioluminescent in vivo imaging of NF-kappaB activation can be used for early and sensitive detection of autoimmune disease in an experimental mouse model, offering new possibilities for the evaluation of anti-inflammatory drugs. PMID:19286564

  3. Surface plasmon resonance imaging reveals multiple binding modes of Agrobacterium transformation mediator VirE2 to ssDNA

    PubMed Central

    Kim, Sanghyun; Zbaida, David; Elbaum, Michael; Leh, Hervé; Nogues, Claude; Buckle, Malcolm

    2015-01-01

    VirE2 is the major secreted protein of Agrobacterium tumefaciens in its genetic transformation of plant hosts. It is co-expressed with a small acidic chaperone VirE1, which prevents VirE2 oligomerization. After secretion into the host cell, VirE2 serves functions similar to a viral capsid in protecting the single-stranded transferred DNA en route to the nucleus. Binding of VirE2 to ssDNA is strongly cooperative and depends moreover on protein–protein interactions. In order to isolate the protein–DNA interactions, imaging surface plasmon resonance (SPRi) studies were conducted using surface-immobilized DNA substrates of length comparable to the protein-binding footprint. Binding curves revealed an important influence of substrate rigidity with a notable preference for poly-T sequences and absence of binding to both poly-A and double-stranded DNA fragments. Dissociation at high salt concentration confirmed the electrostatic nature of the interaction. VirE1–VirE2 heterodimers also bound to ssDNA, though by a different mechanism that was insensitive to high salt. Neither VirE2 nor VirE1–VirE2 followed the Langmuir isotherm expected for reversible monomeric binding. The differences reflect the cooperative self-interactions of VirE2 that are suppressed by VirE1. PMID:26044711

  4. 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. PMID:25860123

  5. 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.

  6. Phylogenetic Comparisons Reveal Multiple Acquisitions of the Toxin Genes by Enterotoxigenic Escherichia coli Strains of Different Evolutionary Lineages▿ †

    PubMed Central

    Turner, Sue M.; Chaudhuri, Roy R.; Jiang, Zhi-Dong; DuPont, Herbert; Gyles, Carlton; Penn, Charles W.; Pallen, Mark J.; Henderson, Ian R.

    2006-01-01

    Escherichia coli is a diverse bacterial species which is widely distributed in the environment but also exists as a commensal and pathogen of different host species. Human intestinal pathogenic E. coli causes over 160 million cases of diarrhea and an estimated 1 million deaths per year. The majority of deaths are attributable to one pathovar of E. coli, namely, enterotoxigenic E. coli. The pathogenesis of enterotoxigenic E. coli is dependent on the production of a colonization factor to promote adhesion to the intestinal epithelium and the elaboration of heat-labile or heat-stable toxins which induce a secretory diarrhea. Despite the high morbidity and mortality associated with enterotoxigenic E. coli infection, little is known of the genetic background of this global pathogen. Here we demonstrate by multilocus sequence typing that enterotoxigenic E. coli isolates are present in all phylogenetic lineages of E. coli, indicating that acquisition of the toxin genes may be sufficient to generate an enterotoxigenic E. coli strain. In addition, screening of diarrheal isolates for the presence of additional genes previously associated with the virulence of enterotoxigenic E. coli revealed that they were not abundant. These observations have significant implications for disease epidemiology and for the design of effective vaccines. PMID:17050815

  7. 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

  8. Telonemia-specific environmental 18S rDNA PCR reveals unknown diversity and multiple marine-freshwater colonizations

    PubMed Central

    2010-01-01

    Background Recent surveys of eukaryote 18S rDNA diversity in marine habitats have uncovered worldwide distribution of the heterotrophic eukaryote phylum Telonemia. Here we investigate the diversity and geographic distribution of Telonemia sequences by in-depth sequencing of several new 18S rDNA clone libraries from both marine and freshwater sites by using a Telonemia-specific PCR strategy. Results In contrast to earlier studies that have employed eukaryote-wide PCR design, we identified a large and unknown diversity of phylotypes and the first rigorous evidence for several freshwater species, altogether comprising 91 unique sequences. Phylogenies of these and publicly available sequences showed 20 statistically supported sub-clades as well as several solitary phylotypes with no clear phylogenetic affiliation. Most of these sub-clades were composed of phylotypes from different geographic regions. Conclusions By using specific PCR primers we reveal a much larger diversity of Telonemia from environmental samples than previously uncovered by eukaryote-wide primers. The new data substantially diminish the geographic structuring of clades identified in earlier studies. Nevertheless, since these clades comprise several distinct phylotypes we cannot exclude endemicity at species level. We identified two freshwater clades and a few solitary phylotypes, implying that Telonemia have colonized freshwater habitats and adapted to the different environmental and ecological conditions at independent occasions. PMID:20534135

  9. Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

    PubMed Central

    Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

    1994-01-01

    Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

  10. 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

  11. Multiple instances of paraphyletic species and cryptic taxa revealed by mitochondrial and nuclear RAD data for Calandrella larks (Aves: Alaudidae).

    PubMed

    Stervander, Martin; Alström, Per; Olsson, Urban; Ottosson, Ulf; Hansson, Bengt; Bensch, Staffan

    2016-09-01

    The avian genus Calandrella (larks) was recently suggested to be non-monophyletic, and was divided into two genera, of which Calandrella sensu stricto comprises 4-5 species in Eurasia and Africa. We analysed mitochondrial cytochrome b (cytb) and nuclear Restriction-site Associated DNA (RAD) sequences from all species, and for cytb we studied 21 of the 22 recognised subspecies, with the aim to clarify the phylogenetic relationships within the genus and to compare large-scale nuclear sequence patterns with a widely used mitochondrial marker. Cytb indicated deep splits among the currently recognised species, although it failed to support the interrelationships among most of these. It also revealed unexpected deep divergences within C. brachydactyla, C. blanfordi/C. erlangeri, C. cinerea, and C. acutirostris. It also suggested that both C. brachydactyla and C. blanfordi, as presently circumscribed, are paraphyletic. In contrast, most of the many subspecies of C. brachydactyla and C. cinerea were unsupported by cytb, although two populations of C. cinerea were found to be genetically distinct. The RAD data corroborated the cytb tree (for the smaller number of taxa analysed) and recovered strongly supported interspecific relationships. However, coalescence analyses of the RAD data, analysed in SNAPP both with and without an outgroup, received equally strong support for two conflicting topologies. We suggest that the tree rooted with an outgroup - which is not recommended for SNAPP - is more trustworthy, and suggest that the reliability of analyses performed without any outgroup species should be thoroughly evaluated. We also demonstrate that degraded museum samples can be phylogenetically informative in RAD analyses following careful bioinformatic treatment. We note that the genus Calandrella is in need of taxonomic revision. PMID:27235550

  12. 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

  13. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    PubMed

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei. PMID:25568942

  14. Genome and Phylogenetic Analyses of Trypanosoma evansi Reveal Extensive Similarity to T. brucei and Multiple Independent Origins for Dyskinetoplasty

    PubMed Central

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M.; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei. PMID:25568942

  15. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    PubMed Central

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.

    2013-01-01

    Cell signaling systems transmit information by post-translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-protein coupled receptor (GPCR). We used published mass spectrometry-based proteomics data to identify putative sites of phosphorylation on pheromone pathway components, and we used evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of putative phosphorylation events that contribute to adjust the input-output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results suggest that relatively small quantitative influences from individual phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes. PMID:23554854

  16. Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

    SciTech Connect

    Pincus, David; Ryan, Christopher J.; Smith, Richard D.; Brent, Roger; Resnekov, Orna; Hakimi, Mohamed Ali

    2013-03-12

    Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sites whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.

  17. Beamformer-based spatiotemporal imaging of linearly-related source components using electromagnetic neural signals.

    PubMed

    Chan, Hui-Ling; Chen, Li-Fen; Chen, I-Tzu; Chen, Yong-Sheng

    2015-07-01

    Functional connectivity calculated using multiple channels of electromagnetic brain signals is often over- or underestimated due to volume conduction or field spread. Considering connectivity measures, coherence is suitable for the detection of rhythmic synchronization, whereas temporal correlation is appropriate for transient synchronization. This paper presents a beamformer-based imaging method, called spatiotemporal imaging of linearly-related source component (SILSC), which is capable of estimating connectivity at the cortical level by extracting the source component with the maximum temporal correlation between the activity of each targeted region and a reference signal. The spatiotemporal correlation dynamics can be obtained by applying SILSC at every brain region and with various time latencies. The results of six simulation studies demonstrated that SILSC is sensitive to detect the source activity correlated to the specified reference signal and is accurate and robust to noise in terms of source localization. In a facial expression imitation experiment, the correlation dynamics estimated by SILSC revealed the regions with mirror properties and the regions involved in motor control network when performing the imitation and execution tasks, respectively, with the left inferior frontal gyrus specified as the reference region. PMID:25804642

  18. 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.

  19. Spatiotemporal dynamics and determinants of planktonic bacterial and microeukaryotic communities in a Chinese subtropical river.

    PubMed

    Wang, Yongming; Liu, Lemian; Chen, Huihuang; Yang, Jun

    2015-11-01

    The spatiotemporal distribution of microbial diversity, community composition, and their major drivers are fundamental issues in microbial ecology. In this study, the planktonic bacterial and microeukaryotic communities of the Jiulong River were investigated across both wet and dry seasons by using denaturing gradient gel electrophoresis (DGGE). We found evidence of temporal change between wet and dry seasons and distinct spatial patterns of bacterial and microeukaryotic communities. Both bacterial and microeukaryotic communities were strongly correlated with temperature, NH4-N, PO4-P, and chlorophyll a, and these environmental factors were significant but incomplete predictors of microbial community composition. Local environmental factors combined with spatial and temporal factors strongly controlled both bacterial and microeukaryotic communities in complex ways, whereas the direct influence of spatial and temporal factors appeared to be relatively small. Path analysis revealed that the microeukaryotic community played key roles in shaping bacterial community composition, perhaps through grazing effects and multiple interactions. Both Betaproteobacteria and Actinobacteria were the most dominant and diverse taxa in bacterial communities, while the microeukaryotic communities were dominated by Ciliophora (zooplankton) and Chlorophyta (phytoplankton). Our results demonstrated that both bacterial and microeukaryotic communities along the Jiulong River displayed a distinct spatiotemporal pattern; however, microeukaryotic communities exhibited a stronger distance-decay relationship than bacterial communities and their spatial patterns were mostly driven by local environmental variables rather than season or spatial processes of the river. Therefore, we have provided baseline data to support further research on river microbial food webs and integrating different microbial groups into river models. PMID:26156239

  20. Multiple, discrete inversion episodes revealed by apatite fission track analysis along the southernmost Atlantic margin of South Africa

    NASA Astrophysics Data System (ADS)

    Wildman, M.; Brown, R. W.; Persano, C.; Stuart, F. M.

    2013-12-01

    was performed for several outcrop samples, including a 604 m vertical profile, and two borehole profiles from the interior plateau with bottom depths of 2.5 (QU 1/65) and 6.2 km (KC 1/70). The results of this novel modelling approach are interpreted alongside independent on and offshore geological observations to lend additional support to the occurrence of multiple, discrete episodes of denudation driven cooling at c. 150 - 130 and 90 Ma, and possibly a later Cretaceous episode of cooling at c. 70 Ma. The existence of a Late Cretaceous or younger period of enhanced denudation is being further explored through ongoing work combining new AFT data with apatite (U-Th)/He data to generate more robust thermal history information and provide new insights into the timing and magnitude of the major periods of uplift and erosion that have formed the first order topography of South Africa. Gallagher, K., 2012, Transdimensional inverse thermal history modeling for quantitative thermochronology: Journal of Geophysical Research: Solid Earth, v. 117(B2).

  1. Multiple Analytical Approaches Reveal Distinct Gene-Environment Interactions in Smokers and Non Smokers in Lung Cancer

    PubMed Central

    Ihsan, Rakhshan; Chauhan, Pradeep Singh; Mishra, Ashwani Kumar; Yadav, Dhirendra Singh; Kaushal, Mishi; Sharma, Jagannath Dev; Zomawia, Eric; Verma, Yogesh; Kapur, Sujala; Saxena, Sunita

    2011-01-01

    Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p<0.001 and OR = 0.51;95%CI = 0.33–0.78,p = 0.002 respectively). In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His), SULT1A1 213GG (Arg/Arg) or AA (His/His) and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33–10.55,p = 0.006), whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg) and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15–7.51,p = 0.01). MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His) and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His) with testing balance accuracy (TBA) of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing

  2. 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

  3. Visual Experience Modulates Spatio-Temporal Dynamics of Circuit Activation

    PubMed Central

    Wang, Lang; Fontanini, Alfredo; Maffei, Arianna

    2011-01-01

    Persistent reduction in sensory drive in early development results in multiple plastic changes of different cortical synapses. How these experience-dependent modifications affect the spatio-temporal dynamics of signal propagation in neocortical circuits is poorly understood. Here we demonstrate that brief visual deprivation significantly affects the propagation of electrical signals in the primary visual cortex. The spatio-temporal spread of circuit activation upon direct stimulation of its input layer (Layer 4) is reduced, as is the activation of L2/3 – the main recipient of the output from L4. Our data suggest that the decrease in spatio-temporal activation of L2/3 depends on reduced L4 output, and is not intrinsically generated within L2/3. The data shown here suggest that changes in the synaptic components of the visual cortical circuit result not only in alteration of local integration of excitatory and inhibitory inputs, but also in a significant decrease in overall circuit activation. Furthermore, our data indicate a differential effect of visual deprivation on L4 and L2/3, suggesting that while feedforward activation of L2/3 is reduced, its activation by long range, within layer inputs is unaltered. Thus, brief visual deprivation induces experience-dependent circuit re-organization by modulating not only circuit excitability, but also the spatio-temporal patterns of cortical activation within and between layers. PMID:21743804

  4. Transient spatiotemporal chaos is extensive in three reaction-diffusion networks

    NASA Astrophysics Data System (ADS)

    Stahlke, Dan; Wackerbauer, Renate

    2009-11-01

    Extensive (asymptotic) spatiotemporal chaos is comprised of statistically similar subsystems that interact only weakly. A systematic study of transient spatiotemporal chaos reveals extensive system behavior in all three reaction-diffusion networks for various boundary conditions. The Lyapunov dimension, the sum of positive Lyapunov exponents, and the logarithm of the transient lifetime grow linearly with the system size. The unstable manifold of the chaotic saddle has nearly the same dimension as the saddle itself, and the stable manifold is nearly space filling.

  5. Meta-Analysis of 13 Genome Scans Reveals Multiple Cleft Lip/Palate Genes with Novel Loci on 9q21 and 2q32-35

    PubMed Central

    Marazita, Mary L.; Murray, Jeffrey C.; Lidral, Andrew C.; Arcos-Burgos, Mauricio; Cooper, Margaret E.; Goldstein, Toby; Maher, Brion S.; Daack-Hirsch, Sandra; Schultz, Rebecca; Mansilla, M. Adela; Field, L. Leigh; Liu, You-e; Prescott, Natalie; Malcolm, Sue; Winter, Robin; Ray, Ajit; Moreno, Lina; Valencia, Consuelo; Neiswanger, Katherine; Wyszynski, Diego F.; Bailey-Wilson, Joan E.; Albacha-Hejazi, Hasan; Beaty, Terri H.; McIntosh, Iain; Hetmanski, Jacqueline B.; Tunçbilek, Gökhan; Edwards, Matthew; Harkin, Louise; Scott, Rodney; Roddick, Laurence G.

    2004-01-01

    Isolated or nonsyndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. A 10-cM genome scan of 388 extended multiplex families with CL/P from seven diverse populations (2,551 genotyped individuals) revealed CL/P genes in six chromosomal regions, including a novel region at 9q21 (heterogeneity LOD score [HLOD]=6.6). In addition, meta-analyses with the addition of results from 186 more families (six populations; 1,033 genotyped individuals) showed genomewide significance for 10 more regions, including another novel region at 2q32-35 (P=.0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder. PMID:15185170

  6. Ancestral state reconstruction reveals multiple independent evolution of diagnostic morphological characters in the "Higher Oribatida" (Acari), conflicting with current classification schemes

    PubMed Central

    2010-01-01

    Background The use of molecular genetic data in phylogenetic systematics has revolutionized this field of research in that several taxonomic groupings defined by traditional taxonomic approaches have been rejected by molecular data. The taxonomic classification of the oribatid mite group Circumdehiscentiae ("Higher Oribatida") is largely based on morphological characters and several different classification schemes, all based upon the validity of diagnostic morphological characters, have been proposed by various authors. The aims of this study were to test the appropriateness of the current taxonomic classification schemes for the Circumdehiscentiae and to trace the evolution of the main diagnostic traits (the four nymphal traits scalps, centrodorsal setae, sclerits and wrinkled cuticle plus octotaxic system and pteromorphs both in adults) on the basis of a molecular phylogenetic hypothesis by means of parsimony, likelihood and Bayesian approaches. Results The molecular phylogeny based on three nuclear markers (28S rDNA, ef-1α, hsp82) revealed considerable discrepancies to the traditional classification of the five "circumdehiscent" subdivisions, suggesting paraphyly of the three families Scutoverticidae, Ameronothridae, Cymbaeremaeidae and also of the genus Achipteria. Ancestral state reconstructions of six common diagnostic characters and statistical evaluation of alternative phylogenetic hypotheses also partially rejected the current morphology-based classification and suggested multiple convergent evolution (both gain and loss) of some traits, after a period of rapid cladogenesis, rendering several subgroups paraphyletic. Conclusions Phylogenetic studies revealed non-monophyly of three families and one genus as a result of a lack of adequate synapomorphic morphological characters, calling for further detailed investigations in a framework of integrative taxonomy. Character histories of six morphological traits indicate that their evolution followed a rather

  7. Spatiotemporal Interpolation for Environmental Modelling.

    PubMed

    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

  8. 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. PMID:27176118

  9. 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

  10. 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

  11. Comparative genome-wide analysis reveals that Burkholderia contaminans MS14 possesses multiple antimicrobial biosynthesis genes but not major genetic loci required for pathogenesis.

    PubMed

    Deng, Peng; Wang, Xiaoqiang; Baird, Sonya M; Showmaker, Kurt C; Smith, Leif; Peterson, Daniel G; Lu, Shien

    2016-06-01

    Burkholderia contaminans MS14 shows significant antimicrobial activities against plant and animal pathogenic fungi and bacteria. The antifungal agent occidiofungin produced by MS14 has great potential for development of biopesticides and pharmaceutical drugs. However, the use of Burkholderia species as biocontrol agent in agriculture is restricted due to the difficulties in distinguishing between plant growth-promoting bacteria and the pathogenic bacteria. The complete MS14 genome was sequenced and analyzed to find what beneficial and virulence-related genes it harbors. The phylogenetic relatedness of B. contaminans MS14 and other 17 Burkholderia species was also analyzed. To research MS14's potential virulence, the gene regions related to the antibiotic production, antibiotic resistance, and virulence were compared between MS14 and other Burkholderia genomes. The genome of B. contaminans MS14 was sequenced and annotated. The genomic analyses reveal the presence of multiple gene sets for antimicrobial biosynthesis, which contribute to its antimicrobial activities. BLAST results indicate that the MS14 genome harbors a large number of unique regions. MS14 is closely related to another plant growth-promoting Burkholderia strain B. lata 383 according to the average nucleotide identity data. Moreover, according to the phylogenetic analysis, plant growth-promoting species isolated from soils and mammalian pathogenic species are clustered together, respectively. MS14 has multiple antimicrobial activity-related genes identified from the genome, but it lacks key virulence-related gene loci found in the pathogenic strains. Additionally, plant growth-promoting Burkholderia species have one or more antimicrobial biosynthesis genes in their genomes as compared with nonplant growth-promoting soil-isolated Burkholderia species. On the other hand, pathogenic species harbor multiple virulence-associated gene loci that are not present in nonpathogenic Burkholderia species. The MS14

  12. Effects of spatiotemporal consistencies on visual learning dynamics and transfer.

    PubMed

    Harris, Hila; Sagi, Dov

    2015-04-01

    Spatiotemporal interactions affect visual performance under repeated stimulation conditions, showing both incremental (commonly related to learning) and decremental (possibly sensory adaptation) effects. Here we examined the role of spatiotemporal consistencies on learning dynamics and transfer. The backward-masked texture-discrimination paradigm was used, with stimulus onset asynchrony (SOA) controlling the observers' performance level. Temporal consistencies were examined by modifying the order in which SOA was varied during a training session: gradually reduced SOA (high consistencies) versus randomized SOA (low consistencies). Spatial consistencies were reduced by interleaving standard target trials with oriented 'dummy' trials containing only the background texture (no target, oriented 45° relative to the target's orientation). Our results showed reduced improvement following training with gradual SOA, as compared with random SOA. However, this difference was eliminated by randomizing SOA only at the initial and final segments of training, revealing a contaminating effect of temporal consistencies on threshold estimation rather than on learning. Inserting the 'dummy' trials (reduced spatial consistencies) facilitated both the learning and the subsequent transfer of learning, but only when sufficient pre-training was provided. These results indicate that visual sensitivity depends on a balance between two opposing processes, perceptual learning and sensory adaptation, both of which depend on spatiotemporal consistencies. Reducing spatiotemporal consistencies during training reduces the short-term spatiotemporal interactions that interfere with threshold estimation, learning, and generalization of learning. We consider the results within a theoretical framework, assuming an adaptable low-level network and a readout mechanism, with orientation and location-specific low-level adaptation interfering with the readout learning. PMID:25737285

  13. Spatiotemporal contrast sensitivity of early vision.

    PubMed

    Van Hateren, J H

    1993-01-01

    Based on the spatial and temporal statistics of natural images, a theory is developed that specifies spatiotemporal filters that maximize the flow of information through noisy channels of limited dynamic range. Sensitivities resulting from these spatiotemporal filters are very similar to the human spatiotemporal contrast sensitivity, including the dependence on ambient light intensity. The theory predicts several psychophysical laws: Ferry-Porter's law, the de Vries-Rose law, Weber's law, Bloch's law, Ricco's law, and Piper's law. PMID:8447098

  14. Spatiotemporal complexity of the aortic sinus vortex

    NASA Astrophysics Data System (ADS)

    Moore, Brandon; Dasi, Lakshmi Prasad

    2014-07-01

    The aortic sinus vortex is a classical flow structure of significant importance to aortic valve dynamics and the initiation and progression of calcific aortic valve disease. We characterize the spatiotemporal characteristics of aortic sinus vortex dynamics in relation to the viscosity of blood analog solution as well as heart rate. High-resolution time-resolved (2 kHz) 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 timescales as revealed using time bin-averaged vectors and corresponding instantaneous streamlines. There exist small timescale vortices and a large timescale 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 spatiotemporal complexity of vortex dynamics is shown to be profoundly influenced by strong leaflet flutter during systole with a peak frequency of 200 Hz and peak amplitude of 4 mm observed in the saline case. While fluid viscosity influences the length and timescales 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.

  15. Single-molecule analysis reveals human UV-damaged DNA-binding protein (UV-DDB) dimerizes on DNA via multiple kinetic intermediates

    PubMed Central

    Ghodke, Harshad; Wang, Hong; Hsieh, Ching L.; Woldemeskel, Selamawit; Watkins, Simon C.; Rapić-Otrin, Vesna; Van Houten, Bennett

    2014-01-01

    How human DNA repair proteins survey the genome for UV-induced photoproducts remains a poorly understood aspect of the initial damage recognition step in nucleotide excision repair (NER). To understand this process, we performed single-molecule experiments, which revealed that the human UV-damaged DNA-binding protein (UV-DDB) performs a 3D search mechanism and displays a remarkable heterogeneity in the kinetics of damage recognition. Our results indicate that UV-DDB examines sites on DNA in discrete steps before forming long-lived, nonmotile UV-DDB dimers (DDB1-DDB2)2 at sites of damage. Analysis of the rates of dissociation for the transient binding molecules on both undamaged and damaged DNA show multiple dwell times over three orders of magnitude: 0.3–0.8, 8.1, and 113–126 s. These intermediate states are believed to represent discrete UV-DDB conformers on the trajectory to stable damage detection. DNA damage promoted the formation of highly stable dimers lasting for at least 15 min. The xeroderma pigmentosum group E (XP-E) causing K244E mutant of DDB2 found in patient XP82TO, supported UV-DDB dimerization but was found to slide on DNA and failed to stably engage lesions. These findings provide molecular insight into the loss of damage discrimination observed in this XP-E patient. This study proposes that UV-DDB recognizes lesions via multiple kinetic intermediates, through a conformational proofreading mechanism. PMID:24760829

  16. Estimating repetitive spatiotemporal patterns from resting-state brain activity data.

    PubMed

    Takeda, Yusuke; Hiroe, Nobuo; Yamashita, Okito; Sato, Masa-Aki

    2016-06-01

    Repetitive spatiotemporal patterns in spontaneous brain activities have been widely examined in non-human studies. These studies have reported that such patterns reflect past experiences embedded in neural circuits. In human magnetoencephalography (MEG) and electroencephalography (EEG) studies, however, spatiotemporal patterns in resting-state brain activities have not been extensively examined. This is because estimating spatiotemporal patterns from resting-state MEG/EEG data is difficult due to their unknown onsets. Here, we propose a method to estimate repetitive spatiotemporal patterns from resting-state brain activity data, including MEG/EEG. Without the information of onsets, the proposed method can estimate several spatiotemporal patterns, even if they are overlapping. We verified the performance of the method by detailed simulation tests. Furthermore, we examined whether the proposed method could estimate the visual evoked magnetic fields (VEFs) without using stimulus onset information. The proposed method successfully detected the stimulus onsets and estimated the VEFs, implying the applicability of this method to real MEG data. The proposed method was applied to resting-state functional magnetic resonance imaging (fMRI) data and MEG data. The results revealed informative spatiotemporal patterns representing consecutive brain activities that dynamically change with time. Using this method, it is possible to reveal discrete events spontaneously occurring in our brains, such as memory retrieval. PMID:26979127

  17. Spatiotemporal contrast enhancement and feature extraction in the bat auditory midbrain and cortex.

    PubMed

    Hoffmann, Susanne; Warmbold, Alexander; Wiegrebe, Lutz; Firzlaff, Uwe

    2013-09-01

    Navigating on the wing in complete darkness is a challenging task for echolocating bats. It requires the detailed analysis of spatial and temporal information gained through echolocation. Thus neural encoding of spatiotemporal echo information is a major function in the bat auditory system. In this study we presented echoes in virtual acoustic space and used a reverse-correlation technique to investigate the spatiotemporal response characteristics of units in the inferior colliculus (IC) and the auditory cortex (AC) of the bat Phyllostomus discolor. Spatiotemporal response maps (STRMs) of IC units revealed an organization of suppressive and excitatory regions that provided pronounced contrast enhancement along both the time and azimuth axes. Most IC units showed either spatially centralized short-latency excitation spatiotemporally imbedded in strong suppression, or the opposite, i.e., central short-latency suppression imbedded in excitation. This complementary arrangement of excitation and suppression was very rarely seen in AC units. In contrast, STRMs in the AC revealed much less suppression, sharper spatiotemporal tuning, and often a special spatiotemporal arrangement of two excitatory regions. Temporal separation of excitatory regions ranged up to 25 ms and was thus in the range of temporal delays occurring in target ranging in bats in a natural situation. Our data indicate that spatiotemporal processing of echo information in the bat auditory midbrain and cortex serves very different purposes: Whereas the spatiotemporal contrast enhancement provided by the IC contributes to echo-feature extraction, the AC reflects the result of this processing in terms of a high selectivity and task-oriented recombination of the extracted features. PMID:23785132

  18. Nonlinear Spatio-Temporal Dynamics and Chaos in Semiconductors

    NASA Astrophysics Data System (ADS)

    Schöll, Eckehard

    2005-08-01

    Nonlinear transport phenomena are an increasingly important aspect of modern semiconductor research. This volume deals with complex nonlinear dynamics, pattern formation, and chaotic behavior in such systems. It bridges the gap between two well-established fields: the theory of dynamic systems and nonlinear charge transport in semiconductors. This unified approach helps reveal important electronic transport instabilities. The initial chapters lay a general framework for the theoretical description of nonlinear self-organized spatio-temporal patterns, such as current filaments, field domains, fronts, and analysis of their stability. Later chapters consider important model systems in detail: impact ionization induced impurity breakdown, Hall instabilities, superlattices, and low-dimensional structures. State-of-the-art results include chaos control, spatio-temporal chaos, multistability, pattern selection, activator-inhibitor kinetics, and global coupling, linking fundamental issues to electronic device applications. This book will be of great value to semiconductor physicists and nonlinear scientists alike.

  19. Nonlinear Spatio-Temporal Dynamics and Chaos in Semiconductors

    NASA Astrophysics Data System (ADS)

    Schöll, Eckehard

    2001-02-01

    Nonlinear transport phenomena are an increasingly important aspect of modern semiconductor research. This volume deals with complex nonlinear dynamics, pattern formation, and chaotic behavior in such systems. It bridges the gap between two well-established fields: the theory of dynamic systems and nonlinear charge transport in semiconductors. This unified approach helps reveal important electronic transport instabilities. The initial chapters lay a general framework for the theoretical description of nonlinear self-organized spatio-temporal patterns, such as current filaments, field domains, fronts, and analysis of their stability. Later chapters consider important model systems in detail: impact ionization induced impurity breakdown, Hall instabilities, superlattices, and low-dimensional structures. State-of-the-art results include chaos control, spatio-temporal chaos, multistability, pattern selection, activator-inhibitor kinetics, and global coupling, linking fundamental issues to electronic device applications. This book will be of great value to semiconductor physicists and nonlinear scientists alike.

  20. 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.

  1. Comparative Genomic Analysis Reveals Multiple Long Terminal Repeats, Lineage-Specific Amplification, and Frequent Interelement Recombination for Cassandra Retrotransposon in Pear (Pyrus bretschneideri Rehd.)

    PubMed Central

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

    2014-01-01

    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. PMID:24899073

  2. Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis

    PubMed Central

    Serres, Sébastien; Bristow, Claire; de Pablos, Rocío M; Merkler, Doron; Soto, Manuel Sarmiento; Sibson, Nicola R; Anthony, Daniel C

    2013-01-01

    Interferon-β (IFN-β) drugs are considered to derive their beneficial effects on multiple sclerosis (MS) progression via their antiinflammatory properties, but the precise mechanism of action remains unclear. Here, we sought to discover how IFN-β impacts on inflammation-associated aggravation of MS-like lesions in rat. Animals with dormant focal experimental allergic encephalomyelitis (EAE) lesions were challenged intravenously with a replication-deficient adenovirus vector carrying interleukin (IL)-1β cDNA (AdIL-1β). Aggravation of inflammation and demyelination within the focal EAE lesion was observed after AdIL-1β injection with associated changes in tissue structure detected by diffusion and magnetization transfer imaging. Postgadolinium-DTPA T1-weighted images revealed contrast enhancement in the ipsilateral meninges, indicating breakdown of the blood–cerebrospinal fluid barrier, and increased left/right regional cerebral blood volume ratio was also observed after AdIL-1β injection. To determine the role of IFN-β on reactivation of the EAE lesion, rats were treated with therapeutic doses of IFN-β and focal EAE lesions showed significantly reduced reactivation in response to systemic AdIL-1β injection. In conclusion, these findings indicate a central role for peripheral IL-1β expression in the mechanism of MS lesion reactivation and that the therapeutic effects of IFN-β may, at least in part, reflect suppression of the effects of peripheral inflammation on MS lesion pathogenesis. PMID:23423190

  3. Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis.

    PubMed

    Serres, Sébastien; Bristow, Claire; de Pablos, Rocío M; Merkler, Doron; Soto, Manuel Sarmiento; Sibson, Nicola R; Anthony, Daniel C

    2013-05-01

    Interferon-β (IFN-β) drugs are considered to derive their beneficial effects on multiple sclerosis (MS) progression via their antiinflammatory properties, but the precise mechanism of action remains unclear. Here, we sought to discover how IFN-β impacts on inflammation-associated aggravation of MS-like lesions in rat. Animals with dormant focal experimental allergic encephalomyelitis (EAE) lesions were challenged intravenously with a replication-deficient adenovirus vector carrying interleukin (IL)-1β cDNA (AdIL-1β). Aggravation of inflammation and demyelination within the focal EAE lesion was observed after AdIL-1β injection with associated changes in tissue structure detected by diffusion and magnetization transfer imaging. Postgadolinium-DTPA T1-weighted images revealed contrast enhancement in the ipsilateral meninges, indicating breakdown of the blood-cerebrospinal fluid barrier, and increased left/right regional cerebral blood volume ratio was also observed after AdIL-1β injection. To determine the role of IFN-β on reactivation of the EAE lesion, rats were treated with therapeutic doses of IFN-β and focal EAE lesions showed significantly reduced reactivation in response to systemic AdIL-1β injection. In conclusion, these findings indicate a central role for peripheral IL-1β expression in the mechanism of MS lesion reactivation and that the therapeutic effects of IFN-β may, at least in part, reflect suppression of the effects of peripheral inflammation on MS lesion pathogenesis. PMID:23423190

  4. 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. PMID:17531318

  5. 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

  6. Natalizumab restores aberrant miRNA expression profile in multiple sclerosis and reveals a critical role for miR-20b

    PubMed Central

    Ingwersen, Jens; Menge, Til; Wingerath, Britta; Kaya, Derya; Graf, Jonas; Prozorovski, Tim; Keller, Andreas; Backes, Christina; Beier, Markus; Scheffler, Matthias; Dehmel, Thomas; Kieseier, Bernd C; Hartung, Hans-Peter; Küry, Patrick; Aktas, Orhan

    2015-01-01

    Objective To identify microRNAs (miRNAs) regulated by anti-α4 integrin monoclonal antibody therapy (natalizumab) in the peripheral blood of patients with relapsing-remitting (RR) multiple sclerosis (MS) and to confirm their role in experimental settings in vivo. Methods In a longitudinal study of 17 RR-MS patients, we investigated blood miRNA expression profiles at baseline and after 1 year of natalizumab therapy by microarray technique and quantitative PCR validation. We compared the baseline expression profiles of these patients to those of 18 age- and sex-matched healthy controls. We confirmed the contribution of resulting candidate miRNAs in an animal model of MS, experimental autoimmune encephalomyelitis (EAE) induced by adoptive transfer of proteolipid protein (PLP)139–151-activated lymphocytes in SJL/J mice or by active immunization of miR-106a∼363-deficient C57BL/6 mice (or wildtype litter mates) with myelin oligodendrocyte glycoprotein (MOG)35–55. Results Our longitudinal analysis revealed that miR-18a, miR-20b, miR-29a, and miR-103 were upregulated and predominantly expressed by CD4+ T cells, whereas miR-326 was downregulated upon natalizumab treatment. A comparison of untreated RR-MS patients at baseline with healthy controls revealed that the four natalizumab-upregulated targets were initially downregulated in MS. All confirmed targets showed disease-dependent expression in splenocytes of mice suffering from EAE. Genetic deletion of the miRNA cluster miR-106a∼363 (containing natalizumab-regulated miR-20b) resulted in a more severe EAE course and an in vivo upregulation of the miR-20b target genes rorgt, stat3, and vegfa. Interpretation Our study indicates that natalizumab restores dysregulated miRNA patterns in MS and reveals the contribution of miR-20b in autoimmune demyelination in vivo. PMID:25642434

  7. 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.

  8. 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

  9. Multiple tree-ring chronologies (ring width, δ13C and δ18O) reveal dry and rainy season signals in Indonesia

    NASA Astrophysics Data System (ADS)

    Schollaen, Karina; Heinrich, Ingo; Neuwirth, Burkhard; Krusic, Paul; D`Arrigo, Rosanne; Karyanto, Oka; Helle, Gerhard

    2013-04-01

    The tropical Indonesian region plays a key role in the global climate system because of the enormous heat and moisture exchange between ocean and atmosphere in that area. Here, we evaluate the influence of rainfall variability on multiple tree-ring parameters of Teak (Tectona grandis) trees growing in a lowland rain forest in Central Java (Indonesia). Three, annually resolved, chronologies of tree-ring width, stable carbon (δ13C) and oxygen (δ18O) isotopes were developed for the twentieth century (1900-2007). Climate response analysis with regional rainfall data has revealed that all three tree-ring parameters are significantly sensitive to rainfall during different intervals of the seasonal monsoon pattern. The amount of rainfall at the beginning of the rainy season (Sep-Nov) is important for tree-ring width, confirming previous studies. The stable isotope records best represent slightly different sub-periods of the prime rainy season (δ13C: Dec-May; δ18O: Nov-Feb) with negative correlations. Tree-ring δ18O additionally responds well to peak dry season rainfall with positive correlation. The correlations of opposite sign reflect the distinct seasonal contrast of the δ18O signatures of rainfall during the dry (18O-enriched rain) and rainy (18O-depleted rain) seasons in conjunction with changing rainfall amount. Dry season periods with rainfall amounts above average have an exceptionally strong influence on tree-ring δ18O in years with below average rainy season rainfall. In such cases, the dry season signal reduces the signal strength of the prime rainy season in tree-ring δ18O. However, the rainy season signal is still strong and stable over the 20th century. Further, the δ18O record correlates with several ENSO events, supported by spectral analysis which reveals significant peaks on the 2-4 year band. Highly resolved intra-annual δ18O isotope analyses suggest that the signals of dry and rainy season can be distinguished clearly and demonstrate a new

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

    PubMed

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

    2016-04-01

    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 it

  11. Spatio-temporal correlations in Coulomb clusters

    NASA Astrophysics Data System (ADS)

    Ghosal, Amit; Ash, Biswarup; Chakrabarti, Jaydeb

    Dynamical response of Coulomb-particles in nanoclusters are investigated at different temperatures characterizing their solid-like (Wigner molecule) and liquid-like behavior. The density correlations probe spatio-temporal relaxation, uncovering distinct behavior at multiple time scales in these systems. They show a stretched-Gaussian or stretched-exponential spatial decay at long times in circular and irregular traps. Interplay of confinement and long-range nature of interactions yields spatially correlated motion of the particles in string-like paths, leaving the system heterogeneous even at long times. While particles in a `solid' flow producing dynamic heterogeneities, their random motion in `liquid' defies central limit theorem. Distinguishing the two confinements, temperature dependent motional signatures serve as a criterion for the crossover between `solid' and `liquid'. The irregular Wigner molecule turns into a nearly homogeneous liquid over a much wider temperature window compared to the circular case. The temperature dependence of different relaxation time scales builds crucial insights. A phenomenological model, relating the unusual dynamics to the heterogeneous nature of the diffusivities in the system, captures much of the subtleties of our numerical simulations.

  12. 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

  13. 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

  14. 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

    2015-01-01

    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

  15. Genome-wide prediction of nucleosome occupancy in maize reveals plant chromatin structural features at genes and other elements at multiple scales.

    PubMed

    Fincher, Justin A; Vera, Daniel L; Hughes, Diana D; McGinnis, Karen M; Dennis, Jonathan H; Bass, Hank W

    2013-06-01

    The nucleosome is a fundamental structural and functional chromatin unit that affects nearly all DNA-templated events in eukaryotic genomes. It is also a biochemical substrate for higher order, cis-acting gene expression codes and the monomeric structural unit for chromatin packaging at multiple scales. To predict the nucleosome landscape of a model plant genome, we used a support vector machine computational algorithm trained on human chromatin to predict the nucleosome occupancy likelihood (NOL) across the maize (Zea mays) genome. Experimentally validated NOL plots provide a novel genomic annotation that highlights gene structures, repetitive elements, and chromosome-scale domains likely to reflect regional gene density. We established a new genome browser (http://www.genomaize.org) for viewing support vector machine-based NOL scores. This annotation provides sequence-based comprehensive coverage across the entire genome, including repetitive genomic regions typically excluded from experimental genomics data. We find that transposable elements often displayed family-specific NOL profiles that included distinct regions, especially near their termini, predicted to have strong affinities for nucleosomes. We examined transcription start site consensus NOL plots for maize gene sets and discovered that most maize genes display a typical +1 nucleosome positioning signal just downstream of the start site but not upstream. This overall lack of a -1 nucleosome positioning signal was also predicted by our method for Arabidopsis (Arabidopsis thaliana) genes and verified by additional analysis of previously published Arabidopsis MNase-Seq data, revealing a general feature of plant promoters. Our study advances plant chromatin research by defining the potential contribution of the DNA sequence to observed nucleosome positioning and provides an invariant baseline annotation against which other genomic data can be compared. PMID:23572549

  16. Single-Molecule Analysis of PIP2;1 Dynamics and Partitioning Reveals Multiple Modes of Arabidopsis Plasma Membrane Aquaporin Regulation[C][W

    PubMed Central

    Li, Xiaojuan; Wang, Xiaohua; Yang, Yong; Li, Ruili; He, Qihua; Fang, Xiaohong; Luu, Doan-Trung; Maurel, Christophe; Lin, Jinxing

    2011-01-01

    PIP2;1 is an integral membrane protein that facilitates water transport across plasma membranes. To address the dynamics of Arabidopsis thaliana PIP2;1 at the single-molecule level as well as their role in PIP2;1 regulation, we tracked green fluorescent protein–PIP2;1 molecules by variable-angle evanescent wave microscopy and fluorescence correlation spectroscopy (FCS). Single-particle tracking analysis revealed that PIP2;1 presented four diffusion modes with large dispersion of diffusion coefficients, suggesting that partitioning and dynamics of PIP2;1 are heterogeneous and, more importantly, that PIP2;1 can move into or out of membrane microdomains. In response to salt stress, the diffusion coefficients and percentage of restricted diffusion increased, implying that PIP2;1 internalization was enhanced. This was further supported by the decrease in PIP2;1 density on plasma membranes by FCS. We additionally demonstrated that PIP2;1 internalization involves a combination of two pathways: a tyrphostin A23-sensitive clathrin-dependent pathway and a methyl-β-cyclodextrin–sensitive, membrane raft–associated pathway. The latter was efficiently stimulated under NaCl conditions. Taken together, our findings demonstrate that PIP2;1 molecules are heterogeneously distributed on the plasma membrane and that clathrin and membrane raft pathways cooperate to mediate the subcellular trafficking of PIP2;1, suggesting that the dynamic partitioning and recycling pathways might be involved in the multiple modes of regulating water permeability. PMID:22010034

  17. Heterogeneous Ordered-Disordered Structure of the Mesodomain in Frozen Sucrose-Water Solutions Revealed by Multiple Electron Paramagnetic Resonance Spectroscopies

    PubMed Central

    Chen, Hanlin; Sun, Li; Warncke, Kurt

    2013-01-01

    The microscopic structure of frozen aqueous sucrose solutions, over concentrations of 0–75% (w/v), is characterized by using multiple continuous-wave and pulsed electron paramagnetic resonance (EPR) spectroscopic and relaxation techniques and the paramagnetic spin probe, TEMPOL. The temperature dependence of the TEMPOL EPR lineshape anisotropy reveals a mobility transition, specified at 205 K in pure water and 255 ±5 K for >1% (w/v) added sucrose. The transition temperature is >>Tg, where Tg is the homogeneous water glass transition temperature, which shows that TEMPOL resides in the mesoscopic domain (mesodomain) at water-ice crystallite boundaries, and that the mesodomain sucrose concentrations are comparable at >1% (w/v) added sucrose. Electron spin echo envelope modulation (ESEEM) spectroscopy of TEMPOL-2H2-sucrose hyperfine interactions also indicates comparable sucrose concentrations in mesodomains at >1% (w/v) added sucrose. Electron spin echo (ESE) – detected longitudinal and phase memory relaxation times (T1 and TM, respectively) at 6 K indicate a general trend of increased mesodomain volume with added sucrose, in three stages: 1-15, 20-50, and >50% (w/v). The calibrated TEMPOL concentrations indicate that the mesodomain volume is less than the predicted maximally freeze-concentrated value [80 (w/w); 120% (w/v)], with transitions at 15-20% and 50% (w/v) starting sucrose. An ordered sucrose hydrate phase, which excludes TEMPOL, and a disordered, amorphous sucrose-water glass phase, in which TEMPOL resides, are proposed to compose a heterogeneous mesodomain. The results show that the ratio of ordered and disordered volume fractions in the mesodomain is exquisitely sensitive to the starting sucrose concentration. PMID:23464733

  18. 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 Central

    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. PMID:25482929

  19. 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.

  20. 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. PMID:27558712

  1. Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells

    PubMed Central

    Hsu, P-Y; Hsu, H-K; Hsiao, T-H; Ye, Z; Wang, E; Profit, A L; Jatoi, I; Chen, Y; Kirma, N B; Jin, V X; Sharp, Z D; Huang, T H-M

    2016-01-01

    Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that distant estrogen response elements (DEREs) located on chromosome 20q13 are frequently amplified and translocated to other chromosomes in ERα-positive breast cancer cells. In this study, we used three-dimensional interphase fluorescence in situ hybridization to decipher spatiotemporal gathering of multiple DEREs in the nucleus. Upon estrogen stimulation, scattered 20q13 DEREs were mobilized to form regulatory depots for synchronized gene expression of target loci. A chromosome conformation capture assay coupled with chromatin immunoprecipitation further uncovered that ERα-bound regulatory depots are tethered to heterochromatin protein 1 (HP1) for coordinated chromatin movement and histone modifications of target loci, resulting in transcription repression. Neutralizing HP1 function dysregulated the formation of DERE-involved regulatory depots and transcription inactivation of candidate tumor-suppressor genes. Deletion of amplified DEREs using the CRISPR/Cas9 genomic-editing system profoundly altered transcriptional profiles of proliferation-associated signaling networks, resulting in reduction of cancer cell growth. These findings reveal a formerly uncharacterized feature wherein multiple copies of the amplicon congregate as transcriptional units in the nucleus for synchronous regulation of function-related loci in tumorigenesis. Disruption of their assembly can be a new strategy for treating breast cancers and other malignancies. PMID:26300005

  2. Microclimate Data Improve Predictions of Insect Abundance Models Based on Calibrated Spatiotemporal Temperatures.

    PubMed

    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

  3. 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

  4. Spatiotemporal SERT expression in cortical map development.

    PubMed

    Chen, Xiaoning; Petit, Emilie I; Dobrenis, Kostantin; Sze, Ji Ying

    2016-09-01

    The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial-defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area-specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders. PMID:27282696

  5. 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.

  6. 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

  7. Multiple tree-ring chronologies (ring width, δ13C and δ18O) reveal dry and rainy season signals of rainfall in Indonesia

    NASA Astrophysics Data System (ADS)

    Schollaen, Karina; Heinrich, Ingo; Neuwirth, Burkhard; Krusic, Paul J.; D'Arrigo, Rosanne D.; Karyanto, Oka; Helle, Gerhard

    2013-08-01

    Climatic hazards, such as severe droughts and floods, affect extensive areas across monsoon Asia and can have profound impacts on the populations of that region. The area surrounding Indonesia, including large portions of the eastern Indian Ocean and Java Sea, plays a key role in the global climate system because of the enormous heat and moisture exchange that occurs between the ocean and atmosphere there. Here, we evaluate the influence of rainfall variability on multiple tree-ring parameters of teak (Tectona grandis) trees growing in a lowland rain forest in Central Java (Indonesia). We assess the potential of, annually resolved, tree-ring width, stable carbon (δ13C) and oxygen (δ18O) isotope records to improve our understanding of the Asian monsoon variability. Climate response analysis with regional, monthly rainfall data reveals that all three tree-ring parameters are significantly correlated to rainfall, albeit during different monsoon seasons. Precipitation in the beginning of the rainy season (Sep-Nov) is important for tree-ring width, confirming previous studies. Compared to ring width, the stable isotope records possess a higher degree of common signal, especially during portions of the peak rainy season (δ13C: Dec-May; δ18O: Nov-Feb) and are negatively correlated to rainfall. In addition, tree-ring δ18O also responds positively to peak dry season rainfall, although the δ18O rainy season signal is stronger and more time-stable. The correlations of opposite sign reflect the distinct seasonal contrast of the δ18O signatures in rainfall (18OPre) during the dry (18O-enriched rain) and rainy (18O-depleted rain) seasons. This difference in 18OPre signal reflects the combination of two signals in the annual tree-ring δ18O record. Highly resolved intra-annual δ18O isotope analyses suggest that the signals of dry and rainy season can be distinguished clearly. Thereby reconstructions can improve our understanding of variations and trends of the

  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. 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.

  11. Spatiotemporal characteristics of pandemic influenza

    PubMed Central

    2014-01-01

    Background Prediction of timing for the onset and peak of an influenza pandemic is of vital importance for preventive measures. In order to identify common spatiotemporal patterns and climate influences for pandemics in Sweden we have studied the propagation in space and time of A(H1N1)pdm09 (10,000 laboratory verified cases), the Asian Influenza 1957–1958 (275,000 cases of influenza-like illness (ILI), reported by local physicians) and the Russian Influenza 1889–1890 (32,600 ILI cases reported by physicians shortly after the end of the outbreak). Methods All cases were geocoded and analysed in space and time. Animated video sequences, showing weekly incidence per municipality and its geographically weighted mean (GWM), were created to depict and compare the spread of the pandemics. Daily data from 1957–1958 on temperature and precipitation from 39 weather stations were collected and analysed with the case data to examine possible climatological effects on the influenza dissemination. Results The epidemic period lasted 11 weeks for the Russian Influenza, 10 weeks for the Asian Influenza and 9 weeks for the A(H1N1)pdm09. The Russian Influenza arrived in Sweden during the winter and was immediately disseminated, while both the Asian Influenza and the A(H1N1)pdm09 arrived during the spring. They were seeded over the country during the summer, but did not peak until October-November. The weekly GWM of the incidence moved along a line from southwest to northeast for the Russian and Asian Influenza but northeast to southwest for the A(H1N1)pdm09. The local epidemic periods of the Asian Influenza were preceded by falling temperature in all but one of the locations analysed. Conclusions The power of spatiotemporal analysis and modeling for pandemic spread was clearly demonstrated. The epidemic period lasted approximately 10 weeks for all pandemics. None of the pandemics had its epidemic period before late autumn. The epidemic period of the Asian Influenza was

  12. 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. PMID:19729155

  13. 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

  14. 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. PMID:19550494

  15. Spatiotemporal phylogenetic analysis and molecular characterization of coxsackievirus A4.

    PubMed

    Chu, Pei-Yu; Lu, Po-Liang; Tsai, Yu-Ling; Hsi, Edward; Yao, Ching-Yuan; Chen, Yu-Hsien; Hsu, Li-Ching; Wang, Sheng-Yu; Wu, Ho-Sheng; Lin, Yi-Ying; Su, Hui-Ju; Lin, Kuei-Hsiang

    2011-08-01

    Coxsackievirus A4 outbreaks occurred in Taiwan in 2004 and 2006. The spatiotemporal transmission of this error-prone RNA virus involves a continuous interaction between rapid sequence variation and natural selection. To elucidate the molecular characteristics of CV-A4 and the spatiotemporal dynamic changes in CV-A4 transmission, worldwide sequences of the 3' VP1 region (420 nt) obtained from GenBank were analyzed together with sequences isolated in Taiwan from 2002 to 2009. Sequences were characterized in terms of recombination, variability, and selection. Phylogenetic trees were constructed using neighbor-joining, maximum likelihood and Monte Carlo Markov Chain methods. Spatiotemporal dynamics of CV-A4 transmission were further estimated by a Bayesian statistical inference framework. No recombination was detected in the 420 nt region. The estimated evolution rate of CV-A4 was 8.65 × 10(-3) substitutions/site/year, and a purifying selection (d(N)/d(S)=0.032) was noted over the 3' VP1 region. All trees had similar topology: two genotypes (GI and GII), each including two subgenotypes (A and B), with the prototype and a Kenyan strain in separate branches. The results revealed that the virus first appeared in USA in 1950. Since 1998, it has evolved into the Kenya, GI-A (Asia) and GII-A (Asia and Europe) strains. Since 2004, GI-B and GII-B have evolved continuously and have remained prevalent. The co-existence of several positive selection lineages of GI-B in 2006 indicates that the subgenotype might have survived lineage extinction. This study revealed rapid lineage turnover of CV-A4 and the replacement of previously circulating strains by a new dominant variant. Therefore, continuous surveillance for further CV-A4 transmission is essential. PMID:21635970

  16. 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

  17. Three-dimensional spatiotemporal focusing of holographic patterns.

    PubMed

    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

  18. 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.

  19. Primate reaching cued by multichannel spatiotemporal cortical microstimulation.

    PubMed

    Fitzsimmons, N A; Drake, W; Hanson, T L; Lebedev, M A; Nicolelis, M A L

    2007-05-23

    Both humans and animals can discriminate signals delivered to sensory areas of their brains using electrical microstimulation. This opens the possibility of creating an artificial sensory channel that could be implemented in neuroprosthetic devices. Although microstimulation delivered through multiple implanted electrodes could be beneficial for this purpose, appropriate microstimulation protocols have not been developed. Here, we report a series of experiments in which owl monkeys performed reaching movements guided by spatiotemporal patterns of cortical microstimulation delivered to primary somatosensory cortex through chronically implanted multielectrode arrays. The monkeys learned to discriminate microstimulation patterns, and their ability to learn new patterns and new behavioral rules improved during several months of testing. Significantly, information was conveyed to the brain through the interplay of microstimulation patterns delivered to multiple electrodes and the temporal order in which these electrodes were stimulated. This suggests multichannel microstimulation as a viable means of sensorizing neural prostheses. PMID:17522304

  20. Transient spatiotemporal chaos is extensive in three reaction-diffusion networks.

    PubMed

    Stahlke, Dan; Wackerbauer, Renate

    2009-11-01

    Extensive (asymptotic) spatiotemporal chaos is comprised of statistically similar subsystems that interact only weakly. A systematic study of transient spatiotemporal chaos reveals extensive system behavior in all three reaction-diffusion networks for various boundary conditions. The Lyapunov dimension, the sum of positive Lyapunov exponents, and the logarithm of the transient lifetime grow linearly with the system size. The unstable manifold of the chaotic saddle has nearly the same dimension as the saddle itself, and the stable manifold is nearly space filling. PMID:20365064

  1. Extracting a low-dimensional description of multiple gene expression datasets reveals a potential driver for tumor-associated stroma in ovarian cancer.

    PubMed

    Celik, Safiye; Logsdon, Benjamin A; Battle, Stephanie; Drescher, Charles W; Rendi, Mara; Hawkins, R David; Lee, Su-In

    2016-01-01

    Patterns in expression data conserved across multiple independent disease studies are likely to represent important molecular events underlying the disease. We present the INSPIRE method to infer modules of co-expressed genes and the dependencies among the modules from multiple expression datasets that may contain different sets of genes. We show that INSPIRE infers more accurate models than existing methods to extract low-dimensional representation of expression data. We demonstrate that applying INSPIRE to nine ovarian cancer datasets leads to a new marker and potential driver of tumor-associated stroma, HOPX, followed by experimental validation. The implementation of INSPIRE is available at http://inspire.cs.washington.edu . PMID:27287041

  2. The dynamics of spatio-temporal Rho GTPase signaling: formation of signaling patterns

    PubMed Central

    Fritz, Rafael Dominik; Pertz, Olivier

    2016-01-01

    Rho GTPases are crucial signaling molecules that regulate a plethora of biological functions. Traditional biochemical, cell biological, and genetic approaches have founded the basis of Rho GTPase biology. The development of biosensors then allowed measuring Rho GTPase activity with unprecedented spatio-temporal resolution. This revealed that Rho GTPase activity fluctuates on time and length scales of tens of seconds and micrometers, respectively. In this review, we describe Rho GTPase activity patterns observed in different cell systems. We then discuss the growing body of evidence that upstream regulators such as guanine nucleotide exchange factors and GTPase-activating proteins shape these patterns by precisely controlling the spatio-temporal flux of Rho GTPase activity. Finally, we comment on additional mechanisms that might feed into the regulation of these signaling patterns and on novel technologies required to dissect this spatio-temporal complexity. PMID:27158467

  3. Hemodynamic changes in the infant cortex during the processing of featural and spatiotemporal information.

    PubMed

    Wilcox, Teresa; Bortfeld, Heather; Woods, Rebecca; Wruck, Eric; Armstrong, Jennifer; Boas, David

    2009-02-01

    Over the last 20 years neuroscientists have learned a great deal about the ventral and dorsal object processing pathways in the adult brain, yet little is known about the functional development of these pathways. The present research assessed the extent to which different patterns of neural activation, as measured by changes in blood volume and oxygenation, are observed in infant visual and temporal cortex in response to events that involve processing of featural differences or spatiotemporal discontinuities. Infants aged 6.5 months were tested. Increased neural activation was observed in visual cortex in response to a featural-difference and a spatiotemporal-discontinuity event. In addition, increased neural activation was observed in temporal cortex in response to the featural-difference but not the spatiotemporal-discontinuity event. The outcome of this experiment reveals early functional specialization of temporal cortex and lays the foundation for future investigation of the maturation of object processing pathways in humans. PMID:19071143

  4. 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. PMID:24992684

  5. Bayesian Spatio-Temporal Analysis and Geospatial Risk Factors of Human Monocytic Ehrlichiosis

    PubMed Central

    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. PMID:24992684

  6. 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.

  7. Quantifying the complexity of excised larynx vibrations from high-speed imaging using spatiotemporal and nonlinear dynamic analyses

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack J.; Tao, Chao; Bieging, Erik; MacCallum, Julia K.

    2007-12-01

    In this paper, we investigate the biomechanical applications of spatiotemporal analysis and nonlinear dynamic analysis to quantitatively describe regular and irregular vibrations of twelve excised larynges from high-speed image recordings. Regular vibrations show simple spatial symmetry, temporal periodicity, and discrete frequency spectra, while irregular vibrations show complex spatiotemporal plots, aperiodic time series, and broadband spectra. Furthermore, the global entropy and correlation length from spatiotemporal analysis and the correlation dimension from nonlinear dynamic analysis reveal a statistical difference between regular and irregular vibrations. In comparison with regular vibrations, the global entropy and correlation dimension of irregular vibrations are statistically higher, while the correlation length is significantly lower. These findings show that spatiotemporal analysis and nonlinear dynamic analysis are capable of describing the complex dynamics of vocal fold vibrations from high-speed imaging and may potentially be helpful for understanding disordered behaviors in biomedical laryngeal systems.

  8. Spatiotemporal hemodynamic response functions derived from physiology.

    PubMed

    Aquino, K M; Robinson, P A; Drysdale, P M

    2014-04-21

    Probing neural activity with functional magnetic resonance imaging (fMRI) relies upon understanding the hemodynamic response to changes in neural activity. Although existing studies have extensively characterized the temporal hemodynamic response, less is understood about the spatial and spatiotemporal hemodynamic responses. This study systematically characterizes the spatiotemporal response by deriving the hemodynamic response due to a short localized neural drive, i.e., the spatiotemporal hemodynamic response function (stHRF) from a physiological model of hemodynamics based on a poroelastic model of cortical tissue. In this study, the model's boundary conditions are clarified and a resulting nonlinear hemodynamic wave equation is derived. From this wave equation, damped linear hemodynamic waves are predicted from the stHRF. The main features of these waves depend on two physiological parameters: wave propagation speed, which depends on mean cortical stiffness, and damping which depends on effective viscosity. Some of these predictions were applied and validated in a companion study (Aquino et al., 2012). The advantages of having such a theory for the stHRF include improving the interpretation of spatiotemporal dynamics in fMRI data; improving estimates of neural activity with fMRI spatiotemporal deconvolution; and enabling wave interactions between hemodynamic waves to be predicted and exploited to improve the signal to noise ratio of fMRI. PMID:24398024

  9. Multiple Infections with Cardinium and Two Strains of Wolbachia in The Spider Mite Tetranychus phaselus Ehara: Revealing New Forces Driving the Spread of Wolbachia

    PubMed Central

    Zhao, Dong-Xiao; Chen, Da-Song; Ge, Cheng; Gotoh, Tetsuo; Hong, Xiao-Yue

    2013-01-01

    Cytoplasmic incompatibility (CI) has been proposed as a major mechanism by which certain strains of Wolbachia to invade and persist in host populations. However, mechanisms that underlie the invasion and persistence of non-CI strains are less well understood. Here, we established a spider mite Tetranychus phaselus population multiply infected by Cardinium as well as two distinct lineages of Wolbachia, designated wCon and wOri, to study the forces driving the spread of the non-CI strain of Wolbachia wOri. Interestingly, we found that wOri provided a longevity advantage to its female hosts under ideal conditions, making wOri stay longer in this population, and then being transmitted to more offspring. Furthermore, the lifespan of uninfected females was reduced when mated with multiple-infected males. As a result, the uninfected population is attenuated by the multiple-infected males. Thus, we infer that the host age effects of multiple infection may represent sufficient forces driving the spread of wOri through the host population. PMID:23355904

  10. 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). PMID:19574627

  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. 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.

  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. 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.

  15. Geomapping generalized eigenvalue frequency distributions for predicting prolific Aedes albopictus and Culex quinquefasciatus habitats based on spatiotemporal field-sampled count data.

    PubMed

    Jacob, Benjamin G; Morris, Joel A; Caamano, Erick X; Griffith, Daniel A; Novak, Robert J

    2011-02-01

    Marked spatiotemporal variabilities in mosquito infection of arboviruses require adaptive strategies for determining optimal field-sampling timeframes, pool screening, and data analyses. In particular, the error distribution and aggregation patterns of adult arboviral mosquitoes can vary significantly by species, which can statistically bias analyses of spatiotemporal-sampled predictor variables generating misinterpretation of prolific habitat surveillance locations. Currently, there is a lack of reliable and consistent measures of risk exposure based on field-sampled georeferenced explanatory covariates which can compromise quantitative predictions generated from arboviral mosquito surveillance models for implementing larval control strategies targeting productive habitats. In this research we used spatial statistics and QuickBird visible and near-infra-red data for determining trapping sites that were related to Culex quinquefasciatus and Aedes albopictus species abundance and distribution in Birmingham, Alabama. Initially, a Land Use Land Cover (LULC) model was constructed from multiple spatiotemporal-sampled georeferenced predictors and the QuickBird data. A Poisson regression model with a non-homogenous, gamma-distributed mean then decomposed the data into positive and negative spatial filter eigenvectors. An autoregressive process in the error term then was used to derive the sample distribution of the Moran's I statistic for determining latent autocorrelation components in the model. Spatial filter algorithms established means, variances, distributional functions, and pairwise correlations for the predictor variables. In doing so, the eigenfunction spatial filter quantified the residual autocorrelation error in the mean response term of the model as a linear combination of various distinct Cx. quinquefasciatus and Ae. albopictus habitat map patterns. The analyses revealed 18-27% redundant information in the data. Prolific habitats of Cx. quinquefasciatus and

  16. Multiple superhyperfine fields in a {DyFe2Dy} coordination cluster revealed using bulk susceptibility and (57)Fe Mössbauer studies.

    PubMed

    Peng, Yan; Mereacre, Valeriu; Anson, Christopher E; Powell, Annie K

    2016-08-01

    A [DyFeDy(μ3-OH)2(pmide)2(p-Me-PhCO2)6] coordination cluster, where pmideH2 = N-(2-pyridylmethyl)iminodiethanol, has been synthesized and the magnetic properties studied. The dc magnetic measurements reveal dominant antiferromagnetic interactions between the metal centres. The ac measurements reveal zero-field quantum tunnelling of the magnetisation (QTM) which can be understood, but not adequately modelled, in terms of at least three relaxation processes when appropriate static (dc) fields are applied. To investigate this further, (57)Fe Mössbauer spectroscopy was used and well-resolved nuclear hyperfine structures could be observed, showing that on the Mössbauer time scale, without applied field or else with very small applied fields, the iron nuclei experience three or more superhyperfine fields arising from the slow magnetisation reversal of the strongly polarized fields of the Dy(III) ions. PMID:27424877

  17. Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides.

    PubMed

    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; Stewart, A Keith

    2012-08-01

    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

  18. 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

  19. Recognition by variance: learning rules for spatiotemporal patterns.

    PubMed

    Barak, Omri; Tsodyks, Misha

    2006-10-01

    Recognizing specific spatiotemporal patterns of activity, which take place at timescales much larger than the synaptic transmission and membrane time constants, is a demand from the nervous system exemplified, for instance, by auditory processing. We consider the total synaptic input that a single readout neuron receives on presentation of spatiotemporal spiking input patterns. Relying on the monotonic relation between the mean and the variance of a neuron's input current and its spiking output, we derive learning rules that increase the variance of the input current evoked by learned patterns relative to that obtained from random background patterns. We demonstrate that the model can successfully recognize a large number of patterns and exhibits a slow deterioration in performance with increasing number of learned patterns. In addition, robustness to time warping of the input patterns is revealed to be an emergent property of the model. Using a leaky integrate-and-fire realization of the readout neuron, we demonstrate that the above results also apply when considering spiking output. PMID:16907629

  20. 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.

  1. 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.

  2. 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. PMID:27411245

  3. 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.

  4. Spatiotemporal Stochastic Forcing In Ensemble Systems

    NASA Astrophysics Data System (ADS)

    Lorenzo, M. N.; Montero, P.; Pérez-Muñuzuri, V.

    In 1998, the ECMWF introduced in the operational Ensemble Prediction System (EPS) a new scheme to simulate random model errors due to parameterized phys- ical processes (Buizza et al., 1999). This scheme is based on the notion that this randomness is coherent between the different parameterization modules and has a certain coherence on the space and time scales represented by the model. Following this idea, we have perturbed with a spatiotemporal correlated noise of the Ornstein- Uhlenbeck type both, a diffusively coupled one-dimensional array of Lorenz chaotic cells (Lorenzo and Pérez-Muñuzuri, 1999, 2001), and a simplified atmospheric global circulation model, PUMA (Portable University Model of the Atmosphere) (Frisius et al., 1998). In both cases, forcing increases the spread of the ensemble for a certain value of the correlation time where the predictability also attains a critical value. On the other hand, for increasing correlation length ( fixed) the numerical results suggest a nonmonotonous behavior of the ensemble spread. The influence of noise amplitude, as well as the effect of a multiplicative or additive contribution of the noise is also shown. Finally, the impact of model resolution and ensemble size on the performance of the ensemble forecast has been analyzed numerically. newline [1] Buizza, R., Miller, M. and Palmer, T.N. (1999) Stochastic representation of model uncertainties in the ECMWF Ensemble Prediction System. Q.J.R. Meteorol. Soc. 125, 2887-2908. [2] Frisius, T., Lunkeit, F., Fraedrich, K. and James, I.N. (1998) Storm-track orga- nization and variability in a simplified atmospheric global circulation model. Q.J.R. Meteorol. Soc. 124, 1019-1043. [3] Lorenzo, M.N. and Pérez-Muñuzuri, V. (1999) Colored noise-induced chaotic ar- ray synchronization. Phys. Rev. E 60 2779-2787. [4] Lorenzo, M.N. and Pérez-Muñuzuri, V. (2001) Influence of low intensity noise on assemblies of diffusively coupled chaotic cells. Chaos 11, 371-376.

  5. 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

  6. Improved spatiotemporal-multiplexing super-multiview display based on planar aligned OLED microdisplays.

    PubMed

    Teng, Dongdong; Pang, Zhiyong; Zhang, Yueli; Wu, Dong; Wang, Jiahui; Liu, Lilin; Wang, Biao

    2015-08-24

    Through gating spectrum plane of multiple planar aligned OLED microdisplays by a timely sequential manner, a super-multiview (SMV) three-dimensional (3D) display based on spatiotemporal-multiplexing was developed in our previous paper. But an upper limit of the allowable sub-viewing-zones (SVZs) for an OLED microdisplay did exist in the previous system, even if microdisplays with very high frame rates could be commercially available. In this manuscript, an improved spatiotemporal-multiplexing SMV displays system is developed, which removes the above limitation through controllable fusing of light beams from adjacent OLED microdisplays. The employment of a liquid-crystal panel as the gating-aperture array allows the improved system to accommodate multiple rows of OLED microdisplays for denser SVZs. Experimentally, a prototype system is demonstrated by 24 OLED microdisplays, resulting in 120 SVZs with an interval small to 1.07mm. PMID:26368135

  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. 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

  9. 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

  10. Comparison of Local Features from Two Spanish Hospitals Reveals Common and Specific Traits at Multiple Levels of the Molecular Epidemiology of Metallo-β-Lactamase-Producing Pseudomonas spp.

    PubMed Central

    Viedma, Esther; Estepa, Vanesa; Castillo-Vera, Jane; Rojo-Bezares, Beatriz; Seral, Cristina; Castillo, Francisco Javier; Sáenz, Yolanda; Torres, Carmen; Chaves, Fernando; Oliver, Antonio

    2014-01-01

    Twenty-seven well-characterized metallo-β-lactamase (MBL)-producing Pseudomonas strains from two distantly located hospitals were analyzed. The results revealed specific features defining the multilevel epidemiology of strains from each hospital in terms of species, clonality, predominance of high-risk clones, composition/diversity of integrons, and linkages of Tn402-related structures. Therefore, despite the global trends driving the epidemiology of MBL-producing Pseudomonas spp., the presence of local features has to be considered in order to understand this threat and implement proper control strategies. PMID:24492368

  11. Complex Multiple-Nucleotide Substitution Mutations Causing Human Inherited Disease Reveal Novel Insights into the Action of Translesion Synthesis DNA Polymerases.

    PubMed

    Chen, Jian-Min; Férec, Claude; Cooper, David N

    2015-11-01

    Translesion synthesis (TLS) DNA polymerases allow the bypass of unrepaired lesions during DNA replication. Based upon mutational signatures of a subtype of multiple-nucleotide substitution (MNS) mutations causing human inherited disease, we have recently postulated two properties of TLS DNA polymerases in DNA repair, namely, the generation of neo-microhomologies potentiating strand-misalignment, and additional microlesions within the templated inserts when recruited to stalled replication forks. To provide further support for this postulate, we analyzed the mutational signatures of a new and complex subtype of pathogenic MNS mutation. Several mutations containing long templated inserts (8-19 bp) that are highly informative with regard to their underlying mutational mechanisms, harbor imprints of TLS DNA polymerase action. Dissecting the mechanism underlying the generation of the 19-bp insert implicated repeated participation of TLS DNA polymerases in the conversion of a damaged base into a complex MNS lesion through a process of successive template switching and bypass repair. PMID:26172832

  12. 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.

  13. Regulatory analysis of the C. elegans genome with spatiotemporal resolution

    PubMed Central

    Araya, Carlos L.; Kawli, Trupti; Kundaje, Anshul; Jiang, Lixia; Wu, Beijing; Vafeados, Dionne; Terrell, Robert; Weissdepp, Peter; Gevirtzman, Louis; Mace, Daniel; Niu, Wei; Boyle, Alan P.; Xie, Dan; Ma, Lijia; Murray, John I.; Reinke, Valerie; Waterston, Robert H.; Snyder, Michael

    2015-01-01

    Summary Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors (TFs) and regulatory proteins across multiple stages of C. elegans development by performing 241 ChIP-seq experiments. Integrating regulatory binding and cellular-resolution expression data yielded a spatiotemporally-resolved metazoan TF binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of TFs, characterizing (1) the genomic coverage and clustering of regulatory binding, (2) the binding preferences of and biological processes regulated by TFs, (3) the global TF co-associations and genomic subdomains that suggest shared patterns of regulation, and (4) key TFs and TF co-associations for fate specification of individual lineages and cell-types. PMID:25164749

  14. 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

  15. A Multiple Decrement Life Table Reveals That Host Plant Resistance and Parasitism Are Major Causes of Mortality for the Wheat Stem Sawfly.

    PubMed

    Buteler, Micaela; Peterson, Robert K D; Hofland, Megan L; Weaver, David K

    2015-12-01

    This study investigated the dynamics of parasitism, host plant resistance, pathogens, and predation on the demography of wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), developing in susceptible (hollow stem) and resistant (solid stem) wheat hosts. This study is also the first to investigate the prevalence and impact of cannibalism on wheat stem sawfly mortality. Wheat stem sawflies were sampled in two commercial wheat fields over 4 yr from the egg stage through adult emergence, and multiple decrement life tables were constructed and analyzed. Cannibalism, host plant resistance, or unknown factors were the most prevalent factors causing egg mortality. Summer mortality of prediapause larvae ranged from 28 to 84%, mainly due to parasitism by Bracon cephi (Gahan) and Bracon lissogaster Muesebeck, cannibalism, and host plant resistance. Winter mortality ranged from 6 to 54% of the overwintering larvae, mainly due to unknown factors or pathogens. Cannibalism is a major cause of irreplaceable mortality because it is absolute, with only a single survivor in every multiple infested stem. Subsequent to obligate cannibalism, mortality of feeding larvae due to host plant resistance was lower in hollow stem wheat than in solid stem wheat. Mortality from host plant resistance was largely irreplaceable. Irreplaceable mortality due to parasitoids was greater in hollow stem wheat than in solid stem wheat. Host plant resistance due to stem solidness and parasitism in hollow stems cause substantial mortality in populations of actively feeding larvae responsible for all crop losses. Therefore, enhancing these mortality factors is vital to effective integrated pest management of wheat stem sawfly. PMID:26314030

  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. Insights into the mode of action of anticandidal herbal monoterpenoid geraniol reveal disruption of multiple MDR mechanisms and virulence attributes in Candida albicans.

    PubMed

    Singh, Shweta; Fatima, Zeeshan; Hameed, Saif

    2016-07-01

    The anticandidal potential of Geraniol (Ger) against Candida albicans has already been established. The present study reveals deeper insights into the mechanisms of action of Ger. We observed that the repertoire of antifungal activity was not only limited to C. albicans and its clinical isolates but also against non-albicans species of Candida. The membrane tampering effect was visualized through transmission electron micrographs, depleted ergosterol levels and altered plasma membrane ATPase activity. Ger also affects cell wall as revealed by spot assays with cell wall-perturbing agents and scanning electron micrographs. Functional calcineurin pathway seems to be indispensable for the antifungal effect of Ger as calcineurin signaling mutant was hypersensitive to Ger while calcineurin overexpressing strain remained resistant. Ger also causes mitochondrial dysfunction, impaired iron homeostasis and genotoxicity. Furthermore, Ger inhibits both virulence attributes of hyphal morphogenesis and biofilm formation. Taken together, our results suggest that Ger is potential antifungal agent that warrants further investigation in clinical applications so that it could be competently employed in therapeutic strategies to treat Candida infections. PMID:26935560

  18. 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. PMID:26147218

  19. The Voronoi spatio-temporal data structure

    NASA Astrophysics Data System (ADS)

    Mioc, Darka

    2002-04-01

    Current GIS models cannot integrate the temporal dimension of spatial data easily. Indeed, current GISs do not support incremental (local) addition and deletion of spatial objects, and they can not support the temporal evolution of spatial data. Spatio-temporal facilities would be very useful in many GIS applications: harvesting and forest planning, cadastre, urban and regional planning, and emergency planning. The spatio-temporal model that can overcome these problems is based on a topological model---the Voronoi data structure. Voronoi diagrams are irregular tessellations of space, that adapt to spatial objects and therefore they are a synthesis of raster and vector spatial data models. The main advantage of the Voronoi data structure is its local and sequential map updates, which allows us to automatically record each event and performed map updates within the system. These map updates are executed through map construction commands that are composed of atomic actions (geometric algorithms for addition, deletion, and motion of spatial objects) on the dynamic Voronoi data structure. The formalization of map commands led to the development of a spatial language comprising a set of atomic operations or constructs on spatial primitives (points and lines), powerful enough to define the complex operations. This resulted in a new formal model for spatio-temporal change representation, where each update is uniquely characterized by the numbers of newly created and inactivated Voronoi regions. This is used for the extension of the model towards the hierarchical Voronoi data structure. In this model, spatio-temporal changes induced by map updates are preserved in a hierarchical data structure that combines events and corresponding changes in topology. This hierarchical Voronoi data structure has an implicit time ordering of events visible through changes in topology, and it is equivalent to an event structure that can support temporal data without precise temporal

  20. Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex.

    PubMed

    Piché, Marilyse; Thomas, Sébastien; Casanova, Christian

    2015-10-01

    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

  1. Working with Spatio-Temporal Data Type

    NASA Astrophysics Data System (ADS)

    Raza, A.

    2012-07-01

    Several aspects of spatiotemporal databases have been explored in past decades, ranging from basic data structure to query processing and indexing. But today, operational temporal GIS does not exist. The key impediments have been the complexity of integrating space and time and the lack of standards. OpenGIS standards for simple feature access (spatial type) do exist, but unlike the spatial type, standards for spatiotemporal data type do not exist. This paper explores a new approach to modeling space and time to provide the basis for implementing a temporal GIS. This approach is based on the concept of data types in databases. A data type provides constructors, accessors, and operators. Most commercial and open source databases provide data types to deal with the spatial component of a GIS, called spatial type. Oracle Spatial, DB2 Spatial Extender and Informix Spatial DataBlade, ST_Geometry for PostgreSQL and Oracle from Esri, PostGIS for PostgreSQL, etc., are some examples. This new spatiotemporal data type is called spatiotemporal type (STT). This STT is implemented in PostgreSQL, an open source relational database management system. The STT is an extension of Esri's ST_Geometry type for PostgreSQL, in which each spatial object has a life span. Constructors, accessors, and relational functions are provided to create STT and support spatial, spatiotemporal, and temporal queries. Some functions are extended based on OpenGIS standards for the spatial type. Examples are provided to demonstrate the application of these functions. The paper concludes with limitations and challenges of implementing STT.

  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. PMID:27209415

  3. 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

  4. Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma

    PubMed Central

    Chng, Wee J.; Schop, Roelandt F.; Price-Troska, Tammy; Ghobrial, Irene; Kay, Neil; Jelinek, Diane F.; Gertz, Morie A.; Dispenzieri, Angela; Lacy, Martha; Kyle, Robert A.; Greipp, Philip R.; Tschumper, Renee C.; Fonseca, Rafael; Bergsagel, Peter Leif

    2006-01-01

    Waldenström macroglobulinemia (WM) is a B-cell malignancy characterized by the ability of the B-cell clone to differentiate into plasma cells. Although the clinical syndrome and the pathologic characteristics are well defined, little is known about its biology and controversy still exists regarding its cell of origin. In this gene-expression study, we compared the transcription profiles of WM with those of other malignant B cells including (chronic lymphocytic leukemia [CLL] and multiple myeloma [MM]) as well as normal cells (peripheral-blood B cells and bone marrow plasma cells). We found that WM has a homogenous gene expression regardless of 6q deletion status and clusters with CLL and normal B cells on unsupervised clustering with very similar expression profiles. Only a small gene set has expression profiles unique to WM compared to CLL and MM. The most significantly up-regulated gene is IL6 and the most significantly associated pathway for this set of genes is MAPK signaling. Thus, IL6 and its downstream signaling may be of biologic importance in WM. Further elucidation of the role of IL-6 in WM is warranted as this may offer a potential therapeutic avenue. PMID:16804116

  5. 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.

  6. 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.

  7. Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.

    PubMed

    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

  8. 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.

  9. Genome-Wide Association Study Reveals Novel Quantitative Trait Loci Associated with Resistance to Multiple Leaf Spot Diseases of Spring Wheat

    PubMed Central

    Bonman, J. Michael; Xiong, Mai; Brown-Guedira, Gina; Adhikari, Tika B.

    2014-01-01

    Accelerated wheat development and deployment of high-yielding, climate resilient, and disease resistant cultivars can contribute to enhanced food security and sustainable intensification. To facilitate gene discovery, we assembled an association mapping panel of 528 spring wheat landraces of diverse geographic origin for a genome-wide association study (GWAS). All accessions were genotyped using an Illumina Infinium 9K wheat single nucleotide polymorphism (SNP) chip and 4781 polymorphic SNPs were used for analysis. To identify loci underlying resistance to the major leaf spot diseases and to better understand the genomic patterns, we quantified population structure, allelic diversity, and linkage disequilibrium. Our results showed 32 loci were significantly associated with resistance to the major leaf spot diseases. Further analysis identified QTL effective against major leaf spot diseases of wheat which appeared to be novel and others that were previously identified by association analysis using Diversity Arrays Technology (DArT) and bi-parental mapping. In addition, several identified SNPs co-localized with genes that have been implicated in plant disease resistance. Future work could aim to select the putative novel loci and pyramid them in locally adapted wheat cultivars to develop broad-spectrum resistance to multiple leaf spot diseases of wheat via marker-assisted selection (MAS). PMID:25268502

  10. Systematic Analysis of Fly Models with Multiple Drivers Reveals Different Effects of Ataxin-1 and Huntingtin in Neuron Subtype-Specific Expression

    PubMed Central

    Sone, Masaki; Okazawa, Hitoshi

    2014-01-01

    The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ) diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases. PMID:25551764

  11. Genome-wide association study reveals novel quantitative trait Loci associated with resistance to multiple leaf spot diseases of spring wheat.

    PubMed

    Gurung, Suraj; Mamidi, Sujan; Bonman, J Michael; Xiong, Mai; Brown-Guedira, Gina; Adhikari, Tika B

    2014-01-01

    Accelerated wheat development and deployment of high-yielding, climate resilient, and disease resistant cultivars can contribute to enhanced food security and sustainable intensification. To facilitate gene discovery, we assembled an association mapping panel of 528 spring wheat landraces of diverse geographic origin for a genome-wide association study (GWAS). All accessions were genotyped using an Illumina Infinium 9K wheat single nucleotide polymorphism (SNP) chip and 4781 polymorphic SNPs were used for analysis. To identify loci underlying resistance to the major leaf spot diseases and to better understand the genomic patterns, we quantified population structure, allelic diversity, and linkage disequilibrium. Our results showed 32 loci were significantly associated with resistance to the major leaf spot diseases. Further analysis identified QTL effective against major leaf spot diseases of wheat which appeared to be novel and others that were previously identified by association analysis using Diversity Arrays Technology (DArT) and bi-parental mapping. In addition, several identified SNPs co-localized with genes that have been implicated in plant disease resistance. Future work could aim to select the putative novel loci and pyramid them in locally adapted wheat cultivars to develop broad-spectrum resistance to multiple leaf spot diseases of wheat via marker-assisted selection (MAS). PMID:25268502

  12. DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome.

    PubMed

    Ollikainen, Miina; Smith, Katherine R; Joo, Eric Ji-Hoon; Ng, Hong Kiat; Andronikos, Roberta; Novakovic, Boris; Abdul Aziz, Nur Khairunnisa; Carlin, John B; Morley, Ruth; Saffery, Richard; Craig, Jeffrey M

    2010-11-01

    Mounting evidence from both animal and human studies suggests that the epigenome is in constant drift over the life course in response to stochastic and environmental factors. In humans, this has been highlighted by a small number of studies that have demonstrated discordant DNA methylation patterns in adolescent or adult monozygotic (MZ) twin pairs. However, to date, it remains unclear when such differences emerge, and how prevalent they are across different tissues. To address this, we examined the methylation of four differentially methylated regions associated with the IGF2/H19 locus in multiple birth tissues derived from 91 twin pairs: 56 MZ and 35 dizygotic (DZ). Tissues included cord blood-derived mononuclear cells and granulocytes, human umbilical vein endothelial cells, buccal epithelial cells and placental tissue. Considerable variation in DNA methylation was observed between tissues and between unrelated individuals. Most interestingly, methylation discordance was also present within twin pairs, with DZ pairs showing greater discordance than MZ pairs. These data highlight the variable contribution of both intrauterine environmental exposures and underlying genetic factors to the establishment of the neonatal epigenome of different tissues and confirm the intrauterine period as a sensitive time for the establishment of epigenetic variability in humans. This has implications for the effects of maternal environment on the development of the newborn epigenome and supports an epigenetic mechanism for the previously described phenomenon of 'fetal programming' of disease risk. PMID:20699328

  13. 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

  14. Transcription factor-pathway co-expression analysis reveals cooperation between SP1 and ESR1 on dysregulating cell cycle arrest in non-hyperdiploid multiple myeloma

    PubMed Central

    Wang, Xujun; Yan, Zhenyu; Fulciniti, Mariateresa; Li, Yingxiang; Gkotzamanidou, Maria; Amin, Samir B; Shah, Parantu K; Zhang, Yong

    2014-01-01

    Multiple myeloma is a hematological cancer of plasma B-cells and remains incurable. Two major subtypes of myeloma, hyperdiploid (HMM) and non-hyperdiploid myeloma (NHMM), have distinct chromosomal alterations and different survival outcomes. Transcription factors (TrFs) have been implicated in myeloma oncogenesis but their dysregulation in myeloma subtypes are less studied. Here we develop a TrF-pathway co-expression analysis to identify altered co-expression between two sample types. We apply the method to the two myeloma subtypes and the cell cycle arrest pathway, which is significantly differentially expressed between the two subtypes. We find that TrFs MYC, NF-κB and HOXA9 have significantly lower co-expression with cell cycle arrest in HMM, co-occurring with their over-activation in HMM. In contrast, TrFs ESR1, SP1 and E2F1 have significantly lower co-expression with cell cycle arrest in NHMM. SP1 ChIP targets are enriched by cell cycle arrest genes. These results motivate a cooperation model of ESR1 and SP1 in regulating cell cycle arrest, and a hypothesis that their over-activation in NHMM disrupts proper regulation of cell cycle arrest. Co-targeting ESR1 and SP1 shows a synergistic effect on inhibiting myeloma proliferation in NHMM cell lines. Therefore, studying TrF-pathway co-expression dysregulation in human cancers facilitates forming novel hypotheses towards clinical utility. PMID:23925045

  15. The glycan role in the glycopeptide immunogenicity revealed by atomistic simulations and spectroscopic experiments on the multiple sclerosis biomarker CSF114(Glc).

    PubMed

    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

  16. Spatio-Temporal Metabolite Profiling of the Barley Germination Process by MALDI MS Imaging.

    PubMed

    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

  17. 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

  18. Molecular characterization of a rice mutator-phenotype derived from an incompatible cross-pollination reveals transgenerational mobilization of multiple transposable elements and extensive epigenetic instability

    PubMed Central

    Wang, Hongyan; Chai, Yang; Chu, Xiucheng; Zhao, Yunyang; Wu, Ying; Zhao, Jihong; Ngezahayo, Frédéric; Xu, Chunming; Liu, Bao

    2009-01-01

    Background Inter-specific hybridization occurs frequently in plants, which may induce genetic and epigenetic instabilities in the resultant hybrids, allopolyploids and introgressants. It remains unclear however whether pollination by alien pollens of an incompatible species may impose a "biological stress" even in the absence of genome-merger or genetic introgression, whereby genetic and/or epigenetic instability of the maternal recipient genome might be provoked. Results We report here the identification of a rice mutator-phenotype from a set of rice plants derived from a crossing experiment involving two remote and apparently incompatible species, Oryza sativa L. and Oenothera biennis L. The mutator-phenotype (named Tong211-LP) showed distinct alteration in several traits, with the most striking being substantially enlarged panicles. Expectably, gel-blotting by total genomic DNA of the pollen-donor showed no evidence for introgression. Characterization of Tong211-LP (S0) and its selfed progenies (S1) ruled out contamination (via seed or pollen) or polyploidy as a cause for its dramatic phenotypic changes, but revealed transgenerational mobilization of several previously characterized transposable elements (TEs), including a MITE (mPing), and three LTR retrotransposons (Osr7, Osr23 and Tos17). AFLP and MSAP fingerprinting revealed extensive, transgenerational alterations in cytosine methylation and to a less extent also genetic variation in Tong211-LP and its immediate progenies. mPing mobility was found to correlate with cytosine methylation alteration detected by MSAP but not with genetic variation detected by AFLP. Assay by q-RT-PCR of the steady-state transcript abundance of a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, and small interference RNA (siRNA) pathway-related proteins showed that, relative to the rice parental line, heritable perturbation in expression of 12 out of the 13 genes occurred

  19. Conditional Knock-Out of Vesicular GABA Transporter Gene from Starburst Amacrine Cells Reveals the Contributions of Multiple Synaptic Mechanisms Underlying Direction Selectivity in the Retina

    PubMed Central

    Pei, Zhe; Chen, Qiang; Koren, David; Giammarinaro, Benno; Acaron Ledesma, Hector

    2015-01-01

    Direction selectivity of direction-selective ganglion cells (DSGCs) in the retina results from patterned excitatory and inhibitory inputs onto DSGCs during motion stimuli. The inhibitory inputs onto DSGCs are directionally tuned to the antipreferred (null) direction and therefore potently suppress spiking during motion in the null direction. However, whether direction-selective inhibition is indispensable for direction selectivity is unclear. Here, we selectively eliminated the directional tuning of inhibitory inputs onto DSGCs by disrupting GABA release from the presynaptic interneuron starburst amacrine cell in the mouse retina. We found that, even without directionally tuned inhibition, direction selectivity can still be implemented in a subset of On-Off DSGCs by direction-selective excitation and a temporal offset between excitation and isotropic inhibition. Our results therefore demonstrate the concerted action of multiple synaptic mechanisms for robust direction selectivity in the retina. SIGNIFICANCE STATEMENT The direction-selective circuit in the retina has been a classic model to study neural computations by the brain. An important but unresolved question is how direction selectivity is implemented by directionally tuned excitatory and inhibitory mechanisms. Here we specifically removed the direction tuning of inhibition from the circuit. We found that direction tuning of inhibition is important but not indispensable for direction selectivity of DSGCs' spiking activity, and that the residual direction selectivity is implemented by direction-selective excitation and temporal offset between excitation and inhibition. Our results highlight the concerted actions of synaptic excitation and inhibition required for robust direction selectivity in the retina and provide critical insights into how patterned excitation and inhibition collectively implement sensory processing. PMID:26400950

  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. 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

  2. Behavioural mapping of a pelagic seabird: combining multiple sensors and a hidden Markov model reveals the distribution of at-sea behaviour.

    PubMed

    Dean, Ben

    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

  3. 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

  4. Coexistence of multiple charge-density waves and superconductivity in SrPt2As2 revealed by 75As-NMR /NQR and 195Pt-NMR

    NASA Astrophysics Data System (ADS)

    Kawasaki, Shinji; Tani, Yoshihiko; Mabuchi, Tomosuke; Kudo, Kazutaka; Nishikubo, Yoshihiro; Mitsuoka, Daisuke; Nohara, Minoru; Zheng, Guo-qing

    2015-02-01

    The relationship between charge-density wave (CDW) orders and superconductivity in arsenide superconductor SrPt2As2 with Tc=5.2 K which crystallizes in the CaBe2Ge2 -type structure was studied by 75As nuclear magnetic resonance (NMR) measurements up to 520 K, and 75As nuclear quadrupole resonance (NQR) and 195Pt-NMR measurements down to 1.5 K. At high temperature, 75As-NMR spectrum and nuclear-spin-relaxation rate (1 /T1) have revealed two distinct CDW orders, one realized in the As-Pt-As layer below TCDWAs (1 )=410 K and the other in the Pt-As-Pt layer below TCDWAs (2 )=255 K . The 1 /T1 measured by 75As-NQR shows a clear Hebel-Slichter peak just below Tc and decreases exponentially well below Tc. Concomitantly, 195Pt Knight shift decreases below Tc. Our results indicate that superconductivity in SrPt2As2 is in the spin-singlet state with an s -wave gap and is robust under the two distinct CDW orders in different layers.

  5. 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

  6. Whole-genome bisulfite sequencing maps from multiple human tissues reveal novel CpG islands associated with tissue-specific regulation.

    PubMed

    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

  7. Stitching together the Multiple Dimensions of Autophagy Using Metabolomics and Transcriptomics Reveals Impacts on Metabolism, Development, and Plant Responses to the Environment in Arabidopsis[C][W

    PubMed Central

    Masclaux-Daubresse, Céline; Clément, Gilles; Anne, Pauline; Routaboul, Jean-Marc; Guiboileau, Anne; Soulay, Fabienne; Shirasu, Ken; Yoshimoto, Kohki

    2014-01-01

    Autophagy is a fundamental process in the plant life story, playing a key role in immunity, senescence, nutrient recycling, and adaptation to the environment. Transcriptomics and metabolomics of the rosette leaves of Arabidopsis thaliana autophagy mutants (atg) show that autophagy is essential for cell homeostasis and stress responses and that several metabolic pathways are affected. Depletion of hexoses, quercetins, and anthocyanins parallel the overaccumulation of several amino acids and related compounds, such as glutamate, methionine, glutathione, pipecolate, and 2-aminoadipate. Transcriptomic data show that the pathways for glutathione, methionine, raffinose, galacturonate, and anthocyanin are perturbed. Anthocyanin depletion in atg mutants, which was previously reported as a possible defect in flavonoid trafficking to the vacuole, appears due to the downregulation of the master genes encoding the enzymes and regulatory proteins involved in flavonoid biosynthesis. Overexpression of the PRODUCTION OF ANTHOCYANIN PIGMENT1 transcription factor restores anthocyanin accumulation in vacuoles of atg mutants. Transcriptome analyses reveal connections between autophagy and (1) salicylic acid biosynthesis and response, (2) cytokinin perception, (3) oxidative stress and plant defense, and possible interactions between autophagy and the COP9 signalosome machinery. The metabolic and transcriptomic signatures identified for the autophagy mutants are discussed and show consistencies with the observed phenotypes. PMID:24808053

  8. Proteomics Analysis of the Non-Muscle Myosin Heavy Chain IIa-Enriched Actin-Myosin Complex Reveals Multiple Functions within the Podocyte

    PubMed Central

    Hays, Thomas; Ma’ayan, Avi; Clark, Neil R.; Tan, Christopher M.; Teixeira, Avelino; Teixeira, Angela; Choi, Jae W.; Burdis, Nora; Jung, Sung Yun; Bajaj, Amol O.; O’Malley, Bert W.; He, John C.; Hyink, Deborah P.; Klotman, Paul E.

    2014-01-01

    MYH9 encodes non-muscle myosin heavy chain IIA (NMMHCIIA), the predominant force-generating ATPase in non-muscle cells. Several lines of evidence implicate a role for MYH9 in podocytopathies. However, NMMHCIIA‘s function in podocytes remains unknown. To better understand this function, we performed immuno-precipitation followed by mass-spectrometry proteomics to identify proteins interacting with the NMMHCIIA-enriched actin-myosin complexes. Computational analyses revealed that these proteins belong to functional networks including regulators of cytoskeletal organization, metabolism and networks regulated by the HIV-1 gene nef. We further characterized the subcellular localization of NMMHCIIA within podocytes in vivo, and found it to be present within the podocyte major foot processes. Finally, we tested the effect of loss of MYH9 expression in podocytes in vitro, and found that it was necessary for cytoskeletal organization. Our results provide the first survey of NMMHCIIA-enriched actin-myosin-interacting proteins within the podocyte, demonstrating the important role of NMMHCIIA in organizing the elaborate cytoskeleton structure of podocytes. Our characterization of NMMHCIIA’s functions goes beyond the podocyte, providing important insights into its general molecular role. PMID:24949636

  9. A spatio-temporal filter approach to synchronous brain activities.

    PubMed

    Nakagawa, T; Ohashi, A

    1980-01-01

    This paper presents a mathematical mechanism for neuronal synchronization in oscillatory brain activities on the basis of the layer structures with recurrent inhibition. To begin with, a linear theory reveals that the recurrent inhibition tends to cause a synchronous uniform oscillation if the loop delay increases, and that an oscillating neuron recruits neighboring neurons by delivering synchronous inputs through the recurrent inhibition loop if the frequency is that of the selfexcitatory oscillation. Then, a quasilinearized dual wave model (DWM), employing the two-sinusoids plus bias input describing functions (TSBDF), shows the competitive relationship between the synchronous oscillation and a spatial wave that is introduced to represent normal brain activity patterns. Results of computer simulations conform well to the predictions of the DWM. Thus, synchronous brain activities are suggested to be the result of the spatio-temporal filter characteristics of the brain layer structures, modified by the neural nonlinearity. PMID:7353063

  10. Pattern dynamics and spatiotemporal chaos in the quantum Zakharov equations.

    PubMed

    Misra, A P; Shukla, P K

    2009-05-01

    The dynamical behavior of the nonlinear interaction of quantum Langmuir waves (QLWs) and quantum ion-acoustic waves (QIAWs) is studied in the one-dimensional quantum Zakharov equations. Numerical simulations of coupled QLWs and QIAWs reveal that many coherent solitary patterns can be excited and saturated via the modulational instability of unstable harmonic modes excited by a modulation wave number of monoenergetic QLWs. The evolution of such solitary patterns may undergo the states of spatially partial coherence (SPC), coexistence of temporal chaos and spatiotemporal chaos (STC), as well as STC. The SPC state is essentially due to ion-acoustic wave emission and due to quantum diffraction, while the STC is caused by the combined effects of SPC and quantum diffraction, as well as by collisions and fusions among patterns in stochastic motion. The energy in the system is strongly redistributed, which may switch on the onset of weak turbulence in dense quantum plasmas. PMID:19518570

  11. Spatiotemporal control and superselectivity in supramolecular polymers using multivalency

    PubMed Central

    Albertazzi, Lorenzo; Martinez-Veracoechea, Francisco J.; Leenders, Christianus M. A.; Voets, Ilja K.; Frenkel, Daan; Meijer, E. W.

    2013-01-01

    Multivalency has an important but poorly understood role in molecular self-organization. We present the noncovalent synthesis of a multicomponent supramolecular polymer in which chemically distinct monomers spontaneously coassemble into a dynamic, functional structure. We show that a multivalent recruiter is able to bind selectively to one subset of monomers (receptors) and trigger their clustering along the self-assembled polymer, behavior that mimics raft formation in cell membranes. This phenomenon is reversible and affords spatiotemporal control over the monomer distribution inside the supramolecular polymer by superselective binding of single-strand DNA to positively charged receptors. Our findings reveal the pivotal role of multivalency in enabling structural order and nonlinear recognition in water-soluble supramolecular polymers, and it offers a design principle for functional, structurally defined supramolecular architectures. PMID:23836666

  12. Pattern dynamics and spatiotemporal chaos in the quantum Zakharov equations

    SciTech Connect

    Misra, A. P.; Shukla, P. K.

    2009-05-15

    The dynamical behavior of the nonlinear interaction of quantum Langmuir waves (QLWs) and quantum ion-acoustic waves (QIAWs) is studied in the one-dimensional quantum Zakharov equations. Numerical simulations of coupled QLWs and QIAWs reveal that many coherent solitary patterns can be excited and saturated via the modulational instability of unstable harmonic modes excited by a modulation wave number of monoenergetic QLWs. The evolution of such solitary patterns may undergo the states of spatially partial coherence (SPC), coexistence of temporal chaos and spatiotemporal chaos (STC), as well as STC. The SPC state is essentially due to ion-acoustic wave emission and due to quantum diffraction, while the STC is caused by the combined effects of SPC and quantum diffraction, as well as by collisions and fusions among patterns in stochastic motion. The energy in the system is strongly redistributed, which may switch on the onset of weak turbulence in dense quantum plasmas.

  13. Actomyosin contractility spatiotemporally regulates actin network dynamics in migrating cells.

    PubMed

    Okeyo, Kennedy Omondi; Adachi, Taiji; Sunaga, Junko; Hojo, Masaki

    2009-11-13

    Coupling interactions among mechanical and biochemical factors are important for the realization of various cellular processes that determine cell migration. Although F-actin network dynamics has been the focus of many studies, it is not yet clear how mechanical forces generated by actomyosin contractility spatiotemporally regulate this fundamental aspect of cell migration. In this study, using a combination of fluorescent speckle microscopy and particle imaging velocimetry techniques, we perturbed the actomyosin system and examined quantitatively the consequence of actomyosin contractility on F-actin network flow and deformation in the lamellipodia of actively migrating fish keratocytes. F-actin flow fields were characterized by retrograde flow at the front and anterograde flow at the back of the lamellipodia, and the two flows merged to form a convergence zone of reduced flow intensity. Interestingly, activating or inhibiting actomyosin contractility altered network flow intensity and convergence, suggesting that network dynamics is directly regulated by actomyosin contractility. Moreover, quantitative analysis of F-actin network deformation revealed that the deformation was significantly negative and predominant in the direction of cell migration. Furthermore, perturbation experiments revealed that the deformation was a function of actomyosin contractility. Based on these results, we suggest that the actin cytoskeletal structure is a mechanically self-regulating system, and we propose an elaborate pathway for the spatiotemporal self-regulation of the actin cytoskeletal structure during cell migration. In the proposed pathway, mechanical forces generated by actomyosin interactions are considered central to the realization of the various mechanochemical processes that determine cell motility. PMID:19665125

  14. 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

  15. 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. PMID:24102001

  16. 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. PMID:26077835

  17. 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

  18. 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

  19. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.

    PubMed

    Beauchemin, Kyle J; Wells, Julie M; Kho, Alvin T; Philip, Vivek M; Kamir, Daniela; Kohane, Isaac S; Graber, Joel H; Bult, Carol J

    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

  20. An Induced Pluripotent Stem Cell Model of Hypoplastic Left Heart Syndrome (HLHS) Reveals Multiple Expression and Functional Differences in HLHS-Derived Cardiac Myocytes

    PubMed Central

    Jiang, Yan; Habibollah, Saba; Tilgner, Katarzyna; Collin, Joseph; Barta, Tomas; Al-Aama, Jumana Yousuf; Tesarov, Lenka; Hussain, Rafiqul; Trafford, Andrew W.; Kirkwood, Graham; Sernagor, Evelyne; Eleftheriou, Cyril G.; Przyborski, Stefan; Stojković, Miodrag; Lako, Majlinda; Keavney, Bernard

    2014-01-01

    Hypoplastic left heart syndrome (HLHS) is a serious congenital cardiovascular malformation resulting in hypoplasia or atresia of the left ventricle, ascending aorta, and aortic and mitral valves. Diminished flow through the left side of the heart is clearly a key contributor to the condition, but any myocardial susceptibility component is as yet undefined. Using recent advances in the field of induced pluripotent stem cells (iPSCs), we have been able to generate an iPSC model of HLHS malformation and characterize the properties of cardiac myocytes (CMs) differentiated from these and control-iPSC lines. Differentiation of HLHS-iPSCs to cardiac lineages revealed changes in the expression of key cardiac markers and a lower ability to give rise to beating clusters when compared with control-iPSCs and human embryonic stem cells (hESCs). HLHS-iPSC-derived CMs show a lower level of myofibrillar organization, persistence of a fetal gene expression pattern, and changes in commitment to ventricular versus atrial lineages, and they display different calcium transient patterns and electrophysiological responses to caffeine and β-adrenergic antagonists when compared with hESC- and control-iPSC-derived CMs, suggesting that alternative mechanisms to release calcium from intracellular stores such as the inositol trisphosphate receptor may exist in HLHS in addition to the ryanodine receptor thought to function in control-iPSC-derived CMs. Together our findings demonstrate that CMs derived from an HLHS patient demonstrate a number of marker expression and functional differences to hESC/control iPSC-derived CMs, thus providing some evidence that cardiomyocyte-specific factors may influence the risk of HLHS. PMID:24591732

  1. An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS) reveals multiple expression and functional differences in HLHS-derived cardiac myocytes.

    PubMed

    Jiang, Yan; Habibollah, Saba; Tilgner, Katarzyna; Collin, Joseph; Barta, Tomas; Al-Aama, Jumana Yousuf; Tesarov, Lenka; Hussain, Rafiqul; Trafford, Andrew W; Kirkwood, Graham; Sernagor, Evelyne; Eleftheriou, Cyril G; Przyborski, Stefan; Stojković, Miodrag; Lako, Majlinda; Keavney, Bernard; Armstrong, Lyle

    2014-04-01

    Hypoplastic left heart syndrome (HLHS) is a serious congenital cardiovascular malformation resulting in hypoplasia or atresia of the left ventricle, ascending aorta, and aortic and mitral valves. Diminished flow through the left side of the heart is clearly a key contributor to the condition, but any myocardial susceptibility component is as yet undefined. Using recent advances in the field of induced pluripotent stem cells (iPSCs), we have been able to generate an iPSC model of HLHS malformation and characterize the properties of cardiac myocytes (CMs) differentiated from these and control-iPSC lines. Differentiation of HLHS-iPSCs to cardiac lineages revealed changes in the expression of key cardiac markers and a lower ability to give rise to beating clusters when compared with control-iPSCs and human embryonic stem cells (hESCs). HLHS-iPSC-derived CMs show a lower level of myofibrillar organization, persistence of a fetal gene expression pattern, and changes in commitment to ventricular versus atrial lineages, and they display different calcium transient patterns and electrophysiological responses to caffeine and β-adrenergic antagonists when compared with hESC- and control-iPSC-derived CMs, suggesting that alternative mechanisms to release calcium from intracellular stores such as the inositol trisphosphate receptor may exist in HLHS in addition to the ryanodine receptor thought to function in control-iPSC-derived CMs. Together our findings demonstrate that CMs derived from an HLHS patient demonstrate a number of marker expression and functional differences to hESC/control iPSC-derived CMs, thus providing some evidence that cardiomyocyte-specific factors may influence the risk of HLHS. PMID:24591732

  2. Impact of time-delayed feedback on spatiotemporal dynamics in the Lugiato-Lefever model

    NASA Astrophysics Data System (ADS)

    Panajotov, K.; Puzyrev, D.; Vladimirov, A. G.; Gurevich, S. V.; Tlidi, M.

    2016-04-01

    We analyze the impact of delayed optical feedback (OF) on the spatiotemporal dynamics of the Lugiato-Lefever model. First, we carry out linear stability analysis and reveal the role of the OF strength and phase on the shape of the bistable curve as well as on Turing, Andronov-Hopf, and traveling-wave instability regions. Further, we demonstrate how the OF impacts the spatial dynamics by shifting the regions with different spatial eigenvalue spectra. In addition, we reveal a clustering behavior of cavity solitons as a function of the OF strength at fixed OF phase. Depending on the feedback parameters, OF can also induce a drift bifurcation of a stationary cavity soliton, as well as an Andronov-Hopf bifurcation of a drifting soliton. We present an analytical expression for the threshold of the drift bifurcation and show that above a certain value of the OF strength the system enters a region of spatiotemporal chaos.

  3. 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

  4. Predicted sub-populations in a marine shrimp proteome as revealed by combined EST and cDNA data from multiple Penaeus species

    PubMed Central

    2010-01-01

    Background Many species of marine shrimp in the Family Penaeidae, viz. Penaeus (Litopenaeus) vannamei, Penaeus monodon, Penaeus (Fenneropenaeus) chinensis, and Penaeus (Marsupenaeus) japonicus, are animals of economic importance in the aquaculture industry. Yet information about their DNA and protein sequences is lacking. In order to predict their collective proteome, we combined over 270,000 available EST and cDNA sequences from the 4 shrimp species with all protein sequences of Drosophila melanogaster and Caenorhabditis elegans. EST data from 4 other crustaceans, the crab Carcinus maenas, the lobster Homarus americanus (Decapoda), the water flea Daphnia pulex, and the brine shrimp Artemia franciscana were also used. Findings Similarity searches from EST collections of the 4 shrimp species matched 64% of the protein sequences of the fruit fly, but only 45% of nematode proteins, indicating that the shrimp proteome content is more similar to that of an insect than a nematode. Combined results with 4 additional non-shrimp crustaceans increased matching to 78% of fruit fly and 56% of nematode proteins, suggesting that present shrimp EST collections still lack sequences for many conserved crustacean proteins. Analysis of matching data revealed the presence of 4 EST groups from shrimp, namely sequences for proteins that are both fruit fly-like and nematode-like, fruit fly-like only, nematode-like only, and non-matching. Gene ontology profiles of proteins for the 3 matching EST groups were analyzed. For non-matching ESTs, a small fraction matched protein sequences from other species in the UniProt database, including other crustacean-specific proteins. Conclusions Shrimp ESTs indicated that the shrimp proteome is comprised of sub-populations of proteins similar to those common to both insect and nematode models, those present specifically in either model, or neither. Combining small EST collections from related species to compensate for their small size allowed

  5. 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.

  6. Comprehensive High-Throughput RNA Sequencing Analysis Reveals Contamination of Multiple Nasopharyngeal Carcinoma Cell Lines with HeLa Cell Genomes

    PubMed Central

    Strong, Michael J.; Baddoo, Melody; Nanbo, Asuka; Xu, Miao; Puetter, Adriane

    2014-01-01

    ABSTRACT In an attempt to explore infectious agents associated with nasopharyngeal carcinomas (NPCs), we employed our high-throughput RNA sequencing (RNA-seq) analysis pipeline, RNA CoMPASS, to investigate the presence of ectopic organisms within a number of NPC cell lines commonly used by NPC and Epstein-Barr virus (EBV) researchers. Sequencing data sets from both CNE1 and HONE1 were found to contain reads for human papillomavirus 18 (HPV-18). Subsequent real-time reverse transcription-PCR (RT-PCR) analysis on a panel of NPC cell lines identified HPV-18 in CNE1 and HONE1 as well as three additional NPC cell lines (CNE2, AdAH, and NPC-KT). Further analysis of the chromosomal integration arrangement of HPV-18 in NPCs revealed patterns identical to those observed in HeLa cells. Clustering based on human single nucleotide variation (SNV) analysis of two separate HeLa cell lines and several NPC cell lines demonstrated two distinct clusters with CNE1, as well as HONE1 clustering with the two HeLa cell lines. In addition, duplex-PCR-based genotyping showed that CNE1, CNE2, and HONE1 do not have a HeLa cell-specific L1 retrotransposon insertion, suggesting that these three HPV-18+ NPC lines are likely products of a somatic hybridization with HeLa cells, which is also consistent with our RNA-seq-based gene level SNV analysis. Taking all of these findings together, we conclude that a widespread HeLa contamination may exist in many NPC cell lines, and authentication of these cell lines is recommended. Finally, we provide a proof of concept for the utility of an RNA-seq-based approach for cell authentication. IMPORTANCE Nasopharyngeal carcinoma (NPC) cell lines are important model systems for analyzing the complex life cycle and pathogenesis of Epstein-Barr virus (EBV). Using an RNA-seq-based approach, we found HeLa cell contamination in several NPC cell lines that are commonly used in the EBV and related fields. Our data support the notion that contamination resulted from

  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. PMID:20828864

  8. 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.

  9. Spatiotemporal dynamics of continuum neural fields

    NASA Astrophysics Data System (ADS)

    Bressloff, Paul C.

    2012-01-01

    We survey recent analytical approaches to studying the spatiotemporal dynamics of continuum neural fields. Neural fields model the large-scale dynamics of spatially structured biological neural networks in terms of nonlinear integrodifferential equations whose associated integral kernels represent the spatial distribution of neuronal synaptic connections. They provide an important example of spatially extended excitable systems with nonlocal interactions and exhibit a wide range of spatially coherent dynamics including traveling waves oscillations and Turing-like patterns.

  10. 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

  11. Spatiotemporal patterns and predictability of cyberattacks.

    PubMed

    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

  12. Spatiotemporal Floral Scent Variation of Penstemon digitalis.

    PubMed

    Burdon, Rosalie C F; Raguso, Robert A; Kessler, André; Parachnowitsch, Amy L

    2015-07-01

    Variability in floral volatile emissions can occur temporally through floral development, during diel cycles, as well as spatially within a flower. These spatiotemporal patterns are hypothesized to provide additional information to floral visitors, but they are rarely measured, and their attendant hypotheses are even more rarely tested. In Penstemon digitalis, a plant whose floral scent has been shown to be under strong phenotypic selection for seed fitness, we investigated spatiotemporal variation in floral scent by using dynamic headspace collection, respectively solid-phase microextraction, and analyzed the volatile samples by combined gas chromatography-mass spectrometry. Total volatile emission was greatest during flowering and peak pollinator activity hours, suggesting its importance in mediating ecological interactions. We also detected tissue and reward-specific compounds, consistent with the hypothesis that complexity in floral scent composition reflects several ecological functions. In particular, we found tissue-specific scents for the stigma, stamens, and staminode (a modified sterile stamen common to all Penstemons). Our findings emphasize the dynamic nature of floral scents and highlight a need for greater understanding of ecological and physiological mechanisms driving spatiotemporal patterns in scent production. PMID:26133675

  13. Spatiotemporal coupling in dispersive nonlinear planar waveguides

    NASA Astrophysics Data System (ADS)

    Ryan, Andrew T.; Agrawal, Govind P.

    1995-12-01

    The multidimensional nonlinear Schrodinger equation governs the spatial and temporal evolution of an optical field inside a nonlinear dispersive medium. Although spatial (diffractive) and temporal (dispersive) effects can be studied independently in a linear medium, they become mutually coupled in a nonlinear medium. We present the results of numerical simulations showing this spatiotemporal coupling for ultrashort pulses propagating in dispersive Kerr media. We investigate how spatiotemporal coupling affects the behavior of the optical field in each of the four regimes defined by the type of group-velocity dispersion (normal or anomalous) and the type of nonlinearity (focusing or defocusing). We show that dispersion, through spatiotemporal coupling, can either enhance or suppress self-focusing and self-defocusing. Similarly, we demonstrate that diffraction can either enhance or suppress pulse compression or broadening. We also discuss how these effects can be controlled with optical phase modulation, such as that provided by a lens (spatial phase modulation) or frequency chirping (temporal phase modulation). Copyright (c) 1995 Optical Society of America

  14. Knee muscle strength in multiple sclerosis: relationship with gait characteristics

    PubMed Central

    Güner, Senem; Hagharı, Sema; Inanıcı, Fatma; Alsancak, Serap; Aytekın, Gokhan

    2015-01-01

    [Purpose] To investigate the relationship between isokinetic knee muscle strength and kinematic, kinetic and spatiotemporal gait parameters of patients with multiple sclerosis (MS). [Subjects and Methods] Twenty-nine MS patients (mean age 31.5±6.5) were investigated in this study. The isokinetic knee muscle strength and gait parameters of MS patients with moderate and severe disability, as determined by the expanded disability status scale (EDSS): EDSS=1–4.5 (n=22, moderate disability) and EDSS>4.5 (n=7, severe disability) were measured. [Results] Isokinetic knee muscle strength, kinematic, kinetic and spatiotemporal gait parameters differed between moderate (EDSS=1–4.5, n=22) and severe disability (EDSS>4.5, n=7). The correlation between each of gait speed, stride length, total range of knee joint movement and the four strength parameters (minimum and maximum quadriceps and hamstring muscle strengths) were significant for the MS group as a whole. Within subgroups, the correlation between minimum hamstring strength and total range of knee movement was significant only in group EDSS>4.5; minimum hamstring correlated with peak knee extensor moment in group EDSS=1–4.5, but at a reduced level of significance. [Conclusion] The present study revealed significant correlations between gait characteristics and isokinetic strength parameters of the quadriceps and hamstring muscles. Our study suggests that rehabilitation protocols for MS patients should include a critical strength training programme particularly for the hamstring and quadriceps muscles. PMID:25931736

  15. 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.

  16. Spatiotemporal Coding of Individual Chemicals by the Gustatory System

    PubMed Central

    Reiter, Sam; Campillo Rodriguez, Chelsey; Sun, Kui

    2015-01-01

    Four of the five major sensory systems (vision, olfaction, somatosensation, and audition) are thought to use different but partially overlapping sets of neurons to form unique representations of vast numbers of stimuli. The only exception is gustation, which is thought to represent only small numbers of basic taste categories. However, using new methods for delivering tastant chemicals and making electrophysiological recordings from the tractable gustatory system of the moth Manduca sexta, we found chemical-specific information is as follows: (1) initially encoded in the population of gustatory receptor neurons as broadly distributed spatiotemporal patterns of activity; (2) dramatically integrated and temporally transformed as it propagates to monosynaptically connected second-order neurons; and (3) observed in tastant-specific behavior. Our results are consistent with an emerging view of the gustatory system: rather than constructing basic taste categories, it uses a spatiotemporal population code to generate unique neural representations of individual tastant chemicals. SIGNIFICANCE STATEMENT Our results provide a new view of taste processing. Using a new, relatively simple model system and a new set of techniques to deliver taste stimuli and to examine gustatory receptor neurons and their immediate followers, we found no evidence for labeled line connectivity, or basic taste categories such as sweet, salty, bitter, and sour. Rather, individual tastant chemicals are represented as patterns of spiking activity distributed across populations of receptor neurons. These representations are transformed substantially as multiple types of receptor neurons converge upon follower neurons, leading to a combinatorial coding format that uniquely, rapidly, and efficiently represents individual taste chemicals. Finally, we found that the information content of these neurons can drive tastant-specific behavior. PMID:26338341

  17. 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. PMID:16411131

  18. 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.

  19. Changes in spatiotemporal patterns of hydrological response after partial deforestation

    NASA Astrophysics Data System (ADS)

    Wiekenkamp, Inge; Huisman, Johan Alexander; Reemt Bogena, Heye; Lin, Henry; Drüe, Clemens; Vereecken, Harry

    2016-04-01

    Predicting the effects of land use change on hydrology can be extremely challenging. It requires looking beyond the current structure and functioning of hydrological systems to predict how the system is influenced in a changed setting. Although the hydrological effects of land use change have been studied extensively, only few high resolution datasets are available to accurately describe, model and predict detailed changes in spatiotemporal patterns of hydrological fluxes and states due to land use change. The TERENO test site Wüstebach provides a unique monitoring setup to measure the major components of the water balance (evapotranspiration, discharge, precipitation) and the spatiotemporal distribution of soil moisture before and after a partial deforestation. Here, we present 5 years of measured hydrological data, including soil moisture and water budget component data 3 years before and 2 years after the partial deforestation. A data-driven investigation was used to understand changes and related feedback mechanisms in spatiotemporal hydrological response patterns. The effects of deforestation on soil moisture and evapotranspiration were analyzed by comparing states and fluxes for the control and the deforested area. The effects on discharge characteristics were analyzed using discharge metrics, including baseflow separation, peakflow rates and time to peak. Changes in preferential flow occurrence were identified using a sensor response time analysis of soil moisture measurements before and after the deforestation where preferential flow was identified as a non-sequential sequence of sensor response times within the soil. As expected from earlier studies, the partial deforestation caused a decrease in evapotranspiration and an increase in discharge. A closer look at the high resolution datasets however reveals new insights in the intra-annual variability of the water balance components. The overall decrease in evapotranspiration caused a large increase in soil

  20. 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

  1. Spatiotemporal three-dimensional phase unwrapping in digital speckle pattern interferometry.

    PubMed

    Wu, Sijin; Zhu, Lianqing; Pan, Siyang; Yang, Lianxiang

    2016-03-01

    We propose a hybrid spatiotemporal three-dimensional phase unwrapping algorithm for use in digital speckle pattern interferometry (DSPI). The feature of the proposed algorithm is the integration of one-dimensional temporal and two-dimensional spatial phase unwrapping algorithms. By demodulating the phase on a single reference point or multiple reference points using temporal phase unwrapping and on each separated phase map region using spatial phase unwrapping, the DSPI with the spatiotemporal three-dimensional phase unwrapping algorithm can realize the measurement of dynamic absolute displacements and the determination of abrupt phase changes which are usually caused by object discontinuities. We demonstrate that the presented algorithm can overcome the drawbacks of the traditional spatial and temporal phase unwrapping algorithms. PMID:26974113

  2. 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

  3. Mining spatiotemporal co-occurrence patterns in solar datasets

    NASA Astrophysics Data System (ADS)

    Aydin, B.; Kempton, D.; Akkineni, V.; Angryk, R.; Pillai, K. G.

    2015-11-01

    We address the problem of mining spatiotemporal co-occurrence patterns (STCOPs) in solar datasets with extended polygon-based geometric representations. Specifically designed spatiotemporal indexing techniques are used in the mining of STCOPs. These include versions of two well-known spatiotemporal trajectory indexing techniques: the scalable and efficient trajectory index and Chebyshev polynomial indexing. We present a framework, STCOP-MINER, implementing a filter-and-refine STCOP mining algorithm, with the indexing techniques mentioned for efficiently performing data analysis.

  4. Super-resolved parallel MRI by spatiotemporal encoding.

    PubMed

    Schmidt, Rita; Baishya, Bikash; Ben-Eliezer, Noam; Seginer, Amir; Frydman, Lucio

    2014-01-01

    Recent studies described an "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 ultrafast MRI 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. This approach enables one to reduce both the excitation and acquisition times of sub-second SPEN acquisitions by the customary acceleration factor R, without compromises in either the method's spatial resolution, SAR deposition, or capability to operate in multi-slice mode. The performance of these new single-shot imaging sequences and their ancillary algorithms were explored and corroborated on phantoms and human volunteers at 3 T. 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

  5. Size-dependent diffusion promotes the emergence of spatiotemporal patterns

    NASA Astrophysics Data System (ADS)

    Zhang, Lai; Thygesen, Uffe Høgsbro; Banerjee, Malay

    2014-07-01

    Spatiotemporal patterns, indicating the spatiotemporal variability of individual abundance, are a pronounced scenario in ecological interactions. Most of the existing models for spatiotemporal patterns treat species as homogeneous groups of individuals with average characteristics by ignoring intraspecific physiological variations at the individual level. Here we explore the impacts of size variation within species resulting from individual ontogeny, on the emergence of spatiotemporal patterns in a fully size-structured population model. We found that size dependency of animal's diffusivity greatly promotes the formation of spatiotemporal patterns, by creating regular spatiotemporal patterns out of temporal chaos. We also found that size-dependent diffusion can substitute large-amplitude base harmonics with spatiotemporal patterns with lower amplitude oscillations but with enriched harmonics. Finally, we found that the single-generation cycle is more likely to drive spatiotemporal patterns compared to predator-prey cycles, meaning that the mechanism of Hopf bifurcation might be more common than hitherto appreciated since the former cycle is more widespread than the latter in case of interacting populations. Due to the ubiquity of individual ontogeny in natural ecosystems we conclude that diffusion variability within populations is a significant driving force for the emergence of spatiotemporal patterns. Our results offer a perspective on self-organized phenomena, and pave a way to understand such phenomena in systems organized as complex ecological networks.

  6. SPATIO-TEMPORAL COMPLEXITY OF THE AORTIC SINUS VORTEX

    PubMed Central

    Moore, Brandon; Dasi, Lakshmi Prasad

    2014-01-01

    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. PMID:25067881

  7. 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.

  8. 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

  9. Spatiotemporal neural integration for bistable perception in a response-time structure-from-motion task.

    PubMed

    Wang, Zhisong; Logothetis, Nikos K; Liang, Hualou

    2009-12-01

    The question of how perception arises from neuronal activity in the visual cortex is of fundamental importance to many issues in cognitive neuroscience. To address this question, we adopt a unique experimental paradigm in which bistable stimuli, namely structure from motion (SFM), are employed to dissociate the visual input from perception while monitoring cortical neural activity. In this paper, we analyze the dynamic responses of the multiunit activity, simultaneously collected from multiple channels in the middle temporal visual cortex of awake behaving macaque monkeys, for decoding the bistable percepts of SFM in a response-time (RT) perceptual discrimination task. Our goal is to understand how the perceptual discriminative information of neuronal population activity evolves and accumulates over time to mediate behaviors. Here, we used a discriminative classifier called the logistic regression and contrasted it with two generative classifiers, namely the quadratic discriminant analysis (QDA) and linear discriminant analysis (LDA), to achieve the spatiotemporal integration of neural activity and dynamically decode the perceptual reports on a single-trial basis. We found that the logistic regression outperforms both QDA and LDA in terms of decoding accuracy for both single-channel and multichannel decoding of bistable percepts. Subsequent analysis of the temporal profile of neural population decoding in relation to RT revealed that the amplitude and latency of the decoding accuracy are highly correlated with the RT, thus indicating that the monkeys respond faster when the decoding accuracy is higher and has shorter latency. These findings suggest that enhanced neuronal discrimination ability and shortened neuronal discrimination latency may impact monkeys' behaviors. PMID:19635689

  10. Genomic and proteomic analyses reveal multiple homologs of genes encoding enzymes of the methanol:coenzyme M methyltransferase system that are differentially expressed in methanol- and acetate-grown Methanosarcina thermophila.

    PubMed

    Ding, Yan-Huai R; Zhang, Shi-Ping; Tomb, Jean-Francois; Ferry, James G

    2002-09-24

    Each of the genomic sequences of Methanosarcina acetivorans, Methanosarcina mazei, and Methanosarcina thermophila revealed two homologs of mtaA, three homologs of mtaB, and three homologs of mtaC encoding enzymes specific for methanogenesis from methanol. Two-dimensional gel electrophoretic analyses of polypeptides from M. thermophila established that methanol induces the expression of mtaA-1, mtaB-1, mtaB-2, mtaB-3, mtaC-1, mtaC-2, and mtaC-3 whereas mtaB-3 and mtaC-3 are constitutively expressed in acetate-grown cells. The gene product of one of three mttC homologs, encoding trimethylamine-specific methyltransferase I, was detected in methanol- but not acetate-grown M. thermophila. A postulated role for the multiple homologs is discussed. PMID:12393212

  11. 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

  12. Multiple Antiferromagnetic Spin Fluctuations and Novel Evolution of Tc in Iron-Based Superconductors LaFe(As1‑xPx)(O1‑yFy) Revealed by 31P-NMR Studies

    NASA Astrophysics Data System (ADS)

    Shiota, Takayoshi; Mukuda, Hidekazu; Uekubo, Masahiro; Engetsu, Fuko; Yashima, Mitsuharu; Kitaoka, Yoshio; Lai, Kwing To; Usui, Hidetomo; Kuroki, Kazuhiko; Miyasaka, Shigeki; Tajima, Setsuko

    2016-05-01

    We report on 31P-NMR studies of LaFe(As1‑xPx)(O1‑yFy) over wide compositions for 0 ≤ x ≤ 1 and 0 ≤ y ≤ 0.14, which provide clear evidence that antiferromagnetic spin fluctuations (AFMSFs) are one of the indispensable elements for enhancing Tc. Systematic 31P-NMR measurements revealed two types of AFMSFs in the temperature evolution, that is, one is the AFMSFs that develop rapidly down to Tc with low-energy characteristics, and the other, with relatively higher energy than the former, develops gradually upon cooling from high temperature. The low-energy AFMSFs in low y (electron doping) over a wide x (pnictoge