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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.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-04-04

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

  5. 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…

  6. 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…

  7. 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.

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

    PubMed Central

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

    2008-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  10. 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

  11. Spatiotemporal structure of REM sleep twitching reveals developmental origins of motor synergies

    PubMed Central

    Blumberg, Mark S.; Coleman, Cassandra M.; Gerth, Ashlynn I.; McMurray, Bob

    2013-01-01

    Summary Background During active (or REM) sleep, infant rats and other mammals exhibit myoclonic twitches of skeletal muscles throughout the body, resulting in jerky, discrete movements of the distal limbs. Hundreds of thousands of limb twitches are produced each day and sensory feedback from these movements is a substantial driver of infant brain activity, suggesting that these movements contribute to motor learning and sensorimotor integration. However, it is not known whether the production of twitches is random or spatiotemporally structured, or whether the patterning of twitching changes with age. Such information is critical if we are to understand how twitches contribute to development. Results We used high-speed videography and 3-D motion tracking to assess the spatiotemporal structure of twitching at forelimb joints in 2- and 8-day-old rats. At both ages, twitches exhibited highly structured spatiotemporal properties at multiple timescales, including synergistic and multi-joint movements within and across forelimbs. Hierarchical cluster analysis and latent class analysis revealed developmental changes in the quantity and patterning of twitching. Critically, we found evidence for a selectionist process whereby movement patterns at the early age compete for retention and expression over development. Conclusions These findings indicate that twitches are not produced randomly, but rather are highly structured at multiple timescales. This structure has important implications for our understanding of the brain and spinal mechanisms that produce twitching and the role that sensory feedback from twitching plays in the development of sensorimotor systems. We suggest that twitches represent a heretofore overlooked form of motor exploration that helps animals probe the biomechanics of their limbs, build motor synergies, and lay a foundation for complex, automatic, and goal-directed wake movements. PMID:24139739

  12. 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.

  13. Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions.

    PubMed

    Wood, Kathleen H; Johnson, Brian S; Welsh, Sarah A; Lee, Jun Y; Cui, Yue; Krizman, Elizabeth; Brodkin, Edward S; Blendy, Julie A; Robinson, Michael B; Bartolomei, Marisa S; Zhou, Zhaolan

    2016-04-01

    DNA methylation is recognized by methyl-CpG-binding domain (MBD) proteins. Multiple MBDs are linked to neurodevelopmental disorders in humans and mice. However, the functions of MBD2 are poorly understood. We characterized Mbd2 knockout mice and determined spatiotemporal expression of MBDs and MBD2-NuRD (nucleosome remodeling deacetylase) interactions. We analyzed behavioral phenotypes, generated biotin-tagged MBD1 and MBD2 knockin mice, and performed biochemical studies of MBD2-NuRD. Most behavioral measures are minimally affected in Mbd2 knockout mice. In contrast to other MBDs, MBD2 shows distinct expression patterns. Unlike most MBDs, MBD2 is ubiquitously expressed in all tissues examined and appears dispensable for brain functions measured in this study. We provide novel genetic tools and reveal new directions to investigate MBD2 functions in vivo.

  14. Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions

    PubMed Central

    Wood, Kathleen H; Johnson, Brian S; Welsh, Sarah A; Lee, Jun Y; Cui, Yue; Krizman, Elizabeth; Brodkin, Edward S; Blendy, Julie A; Robinson, Michael B; Bartolomei, Marisa S; Zhou, Zhaolan

    2016-01-01

    Aim: DNA methylation is recognized by methyl-CpG-binding domain (MBD) proteins. Multiple MBDs are linked to neurodevelopmental disorders in humans and mice. However, the functions of MBD2 are poorly understood. We characterized Mbd2 knockout mice and determined spatiotemporal expression of MBDs and MBD2–NuRD (nucleosome remodeling deacetylase) interactions. Experimental procedures: We analyzed behavioral phenotypes, generated biotin-tagged MBD1 and MBD2 knockin mice, and performed biochemical studies of MBD2–NuRD. Results: Most behavioral measures are minimally affected in Mbd2 knockout mice. In contrast to other MBDs, MBD2 shows distinct expression patterns. Conclusion: Unlike most MBDs, MBD2 is ubiquitously expressed in all tissues examined and appears dispensable for brain functions measured in this study. We provide novel genetic tools and reveal new directions to investigate MBD2 functions in vivo. PMID:27066839

  15. Single Turnover at Molecular Polymerization Catalysts Reveals Spatiotemporally Resolved Reactions.

    PubMed

    Easter, Quinn T; Blum, Suzanne A

    2017-09-11

    Multiple active individual molecular ruthenium catalysts have been pinpointed within growing polynorbornene, thereby revealing information on the reaction dynamics and location that is unavailable through traditional ensemble experiments. This is the first single-turnover imaging of a molecular catalyst by fluorescence microscopy and allows detection of individual monomer reactions at an industrially important molecular ruthenium ring-opening metathesis polymerization (ROMP) catalyst under synthetically relevant conditions (e.g. unmodified industrial catalyst, ambient pressure, condensed phase, ca. 0.03 m monomer). These results further establish the key fundamentals of this imaging technique for characterizing the reactivity and location of active molecular catalysts even when they are the minor components. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Tracking by location and features: object correspondence across spatiotemporal discontinuities during multiple object tracking.

    PubMed

    Papenmeier, Frank; Meyerhoff, Hauke S; Jahn, Georg; Huff, Markus

    2014-02-01

    We examined whether surface feature information is utilized to track the locations of multiple objects. In particular, we tested whether surface features and spatiotemporal information are weighted according to their availability and reliability. Accordingly, we hypothesized that surface features should affect location tracking across spatiotemporal discontinuities. Three kinds of spatiotemporal discontinuities were implemented across five experiments: abrupt scene rotations, abrupt zooms, and a reduced presentation frame rate. Objects were briefly colored across the spatiotemporal discontinuity. Distinct coloring that matched spatiotemporal information across the discontinuity improved tracking performance as compared with homogeneous coloring. Swapping distinct colors across the discontinuity impaired performance. Correspondence by color was further demonstrated by more mis-selected distractors appearing in a former target color than distractors appearing in a former distractor color in the swap condition. This was true even when color never supported tracking and when participants were instructed to ignore color. Furthermore, effects of object color on tracking occurred with unreliable spatiotemporal information but not with reliable spatiotemporal information. Our results demonstrate that surface feature information can be utilized to track the locations of multiple objects. This is in contrast to theories stating that objects are tracked based on spatiotemporal information only. We introduce a flexible-weighting tracking account stating that spatiotemporal information and surface features are both utilized by the location tracking mechanism. The two sources of information are weighted according to their availability and reliability. Surface feature effects on tracking are particularly likely when distinct surface feature information is available and spatiotemporal information is unreliable. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  17. [Pneumococcal septic arthritis revealing a multiple myeloma].

    PubMed

    Renou, F; Gerber, A; Moiton, M-P; Ferrandiz, D; Yvin, J-L

    2007-03-01

    The most common presenting features of multiple myeloma are bone pain, anemia, renal failure or hypercalcemia. Bacterial infection as the initial presentation of this desease is rare. We report the case of a 62-year-old man with pneumococcal septic arthritis of the knee revealing a multiple myeloma. Pneumococcal infection should lead to a suspicion of underlying illness and especially the multiple myeloma.

  18. 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

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

    PubMed

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

    2015-08-01

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

  20. 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

  1. Integrity Verification for Multiple Data Copies in Cloud Storage Based on Spatiotemporal Chaos

    NASA Astrophysics Data System (ADS)

    Long, Min; Li, You; Peng, Fei

    Aiming to strike for a balance between the security, efficiency and availability of the data verification in cloud storage, a novel integrity verification scheme based on spatiotemporal chaos is proposed for multiple data copies. Spatiotemporal chaos is implemented for node calculation of the binary tree, and the location of the data in the cloud is verified. Meanwhile, dynamic operation can be made to the data. Furthermore, blind information is used to prevent a third-party auditor (TPA) leakage of the users’ data privacy in a public auditing process. Performance analysis and discussion indicate that it is secure and efficient, and it supports dynamic operation and the integrity verification of multiple copies of data. It has a great potential to be implemented in cloud storage services.

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

    PubMed

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

    2015-08-01

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

  3. Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

    PubMed

    Riès, Stephanie K; Dhillon, Rummit K; Clarke, Alex; King-Stephens, David; Laxer, Kenneth D; Weber, Peter B; Kuperman, Rachel A; Auguste, Kurtis I; Brunner, Peter; Schalk, Gerwin; Lin, Jack J; Parvizi, Josef; Crone, Nathan E; Dronkers, Nina F; Knight, Robert T

    2017-06-06

    Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

  4. 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

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

    PubMed Central

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

    2016-01-01

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

  6. 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.

  7. Spatio-temporal characterization of the multiple current pulse regime of diffuse barrier discharges in helium with nitrogen admixtures

    NASA Astrophysics Data System (ADS)

    Bogaczyk, Marc; Tschiersch, Robert; Nemschokmichal, Sebastian; Meichsner, Jürgen

    2017-10-01

    This work reports on the spatio-temporal characterization of the multiple current pulse regime of diffuse barrier discharges driven by sine-wave feeding voltage at a frequency of 2~kHz in helium with small nitrogen admixtures. The discharge gap of 3~mm is bounded by glass plates on both plane electrodes. Priority is given to the lateral discharge inhomogeneities, underlying volume- and surface-memory effects, and the breakdown mechanism. Therefore, relevant processes in the discharge volume and on the dielectric surfaces were investigated by ICCD camera imaging and optical emission spectroscopy in combination with electrical measurements and surface charge diagnostics using the electro-optic Pockels effect of a bismuth silicon oxide crystal. The number of current pulses per half-cycle of the sine-wave voltage rises with increasing nitrogen admixture to helium due to the predominant role of the Penning ionization. Here, the transition from the first glow-like breakdown to the last Townsend-like breakdown is favored by residual species from the former breakdowns which enhance the secondary electron emission during the pre-phase of the later breakdowns. Moreover, the surface charge measurements reveal that the consecutive breakdowns occur alternately at central and peripheral regions on the electrode surface. These spatial inhomogeneities are conserved by the surface charge memory effect as pointed out by the recalculated spatio-temporal development of the gap voltage.

  8. 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.

  9. 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.

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

    PubMed

    Meyer, Martin; Baumann, Simon; Jancke, Lutz

    2006-10-01

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

  11. Spatiotemporal receptive fields of barrel cortex revealed by reverse correlation of synaptic input.

    PubMed

    Ramirez, Alejandro; Pnevmatikakis, Eftychios A; Merel, Josh; Paninski, Liam; Miller, Kenneth D; Bruno, Randy M

    2014-06-01

    Of all of the sensory areas, barrel cortex is among the best understood in terms of circuitry, yet least understood in terms of sensory function. We combined intracellular recording in rats with a multi-directional, multi-whisker stimulator system to estimate receptive fields by reverse correlation of stimuli to synaptic inputs. Spatiotemporal receptive fields were identified orders of magnitude faster than by conventional spike-based approaches, even for neurons with little spiking activity. Given a suitable stimulus representation, a linear model captured the stimulus-response relationship for all neurons with high accuracy. In contrast with conventional single-whisker stimuli, complex stimuli revealed markedly sharpened receptive fields, largely as a result of adaptation. This phenomenon allowed the surround to facilitate rather than to suppress responses to the principal whisker. Optimized stimuli enhanced firing in layers 4-6, but not in layers 2/3, which remained sparsely active. Surround facilitation through adaptation may be required for discriminating complex shapes and textures during natural sensing.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

    2016-06-10

    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.

  18. 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.

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

    PubMed Central

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

    2016-01-01

    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

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

    NASA Astrophysics Data System (ADS)

    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), 10.1103/PhysRevLett.112.174103]. 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.

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

    SciTech Connect

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

    2013-04-25

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

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

    PubMed

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

    2017-03-15

    Complex human cognition, such as decision-making under ambiguity, is reflected in dynamic spatio-temporal activity in the brain. Here, we combined event-related potentials with computational modelling of the time course of decision-making and outcome evaluation during the Iowa Gambling Task. Measures of choice probability generated using the Prospect Valence Learning Delta (PVL-Delta) model, in addition to objective trial outcomes (outcome magnitude and valence), were applied as regressors in a general linear model of the EEG signal. The resulting three-dimensional spatio-temporal characterization of task-related neural dynamics demonstrated that outcome valence, outcome magnitude, and PVL-Delta choice probability were expressed in distinctly separate event related potentials. Our findings showed that the P3 component was associated with an experience-based measure of outcome expectancy. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Revealing the Sub-Barrier Phase using a Spatiotemporal Interferometer with Orthogonal Two-Color Laser Fields of Comparable Intensity

    NASA Astrophysics Data System (ADS)

    Han, Meng; Ge, Peipei; Shao, Yun; Liu, Ming-Ming; Deng, Yongkai; Wu, Chengyin; Gong, Qihuang; Liu, Yunquan

    2017-08-01

    We measure photoelectron momentum distributions of Ar atoms in orthogonally polarized two-color laser fields with comparable intensities. The synthesized laser field is used to manipulate the oscillating tunneling barrier and the subsequent motion of electrons onto two spatial dimensions. The subcycle structures associated with the temporal double-slit interference are spatially separated and enhanced. We use such a spatiotemporal interferometer to reveal sub-barrier phase of strong-field tunneling ionization. This study shows that the tunneling process transfers the initial phase onto momentum distribution. Our work has the implication that the sub-barrier phase plays an indispensable role in photoelectron interference processes.

  4. 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.

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

    DOE PAGES

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

    2014-08-08

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

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

    SciTech Connect

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

    2014-08-08

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  8. 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

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

    PubMed

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

    2014-10-15

    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. © 2014 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  10. 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. © 2016 John Wiley & Sons Ltd.

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

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

    PubMed

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

    2010-12-15

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

  13. 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

  14. Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects

    PubMed Central

    Takemoto, Kiwamu; Nagai, Takeharu; Miyawaki, Atsushi; Miura, Masayuki

    2003-01-01

    Indicator molecules for caspase-3 activation have been reported that use fluorescence resonance energy transfer (FRET) between an enhanced cyan fluorescent protein (the donor) and enhanced yellow fluorescent protein (EYFP; the acceptor). Because EYFP is highly sensitive to proton (H+) and chloride ion (Cl−) levels, which can change during apoptosis, this indicator's ability to trace the precise dynamics of caspase activation is limited, especially in vivo. Here, we generated an H+- and Cl−-insensitive indicator for caspase activation, SCAT, in which EYFP was replaced with Venus, and monitored the spatio-temporal activation of caspases in living cells. Caspase-3 activation was initiated first in the cytosol and then in the nucleus, and rapidly reached maximum activation in 10 min or less. Furthermore, the nuclear activation of caspase-3 preceded the nuclear apoptotic morphological changes. In contrast, the completion of caspase-9 activation took much longer and its activation was attenuated in the nucleus. However, the time between the initiation of caspase-9 activation and the morphological changes was quite similar to that seen for caspase-3, indicating the activation of both caspases occurred essentially simultaneously during the initiation of apoptosis. PMID:12527749

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

    PubMed

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

    2014-01-01

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

  16. Spatiotemporal Variation in Avian Migration Phenology: Citizen Science Reveals Effects of Climate Change

    PubMed Central

    Hurlbert, Allen H.; Liang, Zhongfei

    2012-01-01

    A growing number of studies have documented shifts in avian migratory phenology in response to climate change, and yet there is a large amount of unexplained variation in the magnitude of those responses across species and geographic regions. We use a database of citizen science bird observations to explore spatiotemporal variation in mean arrival dates across an unprecedented geographic extent for 18 common species in North America over the past decade, relating arrival dates to mean minimum spring temperature. Across all species and geographic locations, species shifted arrival dates 0.8 days earlier for every °C of warming of spring temperature, but it was common for some species in some locations to shift as much as 3–6 days earlier per °C. Species that advanced arrival dates the earliest in response to warming were those that migrate more slowly, short distance migrants, and species with broader climatic niches. These three variables explained 63% of the interspecific variation in phenological response. We also identify a latitudinal gradient in the average strength of phenological response, with species shifting arrival earlier at southern latitudes than northern latitudes for the same degree of warming. This observation is consistent with the idea that species must be more phenologically sensitive in less seasonal environments to maintain the same degree of precision in phenological timing. PMID:22384050

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

    PubMed

    Hurlbert, Allen H; Liang, Zhongfei

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

  19. 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…

  20. 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…

  1. Neurog1 Genetic Inducible Fate Mapping (GIFM) Reveals the Existence of Complex Spatiotemporal Cyto-Architectures in the Developing Cerebellum.

    PubMed

    Obana, Edwin A; Lundell, Travis G; Yi, Kevin J; Radomski, Kryslaine L; Zhou, Qiong; Doughty, Martin L

    2015-06-01

    Neurog1 is a pro-neural basic helix-loop-helix (bHLH) transcription factor expressed in progenitor cells located in the ventricular zone and subsequently the presumptive white matter tracts of the developing mouse cerebellum. We used genetic inducible fate mapping (GIFM) with a transgenic Neurog1-CreER allele to characterize the contributions of Neurog1 lineages to cerebellar circuit formation in mice. GIFM reveals Neurog1-expressing progenitors are fate-mapped to become Purkinje cells and all GABAergic interneuron cell types of the cerebellar cortex but not glia. The spatiotemporal sequence of GIFM is unique to each neuronal cell type. GIFM on embryonic days (E) 10.5 to E12.5 labels Purkinje cells with different medial-lateral settling patterns depending on the day of tamoxifen delivery. GIFM on E11.5 to P7 labels interneurons and the timing of tamoxifen administration correlates with the final inside-to-outside resting position of GABAergic interneurons in the cerebellar cortex. Proliferative status and long-term BrdU retention of GIFM lineages reveals Purkinje cells express Neurog1 around the time they become post-mitotic. In contrast, GIFM labels mitotic and post-mitotic interneurons. Neurog1-CreER GIFM reveals a correlation between the timing of Neurog1 expression and the spatial organization of GABAergic neurons in the cerebellar cortex with possible implications for cerebellar circuit assembly.

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

    PubMed Central

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

    2012-01-01

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

  3. Spatiotemporal characteristics and pharmacological modulation of multiple gamma oscillations in the CA1 region of the hippocampus

    PubMed Central

    Balakrishnan, Shilpashree; Pearce, Robert A.

    2015-01-01

    Multiple components of “γ-oscillations” between 30–170 Hz in the CA1 region of the hippocampus have been described, based on their coherence with oscillations in other brain regions and on their cross-frequency coupling with local θ-oscillations. However, it remains unclear whether the different sub-bands are generated by a single broadband oscillator coupled to multiple external inputs, or by separate oscillators that incorporate distinct circuit elements. To distinguish between these possibilities, we used high-density linear array recording electrodes in awake behaving mice to examine the spatiotemporal characteristics of γ-oscillations and their responses to midazolam and atropine. We characterized oscillations using current source density (CSD) analysis, and measured θ-γ phase-amplitude coupling by cross frequency coupling (CFC) analysis. Prominent peaks were present in the CSD signal in the mid- and distal apical dendritic layers at all frequencies, and at stratum pyramidale for γslow (30–45 Hz) and γmid (50–90 Hz), but not γfast (90–170 Hz) oscillations. Differences in the strength and timing of θ-γslow and θ-γmid cross frequency coupling, and a lack of coupling at the soma and mid-apical region for γfast oscillations, indicated that separate circuit components generate the three sub-bands. Midazolam altered CSD amplitudes and cross-frequency coupling in a lamina- and frequency specific manner, providing further evidence for separate generator circuits. Atropine altered CSD amplitudes and θ-γ CFC uniformly at all locations. Simulations using a detailed compartmental model were consistent with γslow and γmid oscillations driven primarily by inputs at the mid-apical dendrites, and γfast at the distal apical dendrite. Our results indicate that multiple distinct local circuits generate γ-oscillations in the CA1 region of the hippocampus, and provide detailed information about their spatiotemporal characteristics. PMID:25628540

  4. 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.

  5. 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

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

    PubMed Central

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

    2015-01-01

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

  7. 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.

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

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. Hippo signaling pathway reveals a spatio-temporal correlation with the size of primordial follicle pool in mice.

    PubMed

    Xiang, Cheng; Li, Jia; Hu, Liaoliao; Huang, Jian; Luo, Tao; Zhong, Zhisheng; Zheng, Yuehui; Zheng, Liping

    2015-01-01

    The Hippo signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms and regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Hippo signaling are expressed in mammalian ovaries, but the exact functions of this pathway in primordial follicle development remains unclear. To analyze the spatio-temporal correlation between the core component of Hippo pathway and the size of primordial follicle pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of mice primordial follicle in vitro. Both the protein and mRNA expression of the MST1 and LATS2 were decreased significantly as mouse age increased (p < 0.05), however, the mRNA expression of them increased significantly in 16 m compared with 5 m as well as the protein expression of LATS2.The expression of YAP showed the opposite trend, and the significant protein expression of pYAP was increased before 1 m, after which no significant change was observed. Moreover, the ratio of pYAP/YAP decreased significantly. Culturing ovaries for 8 d in vitro resulted in the activation of primordial follicles in 3 d postnatal mice ovaries, and these developed into primary follicles with the expression of PCNA increasing significantly (p < 0.05). The mRNA and protein expression of MST and LATS decreased significantly (p < 0.05), and the expression of YAP increased significantly (p < 0.05, p < 0.01), whereas the ratio of pYAP/YAP decreased significantly (p < 0.05). The above results reveal that the expression of the core components of Hippo pathway changed during mouse follicular development, especially before and after primordial follicle activation in vitro. The primordial follicle activation may be related to the significant decrease of the ratio of pYAP1/YAP1. In conclusion

  11. 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.

  12. Multimodal imaging of repetition priming: Using fMRI, MEG, and intracranial EEG to reveal spatiotemporal profiles of word processing

    PubMed Central

    McDonald, Carrie R.; Thesen, Thomas; Carlson, Chad; Blumberg, Mark; Girard, Holly M.; Trongnetrpunya, Amy; Sherfey, Jason S.; Devinsky, Orrin; Kuzniecky, Rubin; Dolye, Werner K.; Cash, Sydney S.; Leonard, Matt K.; Hagler, Donald J.; Dale, Anders M.; Halgren, Eric

    2010-01-01

    Repetition priming is a core feature of memory processing whose anatomical correlates remain poorly understood. In this study, we use advanced multimodal imaging (functional magnetic resonance imaging (fMRI) and magnetoencephalography; MEG) to investigate the spatiotemporal profile of repetition priming. We use intracranial electroencephalography (iEEG) to validate our fMRI/MEG measurements. Twelve controls completed a semantic judgment task with fMRI and MEG that included words presented once (new, ‘N’) and words that repeated (old, ‘O’). Six patients with epilepsy completed the same task during iEEG recordings. Blood-oxygen level dependent (BOLD) responses for N vs O words were examined across the cortical surface and within regions of interest. MEG waveforms for N vs O words were estimated using a noise-normalized minimum norm solution, and used to interpret the timecourse of fMRI. Spatial concordance was observed between fMRI and MEG repetition effects from 350–450ms within bilateral occipitotemporal and medial temporal, left prefrontal, and left posterior temporal cortex. Additionally, MEG revealed widespread sources within left temporoparietal regions, whereas fMRI revealed bilateral reductions in occipitotemporal and left superior frontal, and increases in inferior parietal, precuneus, and dorsolateral prefrontal activity. BOLD suppression in left posterior temporal, left inferior prefrontal, and right occipitotemporal cortex correlated with MEG repetition-related reductions. IEEG responses from all three regions supported the timecourse of MEG and localization of fMRI. Furthermore, iEEG decreases to repeated words were associated with decreased gamma power in several regions, providing evidence that gamma oscillations are tightly coupled to cognitive phenomena and reflect regional activations seen in the BOLD signal. PMID:20620212

  13. 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.

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

    PubMed

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

    2011-03-01

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

  15. 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

  16. 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

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

    PubMed

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

    2015-10-01

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

  18. Spatiotemporal evolution of Calophaca (Fabaceae) reveals multiple dispersals in the Central Asian mountains and adjacent regions

    Treesearch

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

    2015-01-01

    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...

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

    PubMed

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

    2016-08-08

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

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

    PubMed

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

    2015-12-14

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

  1. 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

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

    NASA Astrophysics Data System (ADS)

    Crouch, Robert; Oskay, Caglar; Clay, Stephen

    2013-01-01

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

  3. 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.

  4. Spatiotemporal assessment and trade-offs of multiple ecosystem services based on land use changes in Zengcheng, China.

    PubMed

    Sun, Xiao; Li, Feng

    2017-12-31

    Driven by rapid urbanization, land use change has become a significant factor influencing ecosystem services (ESs). To support the decision-making process of city planners and policy makers, assessing the spatiotemporal changes associated with multiple ESs is vital. In this study, we developed a general structure to assess the changes of multiple ESs in Zengcheng, China. A new index also was developed to measure the comprehensive ecosystem service (CES). Trade-offs of various ESs were analyzed by using correlation analysis. We then designed four alternate scenarios to explore the optimal land use strategies to increase the CES value and minimize trade-offs among various ESs. Results demonstrated that rapid expansion of built-up land and traffic land resulted in a decrease of CES in Zengcheng from 2003 to 2013. Although the water supply, water purification, and vegetable and fruit production services increased, the climate regulation, soil conservation, biodiversity protection, recreation opportunity and grain production services decreased during the ten-year period. Government should implement land use policies and ecological engineering measures to improve soil conservation in the northern region; recreation opportunity in the central region; and carbon storage, water purification, biodiversity protection and recreation opportunity in the southern region. Among all alternative scenarios, woodland buffer and soil conservation scenarios exhibit the highest CES values, indicating that policies such as the "Ecological corridor construction" project and the "Grain for Green" project should be implemented. However, a caveat is that these policies improve the ESs at the expense of food production due to significant trade-off relationships. To minimize the trade-offs, a more sustainable intensification of agriculture should be adopted to increase food production without decreasing other ESs or occupying additional land. The land use strategies and ecological engineering

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

    PubMed

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

    2008-08-01

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

  6. The spatiotemporal expression of multiple coho salmon ovarian connexin genes and their hormonal regulation in vitro during oogenesis

    PubMed Central

    2011-01-01

    Background Throughout oogenesis, cell-cell communication via gap junctions (GJs) between oocytes and surrounding follicle cells (theca and granulosa cells), and/or amongst follicle cells is required for successful follicular development. To gain a fundamental understanding of ovarian GJs in teleosts, gene transcripts encoding GJ proteins, connexins (cx), were identified in the coho salmon, Oncorhynchus kisutch, ovary. The spatiotemporal expression of four ovarian cx transcripts was assessed, as well as their potential regulation by follicle-stimulating hormone (FSH), luteinizing hormone (LH) and insulin-like growth factor 1 (IGF1). Methods Salmonid ovarian transcriptomes were mined for cx genes. Four gene transcripts designated cx30.9, cx34.3, cx43.2, and cx44.9 were identified. Changes in gene expression across major stages of oogenesis were determined with real-time, quantitative RT-PCR (qPCR) and cx transcripts were localized to specific ovary cell-types by in situ hybridization. Further, salmon ovarian follicles were cultured with various concentrations of FSH, LH and IGF1 and effects of each hormone on cx gene expression were determined by qPCR. Results Transcripts for cx30.9 and cx44.9 were highly expressed at the perinucleolus (PN)-stage and decreased thereafter. In contrast, transcripts for cx34.3 and cx43.2 were low at the PN-stage and increased during later stages of oogenesis, peaking at the mid vitellogenic (VIT)-stage and maturing (MAT)-stage, respectively. In situ hybridization revealed that transcripts for cx34.3 were only detected in granulosa cells, but other cx transcripts were detected in both oocytes and follicle cells. Transcripts for cx30.9 and cx44.9 were down-regulated by FSH and IGF1 at the lipid droplet (LD)-stage, whereas transcripts for cx34.3 were up-regulated by FSH and IGF1 at the LD-stage, and LH and IGF1 at the late VIT-stage. Transcripts for cx43.2 were down-regulated by IGF1 at the late VIT-stage and showed no response to

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2016-07-01

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

  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. [Multiple facial nodules revealing disseminated cryptococcosis in an immunocompetent patient].

    PubMed

    Rachadi, H; Senouci, K; Lyagoubi, M; Benzekri, A; Mansouri, S; Ramli, I; Ismaili, N; Hassam, B; Benzekri, L

    2016-04-01

    Cryptococcosis is a potentially severe infection that usually occurs in a setting of immunosuppression. Its occurrence outside of this context is rare. We report a case of disseminated cryptococcosis revealed by a spectacular skin disease in an immunocompetent patient. A 40-year-old male patient had been presenting multiple nodules and tumors on his face for one month in a context of asthenia and intermittent fever. Histological examination of a skin biopsy revealed encapsulated yeasts strongly suggestive of Cryptococcus neoformans. Mycological examination of the skin biopsy and cerebrospinal fluid isolated Cryptococcus gattii. The blood cultures were positive. Brain MRI demonstrated cryptococcal parenchymal involvement. Screening for primary or secondary immunodeficiency was negative. The patient received amphotericin B 1mg/kg/day and fluconazole 600mg/day but died 2months after diagnosis. Cryptococcosis is a potentially severe infection caused by C. neoformans. This rare condition occurs most commonly in patients with profound deficiency in terms of cellular immunity. Although rare, the occurrence of cryptococcosis in immunocompetent patients is possible, and in this event the signs are highly polymorphic, which usually makes it very difficult to diagnose. The diagnosis of cryptococcosis is based on the identification by direct examination and after staining with India ink of encapsulated yeasts of the Cryptococcus genus. Culture on Sabouraud medium is essential for identification of the species. Treatment for disseminated cryptococcosis involves amphotericin B, often associated with flucytosine IV. In the event of meningitis infection in non-HIV patients, mortality continues to be around 15%, despite adequate medical treatment. Although rare, cryptococcosis can occur in immunocompetent subjects. The prognosis is severe even after treatment. Copyright © 2016. Published by Elsevier Masson SAS.

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

    PubMed

    Kourtzi, Zoe; Huberle, Elisabeth

    2005-11-01

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

  12. Information Mining of Spatio-Temporal Evolution of Lakes Based on Multiple Dynamic Measurements

    NASA Astrophysics Data System (ADS)

    Feng, W.; Chen, J.

    2017-09-01

    Lakes are important water resources and integral parts of the natural ecosystem, and it is of great significance to study the evolution of lakes. The area of each lake increased and decreased at the same time in natural condition, only but the net change of lakes' area is the result of the bidirectional evolution of lakes. In this paper, considering the effects of net fragmentation, net attenuation, swap change and spatial invariant part in lake evolution, a comprehensive evaluation indexes of lake dynamic evolution were defined,. Such degree contains three levels of measurement: 1) the swap dynamic degree (SDD) reflects the space activity of lakes in the study period. 2) the attenuation dynamic degree (ADD) reflects the net attenuation of lakes into non-lake areas. 3) the fragmentation dynamic degree (FDD) reflects the trend of lakes to be divided and broken into smaller lakes. Three levels of dynamic measurement constitute the three-dimensional "Swap - attenuation - fragmentation" dynamic evolution measurement system of lakes. To show its effectiveness, the dynamic measurement was applied to lakes in Jianghan Plain, the middle Yangtze region of China for a more detailed analysis of lakes from 1984 to 2014. In combination with spatial-temporal location characteristics of lakes, the hidden information in lake evolution in the past 30 years can be revealed.

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

    PubMed

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

    2000-04-01

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

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

    PubMed

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

    2001-09-01

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

  15. The range of the mange: Spatiotemporal patterns of sarcoptic mange in red foxes (Vulpes vulpes) as revealed by camera trapping.

    PubMed

    Carricondo-Sanchez, David; Odden, Morten; Linnell, John D C; Odden, John

    2017-01-01

    Sarcoptic mange is a widely distributed disease that affects numerous mammalian species. We used camera traps to investigate the apparent prevalence and spatiotemporal dynamics of sarcoptic mange in a red fox population in southeastern Norway. We monitored red foxes for five years using 305 camera traps distributed across an 18000 km2 area. A total of 6581 fox events were examined to visually identify mange compatible lesions. We investigated factors associated with the occurrence of mange by using logistic models within a Bayesian framework, whereas the spatiotemporal dynamics of the disease were analysed with space-time scan statistics. The apparent prevalence of the disease fluctuated over the study period with a mean of 3.15% and credible interval [1.25, 6.37], and our best logistic model explaining the presence of red foxes with mange-compatible lesions included time since the beginning of the study and the interaction between distance to settlement and season as explanatory variables. The scan analyses detected several potential clusters of the disease that varied in persistence and size, and the locations in the cluster with the highest probability were closer to human settlements than the other survey locations. Our results indicate that red foxes in an advanced stage of the disease are most likely found closer to human settlements during periods of low wild prey availability (winter). We discuss different potential causes. Furthermore, the disease appears to follow a pattern of small localized outbreaks rather than sporadic isolated events.

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

    PubMed

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

    2014-03-06

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

  17. 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…

  18. 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…

  19. 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…

  20. [Secondary cutaneous plasmacytoma revealing multiple myeloma: about a case].

    PubMed

    Ngolet, Lydie Ocini; N'soundhat, Norbert Lamini; Ndounga, Eliane; Kocko, Innocent; Kidédé, Daphtone Chabel Nkouala; Ntsiba, Honoré

    2016-01-01

    Secondary metastatic cutaneous plasmacytoma is a multiple extramedullary plasma cell proliferation involving skin. Its diagnosis is based on the identification of malignant plasma cells proliferation in the bone marrow and in the skin. Its occurrence is associated with advanced myeloma and a poor prognosis.

  1. 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…

  2. Thaumarchaeal amoA and nirK Gene Abundance Patterns Reveal Spatiotemporal Dynamics of Ammonia-oxidizing Archaeal Populations in Monterey Bay, CA

    NASA Astrophysics Data System (ADS)

    Tolar, B. B.; Reji, L.; Smith, J. M.; Chavez, F.; Francis, C.

    2016-12-01

    Thaumarchaeaota are among the most abundant microorganisms on the planet, and are significant players in the global nitrogen cycle. All cultivated members of the phylum are capable of performing the first and rate-limiting step of nitrification - the aerobic oxidation of ammonia to nitrite. In marine environments, ammonia-oxidizing archaea (AOA) have been found to greatly outnumber their bacterial counterparts. However, much about their ecology remains largely unknown. Monterey Bay, a non-estuarine embayment on the central California coast, is an ideal site for studying the dynamics of natural thaumarchaeal assemblages, given the highly dynamic nature of the Bay waters with seasonal upwelling episodes and the associated steep gradients in environmental variables. In the present study, we examined thaumarchaeal population dynamics in the upper Monterey Bay water column (0-500 m) using multiple molecular markers. Following high-resolution spatiotemporal sampling (i.e., up to 10 depths sampled monthly over a period of 2 years) at two stations in the Bay, we quantified thaumarchaeal functional genes - the ammonia monooxygenase (amoA) gene and its `shallow' and `deep' marine ecotypes, and variants of the marine nitrite reductase (nirK) gene. The abundances of both genes were regressed against environmental variables to gain insights into factors shaping their spatiotemporal dynamics in the Bay. Gene abundances at both stations varied with depth and season, with winter months generally having several orders of magnitude greater abundances. Statistical analyses point to differential controls on the gene abundances, with depth and temperature potentially being the major environmental determinants of thaumarchaeal population size. Our results also highlight the importance of employing multiple marker genes to gain a more highly resolved picture of thaumarchaeal population dynamics in complex environmental systems such as the coastal ocean.

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

    PubMed

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

    2015-03-24

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

  4. Genesis of tropical cyclone Nargis revealed by multiple satellite observations

    NASA Astrophysics Data System (ADS)

    Kikuchi, Kazuyoshi; Wang, Bin; Fudeyasu, Hironori

    2009-03-01

    Tropical cyclone (TC) Nargis recently battered Myanmar on May 2 2008 is one of the most deadly tropical storms in history. Nargis was initiated by an abnormally strong intraseasonal westerly event associated with Madden-Julian oscillation (MJO) in the eastern Indian Ocean. An incipient cyclonic disturbance emerged as an emanation of Rossby wave-induced vortex when the intraseasonal convective anomaly reached the Maritime Continent. The northeastward movement of MJO convection facilitated further development of the disturbance. The incipient disturbance became a tropical disturbance (TD) with a central warm-core structure on April 26. The further development from the TD to TC formation on April 28 is characterized by two distinctive stages: a radial contraction followed by a rapid intensification. The processes responsible for contraction and rapid intensification are discussed by diagnosis of multiple satellite data. This proposed new scenario is instrumental for understanding how a major TC develops in the northern Indian Ocean.

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

    PubMed

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

    2012-07-15

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

  6. 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.

  7. 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.

  8. 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

  9. A unified spatiotemporal modeling approach for predicting concentrations of multiple air pollutants in the multi-ethnic study of atherosclerosis and air pollution.

    PubMed

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

    2015-04-01

    Cohort studies of the relationship between air pollution exposure and chronic health effects require predictions of exposure over long periods of time. 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). 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. 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. 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.

  10. 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

  11. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis.

    PubMed

    Komori, Mika; Blake, Andrew; Greenwood, Mark; Lin, Yen Chih; Kosa, Peter; Ghazali, Danish; Winokur, Paige; Natrajan, Muktha; Wuest, Simone C; Romm, Elena; Panackal, Anil A; Williamson, Peter R; Wu, Tianxia; Bielekova, Bibiana

    2015-07-01

    The management of complex patients with neuroimmunological diseases is hindered by an inability to reliably measure intrathecal inflammation. Currently implemented laboratory tests developed >40 years ago either are not dynamic or fail to capture low levels of central nervous system (CNS) inflammation. Therefore, we aimed to identify and validate biomarkers of CNS inflammation in 2 blinded, prospectively acquired cohorts of untreated patients with neuroimmunological diseases and embedded controls, with the ultimate goal of developing clinically useful tools. Because biomarkers with maximum utility reflect immune phenotypes, we included an assessment of cell specificity in purified primary immune cells. Biomarkers were quantified by optimized electrochemiluminescent immunoassays. Among markers with cell-specific secretion, soluble CD27 is a validated biomarker of intrathecal T-cell activation, with an area under the receiver operating characteristic curve of 0.97. Comparing the quantities of cerebrospinal fluid (CSF) immune cells and their respective cell-specific soluble biomarkers (released by CSF cells as well as their counterparts in CNS tissue) provided invaluable information about stationary CNS immune responses, previously attainable via brain biopsy only. Unexpectedly, progressive and relapsing-remitting multiple sclerosis (MS) patients have comparable numbers of activated intrathecal T and B cells, which are preferentially embedded in CNS tissue in the former group. The cell-specific biomarkers of intrathecal inflammation may improve diagnosis and management of neuroimmunological diseases and provide pharmacodynamic markers for future therapeutic developments in patients with intrathecal inflammation that is not captured by imaging, such as in progressive MS. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  12. 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

  13. Molecular networks involved in mouse cerebral corticogenesis and spatio-temporal regulation of Sox4 and Sox11 novel antisense transcripts revealed by transcriptome profiling.

    PubMed

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

    2009-01-01

    Development of the cerebral cortex requires highly specific spatio-temporal regulation of gene expression. It is proposed that transcriptome profiling of the cerebral cortex at various developmental time points or regions will reveal candidate genes and associated molecular pathways involved in cerebral corticogenesis. Serial analysis of gene expression (SAGE) libraries were constructed from C57BL/6 mouse cerebral cortices of age embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4 to 6 months. Hierarchical clustering analysis of 561 differentially expressed transcripts showed regionalized, stage-specific and co-regulated expression profiles. SAGE expression profiles of 70 differentially expressed transcripts were validated using quantitative RT-PCR assays. Ingenuity pathway analyses of validated differentially expressed transcripts demonstrated that these transcripts possess distinctive functional properties related to various stages of cerebral corticogenesis and human neurological disorders. Genomic clustering analysis of the differentially expressed transcripts identified two highly transcribed genomic loci, Sox4 and Sox11, during embryonic cerebral corticogenesis. These loci feature unusual overlapping sense and antisense transcripts with alternative polyadenylation sites and differential expression. The Sox4 and Sox11 antisense transcripts were highly expressed in the brain compared to other mouse organs and are differentially expressed in both the proliferating and differentiating neural stem/progenitor cells and P19 (embryonal carcinoma) cells. We report validated gene expression profiles that have implications for understanding the associations between differentially expressed transcripts, novel targets and related disorders pertaining to cerebral corticogenesis. The study reports, for the first time, spatio-temporally regulated Sox4 and Sox11 antisense transcripts in the brain, neural stem/progenitor cells and P19 cells, suggesting they have an

  14. 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.

  15. Microsatellite markers reveal multiple origins for Italian weedy rice

    PubMed Central

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

    2013-01-01

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

  16. 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

  17. Response time modeling reveals multiple contextual cuing mechanisms.

    PubMed

    Sewell, David K; Colagiuri, Ben; Livesey, Evan J

    2017-08-24

    Contextual cuing refers to a response time (RT) benefit that occurs when observers search through displays that have been repeated over the course of an experiment. Although it is generally agreed that contextual cuing arises via an associative learning mechanism, there is uncertainty about the type(s) of process(es) that allow learning to influence RT. We contrast two leading accounts of the contextual cuing effect that differ in terms of the general process that is credited with producing the effect. The first, the expedited search account, attributes the cuing effect to an increase in the speed with which the target is acquired. The second, the decision threshold account, attributes the cuing effect to a reduction in the response threshold used by observers when making a subsequent decision about the target (e.g., judging its orientation). We use the diffusion model to contrast the quantitative predictions of these two accounts at the level of individual observers. Our use of the diffusion model allows us to also explore a novel decision-level locus of the cuing effect based on perceptual learning. This novel account attributes the RT benefit to a perceptual learning process that increases the quality of information used to drive the decision process. Our results reveal both individual differences in the process(es) involved in contextual cuing but also identify several striking regularities across observers. We find strong support for both the decision threshold account as well as the novel perceptual learning account. We find relatively weak support for the expedited search account.

  18. 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.

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

    PubMed

    Maschi, Dario; Klyachko, Vitaly A

    2017-04-05

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

  20. Spatio-temporal dynamics in phytobenthos structural properties reveal insights into agricultural catchment dynamics and nutrient fluxes

    NASA Astrophysics Data System (ADS)

    Reaney, S. M.; Snell, M. A.; Barker, P. A.; Aftab, A.; Barber, N. J.; Benskin, C.; Burke, S.; Cleasby, W.; Haygarth, P.; Jonczyk, J. C.; Owen, G. J.; Perks, M. T.; Quinn, P. F.; Surridge, B.

    2016-12-01

    Low order streams are spatially extensive, temporally dynamic, systems within the agricultural landscape. This dynamism extends to the aquatic communities within these streams, including the phytobentos, which demonstrates considerable resilience to diffuse anthropogenic nutrient pressures and changing climate dynamics. The phytobenthos community can substantially contribute to the food web, in particular diatoms, which dominate photo-autotrophic assemblages in low order streams. Diatoms are widely used in ecological monitoring because of their high sensitivity to environmental condition, but knowledge is limited on the ecological effects of winter disturbances and variance introduced by multiple and interacting pressures (N, P, sediment), introducing bias in understanding temporal dynamics in benthic diatom communities. Using the environmental time series data from long term monitoring within the River Eden Demonstration Test Catchment programme, we assess the impact of multiple hydro-chemical stressors on phytobenthic community resilience, and synthesize the impact of an extreme winter event. Monthly data from diatom communities collected in the Eden DTC from March 2011 to present show that river flow, strongly coupled to precipitation, is a key driver of these communities. Discharge has a direct effect on communities through scouring, but is also tightly correlated to nutrient delivery, such that 80% of the annual TP load arrives in 10% of the time. Trophic Diatom Index (TDI) values demonstrated considerable resilience by the stability of inter-monthly TDI scores over 5 seasonal cycles against the characterised highly variable hydrological regime. This research demonstrates that well characterised winter disturbances are critical to understanding drivers of aquatic dynamics. This has implications for catchment diffuse pollution policy, farm management and economics, given the climate projections of increases in frequency and intensity of extreme winter events

  1. Spatiotemporal dynamics of visual vertical judgments: early and late brain mechanisms as revealed by high-density electrical neuroimaging.

    PubMed

    Lopez, C; Mercier, M R; Halje, P; Blanke, O

    2011-05-05

    Constructing and updating an internal model of verticality is fundamental for maintaining an erect posture and facilitating visuo-spatial processing. The judgment of the visual vertical (VV) has been intensively studied in psychophysical investigations and relies mainly on the integration of visual and vestibular signals, although a contribution of postural and somatosensory signals has been reported. Here we used high-density 192-channel evoked potential (EP) mapping and distributed source localization techniques to reveal the neural mechanisms of VV judgments. VV judgments (judging the orientation of visual lines with respect to the subjective vertical) were performed with and without a tilted visual frame. EP mapping revealed a sequence of neural processing steps (EP maps) of which two were specific for VV judgments. An early EP map, observed at ∼75-105 ms post-stimulus, was localized in right lateral temporo-occipital cortex. A later EP map (∼260-290 ms) was localized in bilateral temporo-occipital and parieto-occipital cortex. These data suggest that early VV-related neural processing involves the lateral and ventral visual stream and is related to visual processing concerning orientation, attention and comparison. The later, more dorsal, activation involves multimodal cortex subtending a constantly available and updated internal model of the vertical that we can refer to for the control of one's posture, actions, and visuo-spatial processing. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Scanning STED-FCS reveals spatiotemporal heterogeneity of lipid interaction in the plasma membrane of living cells

    NASA Astrophysics Data System (ADS)

    Honigmann, Alf; Mueller, Veronika; Ta, Haisen; Schoenle, Andreas; Sezgin, Erdinc; Hell, Stefan W.; Eggeling, Christian

    2014-11-01

    The interaction of lipids and proteins plays an important role in plasma membrane bioactivity, and much can be learned from their diffusion characteristics. Here we present the combination of super-resolution STED microscopy with scanning fluorescence correlation spectroscopy (scanning STED-FCS, sSTED-FCS) to characterize the spatial and temporal heterogeneity of lipid interactions. sSTED-FCS reveals transient molecular interaction hotspots for a fluorescent sphingolipid analogue. The interaction sites are smaller than 80 nm in diameter and lipids are transiently trapped for several milliseconds in these areas. In comparison, newly developed fluorescent phospholipid and cholesterol analogues with improved phase-partitioning properties show more homogenous diffusion, independent of the preference for liquid-ordered or disordered membrane environments. Our results do not support the presence of nanodomains based on lipid-phase separation in the basal membrane of our cultured nonstimulated cells, and show that alternative interactions are responsible for the strong local trapping of our sphingolipid analogue.

  3. A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

    PubMed Central

    Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

    2017-01-01

    The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs. DOI: http://dx.doi.org/10.7554/eLife.22772.001 PMID:28695824

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

    PubMed

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

    2017-01-01

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

  5. Genetic visualization with an improved GCaMP calcium indicator reveals spatiotemporal activation of the spinal motor neurons in zebrafish

    PubMed Central

    Muto, Akira; Ohkura, Masamichi; Kotani, Tomoya; Higashijima, Shin-ichi; Nakai, Junichi; Kawakami, Koichi

    2011-01-01

    Animal behaviors are generated by well-coordinated activation of neural circuits. In zebrafish, embryos start to show spontaneous muscle contractions at 17 to 19 h postfertilization. To visualize how motor circuits in the spinal cord are activated during this behavior, we developed GCaMP-HS (GCaMP-hyper sensitive), an improved version of the genetically encoded calcium indicator GCaMP, and created transgenic zebrafish carrying the GCaMP-HS gene downstream of the Gal4-recognition sequence, UAS (upstream activation sequence). Then we performed a gene-trap screen and identified the SAIGFF213A transgenic fish that expressed Gal4FF, a modified version of Gal4, in a subset of spinal neurons including the caudal primary (CaP) motor neurons. We conducted calcium imaging using the SAIGFF213A; UAS:GCaMP-HS double transgenic embryos during the spontaneous contractions. We demonstrated periodic and synchronized activation of a set of ipsilateral motor neurons located on the right and left trunk in accordance with actual muscle movements. The synchronized activation of contralateral motor neurons occurred alternately with a regular interval. Furthermore, a detailed analysis revealed rostral-to-caudal propagation of activation of the ipsilateral motor neuron, which is similar to but much slower than the rostrocaudal delay observed during swimming in later stages. Our study thus demonstrated coordinated activities of the motor neurons during the first behavior in a vertebrate. We propose the GCaMP technology combined with the Gal4FF-UAS system is a powerful tool to study functional neural circuits in zebrafish. PMID:21383146

  6. Spatiotemporal Patterns Produced by Bacteria

    NASA Astrophysics Data System (ADS)

    Shimada, Yuji; Nakahara, Akio; Matsushita, Mitsugu; Matsuyama, Tohey

    1995-06-01

    Spatiotemporal patterns formed by a bacterial colony of Proteus mirabilis on an agar plate were observed. About half or one hour after the colony spread over the entire surface of the agar medium in a petridish, various patterns including target and spiral patterns appeared. They are very similar to those seen in other dissipative systems, such as chemical oscillations and electrohydrodynamic convective systems. Microscopic observations revealed that the collective motion of bacterial cells is responsible for the formation of these spatiotemporal patterns.

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

    PubMed

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

    2013-02-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  9. Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy.

    PubMed

    Steinman, Lawrence; Martin, Roland; Bernard, Claude; Conlon, Paul; Oksenberg, Jorge R

    2002-01-01

    Recent technological breakthroughs allowing for large-scale analysis of gene transcripts and large-scale monitoring of the immune response with protein chips are revealing new participants in the pathogenesis of multiple sclerosis. Some of these participants may be useful targets for therapy.

  10. Multiple remote sensing data sources to assess spatio-temporal patterns of fire incidence over Campos Amazônicos Savanna Vegetation Enclave (Brazilian Amazon).

    PubMed

    Alves, Daniel Borini; Pérez-Cabello, Fernando

    2017-12-01

    Fire activity plays an important role in the past, present and future of Earth system behavior. Monitoring and assessing spatial and temporal fire dynamics have a fundamental relevance in the understanding of ecological processes and the human impacts on different landscapes and multiple spatial scales. This work analyzes the spatio-temporal distribution of burned areas in one of the biggest savanna vegetation enclaves in the southern Brazilian Amazon, from 2000 to 2016, deriving information from multiple remote sensing data sources (Landsat and MODIS surface reflectance, TRMM pluviometry and Vegetation Continuous Field tree cover layers). A fire scars database with 30 m spatial resolution was generated using a Landsat time series. MODIS daily surface reflectance was used for accurate dating of the fire scars. TRMM pluviometry data were analyzed to dynamically establish time limits of the yearly dry season and burning periods. Burned area extent, frequency and recurrence were quantified comparing the results annually/seasonally. Additionally, Vegetation Continuous Field tree cover layers were used to analyze fire incidence over different types of tree cover domains. In the last seventeen years, 1.03millionha were burned within the study area, distributed across 1432 fire occurrences, highlighting 2005, 2010 and 2014 as the most affected years. Middle dry season fires represent 86.21% of the total burned areas and 32.05% of fire occurrences, affecting larger amount of higher density tree surfaces than other burning periods. The results provide new insights into the analysis of burned areas of the neotropical savannas, spatially and statistically reinforcing important aspects linked to the seasonality patterns of fire incidence in this landscape. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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.

  12. 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.

  13. RNA silencing in the life cycle of soybean: multiple restriction systems and spatiotemporal variation associated with plant architecture.

    PubMed

    Mori, Ayumi; Sato, Hiroshi; Kasai, Megumi; Yamada, Tetsuya; Kanazawa, Akira

    2017-06-01

    The expression of transgenes introduced into a plant genome is sometimes suppressed by RNA silencing. Although local and systemic spread of RNA silencing have been studied, little is known about the mechanisms underlying spatial and temporal variation in transgene silencing between individual plants or between plants of different generations, which occurs seemingly stochastically. Here, we analyzed the occurrence, spread, and transmission of RNA silencing of the green fluorescent protein (GFP) gene over multiple generations of the progeny of a single soybean transformant. Observation of GFP fluorescence in entire plants of the T3-T5 generations indicated that the initiation and subsequent spread of GFP silencing varied between individuals, although this GFP silencing most frequently began in the primary leaves. In addition, GFP silencing could spread into the outer layer of seed coat tissues but was hardly detectable in the embryos. These results are consistent with the notion that transgene silencing involves its reset during reproductive phase, initiation after germination, and systemic spread in each generation. GFP silencing was absent in the pulvinus, suggesting that its cortical cells inhibit cell-to-cell spread or induction of RNA silencing. The extent of GFP silencing could differ between the stem and a petiole or between petiolules, which have limited vascular bundles connecting them and thus deter long-distant movement of silencing. Taken together, these observations indicate that the initiation and/or spread of RNA silencing depend on specific features of the architecture of the plant in addition to the mechanisms that can be conserved in higher plants.

  14. Spatiotemporal variation of hand-foot-mouth disease in relation to socioecological factors: A multiple-province analysis in Vietnam.

    PubMed

    Phung, Dung; Nguyen, Huong Xuan; Nguyen, Huong Lien Thi; Do, Cuong Manh; Tran, Quang Dai; Chu, Cordia

    2017-08-20

    Hand-foot-and-mouth disease (HFMD) is a significant public health issue in Asia-pacific countries. Numerous studies have examined the relationship between socio-ecological factors and HFMD however the research findings were inconsistent. This study examined the association between socio-ecologic factors and HFMD in multiple provinces across Vietnam. We applied a spatial autoregressive model using a Bayesian framework to examine the relationship between HFMD and socio-demographic factors. We used a Generalized Linear Model (GLD) with Poisson family to examine the province-specific association between monthly HFMD and climatic factors while controlling for spatial lag, seasonality and long-term trend of HFMD. Then, we used a random-effect meta-analysis to generate pooled effect size of climate-HFMD association for regional and country scale. One percent increase in newborn breastfed within 1h of birth, households with permanent houses, and households accessed to safe water resulted in 1.57% (95% CI: -2.25, -0.93), 0.96% (-1.66, -0.23), and 1.13% (-2.16, -0.18) reduction in HFMD incidence, respectively. At the country-level, HFMD increased 7% (RR: 1.07; 95%CI: 1.052-1.088) and 3.1% (RR: 1.031, 95%CI: 1.024-1.039) for 1°C increase in monthly temperature above 26°C and 1% increase in monthly humidity above 76%. Whereas, HFMD decreased 3.1% associated with 1mm increase in monthly cumulative rainfalls. The climate-HFMD relationship was varied by regions and provinces across the country. The findings reflect an important implication for the climate change adaptation strategies and public-health decision, of which development of weather-based early warning systems should be considered to strengthen communicable disease prevention system. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. 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. © The Author 2016. Published by Oxford University Press.

  18. 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

  19. 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

  20. Multiple Introductions of Zika Virus into the United States Revealed Through Genomic Epidemiology

    DTIC Science & Technology

    2017-02-02

    Multiple introductions of Zika virus into the United States revealed through genomic epidemiology Nathan D Grubaugh1*, Jason T Ladner2,*, Moritz UG...042 DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. UNCLASSIFIED Zika virus (ZIKV) is currently causing an...Medical Research Institute of Infectious Diseases (USAMRIID) Office of Human Use and Ethics and determined not to require IRB review. Florida Zika

  1. Multiple Introductions of Zika Virus into the United States Revealed through Genomic Epidemiology

    DTIC Science & Technology

    2017-02-09

    Multiple introductions of Zika virus into the United States revealed through genomic epidemiology Nathan D Grubaugh1*, Jason T Ladner2,*, Moritz UG...047 DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. UNCLASSIFIED Zika virus (ZIKV) is currently causing an...Medical Research Institute of Infectious Diseases (USAMRIID) Office of Human Use and Ethics and determined not to require IRB review. Florida Zika

  2. 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.

  3. 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.

  4. Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules

    PubMed Central

    Patel-Hett, Sunita; Richardson, Jennifer L.; Schulze, Harald; Drabek, Ksenija; Isaac, Natasha A.; Hoffmeister, Karin; Shivdasani, Ramesh A.; Bulinski, J. Chloë; Galjart, Niels; Hartwig, John H.

    2008-01-01

    The marginal band of microtubules maintains the discoid shape of resting blood platelets. Although studies of platelet microtubule coil structure conclude that it is composed of a single microtubule, no investigations of its dynamics exist. In contrast to previous studies, permeabilized platelets incubated with GTP-rhodamine-tubulin revealed tubulin incorporation at 7.9 (± 1.9) points throughout the coil, and anti-EB1 antibodies stained 8.7 (± 2.0) sites, indicative of multiple free microtubules. To pursue this result, we expressed the microtubule plus-end marker EB3-GFP in megakaryocytes and examined its behavior in living platelets released from these cells. Time-lapse microscopy of EB3-GFP in resting platelets revealed multiple assembly sites within the coil and a bidirectional pattern of assembly. Consistent with these findings, tyrosinated tubulin, a marker of newly assembled microtubules, localized to resting platelet microtubule coils. These results suggest that the resting platelet marginal band contains multiple highly dynamic microtubules of mixed polarity. Analysis of microtubule coil diameters in newly formed resting platelets indicates that microtubule coil shrinkage occurs with aging. In addition, activated EB3-GFP–expressing platelets exhibited a dramatic increase in polymerizing microtubules, which travel outward and into filopodia. Thus, the dynamic microtubules associated with the marginal band likely function during both resting and activated platelet states. PMID:18230754

  5. 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

  6. 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

  7. Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation

    PubMed Central

    Fleischmann, Alexander; Abdus-Saboor, Ishmail; Sayed, Atef; Shykind, Benjamin

    2013-01-01

    The odorant receptor (OR) genes constitute the largest mammalian gene family and are expressed in a monogenic and monoallelic fashion, through an unknown mechanism that likely exploits positive and negative regulation. We devised a genetic strategy in mice to examine OR selection by determining the transcriptional activity of an exogenous promoter homologously integrated into an OR locus. Using the tetracycline-dependent transactivator responsive promoter (teto), we observed that the OR locus imposes spatial and temporal constraints on teto-driven transcription. Conditional expression experiments reveal a developmental change in the permissiveness of the locus. Further, expression of an OR transgene that suppresses endogenous ORs similarly represses the OR-integrated teto. Neurons homozygous for the teto-modified allele demonstrate predominantly monoallelic expression, despite their potential to express both copies. These data reveal multiple axes of regulation, and support a model of initiation of OR choice limited by nonpermissive chromatin and maintained by repression of nonselected alleles. PMID:23700388

  8. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Characterization of New Otic Enhancers of the Pou3f4 Gene Reveal Distinct Signaling Pathway Regulation and Spatio-Temporal Patterns

    PubMed Central

    Robert-Moreno, Àlex; Naranjo, Silvia; de la Calle-Mustienes, Elisa; Gómez-Skarmeta, José Luis; Alsina, Berta

    2010-01-01

    POU3F4 is a member of the POU-homedomain transcription factor family with a prominent role in inner ear development. Mutations in the human POU3F4 coding unit leads to X-linked deafness type 3 (DFN3), characterized by conductive hearing loss and progressive sensorineural deafness. Microdeletions found 1 Mb 5′ upstream of the coding region also displayed the same phenotype, suggesting that cis-regulatory elements might be present in that region. Indeed, we and others have recently identified several enhancers at the 1 Mb 5′ upstream interval of the pou3f4 locus. Here we characterize the spatio-temporal patterns of these regulatory elements in zebrafish transgenic lines. We show that the most distal enhancer (HCNR 81675) is activated earlier and drives GFP reporter expression initially to a broad ear domain to progressively restrict to the sensory patches. The proximal enhancer (HCNR 82478) is switched later during development and promotes expression, among in other tissues, in sensory patches from its onset. The third enhancer (HCNR 81728) is also active at later stages in the otic mesenchyme and in the otic epithelium. We also characterize the signaling pathways regulating these enhancers. While HCNR 81675 is regulated by very early signals of retinoic acid, HCNR 82478 is regulated by Fgf activity at a later stage and the HCNR 81728 enhancer is under the control of Hh signaling. Finally, we show that Sox2 and Pax2 transcription factors are bound to HCNR 81675 genomic region during otic development and specific mutations to these transcription factor binding sites abrogates HCNR 81675 enhancer activity. Altogether, our results suggest that pou3f4 expression in inner ear might be under the control of distinct regulatory elements that fine-tune the spatio-temporal activity of this gene and provides novel data on the signaling mechanisms controlling pou3f4 function. PMID:21209840

  10. 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.

  11. Hearing without listening: functional connectivity reveals the engagement of multiple nonauditory networks during basic sound processing.

    PubMed

    Langers, Dave R M; Melcher, Jennifer R

    2011-01-01

    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.

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

    PubMed Central

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

    2013-01-01

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

  13. High Spatiotemporal Resolution Prostate MRI

    DTIC Science & Technology

    2016-09-01

    8 reconstruction of scans made of phantoms or of human subjects originating from multiple MRI scanners across Mayo. We are pleased with the...red lines are for the unenhanced test scans of the 32-Channel Prostate DCE- MRI June 1, 2016 Page 10 volunteer. The green shaded region shows...1 AD AWARD NUMBER: W81XWH-15-1-0341 TITLE: High Spatiotemporal Resolution Prostate MRI PRINCIPAL INVESTIGATOR: Stephen J. Riederer CONTRACTING

  14. Mechanically untying a protein slipknot: multiple pathways revealed by force spectroscopy and steered molecular dynamics simulations.

    PubMed

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

    2012-06-27

    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 mechanical 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 via either a two- 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 providing 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 was 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 mechanical unfolding pathway of AFV3-109 and point to the generality of a kinetic partitioning mechanism for protein folding/unfolding.

  15. 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

  16. 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. © 2012 Blackwell Publishing Ltd.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. 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.

  20. 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

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

    PubMed

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

    2013-02-01

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

  2. Asymmetric configurations in a reengineered homodimer reveal multiple subunit communication pathways in protein allostery

    PubMed Central

    Lanfranco, Maria Fe; Gárate, Fernanda; Engdahl, Ashton J.; Maillard, Rodrigo A.

    2017-01-01

    Many allosteric proteins form homo-oligomeric complexes to regulate a biological function. In homo-oligomers, subunits establish communication pathways that are modulated by external stimuli like ligand binding. A challenge for dissecting the communication mechanisms in homo-oligomers is identifying intermediate liganded states, which are typically transiently populated. However, their identities provide the most mechanistic information on how ligand-induced signals propagate from bound to empty subunits. Here, we dissected the directionality and magnitude of subunit communication in a reengineered single-chain version of the homodimeric transcription factor cAMP receptor protein. By combining wild-type and mutant subunits in various asymmetric configurations, we revealed a linear relationship between the magnitude of cooperative effects and the number of mutant subunits. We found that a single mutation is sufficient to change the global allosteric behavior of the dimer even when one subunit was wild type. Dimers harboring two mutations with opposite cooperative effects had different allosteric properties depending on the arrangement of the mutations. When the two mutations were placed in the same subunit, the resulting cooperativity was neutral. In contrast, when placed in different subunits, the observed cooperativity was dominated by the mutation with strongest effects over cAMP affinity relative to wild type. These results highlight the distinct roles of intrasubunit interactions and intersubunit communication in allostery. Finally, dimers bound to either one or two cAMP molecules had similar DNA affinities, indicating that both asymmetric and symmetric liganded states activate DNA interactions. These studies have revealed the multiple communication pathways that homo-oligomers employ to transduce signals. PMID:28188293

  3. Phylogeny of a genomically diverse group of elymus (poaceae) allopolyploids reveals multiple levels of reticulation.

    PubMed

    Mason-Gamer, Roberta J

    2013-01-01

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

  4. Full genomic analysis of new variant rabbit hemorrhagic disease virus revealed multiple recombination events.

    PubMed

    Lopes, Ana M; Dalton, Kevin P; Magalhães, Maria J; Parra, Francisco; Esteves, Pedro J; Holmes, Edward C; Abrantes, Joana

    2015-06-01

    Rabbit hemorrhagic disease virus (RHDV), a Lagovirus of the family Caliciviridae, causes rabbit hemorrhagic disease (RHD) in the European rabbit (Oryctolagus cuniculus). The disease was first documented in 1984 in China and rapidly spread worldwide. In 2010, a new RHDV variant emerged, tentatively classified as 'RHDVb'. RHDVb is characterized by affecting vaccinated rabbits and those <2 months old, and is genetically distinct (~20 %) from older strains. To determine the evolution of RHDV, including the new variant, we generated 28 full-genome sequences from samples collected between 1994 and 2014. Phylogenetic analysis of the gene encoding the major capsid protein, VP60, indicated that all viruses sampled from 2012 to 2014 were RHDVb. Multiple recombination events were detected in the more recent RHDVb genomes, with a single major breakpoint located in the 5' region of VP60. This breakpoint divides the genome into two regions: one that encodes the non-structural proteins and another that encodes the major and minor structural proteins, VP60 and VP10, respectively. Additional phylogenetic analysis of each region revealed two types of recombinants with distinct genomic backgrounds. Recombinants always include the structural proteins of RHDVb, with non-structural proteins from non-pathogenic lagoviruses or from pathogenic genogroup 1 strains. Our results show that in contrast to the evolutionary history of older RHDV strains, recombination plays an important role in generating diversity in the newly emerged RHDVb. © 2015 The Authors.

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

    PubMed

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

    1995-02-01

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

  6. 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

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

    PubMed

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

    2015-04-01

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

  8. 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

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

    PubMed Central

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

    2010-01-01

    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

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

    PubMed Central

    Mason-Gamer, Roberta J.

    2013-01-01

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

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

    PubMed

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

    2015-12-04

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

  12. 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

  13. 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

  14. 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

  15. 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.

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

    PubMed Central

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

    1990-01-01

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

  17. Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions

    PubMed Central

    Schmidt, Linnéa; Kling, Teresia; Monsefi, Naser; Olsson, Maja; Hansson, Caroline; Baskaran, Sathishkumar; Lundgren, Bo; Martens, Ulf; Häggblad, Maria; Westermark, Bengt; Forsberg Nilsson, Karin; Uhrbom, Lene; Karlsson-Lindahl, Linda; Gerlee, Philip; Nelander, Sven

    2013-01-01

    Background Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers. Methods We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling. Results Of the 5 × 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses. Conclusion We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases. PMID:24101737

  18. Non-Invasive Imaging Provides Spatiotemporal Information on Disease Progression and Response to Therapy in a Murine Model of Multiple Myeloma

    PubMed Central

    Riedel, Simone S.; Mottok, Anja; Brede, Christian; Bäuerlein, Carina A.; Jordán Garrote, Ana-Laura; Ritz, Miriam; Mattenheimer, Katharina; Rosenwald, Andreas; Einsele, Hermann; Bogen, Bjarne; Beilhack, Andreas

    2012-01-01

    Background Multiple myeloma (MM) is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy. Material and Methods A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM) that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI). Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology. Results Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells. Conclusions This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This

  19. 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

  20. Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.

    PubMed

    Bouts, Mark J R J; Westmoreland, Susan V; de Crespigny, Alex J; Liu, Yutong; Vangel, Mark; Dijkhuizen, Rick M; Wu, Ona; D'Arceuil, Helen E

    2015-12-15

    Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis. These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2012-07-10

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

  3. 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

  4. 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.

  5. Multiple satellite-based analysis reveals complex climate effects of temperate forests and related energy budget

    NASA Astrophysics Data System (ADS)

    Ma, Wei; Jia, Gensuo; Zhang, Anzhi

    2017-04-01

    Forest conversion-driven biophysical processes have been examined in various case studies that largely depend on sensitivity analysis of climate modeling. However, much remains unknown in the real world due to the complicated process and uncertainty in magnitude, especially in the temperate bioclimate regions. This study applied satellite-based observation to investigate the biophysical climate response to potential forest conversion in China, especially on the spatial and temporal patterns and underlying mechanisms. We evaluated the differences of land surface temperature (ΔLST) between adjacent forest and cropland, in terms of the latitudinal and seasonal patterns. Compared to cropland, the temperate forest to the south of 40°N showed the cooling effect of -0.61 ± 0.02°C (95% confidence interval, and hereafter), and it presented the warming effect of 0.48 ± 0.06°C to the north of 48°N (the transition zone was between 40°N and 48°N). Seasonal analysis further demonstrated that the cooling effects of temperate forest in China in spring (March, April, May), summer (June, July, August), and autumn (September, October, November) were -0.53 ± 0.02°C, -0.55 ± 0.02°C, and -0.30 ± 0.02°C, respectively, while the forest caused the warming effect of 0.10 ± 0.04°C in winter (December, January, February). However, the biophysical climate response to forest conversion in temperate regions was complex and showed highly spatial and temporal heterogeneity. We further assessed the role of two major biophysical processes, i.e., albedo and evapotranspiration (ET), in shaping land surface temperature from surface energy budget perspective. Results showed that the latitudinal, seasonal, and spatiotemporal patterns of ΔLST was determined by the net effect of ET-induced latent heat changes and albedo-induced solar radiation absorption changes.

  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. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  9. Spatio-temporal clustering

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed Central

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

    2012-01-01

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

  11. Single-molecule chemo-mechanical unfolding reveals multiple transition state barriers in a small single-domain protein

    NASA Astrophysics Data System (ADS)

    Guinn, Emily J.; Jagannathan, Bharat; Marqusee, Susan

    2015-04-01

    A fundamental question in protein folding is whether proteins fold through one or multiple trajectories. While most experiments indicate a single pathway, simulations suggest proteins can fold through many parallel pathways. Here, we use a combination of chemical denaturant, mechanical force and site-directed mutations to demonstrate the presence of multiple unfolding pathways in a simple, two-state folding protein. We show that these multiple pathways have structurally different transition states, and that seemingly small changes in protein sequence and environment can strongly modulate the flux between the pathways. These results suggest that in vivo, the crowded cellular environment could strongly influence the mechanisms of protein folding and unfolding. Our study resolves the apparent dichotomy between experimental and theoretical studies, and highlights the advantage of using a multipronged approach to reveal the complexities of a protein's free-energy landscape.

  12. 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.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2007-08-01

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

  15. 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

  16. 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.

  17. Genome-wide enrichment screening reveals multiple targets and resistance genes for triclosan in Escherichia coli.

    PubMed

    Yu, Byung Jo; Kim, Jung Ae; Ju, Hyun Mok; Choi, Soo-Kyung; Hwang, Seung Jin; Park, Sungyoo; Kim, Euijoong; Pan, Jae-Gu

    2012-10-01

    Triclosan is a widely used biocide effective against different microorganisms. At bactericidal concentrations, triclosan appears to affect multiple targets, while at bacteriostatic concentrations, triclosan targets FabI. The site-specific antibiotic-like mode-of-action and a widespread use of triclosan in household products claimed to possibly induce cross-resistance to other antibiotics. Thus, we set out to define more systematically the genes conferring resistance to triclosan; A genomic library of Escherichia coli strain W3110 was constructed and enriched in a selective medium containing a lethal concentration of triclosan. The genes enabling growth in the presence of triclosan were identified by using a DNA microarray and confirmed consequently by ASKA clones overexpressing the selected 62 candidate genes. Among these, forty-seven genes were further confirmed to enhance the resistance to triclosan; these genes, including the FabI target, were involved in inner or outer membrane synthesis, cell-surface material synthesis, transcriptional activation, sugar phosphotransferase (PTS) systems, various transporter systems, cell division, and ATPase and reductase/dehydrogenase reactions. In particular, overexpression of pgsA, rcsA, or gapC conferred to E. coli cells a similar level of triclosan resistance induced by fabI overexpression. These results indicate that triclosan may have multiple targets other than well-known FabI and that there are several undefined novel mechanisms for the resistance development to triclosan, thus probably inducing cross antibiotic resistance.

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

    PubMed

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

    2015-09-30

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

  19. 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

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

    PubMed Central

    Liu, Gang; Dong, Chuanpeng; Liu, Lei

    2016-01-01

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

  1. Multiple aspects of northern hemispheric wintertime cold extremes as revealed by Markov chain analysis

    NASA Astrophysics Data System (ADS)

    Kim, Hye-Sil; Choi, Yong-Sang; Kim, Joo-Hong; Kim, WonMoo

    2017-02-01

    High-impact cold extremes have continued to bring devastating socioeconomic losses in recent years. In order to explain the exposure to cold extremes more comprehensively, this study investigates multiple aspects of boreal winter cold extremes, i.e., frequency, persistence, and entropy (Markovian descriptors). Cold extremes are defined by the bottom 10th percentile of daily minimum temperatures during 1950-2014 over the northern hemisphere. The spatial and temporal distributions of Markovian descriptors during 65 years are examined. Climatological mean fields show the spatial coincidence of higher frequency, shorter persistence, and higher entropy of cold extremes, and vice versa. In regard to the temporal variations over six representative regions of North America, Europe, and Asia, all regions share a decreasing tendency of frequency with the increases in regional winter mean temperature. By contrast, persistence and entropy show their intrinsic decadal variability depending on regions irrespective of the regional temperature variability, which give different information from frequency. Therefore, the exposure to cold extremes would not simply decrease with regional warming. Rather these results indicate that the descriptors with multiple aspects of the extremes would be needed to embrace the topical features as well as the holistic nature of cold extremes.

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

    PubMed

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

    2008-10-08

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-12-19

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

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

    PubMed

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

    2011-06-01

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

  8. 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.

  9. Haplotype analysis of α-thalassemia chromosomes reveals heterogeneity and multiple founders in Ashkenazi Jews.

    PubMed

    Shaulov, Adir; Filon, Dvora; Rund, Deborah

    2016-11-01

    α-Thalassemia (α-thal) is among the world's most common single gene disorders, generally attributed to a selective advantage of heterozygotes against malaria mortality. A high frequency of -α(3.7) deletion heterozygosity has been previously reported in Ashkenazi Jews despite lack of obvious malarial selection pressure in this population. Using haplotype and -α(3.7) subtype analysis we analyzed a subset of -α(3.7) homozygotes from various Israeli ethnic groups. We found a high frequency of the common Ia haplotype in Yemenite Jews and Arabs (54% and 13% respectively). Ashkenazi Jews exhibited a high frequency of IIIb alleles (67%) previously reported only in Aboriginal Australians and not found in other Israeli ethnicities. Both Yemenites and Ashkenazim carried the rare IIh alleles (18% and 15% respectively). These results may suggest multiple founder effects in Ashkenazi Jews as well a common founder for both Yemenite and Ashkenazi Jews. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Dissecting the Multiple Myeloma-bone microenvironment reveals new therapeutic opportunities

    PubMed Central

    Shay, G; Hazlehurst, L; Lynch, CC

    2015-01-01

    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

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

    PubMed Central

    Riachy, Moussa Albert

    2011-01-01

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

  12. 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.

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

    PubMed

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

    2014-10-01

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

  14. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    PubMed Central

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

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

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

    PubMed

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

    2003-12-22

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

  16. 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

  17. Multiple Spectral Ratio Analyses Reveal Earthquake Source Spectra of Small Earthquakes and Moment Magnitudes of Microearthquakes

    NASA Astrophysics Data System (ADS)

    Uchide, T.; Imanishi, K.

    2016-12-01

    Spectral studies for macroscopic earthquake source parameters are helpful for characterizing earthquake rupture process and hence understanding earthquake source physics and fault properties. Those studies require us mute wave propagation path and site effects in spectra of seismograms to accentuate source effect. We have recently developed the multiple spectral ratio method [Uchide and Imanishi, BSSA, 2016] employing many empirical Green's function (EGF) events to reduce errors from the choice of EGF events. This method helps us estimate source spectra more accurately as well as moment ratios among reference and EGF events, which are useful to constrain the seismic moment of microearthquakes. First, we focus on earthquake source spectra. The source spectra have generally been thought to obey the omega-square model with single corner-frequency. However recent studies imply the existence of another corner frequency for some earthquakes. We analyzed small shallow inland earthquakes (3.5 < Mw < 4.5; depth < 20 km) in whole Japan and found both single- and double-corner-frequency source spectra not only in Fukushima Hamadori and northern Ibaraki prefecture area as reported in Uchide and Imanishi [2016] but also the other regions such as Wakayama and Kumamoto areas. Therefore, a model for earthquake source spectra to include all these observations is needed. Next, we focus on seismic moments of microearthquakes in Japan inferred from those of small earthquakes from NIED F-net moment tensor catalog and moment ratios from the multiple spectral ratio analyses. For 20000 microearthquakes in Fukushima Hamadori and northern Ibaraki prefecture area, we found that the JMA magnitudes (Mj) based on displacement or velocity amplitude are systematically below Mw. The slope of the Mj-Mw relation is 0.5 for Mj < 3 and 1 for Mj > 5. We propose a fitting curve for the obtained relationship as Mw = (1/2)Mj + (1/2)(Mjγ + Mcorγ)1/γ+ c, where Mcor is a corner magnitude, γ determines

  18. 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

  19. 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

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

    PubMed

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

    2007-10-09

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

  1. Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque.

    PubMed

    Nöllmann, Marcelo; Stone, Michael D; Bryant, Zev; Gore, Jeff; Crisona, Nancy J; Hong, Seok-Cheol; Mitelheiser, Sylvain; Maxwell, Anthony; Bustamante, Carlos; Cozzarelli, Nicholas R

    2007-04-01

    E. coli DNA gyrase uses the energy of ATP hydrolysis to introduce essential negative supercoils into the genome, thereby working against the mechanical stresses that accumulate in supercoiled DNA. Using a magnetic-tweezers assay, we demonstrate that small changes in force and torque can switch gyrase among three distinct modes of activity. Under low mechanical stress, gyrase introduces negative supercoils by a mechanism that depends on DNA wrapping. Elevated tension or positive torque suppresses DNA wrapping, revealing a second mode of activity that resembles the activity of topoisomerase IV. This 'distal T-segment capture' mode results in active relaxation of left-handed braids and positive supercoils. A third mode is responsible for the ATP-independent relaxation of negative supercoils. We present a branched kinetic model that quantitatively accounts for all of our single-molecule results and agrees with existing biochemical data.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. Revealing radiotherapy- and chemoradiation-induced pathway dynamics in glioblastoma by analyzing multiple differential networks.

    PubMed

    Zhou, Jia; Chen, Chao; Li, Hua-Feng; Hu, Yu-Jie; Xie, Hong-Ling

    2017-07-01

    The progression of glioblastoma (GBM) is driven by dynamic alterations in the activity and connectivity of gene pathways. Revealing these dynamic events is necessary in order to understand the pathological mechanisms of, and develop effective treatments for, GBM. The present study aimed to investigate dynamic alterations in pathway activity and connectivity across radiotherapy and chemoradiation conditions in GBM, and to give system‑level insights into molecular mechanisms for GBM therapy. A total of two differential co‑expression networks (DCNs) were constructed using Pearson correlation coefficient analysis and one sided t‑tests, based on gene expression profiles and protein‑protein interaction networks, one for each condition. Subsequently, shared differential modules across DCNs were detected via significance analysis for candidate modules, which were obtained according to seed selection, module search by seed expansion and refinement of searched modules. As condition‑specific differential modules mediate differential biological processes, the module connectivity dynamic score (MCDS) was implemented to explore dynamic alterations among them. Based on DCNs with 287 nodes and 1,052 edges, a total of 28 seed genes and seven candidate modules were identified. Following significance analysis, five shared differential modules were identified in total. Dynamic alterations among these differential modules were identified using the MCDS, and one module with significant dynamic alterations was identified, termed the dynamic module. The present study revealed the dynamic alterations of shared differential modules, identified one dynamic module between the radiotherapy and chemoradiation conditions, and demonstrated that pathway dynamics may applied to the study of the pathogenesis and therapy of GBM.

  5. How Question Types Reveal Student Thinking: An Experimental Comparison of Multiple-True-False and Free-Response Formats

    PubMed Central

    Hubbard, Joanna K.; Potts, Macy A.; Couch, Brian A.

    2017-01-01

    Assessments represent an important component of undergraduate courses because they affect how students interact with course content and gauge student achievement of course objectives. To make decisions on assessment design, instructors must understand the affordances and limitations of available question formats. Here, we use a crossover experimental design to identify differences in how multiple-true-false (MTF) and free-response (FR) exam questions reveal student thinking regarding specific conceptions. We report that correct response rates correlate across the two formats but that a higher percentage of students provide correct responses for MTF questions. We find that MTF questions reveal a high prevalence of students with mixed (correct and incorrect) conceptions, while FR questions reveal a high prevalence of students with partial (correct and unclear) conceptions. These results suggest that MTF question prompts can direct students to address specific conceptions but obscure nuances in student thinking and may overestimate the frequency of particular conceptions. Conversely, FR questions provide a more authentic portrait of student thinking but may face limitations in their ability to diagnose specific, particularly incorrect, conceptions. We further discuss an intrinsic tension between question structure and diagnostic capacity and how instructors might use multiple formats or hybrid formats to overcome these obstacles. PMID:28450446

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

    PubMed

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

    2012-09-01

    We conducted a pilot survey of genetic variation of A. cantonensis using small subunit (SSU) ribosomal (r) RNA and mitochondrial cytochrome c oxidase subunit I (coxI) gene sequences. Two distinct SSU genotypes (G1 and G2) were identified among 17 individual A. cantonensis worms from 17 different geographical localities in Japan, Mainland China, Taiwan, and Thailand. The partial coxI sequences were determined for 83 worms from 18 different geographical localities from Japan, Mainland China, Taiwan, and Thailand. Phylogenetic analysis showed eight distinct coxI haplotypes (ac1 to ac8). In 16 out of 18 localities, only a single coxI haplotype was found. However, in two localities, two coxI haplotypes coexisted. The common haplotypes found were: haplotype ac1 (Tokyo, Chiba, Kanagawa, Amamioshima Island, and Taichung), haplotype ac2 (Ishikawa, Shenzhen, and Lianjiang), haplotype ac5 (the Okinawa and the Ogasawara Islands), and haplotype ac7 (Miyagi, Aichi, and Kanagawa). Each of these regions is separated from the others by high mountain ranges or oceans. In addition, the lower genetic variation and particular geographical distribution of A. cantonensis in each location could indicate a founder effect, which may have resulted from multiple independent origins, and suggests that haplotypes migrated from endemic areas via human-related transportation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. 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

  8. 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.

  9. 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

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

    PubMed Central

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

    2014-01-01

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

  11. Multiple gene genealogies reveal important relationships between species of Phaeophleospora infecting Eucalyptus leaves.

    PubMed

    Andjic, Vera; Hardy, Giles E StJ; Cortinas, Maria Noel; Wingfield, Michael J; Burgess, Treena I

    2007-03-01

    The majority of Eucalyptus species are native to Australia, but worldwide there are over 3 million ha of exotic plantations, especially in the tropics and subtropics. Of the numerous known leaf diseases, three species of Phaeophleospora can cause severe defoliation of young Eucalyptus; Phaeophleospora destructans, Phaeophleospora eucalypti and Phaeophleospora epicoccoides. Phaeophleospora destructans has a major impact on seedling survival in Asia and has not, as yet, been found in Australia where it is considered a serious threat to the biosecurity of native eucalypts. It can be difficult to distinguish Phaeophleospora species based on symptoms and micromorphology and an unequivocal diagnostic tool for quarantine purposes would be useful. In this study, a multiple gene genealogy of these Phaeophleospora species and designed specific primers has been constructed to detect their presence from leaf samples. The phylogenetic position of these Phaeophleospora species within Mycosphaerella was established. They are closely related to each other and to other important Eucalyptus pathogens, Mycosphaerella nubilosa, Mycosphaerella cryptica and Colletogloeopsis zuluensis. The specific primers developed can now be used for diagnostic and screening purposes within Australia.

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

    NASA Astrophysics Data System (ADS)

    Berenstein, David; Liu, Tao; Perkins, Erik

    2013-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. 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

  15. Multiple repetitions reveal functionally- and anatomically-distinct patterns of hippocampal activity during continuous recognition memory

    PubMed Central

    Johnson, Jeffrey D.; Muftuler, L. Tugan; Rugg, Michael D.

    2008-01-01

    We used a continuous recognition procedure that included multiple presentations of test items, along with high-resolution functional magnetic resonance imaging (fMRI), to investigate the relationship between item novelty and recognition-related activity in the medial temporal lobe (MTL). In several regions of hippocampus and parahippocampal cortex, activity elicited by new items exceeded that for old items, whereas no MTL regions exhibited greater activity for old items. Critically, anatomically-distinct regions of MTL were engaged by item novelty in two different ways, as evidenced by statistically-dissociable profiles of activity. In bilateral medial hippocampus and left posterior parahippocampal cortex, activity followed a categorical profile in which it was greater for new than old items but did not differ further with additional presentations of old items. By contrast, effects in adjacent regions of right lateral hippocampus and left parahippocampal cortex were graded, whereby activity declined linearly with respect to each successive item presentation. These findings suggest that the relationship between hippocampal (and parahippocampal) activity and continuous psychological dimensions, such as item novelty, cannot be captured by a unitary function. PMID:18548578

  16. 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

  17. Multiple-criteria decision analysis reveals high stakeholder preference to remove pharmaceuticals from hospital wastewater.

    PubMed

    Lienert, Judit; Koller, Mirjam; Konrad, Jonas; McArdell, Christa S; Schuwirth, Nele

    2011-05-01

    Point-source measures have been suggested to decrease pharmaceuticals in water bodies. We analyzed 68 and 50 alternatives, respectively, for a typical Swiss general and psychiatric hospital to decrease pharmaceutical discharge. Technical alternatives included reverse osmosis, ozonation, and activated carbon; organizational alternatives included urine separation. To handle this complex decision, we used Multiple-Criteria Decision Analysis (MCDA) and combined expert predictions (e.g., costs, pharmaceutical mass flows, ecotoxicological risk, pathogen removal) with subjective preference-valuations from 26 stakeholders (authorities, hospital-internal actors, experts). The general hospital contributed ca. 38% to the total pharmaceutical load at the wastewater treatment plant, the psychiatry contributed 5%. For the general hospital, alternatives removing all pharmaceuticals (especially reverse osmosis, or vacuum-toilets and incineration), performed systematically better than the status quo or urine separation, despite higher costs. They now require closer scrutiny. To remove X-ray contrast agents, introducing roadbags is promising. For the psychiatry with a lower pharmaceutical load, costs were more critical. Stakeholder feedback concerning MCDA was very positive, especially because the results were robust across different stakeholder-types. Our MCDA results provide insight into an important water protection issue: implementing measures to decrease pharmaceuticals will likely meet acceptance. Hospital point-sources merit consideration if the trade-off between costs and pharmaceutical removal is reasonable.

  18. An atlas of gene regulatory networks reveals multiple three-gene mechanisms for interpreting morphogen gradients

    PubMed Central

    Cotterell, James; Sharpe, James

    2010-01-01

    The interpretation of morphogen gradients is a pivotal concept in developmental biology, and several mechanisms have been proposed to explain how gene regulatory networks (GRNs) achieve concentration-dependent responses. However, the number of different mechanisms that may exist for cells to interpret morphogens, and the importance of design features such as feedback or local cell–cell communication, is unclear. A complete understanding of such systems will require going beyond a case-by-case analysis of real morphogen interpretation mechanisms and mapping out a complete GRN ‘design space.' Here, we generate a first atlas of design space for GRNs capable of patterning a homogeneous field of cells into discrete gene expression domains by interpreting a fixed morphogen gradient. We uncover multiple very distinct mechanisms distributed discretely across the atlas, thereby expanding the repertoire of morphogen interpretation network motifs. Analyzing this diverse collection of mechanisms also allows us to predict that local cell–cell communication will rarely be responsible for the basic dose-dependent response of morphogen interpretation networks. PMID:21045819

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed

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

    2016-12-01

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

  1. Genetic control of photoperiod sensitivity in maize revealed by joint multiple population analysis.

    PubMed

    Coles, Nathan D; McMullen, Michael D; Balint-Kurti, Peter J; Pratt, Richard C; Holland, James B

    2010-03-01

    Variation in maize for response to photoperiod is related to geographical adaptation in the species. Maize possesses homologs of many genes identified as regulators of flowering time in other species, but their relation to the natural variation for photoperiod response in maize is unknown. Candidate gene sequences were mapped in four populations created by crossing two temperate inbred lines to two photoperiod-sensitive tropical inbreds. Whole-genome scans were conducted by high-density genotyping of the populations, which were phenotyped over 3 years in both short- and long-day environments. Joint multiple population analysis identified genomic regions controlling photoperiod responses in flowering time, plant height, and total leaf number. Four key genome regions controlling photoperiod response across populations were identified, referred to as ZmPR1-4. Functional allelic differences within these regions among phenotypically similar founders suggest distinct evolutionary trajectories for photoperiod adaptation in maize. These regions encompass candidate genes CCA/LHY, CONZ1, CRY2, ELF4, GHD7, VGT1, HY1/SE5, TOC1/PRR7/PPD-1, PIF3, ZCN8, and ZCN19.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

    Haematopoiesis is the complex developmental process that maintains the turnover of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whether this paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium berghei infection, as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. We show that, despite highly variable inter-host responses, primitive HSCs become highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1(+) progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and its host's haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host. © 2016 The Authors.

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

    PubMed

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

    2016-10-01

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

  8. Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients

    PubMed Central

    2014-01-01

    Background Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. Methods We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Results Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients’ clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Conclusions Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology

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

    PubMed Central

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

    2014-01-01

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

  10. Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis.

    PubMed

    Zelzer, Elazar; McLean, William; Ng, Yin-Shan; Fukai, Naomi; Reginato, Anthony M; Lovejoy, Stephanie; D'Amore, Patricia A; Olsen, Bjorn R

    2002-04-01

    Angiogenesis is an essential component of skeletal development and VEGF signaling plays an important if not pivotal role in this process. Previous attempts to examine the roles of VEGF in vivo have been largely unsuccessful because deletion of even one VEGF allele leads to embryonic lethality before skeletal development is initiated. The availability of mice expressing only the VEGF120 isoform (which do survive to term) has offered an opportunity to explore the function of VEGF during embryonic skeletal development. Our study of these mice provides new in vivo evidence for multiple important roles of VEGF in both endochondral and intramembranous bone formation, as well as some insights into isoform-specific functions. There are two key differences in vascularization of developing bones between wild-type and VEGF(120/120) mice. VEGF(120/120) mice have not only a delayed recruitment of blood vessels into the perichondrium but also show delayed invasion of vessels into the primary ossification center, demonstrating a significant role of VEGF at both an early and late stage of cartilage vascularization. These findings are the basis for a two-step model of VEGF-controlled vascularization of the developing skeleton, a hypothesis that is supported by the new finding that VEGF is expressed robustly in the perichondrium and surrounding tissue of cartilage templates of future bones well before blood vessels appear in these regions. We also describe new in vivo evidence for a possible role of VEGF in chondrocyte maturation, and document that VEGF has a direct role in regulating osteoblastic activity based on in vivo evidence and organ culture experiments.

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

    PubMed

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

    2008-03-01

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

  12. Fine-root responses to fertilization reveal multiple nutrient limitation in a lowland tropical forest.

    PubMed

    Wurzburger, Nina; Wright, S Joseph

    2015-08-01

    Questions remain as to which soil nutrients limit primary production in tropical forests. Phosphorus (P) has long been considered the primary limiting element in lowland forests, but recent evidence demonstrates substantial heterogeneity in response to nutrient addition, highlighting a need to understand and diagnose nutrient limitation across diverse forests. Fine-root characteristics including their abundance, functional traits, and mycorrhizal symbionts can be highly responsive to changes in soil nutrients and may help to diagnose nutrient limitation. Here, we document the response of fine roots to long-term nitrogen (N), P, and potassium (K) fertilization in a lowland forest in Panama. Because this experiment has demonstrated that N and K together limit tree growth and P limits fine litter production, we hypothesized that fine roots would also respond to nutrient addition. Specifically we hypothesized that N, P, and K addition would reduce the biomass, diameter, tissue density, and mycorrhizal colonization of fine roots, and increase nutrient concentration in root tissue. Most morphological root traits responded to the single addition of K and the paired addition of N and P, with the greatest response to all three nutrients combined. The addition of N, P, and K together reduced fine-root biomass, length, and tissue density, and increased specific root length, whereas root diameter remained unchanged. Nitrogen addition did not alter root N concentration, but P and K addition increased root P and K concentration, respectively. Mycorrhizal colonization of fine roots declined with N, increased with P, and was unresponsive to K addition. Although plant species composition remains unchanged after 14 years of fertilization, fine-root characteristics responded to N, P, and K addition, providing some of the strongest stand-level responses in this experiment. Multiple soil nutrients regulate fine-root abundance, morphological and chemical traits, and their association

  13. Multiple severe typhoons in recent history revealed by coral boulders of northwestern Luzon, Philippines

    NASA Astrophysics Data System (ADS)

    Gong, Shou-Yeh; Wu, Tso-Ren; Liu, Sze-Chieh; Shen, Chuan-Chou; Siringan, Fernando; Lin, Han-Wei

    2017-04-01

    Meter-sized coral boulders occurred on Holocene reef flat at Pasuquin, Ilocos Norte and Cabugao, Ilocos Sur, Philippines. Boulders larger than 3 meters were located and measured by field survey and UAV photogrammetry. Boulders now distributed 45-140 m away from edge of Holocene reef flat, and above highest high tide. The lithology of those boulders is the same as the underlying Holocene coral reef at the sites, hence believed to be broken from reef edge locally. Fossil corals in those boulders mostly appeal not in upward-growing attitude but overturned or tilted. Several tens of photos were taken around selected boulders from different angles, and 3D models were established from the photos. Dimension and volumes were calculated from 3D models. Boulder volumes can be estimated much more accurately this way than simply multiple X, Y, and Z as many previous studies did. The volumes of boulders larger than 3 m in length vary from 10-52.6 m3. Assuming 2.1 g/cm3 for wet density, weights of boulders are estimated to range from 21-110 metric tons. Boulders of such size and weight obviously can't be moved by normal waves, and likely dislodged by Extreme Wave Event (EWE). Small and well-preserved corals were found in depressions on boulder surface and interpreted to represent timing of final displacement. Corals found on seven boulders at Pasuquin were 230Th dated to be 1782, 1904, 1946, 1957, 1978 and 2003 AD respectively. No tsunami was reported in historical records in northern Luzon for those years, but several documented typhoons could be responsible for displacement of each of those boulders. Another Porites boulder at Cabugao was dated to be tilted five times from 673-838 AD, averaging one EWE every 33 years. Such frequent occurrence of EWE is unlikely resulted from tsunami. Therefore, those coral boulders at Pasuquin and Cabugao are interpreted to be displaced by severe typhoons.

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

    PubMed Central

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

    2016-01-01

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

  15. Multiple Mitochondrial Introgression Events and Heteroplasmy in Trypanosoma cruzi Revealed by Maxicircle MLST and Next Generation Sequencing

    PubMed Central

    Messenger, Louisa A.; Llewellyn, Martin S.; Bhattacharyya, Tapan; Franzén, Oscar; Lewis, Michael D.; Ramírez, Juan David; Carrasco, Hernan J.; Andersson, Björn; Miles, Michael A.

    2012-01-01

    Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles (∼20 kb) and thousands of minicircles (0.5–10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30–35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs. Methodology/Principal Findings To describe intra-DTU diversity, we developed a highly resolutive maxicircle multilocus sequence typing (mtMLST) scheme based on ten gene fragments. A panel of 32 TcI isolates was genotyped using the mtMLST scheme, GPI, mini-exon and 25 microsatellite loci. Comparison of nuclear and mitochondrial data revealed clearly incongruent phylogenetic histories among different geographical populations as well as major DTUs. In parallel, we exploited read depth data, generated by Illumina sequencing of the maxicircle genome from the TcI reference strain Sylvio X10/1, to provide the first evidence of mitochondrial heteroplasmy (heterogeneous mitochondrial genomes in an individual cell) in T. cruzi. Conclusions/Significance mtMLST provides a powerful approach to genotyping at the sub-DTU level. This strategy will facilitate attempts to resolve phenotypic variation in T. cruzi and to address epidemiologically important hypotheses in conjunction with intensive spatio-temporal sampling. The observations of both general and specific incidences of nuclear

  16. Spatiotemporal Categorical Map Fusion (SCaMF) - A methodology to fuse multiple categorical maps in space and time using parallel computing

    NASA Astrophysics Data System (ADS)

    Rodriguez Jeangros, N.; Hering, A. S.; Kaiser, T.; McCray, J. E.

    2016-12-01

    Land cover (LC) is a critical variable driving many environmental processes, so its assessment, monitoring, and characterization are essential inputs to study those processes. However, existing LC products, derived primarily from satellite spectral imagery, each have different temporal and spatial resolutions and different LC classes. Most effort is focused on either fusing a pair of LC products over a small space-time region or on interpolating missing values in an individual LC product. We developed a method for fusing multiple existing LC products to produce a single LC record for a large spatial-temporal grid. The methodology is also suitable other categorical maps and for down or up-scaling a single LC product. We first reconcile the LC classes of different LC products, and then we present a probabilistic nearest neighbor estimator of LC class. This estimator depends on three unknown parameters, which are estimated using numerical optimization to maximize an agreement criterion that we define. Each pixel in the grid has an independent estimator, and therefore, the methodology is highly suitable for a parallel implementation. We implemented the methodology in C++ using MPI libraries for the parallelism. Initially, we had one master process and multiple worker processes, the master was receiving the processed data for individual pixels from the workers and writing it on the file using the GDAL library, a library used for processing geospatial data. In this case the limiting factor for the simulation duration was the capacity of the master process to write the file pixel per pixel. Then, we increased the number of pixels processed in each worker before the master received the data and wrote it in the file, reducing the simulation time. Finally, we modified the code to supplement the use of the GDAL library with MPI IO so that a file could be written simultaneously by different worker processes without having to send their results to the master process. Running a

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

    PubMed

    Rothlein, David; Rapp, Brenda

    2014-04-01

    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 shortcomings 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 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

  19. 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.

  20. 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

  1. The Eurasian invasion: phylogenomic data reveal multiple Southeast Asian origins for Indian Dragon Lizards.

    PubMed

    Grismer, Jesse L; Schulte, James A; Alexander, Alana; Wagner, Philipp; Travers, Scott L; Buehler, Matt D; Welton, Luke J; Brown, Rafe M

    2016-02-19

    The Indian Tectonic Plate split from Gondwanaland approximately 120 MYA and set the Indian subcontinent on a ~ 100 million year collision course with Eurasia. Many phylogenetic studies have demonstrated the Indian subcontinent brought with it an array of endemic faunas that evolved in situ during its journey, suggesting this isolated subcontinent served as a source of biodiversity subsequent to its collision with Eurasia. However, recent molecular studies suggest that Eurasia may have served as the faunal source for some of India's biodiversity, colonizing the subcontinent through land bridges between India and Eurasia during the early to middle Eocene (~35-40 MYA). In this study we investigate whether the Draconinae subfamily of the lizard family Agamidae is of Eurasian or Indian origin, using a multi locus Sanger dataset and a novel dataset of 4536 ultraconserved nuclear element loci. Results from our phylogenetic and biogeographic analyses revealed support for two independent colonizations of India from Eurasian ancestors during the early to late Eocene prior to the subcontinent's hard collision with Eurasia. These results are consistent with other faunal groups and new geologic models that suggest ephemeral Eocene land bridges may have allowed for dispersal and exchange of floras and faunas between India and Eurasia during the Eocene.

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

    PubMed Central

    Salje, Jeanne

    2014-01-01

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

  3. 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

  4. 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.

  5. The genotypes of citrus tristeza virus isolates from China revealed by sequence analysis of multiple molecular markers.

    PubMed

    Wu, Guan-Wei; Pan, Song; Wang, Guo-Ping; Tang, Min; Liu, Yong; Yang, Fan; Hong, Ni

    2013-01-01

    The genotypes of ten citrus tristeza virus (CTV) isolates from central China were determined by examining multiple molecular markers (MMMs) using 11 primer pairs. The results revealed that one isolate contained a single T30 genotype, two isolates contained a single VT genotype, and the other seven isolates were mixtures of two or more genotypes. Sequence analysis of amplified MMMs showed a high genetic diversity in Chinese CTV populations. The genotypes resembling T36, RB and B165 were identified from Chinese CTV isolates for the first time. Our results suggest that genotype assignment of CTV cannot be based solely on the amplification profiles of MMMs, and sequencing of MMMs is required.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-12-01

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

  8. Kinetic analyses reveal multiple steps in forming TonB-FhuA complexes from Escherichia coli.

    PubMed

    Khursigara, Cezar M; De Crescenzo, Gregory; Pawelek, Peter D; Coulton, James W

    2005-03-08

    FhuA, an outer membrane receptor of Escherichia coli, facilitates transport of hydroxamate siderophores and siderophore-antibiotic conjugates. The cytoplasmic membrane complex TonB-ExbB-ExbD provides energy for transport via the proton motive force. This energy is transduced by protein-protein interactions between TonB and FhuA, but the molecular determinants of these interactions remain uncharacterized. Our analyses of FhuA and two recombinant TonB species by surface plasmon resonance revealed that TonB undergoes a kinetically limiting rearrangement upon initial interaction with FhuA: an intermediate TonB-FhuA complex of 1:1 stoichiometry was detected. The intermediate then recruits a second TonB protein. Addition of ferricrocin, a FhuA-specific ligand, enhanced amounts of the 2:1 complex but was not essential for its formation. To assess the role of the cork domain of FhuA in forming a 2:1 TonB-FhuA complex, we tested a FhuA deletion (residues 21-128) for its ability to interact with TonB. Analytical ultracentrifugation demonstrated that deletion of this region of the cork domain resulted in a 1:1 complex. Furthermore, the high-affinity 2:1 complex requires the N-terminal region of TonB. Together these in vitro experiments establish that TonB-FhuA interactions require sequential steps of kinetically limiting rearrangements. Additionally, domains that contribute to complex formation were identified in TonB and in FhuA.

  9. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    PubMed Central

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

    Objective Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Methods Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. Results 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. Conclusions These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast

  10. Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes.

    PubMed

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

    Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and

  11. Multiple Oxygen Tension Environments Reveal Diverse Patterns of Transcriptional Regulation in Primary Astrocytes

    PubMed Central

    Zhou, Yu; Wang, Liyun; Park, Sung-Soo; Martin, Bronwen; Wang, Rui; Becker, Kevin G.; Wood, William H.; Zhang, Yongqing; Peers, Chris; Maudsley, Stuart

    2011-01-01

    The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity. PMID:21738745

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

    PubMed Central

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

    2017-01-01

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

  13. 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

  14. 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.

  15. Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children

    PubMed Central

    Haberer, Jessica E.; Kiwanuka, Julius; Nansera, Denis; Ragland, Kathleen; Mellins, Claude; Bangsberg, David R.

    2012-01-01

    Background Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of ≥48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = −0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6–5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0–2.0; p = 0.04), and caregiver’s alcohol use (AOR 3.1, 95%CI 1.8–5.2; p<0.0001). Child’s use of co-trimoxazole (AOR 0.5, 95%CI 0.4–0.9; p = 0.009), caregiver’s use of ART (AOR 0.6, 95%CI 0.4–0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4–0.8; p = 0.001), and caregiver feeling ashamed of child’s HIV status (AOR 0.5, 95%CI 0.3–0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5–11.5; p = 0.009) and caregiver’s alcohol use (AOR 5.5, 95%CI 2.8–10.7; p<0.0001) were associated with ≥48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1–0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6–0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance Adherence success depends on a well-established medication taking routine, including caregiver support and adequate

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. 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

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

    PubMed

    Park, Youngjin; González-Martínez, Rosa M; Navarro-Cerrillo, Gloria; Chakroun, Maissa; Kim, Yonggyun; Ziarsolo, Pello; Blanca, Jose; Cañizares, Joaquin; Ferré, Juan; Herrero, Salvador

    2014-06-09

    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. 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. 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.

  20. iTRAQ-based quantitative proteomic analysis reveals multiple effects of Emodin to Haemophilus parasuis.

    PubMed

    Li, Li; Tian, Ye; Yu, Jiankang; Song, Xu; Jia, Renyong; Cui, Qiankun; Tong, Wenzhi; Zou, Yuanfeng; Li, Lixia; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Yue, Guizhou; Ye, Gang; Zhao, Ling; Shi, Fei; Lv, Cheng; Cao, Sanjie; Yin, Zhongqiong

    2017-08-23

    Haemophilus parasuis, a symbiotic bacteria of upper respiratory tract of swine, is the etiological agent of Glässer's disease, which is characterized by fibrinous polyserositis. Emodin, exhibits antibacterial activity against H. parasuis, yet the action mode has not been fully understood. In present study, isobaric tag for relative and absolute quantification (iTRAQ) method was applied to analyze the global protein alteration of H. parasuis in response to 16μg/mL Emodin. In total, 338 proteins exhibiting significant differential expressions were identified. It was speculated that, through application of bioinformatics analysis to theses differentially expressed proteins, Emodin mainly inhibited some key proteins expression of ABC transport system, carbohydrate metabolism pathway and bacterial cell division by inhibiting the ribosome synthesis, resulting in the growth inhibition of H. parasuis. Remarkably, nine virulence-associated proteins were detected differently expressed, further experiments revealed that after treatment with Emodin, H. parasuis could be inhibited to adhere to and invade into porcine kidney epithelial cells (PK-15 line) and exhibited increased sensitivity to serum complement in a concentration-dependent manner. Phagocytosis assay showed Emodin also could enhance phagocytic activity of porcine alveolar macrophages PAM to H. parasuis. These results indicated that Emodin also can attenuate virulence of H. parasuis and reduce infection. The Glässer's disease caused by H. parasuis has become a typical bacterial disease and cause serious economic loss to the swine industry around the world. Antibiotics are extensively used to control the infection, but increasing antibiotic resistance has been a severe problem. Hence, novel treatment agents are needed. So far, few antibacterial agents were reported that could control H. parasuis infection. In the present study, the state-of-the-art quantitative proteomic technology was applied to uncover

  1. How to reveal people's preferences: Comparing time consistency and predictive power of multiple price list risk elicitation methods.

    PubMed

    Csermely, Tamás; Rabas, Alexander

    2016-01-01

    The question of how to measure and classify people's risk preferences is of substantial importance in the field of economics. Inspired by the multitude of ways used to elicit risk preferences, we conduct a holistic investigation of the most prevalent method, the multiple price list (MPL) and its derivations. In our experiment, we find that revealed preferences differ under various versions of MPLs as well as yield unstable results within a 30-minute time frame. We determine the most stable elicitation method with the highest forecast accuracy by using multiple measures of within-method consistency and by using behavior in two economically relevant games as benchmarks. A derivation of the well-known method by Holt and Laury (American Economic Review 92(5):1644-1655, 2002), where the highest payoff is varied instead of probabilities, emerges as the best MPL method in both dimensions. As we pinpoint each MPL characteristic's effect on the revealed preference and its consistency, our results have implications for preference elicitation procedures in general.

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

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

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-04-01

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

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

    PubMed Central

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

    2016-01-01

    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

  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.

  9. Spatiotemporal multipartite entanglement

    SciTech Connect

    Kolobov, Mikhail I.; Patera, Giuseppe

    2011-05-15

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

  10. Spatiotemporal Optical Vortices

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

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

    PubMed

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

    2014-07-01

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

  12. 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.

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

    PubMed Central

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

    2016-01-01

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

  14. 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.

  15. Spatiotemporal Interactions in Retinal Prosthesis Subjects

    PubMed Central

    Greenberg, Robert J.; Fine, Ione

    2010-01-01

    Purpose. Vision loss due to retinitis pigmentosa affects an estimated 15 million people worldwide. Through collaboration between Second Sight Medical Products, Inc., and the Doheny Eye Institute, six blind human subjects underwent implantation with epiretinal 4 × 4 electrode arrays designed to directly stimulate the remaining cells of the retina, with the goal of restoring functional vision by applying spatiotemporal patterns of stimulation. To better understand spatiotemporal interactions between electrodes during synchronous and asynchronous stimulation, the authors investigated how percepts changed as a function of pulse timing across the electrodes. Methods. Pulse trains (20, 40, 80, and 160 Hz) were presented on groups of electrodes with 800, 1600, or 2400 μm center-to-center separation. Stimulation was either synchronous (pulses were presented simultaneously across electrodes) or asynchronous (pulses were phase shifted). Using a same-different discrimination task, the authors were able to evaluate how the perceptual quality of the stimuli changed as a function of phase shifts across multiple electrodes. Results. Even after controlling for electric field interactions, subjects could discriminate between spatiotemporal pulse train patterns based on differences of phase across electrodes as small as 3 ms. These findings suggest that the quality of the percept is affected not only by electric field interactions but also by spatiotemporal interactions at the neural level. Conclusions. During multielectrode stimulation, interactions between electrodes have a significant influence on the quality of the percept. Understanding how these spatiotemporal interactions at the neural level influence percepts during multielectrode stimulation is fundamental to the successful design of a retinal prosthesis. PMID:19741248

  16. 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

  17. 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

  18. Single-copy nuclear genes place haustorial Hydnoraceae within piperales and reveal a cretaceous origin of multiple parasitic angiosperm lineages.

    PubMed

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

    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.

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

    PubMed

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

    2003-06-01

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

  20. 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.

  1. Indeterminacy of spatiotemporal cardiac alternans

    NASA Astrophysics Data System (ADS)

    Zhao, Xiaopeng

    2008-07-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in electrocardiogram morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the United States each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Using numerical simulation and theoretical analysis, we show that the coexistence of multiple alternans patterns is induced by the interaction between electrotonic coupling and an instability in calcium cycling.

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

    PubMed

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

    2016-11-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Analysis of a zebrafish dync1h1 mutant reveals multiple functions for cytoplasmic dynein 1 during retinal photoreceptor development

    PubMed Central

    2010-01-01

    Background Photoreceptors of the retina are highly compartmentalized cells that function as the primary sensory neurons for receiving and initiating transmission of visual information. Proper morphogenesis of photoreceptor neurons is essential for their normal function and survival. We have characterized a zebrafish mutation, cannonball, that completely disrupts photoreceptor morphogenesis. Results Analysis revealed a non-sense mutation in cytoplasmic dynein heavy chain 1 (dync1h1), a critical subunit in Dynein1, to underlie the cannonball phenotypes. Dynein1 is a large minus-end directed, microtubule motor protein complex that has been implicated in multiple, essential cellular processes. In photoreceptors, Dynein1 is thought to mediate post-Golgi vesicle trafficking, while Dynein2 is thought to be responsible for outer segment maintenance. Surprisingly, cannonball embryos survive until larval stages, owing to wild-type maternal protein stores. Retinal photoreceptor neurons, however, are significantly affected by loss of Dync1h1, as transmission electron microscopy and marker analyses demonstrated defects in organelle positioning and outer segment morphogenesis and suggested defects in post-Golgi vesicle trafficking. Furthermore, dosage-dependent antisense oligonucleotide knock-down of dync1h1 revealed outer segment abnormalities in the absence of overt inner segment polarity and trafficking defects. Consistent with a specific function of Dync1h1 within the outer segment, immunolocalization showed that this protein and other subunits of Dynein1 and Dynactin localized to the ciliary axoneme of the outer segment, in addition to their predicted inner segment localization. However, knock-down of Dynactin subunits suggested that this protein complex, which is known to augment many Dynein1 activities, is only essential for inner segment processes as outer segment morphogenesis was normal. Conclusions Our results indicate that Dynein1 is required for multiple cellular

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. Multiplicity

    DTIC Science & Technology

    1991-04-01

    practice as a "[descent] into that inner circle of the Inferno where the damned endlessly degate multiplicity for sentencing." United States v. Barnard...select the charges to be brought in a particular case"). 19 Brown v. Ohio, 432 U.S. 161, 165 (1977). 20 Whalen v. United States, 445 U.S. at 689. 21...parte Lange, 8-5 U.S. (19 Wall.) 163 (1874). Cf. Brown v. Ohio, 432 U.S. at 165 ("once the legislature has acted courts may not impose more than one

  7. 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.

  8. Cutting edge genomics reveal new insights into tumour development, disease progression and therapeutic impacts in multiple myeloma.

    PubMed

    Dutta, Ankit K; Hewett, Duncan R; Fink, J Lynn; Grady, John P; Zannettino, Andrew C W

    2017-07-01

    Multiple Myeloma (MM) is a haematological malignancy characterised by the clonal expansion of plasma cells (PCs) within the bone marrow. Despite advances in therapy, MM remains a largely incurable disease with a median survival of 6 years. In almost all cases, the development of MM is preceded by the benign PC condition Monoclonal Gammopathy of Undetermined Significance (MGUS). Recent studies show that the transformation of MGUS to MM is associated with complex genetic changes. Understanding how these changes contribute to evolution will present targets for clinical intervention. We discuss three models of MM evolution; the linear, the expansionist and the intraclonal heterogeneity models. Of particular interest is the intraclonal heterogeneity model. Here, distinct populations of MM PCs carry differing combinations of genetic mutations. Acquisition of additional mutations can contribute to subclonal lineages where "driver" mutations may influence selective pressure and dominance, and "passenger" mutations are neutral in their effects. Furthermore, studies show that clinical intervention introduces additional selective pressure on tumour cells and can influence subclone survival, leading to therapy resistance. This review discusses how Next Generation Sequencing approaches are revealing critical insights into the genetics of MM development, disease progression and treatment. MM disease progression will illuminate possible mechanisms underlying the tumour. © 2017 John Wiley & Sons Ltd.

  9. 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. Copyright © 2014 the American Physiological Society.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-05-18

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2017-03-06

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  16. 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. © 2015 Phycological Society of America.

  17. Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis

    PubMed Central

    Goldman, Devorah C.; Donley, Nathan; Christian, Jan L.

    2010-01-01

    Vertebrate Bmp2 and Bmp4 diverged from a common ancestral gene and encode closely related proteins. Mice homozygous for null mutations in either gene show early embryonic lethality, thereby precluding analysis of shared functions. In the current studies, we present phenotypic analysis of compound mutant mice heterozygous for a null allele of Bmp2 in combination with null or hypomorphic alleles of Bmp4. Whereas mice lacking a single copy of Bmp2 or Bmp4 are viable and have subtle developmental defects, compound mutants show embryonic and postnatal lethality due to defects in multiple organ systems including the allantois, placental vasculature, ventral body wall, skeleton, eye and heart. Within the heart, BMP2 and BMP4 function coordinately to direct normal lengthening of the outflow tract, proper positioning of the outflow vessels, and septation of the atria, ventricle and atrioventricular canal. Our results identify numerous BMP4-dependent developmental processes that are also very sensitive to BMP2 dosage, thus revealing novel functions of Bmp2. PMID:19116164

  18. 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.

  19. 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

  20. Molecular phylogeny of bark and ambrosia beetles reveals multiple origins of fungus farming during periods of global warming.

    PubMed

    Jordal, Bjarte H; Cognato, Anthony I

    2012-08-01

    Fungus farming is an unusual life style in insects that has evolved many times in the wood boring weevils named 'ambrosia beetles'. Multiple occurrences of this behaviour allow for a detailed comparison of the different origins of fungus farming through time, its directionality, and possible ancestral states. We tested these hypotheses with a phylogeny representing the largest data set to date, nearly 4 kb of nucleotides from COI, EF-1α, CAD, ArgK, 28S, and 200 scolytine taxa. Phylogenetic analyses using Bayesian or parsimony approaches placed the root of Scolytinae close to the tribe Scolytini and Microborus, but otherwise indicated low resolution at older nodes. More recent clades were well resolved, including ten origins of fungus farming. There were no subsequent reversals to bark or phloem feeding in the fungus farming clades. The oldest origin of fungus farming was estimated near 50 Ma, long after the origin of Scolytinae (100-120 Ma). Younger origins included the species rich Xyleborini, dated to 21 Ma. Sister group comparisons and test of independence between traits indicated that neither gregarious larval feeding nor regular inbreeding by sibling mating was strongly correlated with the origin of fungus farming. Origins of fungus farming corresponded mainly with two periods of global warming in the Cenozoic era, which were characterised by broadly distributed tropical forests. Hence, it seems likely that warm climates and expanding tropical angiosperm forests played critical roles in the successful radiation of diverse fungus farming groups. However, further investigation will likely reveal additional biological factors that promote fungus farming.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-12-06

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

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

    PubMed

    Burraco, Pablo; Gomez-Mestre, Ivan

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

  4. Molecular phylogeny of bark and ambrosia beetles reveals multiple origins of fungus farming during periods of global warming

    PubMed Central

    2012-01-01

    Background Fungus farming is an unusual life style in insects that has evolved many times in the wood boring weevils named ‘ambrosia beetles’. Multiple occurrences of this behaviour allow for a detailed comparison of the different origins of fungus farming through time, its directionality, and possible ancestral states. We tested these hypotheses with a phylogeny representing the largest data set to date, nearly 4 kb of nucleotides from COI, EF-1α, CAD, ArgK, 28S, and 200 scolytine taxa. Results Phylogenetic analyses using Bayesian or parsimony approaches placed the root of Scolytinae close to the tribe Scolytini and Microborus, but otherwise indicated low resolution at older nodes. More recent clades were well resolved, including ten origins of fungus farming. There were no subsequent reversals to bark or phloem feeding in the fungus farming clades. The oldest origin of fungus farming was estimated near 50 Ma, long after the origin of Scolytinae (100-120 Ma). Younger origins included the species rich Xyleborini, dated to 21 Ma. Sister group comparisons and test of independence between traits indicated that neither gregarious larval feeding nor regular inbreeding by sibling mating was strongly correlated with the origin of fungus farming. Conclusion Origins of fungus farming corresponded mainly with two periods of global warming in the Cenozoic era, which were characterised by broadly distributed tropical forests. Hence, it seems likely that warm climates and expanding tropical angiosperm forests played critical roles in the successful radiation of diverse fungus farming groups. However, further investigation will likely reveal additional biological factors that promote fungus farming. PMID:22852794

  5. Species delimitation in lemurs: multiple genetic loci reveal low levels of species diversity in the genus Cheirogaleus

    PubMed Central

    Groeneveld, Linn F; Weisrock, David W; Rasoloarison, Rodin M; Yoder, Anne D; Kappeler, Peter M

    2009-01-01

    Background Species are viewed as the fundamental unit in most subdisciplines of biology. To conservationists this unit represents the currency for global biodiversity assessments. Even though Madagascar belongs to one of the top eight biodiversity hotspots of the world, the taxonomy of its charismatic lemuriform primates is not stable. Within the last 25 years, the number of described lemur species has more than doubled, with many newly described species identified among the nocturnal and small-bodied cheirogaleids. Here, we characterize the diversity of the dwarf lemurs (genus Cheirogaleus) and assess the status of the seven described species, based on phylogenetic and population genetic analysis of mtDNA (cytb + cox2) and three nuclear markers (adora3, fiba and vWF). Results This study identified three distinct evolutionary lineages within the genus Cheirogaleus. Population genetic cluster analyses revealed a further layer of population divergence with six distinct genotypic clusters. Conclusion Based on the general metapopulation lineage concept and multiple concordant data sets, we identify three exclusive groups of dwarf lemur populations that correspond to three of the seven named species: C. major, C. medius and C. crossleyi. These three species were found to be genealogically exclusive in both mtDNA and nDNA loci and are morphologically distinguishable. The molecular and morphometric data indicate that C. adipicaudatus and C. ravus are synonymous with C. medius and C. major, respectively. Cheirogaleus sibreei falls into the C. medius mtDNA clade, but in morphological analyses the membership is not clearly resolved. We do not have sufficient data to assess the status of C. minusculus. Although additional patterns of population differentiation are evident, there are no clear subdivisions that would warrant additional specific status. We propose that ecological and more geographic data should be collected to confirm these results. PMID:19193227

  6. 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.

  7. 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.

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

    PubMed

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

    2016-10-01

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

  9. Spatiotemporal analysis of sensor logs using growth ring maps.

    PubMed

    Bak, Peter; Mansmann, Florian; Janetzko, Halldor; Keim, Daniel A

    2009-01-01

    Spatiotemporal analysis of sensor logs is a challenging research field due to three facts: a) traditional two-dimensional maps do not support multiple events to occur at the same spatial location, b) three-dimensional solutions introduce ambiguity and are hard to navigate, and c) map distortions to solve the overlap problem are unfamiliar to most users. This paper introduces a novel approach to represent spatial data changing over time by plotting a number of non-overlapping pixels, close to the sensor positions in a map. Thereby, we encode the amount of time that a subject spent at a particular sensor to the number of plotted pixels. Color is used in a twofold manner; while distinct colors distinguish between sensor nodes in different regions, the colors' intensity is used as an indicator to the temporal property of the subjects' activity. The resulting visualization technique, called Growth Ring Maps, enables users to find similarities and extract patterns of interest in spatiotemporal data by using humans' perceptual abilities. We demonstrate the newly introduced technique on a dataset that shows the behavior of healthy and Alzheimer transgenic, male and female mice. We motivate the new technique by showing that the temporal analysis based on hierarchical clustering and the spatial analysis based on transition matrices only reveal limited results. Results and findings are cross-validated using multidimensional scaling. While the focus of this paper is to apply our visualization for monitoring animal behavior, the technique is also applicable for analyzing data, such as packet tracing, geographic monitoring of sales development, or mobile phone capacity planning.

  10. Spatiotemporal control of cardiac alternans

    NASA Astrophysics Data System (ADS)

    Echebarria, Blas; Karma, Alain

    2002-09-01

    Electrical alternans are believed to be linked to the onset of life-threatening ventricular arrhythmias and sudden cardiac death. Recent studies have shown that alternans can be suppressed temporally by dynamic feedback control of the pacing interval. Here we investigate theoretically whether control can suppress alternans both temporally and spatially in homogeneous tissue paced at a single site. We first carry out ionic model simulations in a one-dimensional cable geometry which show that control is only effective up to a maximum cable length that decreases sharply away from the alternans bifurcation point. We then explain this finding by a linear stability analysis of an amplitude equation that describes the spatiotemporal evolution of alternans. This analysis reveals that control failure above a critical cable length is caused by the formation of standing wave patterns of alternans that are eigenfunctions of a forced Helmholtz equation, and therefore remarkably analogous to sound harmonics in an open pipe. We discuss the implications of these results for using control to suppress alternans in the human ventricles as well as to probe fundamental aspects of alternans morphogenesis.

  11. 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

  12. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    PubMed

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

  13. Spatiotemporal Data Organization and Application Research

    NASA Astrophysics Data System (ADS)

    Tan, C.; Yan, S.

    2017-09-01

    Organization and management of spatiotemporal data is a key support technology for intelligence in all fields of the smart city. The construction of a smart city cannot be realized without spatiotemporal data. Oriented to support intelligent applications this paper proposes an organizational model for spatiotemporal data, and details the construction of a spatiotemporal big data calculation, analysis, and service framework for highly efficient management and intelligent application of spatiotemporal data for the entire data life cycle.

  14. 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.

  15. Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps*

    PubMed Central

    Dao Thi, Viet Loan; Granier, Christelle; Zeisel, Mirjam B.; Guérin, Maryse; Mancip, Jimmy; Granio, Ophélia; Penin, François; Lavillette, Dimitri; Bartenschlager, Ralf; Baumert, Thomas F.; Cosset, François-Loïc; Dreux, Marlène

    2012-01-01

    Hepatitis C virus (HCV) particles assemble along the very low density lipoprotein pathway and are released from hepatocytes as entities varying in their degree of lipid and apolipoprotein (apo) association as well as buoyant densities. Little is known about the cell entry pathway of these different HCV particle subpopulations, which likely occurs by regulated spatiotemporal processes involving several cell surface molecules. One of these molecules is the scavenger receptor BI (SR-BI), a receptor for high density lipoprotein that can bind to the HCV glycoprotein E2. By studying the entry properties of infectious virus subpopulations differing in their buoyant densities, we show that these HCV particles utilize SR-BI in a manifold manner. First, SR-BI mediates primary attachment of HCV particles of intermediate density to cells. These initial interactions involve apolipoproteins, such as apolipoprotein E, present on the surface of HCV particles, but not the E2 glycoprotein, suggesting that lipoprotein components in the virion act as host-derived ligands for important entry factors such as SR-BI. Second, we found that in contrast to this initial attachment, SR-BI mediates entry of HCV particles independent of their buoyant density. This function of SR-BI does not depend on E2/SR-BI interaction but relies on the lipid transfer activity of SR-BI, probably by facilitating entry steps along with other HCV entry co-factors. Finally, our results underscore a third function of SR-BI governed by specific residues in hypervariable region 1 of E2 leading to enhanced cell entry and depending on SR-BI ability to bind to E2. PMID:22767607

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

    PubMed

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

    2017-02-01

    Ecological invasions and colonizations occur dynamically through space and time. Estimating the distribution and abundance of colonizing species is critical for efficient management or conservation. We describe a statistical framework for simultaneously estimating spatiotemporal occupancy and abundance dynamics of a colonizing species. Our method accounts for several issues that are common when modeling spatiotemporal ecological data including multiple levels of detection probability, multiple data sources, and computational limitations that occur when making fine-scale inference over a large spatiotemporal domain. We apply the model to estimate the colonization dynamics of sea otters (Enhydra lutris) in Glacier Bay, in southeastern Alaska. © 2016 by the Ecological Society of America.

  17. Bilinearity in Spatiotemporal Integration of Synaptic Inputs

    PubMed Central

    Li, Songting; Liu, Nan; Zhang, Xiao-hui; Zhou, Douglas; Cai, David

    2014-01-01

    Neurons process information via integration of synaptic inputs from dendrites. Many experimental results demonstrate dendritic integration could be highly nonlinear, yet few theoretical analyses have been performed to obtain a precise quantitative characterization analytically. Based on asymptotic analysis of a two-compartment passive cable model, given a pair of time-dependent synaptic conductance inputs, we derive a bilinear spatiotemporal dendritic integration rule. The summed somatic potential can be well approximated by the linear summation of the two postsynaptic potentials elicited separately, plus a third additional bilinear term proportional to their product with a proportionality coefficient . The rule is valid for a pair of synaptic inputs of all types, including excitation-inhibition, excitation-excitation, and inhibition-inhibition. In addition, the rule is valid during the whole dendritic integration process for a pair of synaptic inputs with arbitrary input time differences and input locations. The coefficient is demonstrated to be nearly independent of the input strengths but is dependent on input times and input locations. This rule is then verified through simulation of a realistic pyramidal neuron model and in electrophysiological experiments of rat hippocampal CA1 neurons. The rule is further generalized to describe the spatiotemporal dendritic integration of multiple excitatory and inhibitory synaptic inputs. The integration of multiple inputs can be decomposed into the sum of all possible pairwise integration, where each paired integration obeys the bilinear rule. This decomposition leads to a graph representation of dendritic integration, which can be viewed as functionally sparse. PMID:25521832

  18. Spatiotemporal Organization of Catalysts Driven by Enhanced Diffusion.

    PubMed

    Weistuch, C; Pressé, S

    2017-09-27

    Recently, both microfluidic and fluorescence correlation spectroscopy experiments have revealed that diffusion coefficients of active biological catalysts (enzymes) rise proportionately to their catalytic rate. Similar effects have also been observed for active material catalysts, such as platinum nanocatalysts in hydrogen peroxide solution. While differences in diffusion coefficients have recently been cleverly exploited to spatially separate active from inactive catalysts, here we investigate the consequences of these novel findings on the spatiotemporal organization of catalysts. In particular, we show that chemical reactions-such as coupled catalytic reactions-may drive effective attraction or repulsion between catalysts which in turn drives their spatiotemporal organization. This, we argue, may have implications for internal cell signaling.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  20. Rainfall spatiotemporal variability relation to wetlands hydroperiods

    NASA Astrophysics Data System (ADS)

    Serrano-Hidalgo, Carmen; Guardiola-Albert, Carolina; Fernandez-Naranjo, Nuria

    2017-04-01

    Doñana natural space (Southwestern Spain) is one of the largest protected wetlands in Europe. The wide marshes present in this natural space have such ecological value that this wetland has been declared a Ramsar reserve in 1982. Apart from the extensive marsh, there are also small lagoons and seasonally flooded areas which are likewise essential to maintain a wide variety of valuable habitats. Hydroperiod, the length of time each point remains flooded along an annual cycle, is a critical ecological parameter that shapes aquatic plants and animals distribution and determines available habitat for many of the living organisms in the marshes. Recently, there have been published two different works estimating the hydroperiod of Doñana lagoons with Landsat Time Series images (Cifuentes et al., 2015; Díaz-Delgado et al., 2016). In both works the flooding cycle hydroperiod in Doñana marshes reveals a flooding regime mainly driven by rainfall, evapotranspiration, topography and local hydrological management actions. The correlation found between rainfall and hydroperiod is studied differently in both works. While in one the rainfall is taken from one raingauge (Cifuentes et al., 2015), the one performed by Díaz-Delgado (2016) uses annual rainfall maps interpolated with the inverse of the distance method. The rainfall spatiotemporal variability in this area can be highly significant; however the amount of this importance has not been quantified at the moment. In the present work the geostatistical tool known as spatiotemporal variogram is used to study the rainfall spatiotemporal variability. The spacetime package implemented in R (Pebesma, 2012) facilities its computation from a high rainfall data base of more than 100 raingauges from 1950 to 2016. With the aid of these variograms the rainfall spatiotemporal variability is quantified. The principal aim of the present work is the study of the relation between the rainfall spatiotemporal variability and the

  1. Bifurcations in Spatiotemporal Systems.

    NASA Astrophysics Data System (ADS)

    Vastano, John Andrew

    The bifurcations leading from simple to complex spatial and temporal behavior in extended systems are just beginning to be characterized. Numerical studies of several one-dimensional reaction-diffusion systems have been conducted to discover the possible bifurcations and to test new diagnostic tools for spatiotemporal systems. Steady state pattern formation was studied in an open reactor with a simple autocatalytic model chemistry. When the diffusion coefficients of all the chemical species are equal, patterns can only form by bifurcations from an already unstable homogeneous state. When the diffusion coefficients are different, patterns can arise via a bifurcation off of the stable homogeneous state. These "Turing bifurcations" yield patterns that have an intrinsic wavelength determined by the interplay of chemical reaction and diffusion. A description of all bifurcations from the steady state for the model system was obtained by using a steady state continuation technique to follow stable and unstable branches of bifurcating solutions. The bifurcations leading to time-dependent patterns in reaction-diffusion systems were studied in a system that models a current experiment by W. Y. Tam and H. L. Swinney. The model chemistry used displays only steady state and limit cycle behavior in a well-mixed system, but when diffusive effects were included, a regime was found in which the system undergoes a transition to chaos as a chemical parameter is tuned. The bifurcation sequence was shown to be that of a single, periodically forced, nonlinear oscillator. The physical mechanisms that cause this behavior were discovered. The model results were shown to be in good agreement with experimental results, indicating that the same physical processes occur in the experiment. In some extended systems the physical mechanisms that create globally observed chaotic behavior are localized. A novel method for characterizing these systems was suggested: an information

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  3. An Integrated Model of Multiple-Condition ChIP-Seq Data Reveals Predeterminants of Cdx2 Binding

    PubMed Central

    Mazzoni, Esteban O.; Sherwood, Richard I.; Kakumanu, Akshay; Morrison, Carolyn A.; Wichterle, Hynek; Gifford, David K.

    2014-01-01

    Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS's multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions. We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2–5. PMID:24675637

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

    PubMed Central

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

    2014-01-01

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

  5. CUTOFF: A spatio-temporal imputation method

    NASA Astrophysics Data System (ADS)

    Feng, Lingbing; Nowak, Gen; O'Neill, T. J.; Welsh, A. H.

    2014-11-01

    Missing values occur frequently in many different statistical applications and need to be dealt with carefully, especially when the data are collected spatio-temporally. We propose a method called CUTOFF imputation that utilizes the spatio-temporal nature of the data to accurately and efficiently impute missing values. The main feature of this method is that the estimate of a missing value is produced by incorporating similar observed temporal information from the value's nearest spatial neighbors. Extensions to this method are also developed to expand the method's ability to accommodate other data generating processes. We develop a cross-validation procedure that optimally chooses parameters for CUTOFF, which can be used by other imputation methods as well. We analyze some rainfall data from 78 gauging stations in the Murray-Darling Basin in Australia using the CUTOFF imputation method and compare its performance to four well-studied competing imputation methods, namely, k-nearest neighbors, singular value decomposition, multiple imputation and random forest. Empirical results show that our method captures the temporal patterns well and is effective at imputing large gaps in the data. Compared to the competing methods, CUTOFF is more accurate and much faster. We analyze further examples to demonstrate CUTOFF's applications to two different data sets and provide extra evidence of its validity and usefulness. We implement a simulation study based on the Murray-Darling Basin data to evaluate the method; the results show that our method performs well in both accuracy and computational efficiency.

  6. Controllable spatiotemporal nonlinear effects in multimode fibres

    NASA Astrophysics Data System (ADS)

    Wright, Logan G.; Christodoulides, Demetrios N.; Wise, Frank W.

    2015-05-01

    Multimode fibres are of interest for next-generation telecommunications systems and the construction of high-energy fibre lasers. However, relatively little work has explored nonlinear pulse propagation in multimode fibres. Here, we consider highly nonlinear ultrashort pulse propagation in the anomalous-dispersion regime of a graded-index multimode fibre. Low modal dispersion and strong nonlinear coupling between the fibre's many spatial modes result in interesting behaviour. We observe spatiotemporal effects reminiscent of nonlinear optics in bulk media—self-focusing and multiple filamentation—at a fraction of the usual power. By adjusting the spatial initial conditions, we generate on-demand, megawatt, ultrashort pulses tunable between 1,550 and 2,200 nm dispersive waves over one octave; intense combs of visible light; and a multi-octave-spanning supercontinuum. Our results indicate that multimode fibres present unique opportunities for observing new spatiotemporal dynamics and phenomena. They also enable the realization of a new type of tunable, broadband fibre source that could be useful for many applications.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Darling, John A; Folino-Rorem, Nadine C

    2009-12-01

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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2015-12-01

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

  11. Integrated Systems View on Networking by Hormones in Arabidopsis Immunity Reveals Multiple Crosstalk for Cytokinin[W

    PubMed Central

    Naseem, Muhammad; Philippi, Nicole; Hussain, Anwar; Wangorsch, Gaby; Ahmed, Nazeer; Dandekar, Thomas

    2012-01-01

    Phytohormones signal and combine to maintain the physiological equilibrium in the plant. Pathogens enhance host susceptibility by modulating the hormonal balance of the plant cell. Unlike other plant hormones, the detailed role of cytokinin in plant immunity remains to be fully elucidated. Here, extensive data mining, including of pathogenicity factors, host regulatory proteins, enzymes of hormone biosynthesis, and signaling components, established an integrated signaling network of 105 nodes and 163 edges. Dynamic modeling and system analysis identified multiple cytokinin-mediated regulatory interactions in plant disease networks. This includes specific synergism between cytokinin and salicylic acid pathways and previously undiscovered aspects of antagonism between cytokinin and auxin in plant immunity. Predicted interactions and hormonal effects on plant immunity are confirmed in subsequent experiments with Pseudomonas syringae pv tomato DC3000 and Arabidopsis thaliana. Our dynamic simulation is instrumental in predicting system effects of individual components in complex hormone disease networks and synergism or antagonism between pathways. PMID:22643121

  12. 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.

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

    PubMed

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

    2017-03-01

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

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

    PubMed Central

    Lemmon, Zachary H.; Doebley, John F.

    2014-01-01

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

  15. 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

  16. 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.

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

    SciTech Connect

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

    2016-04-15

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

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

    PubMed Central

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

    2017-01-01

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

  19. 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.

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

    Deco, Gustavo; Romo, Ranulfo

    2014-01-01

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

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

    PubMed

    Hinsch, A; Buchholz, M; Odinga, S; Borkowski, C; Koop, C; Izbicki, J R; Wurlitzer, M; Krech, T; Wilczak, W; Steurer, S; Jacobsen, F; Burandt, E-C; Stahl, P; Simon, R; Sauter, G; Schlüter, H

    2017-03-01

    For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Reduction of Benzenoid Synthesis in Petunia Flowers Reveals Multiple Pathways to Benzoic Acid and Enhancement in Auxin Transport[W

    PubMed Central

    Orlova, Irina; Marshall-Colón, Amy; Schnepp, Jennifer; Wood, Barbara; Varbanova, Marina; Fridman, Eyal; Blakeslee, Joshua J.; Peer, Wendy Ann; Murphy, Angus S.; Rhodes, David; Pichersky, Eran; Dudareva, Natalia

    2006-01-01

    In plants, benzoic acid (BA) is believed to be synthesized from Phe through shortening of the propyl side chain by two carbons. It is hypothesized that this chain shortening occurs via either a β-oxidative or non-β-oxidative pathway. Previous in vivo isotope labeling and metabolic flux analysis of the benzenoid network in petunia (Petunia hybrida) flowers revealed that both pathways yield benzenoid compounds and that benzylbenzoate is an intermediate between l-Phe and BA. To test this hypothesis, we generated transgenic petunia plants in which the expression of BPBT, the gene encoding the enzyme that uses benzoyl-CoA and benzyl alcohol to make benzylbenzoate, was reduced or eliminated. Elimination of benzylbenzoate formation decreased the endogenous pool of BA and methylbenzoate emission but increased emission of benzyl alcohol and benzylaldehyde, confirming the contribution of benzylbenzoate to BA formation. Labeling experiments with 2H5-Phe revealed a dilution of isotopic abundance in most measured compounds in the dark, suggesting an alternative pathway from a precursor other than Phe, possibly phenylpyruvate. Suppression of BPBT activity also affected the overall morphology of petunia plants, resulting in larger flowers and leaves, thicker stems, and longer internodes, which was consistent with the increased auxin transport in transgenic plants. This suggests that BPBT is involved in metabolic processes in vegetative tissues as well. PMID:17194766

  4. Auditory Perception of Spatiotemporal Patterns

    ERIC Educational Resources Information Center

    Tolkmitt, Frank J.; Brindley, Robin

    1977-01-01

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

  5. Contrasting Responses of the Humboldt Current Ecosystem between the Holocene and MIS5e Interglacials Revealed from Multiple Sediment Records

    NASA Astrophysics Data System (ADS)

    Salvatteci, R.; Schneider, R. R.; Blanz, T.; Martinez, P.; Crosta, X.

    2016-12-01

    The Humboldt Current Ecosystem (HCE) off Peru yields about 10% of the global fish catch, producing more fish per unit area than any other region in the world. The high productivity is maintained by the upwelling of cold, nutrient-rich water from the oxygen minimum zone (OMZ), driven by strong trade winds. However, the potential impacts of climate change on upwelling dynamics and oceanographic conditions in the near future are uncertain, threatening local and global economies. Here, we unravel the response of the HCE to contrasting climatic conditions during the last two interglacials (i.e. Holocene and MIS5e) providing an independent insight about the relation between climatic factors and upwelling and productivity dynamics. For this purpose, we used multiple cores to reconstruct past changes in OMZ and upwelling intensity, productivity and fish biomass variability. Chronologies for the Holocene were obtained by multiple 14C ages and laminae correlations among cores, while for the MIS5e they were mainly done by correlation of prominent features in several proxies with other published records. We used a multiproxy approach including alkenones to reconstruct sea surface temperatures, δ15N as a proxy for water column denitrification, redox sensitive metals as proxies for sediment redox conditions, and diatom and fish debris assemblages to reconstruct ecological changes. The results show a very different response of the HCE to climate conditions during the last 2 interglacials, likely driven by changes in Tropical Pacific dynamics. During the Holocene we find that 1) the Late Holocene exhibits higher multi-centennial scale variability compared to the Early Holocene, 2) increased upwelling and a weak OMZ during the mid-Holocene, and 3) long term increase in productivity (diatoms and fishes) from the Early to the Late Holocene. During the MIS5e we find an 1) intense OMZ, 2) strong water column stratification, 3) high siliceous biomass, and 4) low fish biomass compared

  6. 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

  7. 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.

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

    PubMed

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

    2013-09-01

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

  9. Comparative analysis of mRNA isoform expression in cardiac hypertrophy and development reveals multiple post-transcriptional regulatory modules.

    PubMed

    Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F; Sadoshima, Junichi; Tian, Bin

    2011-01-01

    Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the "fetal gene program". Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3'UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload.

  10. 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

  11. 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. © The Author 2014. Published by

  12. Revealing the popularity of traditional medicine in light of multiple recourses and outcome measurements from a user's perspective in Ghana.

    PubMed

    Sato, Azusa

    2012-12-01

    Traditional medicine is known to be popular in sub-Saharan Africa, where over 80% have reported its utilization. It is claimed to be easily accessible, affordable, available and acceptable, but little is known about at which stage of treatment-seeking individuals turn to traditional medicines and the resulting satisfaction once used. This is due to a paucity of quantitative demand data on how many recourses of care people take for one episode of illness, whether individuals use traditional medicines as a secondary option to orthodox medicines, and if used, how satisfied they are with results. This study presents descriptive data from fieldwork carried out on 772 households in two regions of Ghana to ascertain actions taken for self-reported episodes of acute and previously diagnosed chronic diseases. Quantitative results that show by looking merely at first recourse, use of traditional medicines is fairly low, but once second recourses are accounted for there is a doubling and tripling of incidence of traditional medicine use for acute and chronic diseases, respectively. A commonly used patient-reported outcome measurement, the EuroQol 5 Dimension (EQ5D), is used to measure satisfaction before and after traditional medicine use, to reveal significantly positive changes. The study shows that whilst individuals are highly satisfied with traditional medicine, it is more often the second recourse of treatment with a revealed preference for orthodox medicines as a first recourse. This suggests that research is needed to investigate why individuals turn to traditional medicine only as a second recourse and to clarify the insufficiencies of orthodox treatment. Policies which guide individuals to take the most efficient recourses for given symptoms, and further exploration of key reasons behind high levels of satisfaction following utilization, are encouraged.

  13. Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

    PubMed Central

    Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F.; Sadoshima, Junichi; Tian, Bin

    2011-01-01

    Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload. PMID:21799842

  14. 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

  15. 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.

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

    PubMed Central

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

    2012-01-01

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

  17. Transcriptome and proteomic analyses reveal multiple differences associated with chloroplast development in the spaceflight-induced wheat albino mutant mta.

    PubMed

    Shi, Kui; Gu, Jiayu; Guo, Huijun; Zhao, Linshu; Xie, Yongdun; Xiong, Hongchun; Li, Junhui; Zhao, Shirong; Song, Xiyun; Liu, Luxiang

    2017-01-01

    Chloroplast development is an integral part of plant survival and growth, and occurs in parallel with chlorophyll biosynthesis. However, little is known about the mechanisms underlying chloroplast development in hexaploid wheat. Here, we obtained a spaceflight-induced wheat albino mutant mta. Chloroplast ultra-structural observation showed that chloroplasts of mta exhibit abnormal morphology and distribution compared to wild type. Photosynthetic pigments content was also significantly decreased in mta. Transcriptome and chloroplast proteome profiling of mta and wild type were done to identify differentially expressed genes (DEGs) and proteins (DEPs), respectively. In total 4,588 DEGs including 1,980 up- and 2,608 down-regulated, and 48 chloroplast DEPs including 15 up- and 33 down-regulated were identified in mta. Classification of DEGs revealed that most were involved in chloroplast development, chlorophyll biosynthesis, or photosynthesis. Besides, transcription factors such as PIF3, GLK and MYB which might participate in those pathways were also identified. The correlation analysis between DEGs and DEPs revealed that the transcript-to-protein in abundance was functioned into photosynthesis and chloroplast relevant groups. Real time qPCR analysis validated that the expression level of genes encoding photosynthetic proteins was significantly decreased in mta. Together, our results suggest that the molecular mechanism for albino leaf color formation in mta is a thoroughly regulated and complicated process. The combined analysis of transcriptome and proteome afford comprehensive information for further research on chloroplast development mechanism in wheat. And spaceflight provides a potential means for mutagenesis in crop breeding.

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

    PubMed

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

    2015-09-10

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-01-01

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

  2. Multiparametric flow cytometric analysis of whole blood reveals changes in minor lymphocyte subpopulations of multiple sclerosis patients.

    PubMed

    Teniente-Serra, Aina; Grau-López, Laia; Mansilla, M José; Fernández-Sanmartín, Marco; Ester Condins, Anna; Ramo-Tello, Cristina; Martínez-Cáceres, Eva

    2016-06-01

    The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. Peripheral blood from 40 healthy donors (HD) and 66 MS patients [23 relapsing-remitting (RRMS) without treatment, 27 RRMS undergoing treatment (16 IFN-β, 11 natalizumab), and 16 progressive forms (eight secondary progressive and eight primary progressive)] was analysed by multiparametric flow cytometry. Untreated MS patients showed a decrease in early effector memory (CD45RA(-)CCR7(-)CD27(+)) CD4(+) and CD8(+) T cells and an increase in Th17 lymphocytes in peripheral blood compared with HD. Regarding the effect of treatment, whereas no differences in relative percentages of cellular subpopulations were observed in patients under IFN-β treatment, those under treatment with natalizumab had an increased percentage of early effector memory CD4(+) (CD45RA(-)CCR7(-)CD27(+)), central memory CD8(+) (CD45RA(-)CCR7(+)CD27(+)) T cells, recent thymic emigrants (CD4(+) CD45RA(+)CCR7(+)CD27(+)CD31(+)PTK7(+)) and transitional B cells (CD19(+)CD27(-)CD24(hi)CD38(hi)). Multiparametric flow cytometry analysis of whole blood is a robust, reproducible, and sensitive technology to monitor the effect of MS treatments even in minor lymphocyte subpopulations that might represent useful biomarkers of treatment response.

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

    PubMed

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

    2011-02-04

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

  4. Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis.

    PubMed

    Sureda-Gómez, Miquel; Martín-Durán, José M; Adell, Teresa

    2016-11-15

    The β-catenin-dependent Wnt pathway exerts multiple context-dependent roles in embryonic and adult tissues. In planarians, β-catenin-1 is thought to specify posterior identities through the generation of an anteroposterior gradient. However, the existence of such a gradient has not been directly demonstrated. Here, we use a specific polyclonal antibody to demonstrate that nuclear β-CATENIN-1 exists as an anteroposterior gradient from the pre-pharyngeal region to the tail of the planarian Schmidtea polychroa High levels in the posterior region steadily decrease towards the pre-pharyngeal region but then increase again in the head region. During regeneration, β-CATENIN-1 is nuclearized in both anterior and posterior blastemas, but the canonical WNT1 ligand only influences posterior nuclearization. Additionally, β-catenin-1 is required for proper anterior morphogenesis, consistent with the high levels of nuclear β-CATENIN-1 observed in this region. We further demonstrate that β-CATENIN-1 is abundant in developing and differentiated organs, and is particularly required for the specification of the germline. Altogether, our findings provide the first direct evidence of an anteroposterior nuclear β-CATENIN-1 gradient in adult planarians and uncover novel, context-dependent roles for β-catenin-1 during anterior regeneration and organogenesis. © 2016. Published by The Company of Biologists Ltd.

  5. 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.

  6. 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. © 2015 John Wiley & Sons Ltd.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2001-08-01

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

  10. Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

    PubMed

    Hubbard, Nicholas A; Turner, Monroe P; Ouyang, Minhui; Himes, Lyndahl; Thomas, Binu P; Hutchison, Joanna L; Faghihahmadabadi, Shawheen; Davis, Scott L; Strain, Jeremy F; Spence, Jeffrey; Krawczyk, Daniel C; Huang, Hao; Lu, Hanzhang; Hart, John; Frohman, Teresa C; Frohman, Elliot M; Okuda, Darin T; Rypma, Bart

    2017-11-01

    Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO2 ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO2 . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    SciTech Connect

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

    2016-11-22

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

  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. Multiple M. tuberculosis Phenotypes in Mouse and Guinea Pig Lung Tissue Revealed by a Dual-Staining Approach

    PubMed Central

    Ryan, Gavin J.; Hoff, Donald R.; Driver, Emily R.; Voskuil, Martin I.; Gonzalez-Juarrero, Mercedes; Basaraba, Randall J.; Crick, Dean C.; Spencer, John S.; Lenaerts, Anne J.

    2010-01-01

    A unique hallmark of tuberculosis is the granulomatous lesions formed in the lung. Granulomas can be heterogeneous in nature and can develop a necrotic, hypoxic core which is surrounded by an acellular, fibrotic rim. Studying bacilli in this in vivo microenvironment is problematic as Mycobacterium tuberculosis can change its phenotype and also become acid-fast negative. Under in vitro models of differing environments, M. tuberculosis alters its metabolism, transcriptional profile and rate of replication. In this study, we investigated whether these phenotypic adaptations of M. tuberculosis are unique for certain environmental conditions and if they could therefore be used as differential markers. Bacilli were studied using fluorescent acid-fast auramine-rhodamine targeting the mycolic acid containing cell wall, and immunofluorescence targeting bacterial proteins using an anti-M. tuberculosis whole cell lysate polyclonal antibody. These techniques were combined and simultaneously applied to M. tuberculosis in vitro culture samples and to lung sections of M. tuberculosis infected mice and guinea pigs. Two phenotypically different subpopulations of M. tuberculosis were found in stationary culture whilst three subpopulations were found in hypoxic culture and in lung sections. Bacilli were either exclusively acid-fast positive, exclusively immunofluorescent positive or acid-fast and immunofluorescent positive. These results suggest that M. tuberculosis exists as multiple populations in most conditions, even within seemingly a single microenvironment. This is relevant information for approaches that study bacillary characteristics in pooled samples (using lipidomics and proteomics) as well as in M. tuberculosis drug development. PMID:20559431

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

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. 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.

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

    PubMed

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

    2007-01-01

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

  18. Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function.

    PubMed

    Fidler, Trevor P; Campbell, Robert A; Funari, Trevor; Dunne, Nicholas; Balderas Angeles, Enrique; Middleton, Elizabeth A; Chaudhuri, Dipayan; Weyrch, Andrew S; Abel, E Dale

    2017-07-25

    Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT) 1 and GLUT3 (double knockout [DKO]) specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca(2+) signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  20. The Analysis of Mutant Alleles of Different Strength Reveals Multiple Functions of Topoisomerase 2 in Regulation of Drosophila Chromosome Structure

    PubMed Central

    Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-01-01

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

  1. 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].

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.

    PubMed

    Hirschhorn, J N; Lindgren, C M; Daly, M J; Kirby, A; Schaffner, S F; Burtt, N P; Altshuler, D; Parker, A; Rioux, J D; Platko, J; Gaudet, D; Hudson, T J; Groop, L C; Lander, E S

    2001-07-01

    Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide P<.06), 7q31.3-36 (LOD 3.40 at marker D7S2195 in Sweden, P<.02), 12p11.2-q14 (LOD 3.35 at markers D12S10990-D12S398 in Finland, P<.05) and 13q32-33 (LOD 3.56 at markers D13S779-D13S797 in Finland, P<.05). In a companion article (Perola et al. 2001 [in this issue]), strong supporting evidence is obtained for linkage to the region on chromosome 7. These studies suggest that highly heritable complex traits such as stature may be genetically tractable and provide insight into the genetic architecture of complex traits.

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

    PubMed Central

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

    2007-01-01

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

  6. The integration of multiple independent data reveals an unusual response to Pleistocene climatic changes in the hard tick Ixodes ricinus.

    PubMed

    Porretta, Daniele; Mastrantonio, Valentina; Mona, Stefano; Epis, Sara; Montagna, Matteo; Sassera, Davide; Bandi, Claudio; Urbanelli, Sandra

    2013-03-01

    In the last few years, improved analytical tools and the integration of genetic data with multiple sources of information have shown that temperate species exhibited more complex responses to ice ages than previously thought. In this study, we investigated how Pleistocene climatic changes affected the current distribution and genetic diversity of European populations of the tick Ixodes ricinus, an ectoparasite with high ecological plasticity. We first used mitochondrial and nuclear genetic markers to investigate the phylogeographic structure of the species and its Pleistocene history using coalescent-based methods; then we used species distribution modelling to infer the climatic niche of the species at last glacial maximum; finally, we reviewed the literature on the I. ricinus hosts to identify the locations of their glacial refugia. Our results support the scenario that during the last glacial phase, I. ricinus never experienced a prolonged allopatric divergence in separate glacial refugia, but persisted with interconnected populations across Southern and Central Europe. The generalist behaviour in host choice of I. ricinus would have played a major role in maintaining connections between its populations. Although most of the hosts persisted in separate refugia, from the point of view of I. ricinus, they represented a continuity of 'bridges' among populations. Our study highlights the importance of species-specific ecology in affecting responses to Pleistocene glacial-interglacial cycles. Together with other cases in Europe and elsewhere, it contributes to setting new hypotheses on how species with wide ecological plasticity coped with Pleistocene climatic changes. © 2013 Blackwell Publishing Ltd.

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

    PubMed

    Behrmann-Godel, J; Yohannes, E

    2015-03-01

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

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

    DOE PAGES

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

    2016-10-27

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

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2017-03-01

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

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

    PubMed

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

    2016-11-22

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

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

    PubMed Central

    1996-01-01

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

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

    SciTech Connect

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

    2016-10-27

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

  14. Reticulate evolution: frequent introgressive hybridization among chinese hares (genus lepus) revealed by analyses of multiple mitochondrial and nuclear DNA loci

    PubMed Central

    2011-01-01

    Background Interspecific hybridization may lead to the introgression of genes and genomes across species barriers and contribute to a reticulate evolutionary pattern and thus taxonomic uncertainties. Since several previous studies have demonstrated that introgressive hybridization has occurred among some species within Lepus, therefore it is possible that introgressive hybridization events also occur among Chinese Lepus species and contribute to the current taxonomic confusion. Results Data from four mtDNA genes, from 116 individuals, and one nuclear gene, from 119 individuals, provides the first evidence of frequent introgression events via historical and recent interspecific hybridizations among six Chinese Lepus species. Remarkably, the mtDNA of L. mandshuricus was completely replaced by mtDNA from L. timidus and L. sinensis. Analysis of the nuclear DNA sequence revealed a high proportion of heterozygous genotypes containing alleles from two divergent clades and that several haplotypes were shared among species, suggesting repeated and recent introgression. Furthermore, results from the present analyses suggest that Chinese hares belong to eight species. Conclusion This study provides a framework for understanding the patterns of speciation and the taxonomy of this clade. The existence of morphological intermediates and atypical mitochondrial gene genealogies resulting from frequent hybridization events likely contribute to the current taxonomic confusion of Chinese hares. The present study also demonstrated that nuclear gene sequence could offer a powerful complementary data set with mtDNA in tracing a complete evolutionary history of recently diverged species. PMID:21794180

  15. 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.

  16. 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

  17. Microsatellite analysis of Damask rose (Rosa damascena Mill.) accessions from various regions in Iran reveals multiple genotypes.

    PubMed

    Babaei, Alireza; Tabaei-Aghdaei, Seyed Reza; Khosh-Khui, Morteza; Omidbaigi, Reza; Naghavi, Mohammad Reza; Esselink, Gerhard D; Smulders, Marinus J M

    2007-03-08

    Damask roses (Rosa damascena Mill.) are mainly used for essential oil production. Previous studies have indicated that all production material in Bulgaria and Turkey consists of only one genotype. Nine polymorphic microsatellite markers were used to analyze the genetic diversity of 40 accessions of R. damascena collected across major and minor rose oil production areas in Iran. All microsatellite markers showed a high level of polymorphism (5-15 alleles per microsatellite marker, with an average of 9.11 alleles per locus). Cluster analysis of genetic similarities revealed that these microsatellites identified a total of nine different genotypes. The genotype from Isfahan province, which is the major production area, was by far the most common genotype (27/40 accessions). It was identical to the Bulgarian genotype. Other genotypes (each represented by 1-4 accessions) were collected from minor production areas in several provinces, notably in the mountainous Northwest of Iran. This is the first study that uncovered genetic diversity within Damask rose. Our results will guide new collection activities to establish larger collections and manage the Iranian Damask rose genetic resources. The genotypes identified here may be directly useful for breeding.

  18. Microsatellite analysis of Damask rose (Rosa damascena Mill.) accessions from various regions in Iran reveals multiple genotypes

    PubMed Central

    Babaei, Alireza; Tabaei-Aghdaei, Seyed Reza; Khosh-Khui, Morteza; Omidbaigi, Reza; Naghavi, Mohammad Reza; Esselink, Gerhard D; Smulders, Marinus JM

    2007-01-01

    Background Damask roses (Rosa damascena Mill.) are mainly used for essential oil production. Previous studies have indicated that all production material in Bulgaria and Turkey consists of only one genotype. Nine polymorphic microsatellite markers were used to analyze the genetic diversity of 40 accessions of R. damascena collected across major and minor rose oil production areas in Iran. Results All microsatellite markers showed a high level of polymorphism (5–15 alleles per microsatellite marker, with an average of 9.11 alleles per locus). Cluster analysis of genetic similarities revealed that these microsatellites identified a total of nine different genotypes. The genotype from Isfahan province, which is the major production area, was by far the most common genotype (27/40 accessions). It was identical to the Bulgarian genotype. Other genotypes (each represented by 1–4 accessions) were collected from minor production areas in several provinces, notably in the mountainous Northwest of Iran. Conclusion This is the first study that uncovered genetic diversity within Damask rose. Our results will guide new collection activities to establish larger collections and manage the Iranian Damask rose genetic resources. The genotypes identified here may be directly useful for breeding. PMID:17346330

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

    PubMed

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

    2011-01-01

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

  20. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. 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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2001-11-01

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

  6. Novel rank-based statistical methods reveal microRNAs with differential expression in multiple cancer types.

    PubMed

    Navon, Roy; Wang, Hui; Steinfeld, Israel; Tsalenko, Anya; Ben-Dor, Amir; Yakhini, Zohar

    2009-11-25

    MicroRNAs (miRNAs) regulate target genes at the post-transcriptional level and play important roles in cancer pathogenesis and development. Variation amongst individuals is a significant confounding factor in miRNA (or other) expression studies. The true character of biologically or clinically meaningful differential expression can be obscured by inter-patient variation. In this study we aim to identify miRNAs with consistent differential expression in multiple tumor types using a novel data analysis approach. Using microarrays we profiled the expression of more than 700 miRNAs in 28 matched tumor/normal samples from 8 different tumor types (breast, colon, liver, lung, lymphoma, ovary, prostate and testis). This set is unique in putting emphasis on minimizing tissue type and patient related variability using normal and tumor samples from the same patient. We develop scores for comparing miRNA expression in the above matched sample data based on a rigorous characterization of the distribution of order statistics over a discrete state set, including exact p-values. Specifically, we compute a Rank Consistency Score (RCoS) for every miRNA measured in our data. Our methods are also applicable in various other contexts. We compare our methods, as applied to matched samples, to paired t-test and to the Wilcoxon Signed Rank test. We identify consistent (across the cancer types measured) differentially expressed miRNAs. 41 miRNAs are under-expressed in cancer compared to normal, at FDR (False Discovery Rate) of 0.05 and 17 are over-expressed at the same FDR level. Differentially expressed miRNAs include known oncomiRs (e.g miR-96) as well as miRNAs that were not previously universally associated with cancer. Specific examples include miR-133b and miR-486-5p, which are consistently down regulated and mir-629* which is consistently up regulated in cancer, in the context of our cohort. Data is available in GEO. Software is available at: http://bioinfo.cs.technion.ac.il/people/zohar/RCoS/

  7. 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

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

    PubMed

    Ornelas-García, Claudia Patricia; Domínguez-Domínguez, Omar; Doadrio, Ignacio

    2008-12-22

    occurred by two independent routes, with lineage turnover over a large part of the region. 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 (approximately 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 (approximately 3.3 Mya).

  9. Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder

    PubMed Central

    2013-01-01

    Background We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Methods Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. Results The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher

  10. Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder.

    PubMed

    Sarachana, Tewarit; Hu, Valerie W

    2013-05-22

    We have recently identified the nuclear hormone receptor RORA (retinoic acid-related orphan receptor-alpha) as a novel candidate gene for autism spectrum disorder (ASD). Our independent cohort studies have consistently demonstrated the reduction of RORA transcript and/or protein levels in blood-derived lymphoblasts as well as in the postmortem prefrontal cortex and cerebellum of individuals with ASD. Moreover, we have also shown that RORA has the potential to be under negative and positive regulation by androgen and estrogen, respectively, suggesting the possibility that RORA may contribute to the male bias of ASD. However, little is known about transcriptional targets of this nuclear receptor, particularly in humans. Here we identify transcriptional targets of RORA in human neuronal cells on a genome-wide level using chromatin immunoprecipitation (ChIP) with an anti-RORA antibody followed by whole-genome promoter array (chip) analysis. Selected potential targets of RORA were then validated by an independent ChIP followed by quantitative PCR analysis. To further demonstrate that reduced RORA expression results in reduced transcription of RORA targets, we determined the expression levels of the selected transcriptional targets in RORA-deficient human neuronal cells, as well as in postmortem brain tissues from individuals with ASD who exhibit reduced RORA expression. The ChIP-on-chip analysis reveals that RORA1, a major isoform of RORA protein in human brain, can be recruited to as many as 2,764 genomic locations corresponding to promoter regions of 2,544 genes across the human genome. Gene ontology analysis of this dataset of genes that are potentially directly regulated by RORA1 reveals statistically significant enrichment in biological functions negatively impacted in individuals with ASD, including neuronal differentiation, adhesion and survival, synaptogenesis, synaptic transmission and plasticity, and axonogenesis, as well as higher level functions such as

  11. Mixture models reveal multiple positional bias types in RNA-Seq data and lead to accurate transcript concentration estimates.

    PubMed

    Tuerk, Andreas; Wiktorin, Gregor; Güler, Serhat

    2017-05-01

    Accuracy of transcript quantification with RNA-Seq is negatively affected by positional fragment bias. This article introduces Mix2 (rd. "mixquare"), a transcript quantification method which uses a mixture of probability distributions to model and thereby neutralize the effects of positional fragment bias. The parameters of Mix2 are trained by Expectation Maximization resulting in simultaneous transcript abundance and bias estimates. We compare Mix2 to Cufflinks, RSEM, eXpress and PennSeq; state-of-the-art quantification methods implementing some form of bias correction. On four synthetic biases we show that the accuracy of Mix2 overall exceeds the accuracy of the other methods and that its bias estimates converge to the correct solution. We further evaluate Mix2 on real RNA-Seq data from the Microarray and Sequencing Quality Control (MAQC, SEQC) Consortia. On MAQC data, Mix2 achieves improved correlation to qPCR measurements with a relative increase in R2 between 4% and 50%. Mix2 also yields repeatable concentration estimates across technical replicates with a relative increase in R2 between 8% and 47% and reduced standard deviation across the full concentration range. We further observe more accurate detection of differential expression with a relative increase in true positives between 74% and 378% for 5% false positives. In addition, Mix2 reveals 5 dominant biases in MAQC data deviating from the common assumption of a uniform fragment distribution. On SEQC data, Mix2 yields higher consistency between measured and predicted concentration ratios. A relative error of 20% or less is obtained for 51% of transcripts by Mix2, 40% of transcripts by Cufflinks and RSEM and 30% by eXpress. Titration order consistency is correct for 47% of transcripts for Mix2, 41% for Cufflinks and RSEM and 34% for eXpress. We, further, observe improved repeatability across laboratory sites with a relative increase in R2 between 8% and 44% and reduced standard deviation.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2009-06-01

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