Resistance to Change and Frequency of Response-Dependent Stimuli Uncorrelated with Reinforcement

ERIC Educational Resources Information Center

Podlesnik, Christopher A.; Jimenez-Gomez, Corina; Ward, Ryan D.; Shahan, Timothy A.

2009-01-01

Stimuli uncorrelated with reinforcement have been shown to enhance response rates and resistance to disruption; however, the effects of different rates of stimulus presentations have not been assessed. In two experiments, we assessed the effects of adding different rates of response-dependent brief stimuli uncorrelated with primary reinforcement…

Frequency dependence limits divergent evolution by favouring rare immigrants over residents.

PubMed

Bolnick, Daniel I; Stutz, William E

2017-06-08

Two distinct forms of natural selection promote adaptive biological diversity. Divergent selection occurs when different environments favour different phenotypes, leading to increased differences between populations. Negative frequency-dependent selection occurs when rare variants within a population are favoured over common ones, increasing diversity within populations. These two diversifying forces promote genetic variation at different spatial scales, and may act in opposition, but their relative effects remain unclear because they are rarely measured concurrently. Here we show that negative frequency-dependent selection within populations can favor rare immigrants over locally adapted residents. We reciprocally transplanted lake and stream ecotypes of threespine stickleback into lake and stream habitats, while manipulating the relative abundance of residents versus immigrants. We found negative frequency-dependence: survival was highest for the locally rare ecotype, rather than natives. Also, individuals with locally rare major histocompatibility complex (MHC) class IIb genotypes were infected by fewer parasites. This negative frequency-dependent selection will tend to favour rare immigrants over common residents, amplifying the effect of migration and undermining the efficacy of divergent natural selection to drive population differences. The only signal of divergent selection was a tendency for foreign fish to have higher parasite loads than residents, after controlling for MHC genotype rarity. Frequency-dependent ecological interactions have long been thought to promote speciation. Our results suggest a more nuanced view in which negative frequency dependence alters the fate of migrants to promote or constrain evolutionary divergence between populations.

Pediatric emotional dysregulation and behavioral disruptiveness treated with hypnosis: a time-series design.

PubMed

Iglesias, Alex; Iglesias, Adam

2014-01-01

A case of pediatric oppositional defiant disorder (ODD) with concomitant emotional dysregulation and secondary behavioral disruptiveness was treated with hypnosis by means of the hypnotic hold, a method adapted by the authors. An A-B-A-B time-series design with multiple replications was employed to measure the relationship of the hypnotic treatment to the dependent measure: episodes of emotional dysregulation with accompanying behavioral disruptiveness. The findings indicated a statistically significant relationship between the degree of change from phase to phase and the treatment. Follow-up at 6 months indicated a significant reduction of the frequency of targeted episodes of emotional dysregulation and behavioral disruptiveness at home.

The evolution of genetic and conditional alternative reproductive tactics

PubMed Central

2016-01-01

Frequency-dependent selection may drive adaptive diversification within species. It is yet unclear why the occurrence of alternative reproductive tactics (ARTs) is highly divergent between major animal taxa. Here we aim to clarify the environmental and social conditions favouring the evolution of intra-population variance of male reproductive phenotypes. Our results suggest that genetically determined ARTs that are fixed for life evolve when there is strong selection on body size due to size-dependent competitiveness, in combination with environmental factors reducing size benefits. The latter may result from growth costs or, more generally, from age-dependent but size-independent mortality causes. This generates disruptive selection on growth trajectories underlying tactic choice. In many parameter settings, the model also predicts ARTs to evolve that are flexible and responsive to current conditions. Interestingly, the conditions favouring the evolution of flexible tactics diverge considerably from those favouring genetic variability. Nevertheless, in a restricted but relevant parameter space, our model predicts the simultaneous emergence and maintenance of a mixture of multiple tactics, both genetically and conditionally determined. Important conditions for the emergence of ARTs include size variation of competitors, which is inherently greater in species with indeterminate growth than in taxa reproducing only after reaching their terminal body size. This is probably the reason why ARTs are more common in fishes than in other major taxa. PMID:26911960

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bacon, L. D.

Hybrid Band{trademark} (H-band) is a Lockheed Martin Missiles and Fire Control (LMMFC) designation for a specific RF modulation that causes disruption of select electronic components and circuits. H-Band enables conventional high-power microwave (HPM) effects (with a center frequency of 1 to 2 GHz, for example) using a higher frequency carrier signal. The primary technical objective of this project was to understand the fundamental physics of Hybrid Band{trademark} Radio Frequency effects on electronic systems. The follow-on objective was to develop and validate a Hybrid Band{trademark} effects analysis process.

Maintenance of genetic variation with a frequency-dependent selection model as compared to the overdominant model.

PubMed

Hedrick, P W

1972-12-01

A frequency-dependent selection model proposed by Huang, Singh and Kojima (1971) was found to be more effective at maintaining genetic variation in a finite population than the overdominant model. The fourth moment parameter of the distribution of unfixed states showed that there was a more platykurtic distribution for the frequency-dependent model. This agreed well with the expected gene frequency change found for an infinite population.

Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation

PubMed Central

Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F.

2014-01-01

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. PMID:25451612

Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

PubMed

Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

2015-02-01

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

Frequency-dependent and correlational selection pressures have conflicting consequences for assortative mating in a color-polymorphic lizard, Uta stansburiana.

PubMed

Lancaster, Lesley T; McAdam, Andrew G; Hipsley, Christy A; Sinervo, Barry R

2014-08-01

Genetically determined polymorphisms incorporating multiple traits can persist in nature under chronic, fluctuating, and sometimes conflicting selection pressures. Balancing selection among morphs preserves equilibrium frequencies, while correlational selection maintains favorable trait combinations within each morph. Under negative frequency-dependent selection, females should mate (often disassortatively) with rare male morphotypes to produce conditionally fit offspring. Conversely, under correlational selection, females should mate assortatively to preserve coadapted gene complexes and avoid ontogenetic conflict. Using controlled breeding designs, we evaluated consequences of assortative mating patterns in color-polymorphic side-blotched lizards (Uta stansburiana), to identify conflict between these sources of selection. Females who mated disassortatively, and to conditionally high-quality males in the context of frequency-dependent selection, experienced highest fertility rates. In contrast, assortatively mated females experienced higher fetal viability rates. The trade-off between fertility and egg viability resulted in no overall fitness benefit to either assortative or disassortative mating patterns. These results suggest that ongoing conflict between correlational and frequency dependent selection in polymorphic populations may generate a trade-off between rare-morph advantage and phenotypic integration and between assortative and disassortative mating decisions. More generally, interactions among multiple sources of diversity-promoting selection can alter adaptations and dynamics predicted to arise under any of these regimes alone.

Self-extinction through optimizing selection.

PubMed

Parvinen, Kalle; Dieckmann, Ulf

2013-09-21

Evolutionary suicide is a process in which selection drives a viable population to extinction. So far, such selection-driven self-extinction has been demonstrated in models with frequency-dependent selection. This is not surprising, since frequency-dependent selection can disconnect individual-level and population-level interests through environmental feedback. Hence it can lead to situations akin to the tragedy of the commons, with adaptations that serve the selfish interests of individuals ultimately ruining a population. For frequency-dependent selection to play such a role, it must not be optimizing. Together, all published studies of evolutionary suicide have created the impression that evolutionary suicide is not possible with optimizing selection. Here we disprove this misconception by presenting and analyzing an example in which optimizing selection causes self-extinction. We then take this line of argument one step further by showing, in a further example, that selection-driven self-extinction can occur even under frequency-independent selection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Maintenance of Genetic Variation with a Frequency-Dependent Selection Model as Compared to the Overdominant Model

PubMed Central

Hedrick, Philip W.

1972-01-01

A frequency-dependent selection model proposed by Huang, Singh and Kojima (1971) was found to be more effective at maintaining genetic variation in a finite population than the overdominant model. The fourth moment parameter of the distribution of unfixed states showed that there was a more platykurtic distribution for the frequency-dependent model. This agreed well with the expected gene frequency change found for an infinite population. PMID:4652882

Fibrillar disruption by AC electric field induced oscillation: A case study with human serum albumin.

PubMed

Sen, Shubhatam; Chakraborty, Monojit; Goley, Snigdha; Dasgupta, Swagata; DasGupta, Sunando

2017-07-01

The effect of oscillation induced by a frequency-dependent alternating current (AC) electric field to dissociate preformed amyloid fibrils has been investigated. An electrowetting-on-dielectric type setup has been used to apply the AC field of varying frequencies on preformed fibrils of human serum albumin (HSA). The disintegration potency has been monitored by a combination of spectroscopic and microscopic techniques. The experimental results suggest that the frequency of the applied AC field plays a crucial role in the disruption of preformed HSA fibrils. The extent of stress generated inside the droplet due to the application of the AC field at different frequencies has been monitored as a function of the input frequency of the applied AC voltage. This has been accomplished by assessing the morphology deformation of the oscillating HSA fibril droplets. The shape deformation of the oscillating droplets is characterized using image analysis by measuring the dynamic changes in the shape dependent parameters such as contact angle and droplet footprint radius and the amplitude. It is suggested that the cumulative effects of the stress generated inside the HSA fibril droplets due to the shape deformation induced hydrodynamic flows and the torque induced by the intrinsic electric dipoles of protein due to their continuous periodic realignment in presence of the AC electric field results in the destruction of the fibrillar species. Copyright © 2017. Published by Elsevier B.V.

Directional, stabilizing, and disruptive trait selection as alternative mechanisms for plant community assembly.

PubMed

Rolhauser, Andrés G; Pucheta, Eduardo

2017-03-01

How plant functional traits (e.g., seed mass) drive species abundance within communities remains an unsolved question. Borrowing concepts from natural selection theory, we propose that trait-abundance relationships can generally correspond to one of three modes of trait selection: directional (a rectilinear relationship, where species at one end of a trait axis are most abundant), stabilizing (an n-shaped relationship), and disruptive (a u-shaped relationship). Stabilizing selection (i.e., the functional convergence of abundant species) would result from positive density-dependent interactions (e.g., facilitation) or due to generalized trade-offs in resource acquisition/use, while disruptive selection (i.e., the divergence of abundant species) would result from negative density-dependent interactions (e.g., competition) or due to environmental heterogeneity. These selection modes can be interpreted as proxies for community-level trait-fitness functions, which establish the degree to which traits are truly "functional". We searched for selection modes in a desert annual-plant community in Argentina (which was divided into winter and summer guilds) to test the hypothesis that the relative importance of disruptive mechanisms (competition, disturbances) decreases with the increase of abiotic stress, a stabilizing agent. Average density was analyzed as a function of eight traits generally linked to resource acquisition and competitive ability (maximum plant height, leaf size, specific leaf area, specific root length), resource retention and stress tolerance (leaf dissection, leaf dry matter content, specific root volume), and regeneration (seed mass) using multiple quadratic-regression models. Trait selection was stabilizing and/or directional when the environment was harshest (winter) and disruptive and/or directional when conditions were milder (summer). Selection patterns differed between guilds for two important traits: plant height and seed mass. These results suggest that abiotic stress may drive within-community functional convergence independently of the trait considered, opposing the view that some traits may be inherently convergent while others divergent. Our quadratic model-based approach provides standardized metrics of both linear and nonlinear selection that may allow simple comparisons among communities subjected to contrasting environmental conditions. These concepts, rooted in natural selection theory, may clarify the functional link between traits and species abundance, and thus help untangle the contributions of deterministic and stochastic processes on community assembly. © 2017 by the Ecological Society of America.

What explains rare and conspicuous colours in a snail? A test of time-series data against models of drift, migration or selection.

PubMed

Johannesson, K; Butlin, R K

2017-01-01

It is intriguing that conspicuous colour morphs of a prey species may be maintained at low frequencies alongside cryptic morphs. Negative frequency-dependent selection by predators using search images ('apostatic selection') is often suggested without rejecting alternative explanations. Using a maximum likelihood approach we fitted predictions from models of genetic drift, migration, constant selection, heterozygote advantage or negative frequency-dependent selection to time-series data of colour frequencies in isolated populations of a marine snail (Littorina saxatilis), re-established with perturbed colour morph frequencies and followed for >20 generations. Snails of conspicuous colours (white, red, banded) are naturally rare in the study area (usually <10%) but frequencies were manipulated to levels of ~50% (one colour per population) in 8 populations at the start of the experiment in 1992. In 2013, frequencies had declined to ~15-45%. Drift alone could not explain these changes. Migration could not be rejected in any population, but required rates much higher than those recorded. Directional selection was rejected in three populations in favour of balancing selection. Heterozygote advantage and negative frequency-dependent selection could not be distinguished statistically, although overall the results favoured the latter. Populations varied idiosyncratically as mild or variable colour selection (3-11%) interacted with demographic stochasticity, and the overall conclusion was that multiple mechanisms may contribute to maintaining the polymorphisms.

Strings on a Violin: Location Dependence of Frequency Tuning in Active Dendrites.

PubMed

Das, Anindita; Rathour, Rahul K; Narayanan, Rishikesh

2017-01-01

Strings on a violin are tuned to generate distinct sound frequencies in a manner that is firmly dependent on finger location along the fingerboard. Sound frequencies emerging from different violins could be very different based on their architecture, the nature of strings and their tuning. Analogously, active neuronal dendrites, dendrites endowed with active channel conductances, are tuned to distinct input frequencies in a manner that is dependent on the dendritic location of the synaptic inputs. Further, disparate channel expression profiles and differences in morphological characteristics could result in dendrites on different neurons of the same subtype tuned to distinct frequency ranges. Alternately, similar location-dependence along dendritic structures could be achieved through disparate combinations of channel profiles and morphological characteristics, leading to degeneracy in active dendritic spectral tuning. Akin to strings on a violin being tuned to different frequencies than those on a viola or a cello, different neuronal subtypes exhibit distinct channel profiles and disparate morphological characteristics endowing each neuronal subtype with unique location-dependent frequency selectivity. Finally, similar to the tunability of musical instruments to elicit distinct location-dependent sounds, neuronal frequency selectivity and its location-dependence are tunable through activity-dependent plasticity of ion channels and morphology. In this morceau, we explore the origins of neuronal frequency selectivity, and survey the literature on the mechanisms behind the emergence of location-dependence in distinct forms of frequency tuning. As a coda to this composition, we present some future directions for this exciting convergence of biophysical mechanisms that endow a neuron with frequency multiplexing capabilities.

Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission

PubMed Central

Banks, Paul James; Burroughs, Amelia Caroline; Barker, Gareth Robert Isaac; Brown, Jon Thomas; Warburton, Elizabeth Clea; Bashir, Zafar Iqbal

2015-01-01

Functional connectivity between the hippocampus and prefrontal cortex (PFC) is essential for associative recognition memory and working memory. Disruption of hippocampal–PFC synchrony occurs in schizophrenia, which is characterized by hypofunction of NMDA receptor (NMDAR)-mediated transmission. We demonstrate that activity of dopamine D2-like receptors (D2Rs) leads selectively to long-term depression (LTD) of hippocampal–PFC NMDAR-mediated synaptic transmission. We show that dopamine-dependent LTD of NMDAR-mediated transmission profoundly disrupts normal synaptic transmission between hippocampus and PFC. These results show how dopaminergic activation induces long-term hypofunction of NMDARs, which can contribute to disordered functional connectivity, a characteristic that is a hallmark of psychiatric disorders such as schizophrenia. PMID:26286993

Ecological genetics of the Bromus tectorum (Poaceae) - Ustilago Bullata (Ustilaginaceae): A role for frequency dependent selection?

Treesearch

Susan E. Meyer; David L. Nelson; Suzette Clement; Alisa Ramakrishnan

2010-01-01

Evolutionary processes that maintain genetic diversity in plants are likely to include selection imposed by pathogens. Negative frequency-dependent selection is a mechanism for maintenance of resistance polymorphism in plant - pathogen interactions. We explored whether such selection operates in the Bromus tectorum - Ustilago bullata pathosystem. Gene-for-gene...

Intracerebral evidence of rhythm transform in the human auditory cortex.

PubMed

Nozaradan, Sylvie; Mouraux, André; Jonas, Jacques; Colnat-Coulbois, Sophie; Rossion, Bruno; Maillard, Louis

2017-07-01

Musical entrainment is shared by all human cultures and the perception of a periodic beat is a cornerstone of this entrainment behavior. Here, we investigated whether beat perception might have its roots in the earliest stages of auditory cortical processing. Local field potentials were recorded from 8 patients implanted with depth-electrodes in Heschl's gyrus and the planum temporale (55 recording sites in total), usually considered as human primary and secondary auditory cortices. Using a frequency-tagging approach, we show that both low-frequency (<30 Hz) and high-frequency (>30 Hz) neural activities in these structures faithfully track auditory rhythms through frequency-locking to the rhythm envelope. A selective gain in amplitude of the response frequency-locked to the beat frequency was observed for the low-frequency activities but not for the high-frequency activities, and was sharper in the planum temporale, especially for the more challenging syncopated rhythm. Hence, this gain process is not systematic in all activities produced in these areas and depends on the complexity of the rhythmic input. Moreover, this gain was disrupted when the rhythm was presented at fast speed, revealing low-pass response properties which could account for the propensity to perceive a beat only within the musical tempo range. Together, these observations show that, even though part of these neural transforms of rhythms could already take place in subcortical auditory processes, the earliest auditory cortical processes shape the neural representation of rhythmic inputs in favor of the emergence of a periodic beat.

Simulating Impacts of Disruptions to Liquid Fuels Infrastructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Michael; Corbet, Thomas F.; Baker, Arnold B.

This report presents a methodology for estimating the impacts of events that damage or disrupt liquid fuels infrastructure. The impact of a disruption depends on which components of the infrastructure are damaged, the time required for repairs, and the position of the disrupted components in the fuels supply network. Impacts are estimated for seven stressing events in regions of the United States, which were selected to represent a range of disruption types. For most of these events the analysis is carried out using the National Transportation Fuels Model (NTFM) to simulate the system-level liquid fuels sector response. Results are presentedmore » for each event, and a brief cross comparison of event simulation results is provided.« less

Network models of frequency modulated sweep detection.

PubMed

Skorheim, Steven; Razak, Khaleel; Bazhenov, Maxim

2014-01-01

Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The 'facilitation' model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The 'duration tuned' model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The 'inhibitory sideband' model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.

A high efficiency gene disruption strategy using a positive-negative split selection marker and electroporation for Fusarium oxysporum.

PubMed

Liang, Liqin; Li, Jianqiang; Cheng, Lin; Ling, Jian; Luo, Zhongqin; Bai, Miao; Xie, Bingyan

2014-11-01

The Fusarium oxysporum species complex consists of fungal pathogens that cause serial vascular wilt disease on more than 100 cultivated species throughout the world. Gene function analysis is rapidly becoming more and more important as the whole-genome sequences of various F. oxysporum strains are being completed. Gene-disruption techniques are a common molecular tool for studying gene function, yet are often a limiting step in gene function identification. In this study we have developed a F. oxysporum high-efficiency gene-disruption strategy based on split-marker homologous recombination cassettes with dual selection and electroporation transformation. The method was efficiently used to delete three RNA-dependent RNA polymerase (RdRP) genes. The gene-disruption cassettes of three genes can be constructed simultaneously within a short time using this technique. The optimal condition for electroporation is 10μF capacitance, 300Ω resistance, 4kV/cm field strength, with 1μg of DNA (gene-disruption cassettes). Under these optimal conditions, we were able to obtain 95 transformants per μg DNA. And after positive-negative selection, the transformants were efficiently screened by PCR, screening efficiency averaged 85%: 90% (RdRP1), 85% (RdRP2) and 77% (RdRP3). This gene-disruption strategy should pave the way for high throughout genetic analysis in F. oxysporum. Copyright © 2014 Elsevier GmbH. All rights reserved.

Frequency-dependent sexual selection.

PubMed

O'Donald, P; Majerus, M E

1988-07-06

Sexual selection by female choice is expected to give rise to a frequency-dependent sexual advantage in favour of preferred male phenotypes: the rarer the preferred phenotypes, the more often they are chosen as mates. This 'rare-male advantage' can maintain a polymorphism when two or more phenotypes are mated preferentially: each phenotype gains an advantage when it is rarer than the others; no preferred phenotype can then be lost from the population. Expression of preference may be complete or partial. In models of complete preference, females with a preference always mate preferentially. Models of partial preference are more realistic: in these models, the probability that a female mates preferentially depends on the frequency with which she encounters the males she prefers. Two different 'encounter models' of partial preference have been derived: the O'Donald model and the Charlesworth model. The encounter models contain the complete preference model as a limiting case. In this paper, the Charlesworth model is generalized to allow for female preference of more than one male phenotype. Levels of frequency dependence can then be compared in the O'Donald and Charlesworth models. The complete preference model and both encounter models are formulated in the same genetical terms of preferences for dominant and recessive male phenotypes. Polymorphic equilibria and conditions for stability are derived for each of the three models. The models are then fitted to data of frequencies of matings observed in experiments with the two-spot ladybird. The complete preference model gives as good a fit as the encounter models to the data of these and other experiments. The O'Donald and Charlesworth encounter models are shown to produce a very similar frequency-dependent relation. Generally, as females become less choosy, they express their preference with more dependence on male frequency, whereas the resulting selection of the males becomes less frequency dependent. More choosy females are more constant in expressing their preference, producing greater frequency dependence in the selection of the males.

Two-Step Mechanism of Membrane Disruption by Aβ through Membrane Fragmentation and Pore Formation

PubMed Central

Sciacca, Michele F.M.; Kotler, Samuel A.; Brender, Jeffrey R.; Chen, Jennifer; Lee, Dong-kuk; Ramamoorthy, Ayyalusamy

2012-01-01

Disruption of cell membranes by Aβ is believed to be one of the key components of Aβ toxicity. However, the mechanism by which this occurs is not fully understood. Here, we demonstrate that membrane disruption by Aβ occurs by a two-step process, with the initial formation of ion-selective pores followed by nonspecific fragmentation of the lipid membrane during amyloid fiber formation. Immediately after the addition of freshly dissolved Aβ1–40, defects form on the membrane that share many of the properties of Aβ channels originally reported from single-channel electrical recording, such as cation selectivity and the ability to be blockaded by zinc. By contrast, subsequent amyloid fiber formation on the surface of the membrane fragments the membrane in a way that is not cation selective and cannot be stopped by zinc ions. Moreover, we observed that the presence of ganglioside enhances both the initial pore formation and the fiber-dependent membrane fragmentation process. Whereas pore formation by freshly dissolved Aβ1–40 is weakly observed in the absence of gangliosides, fiber-dependent membrane fragmentation can only be observed in their presence. These results provide insights into the toxicity of Aβ and may aid in the design of specific compounds to alleviate the neurodegeneration of Alzheimer’s disease. PMID:22947931

Negative frequency-dependent selection between Pasteuria penetrans and its host Meloidogyne arenaria

USDA-ARS?s Scientific Manuscript database

In negative frequency-dependant selection (NFDS), parasite genotypes capable of infecting the numerically dominant host genotype are favored, while host genotypes resistant to the dominant parasite genotype are favored, creating a cyclical pattern of resistant genotypes in the host population and, a...

Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers.

PubMed

Samak, Geetha; Gangwar, Ruchika; Meena, Avtar S; Rao, Roshan G; Shukla, Pradeep K; Manda, Bhargavi; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2016-12-13

Ethanol is metabolized into acetaldehyde in most tissues. In this study, we investigated the synergistic effect of ethanol and acetaldehyde on the tight junction integrity in Caco-2 cell monolayers. Expression of alcohol dehydrogenase sensitized Caco-2 cells to ethanol-induced tight junction disruption and barrier dysfunction, whereas aldehyde dehydrogenase attenuated acetaldehyde-induced tight junction disruption. Ethanol up to 150 mM did not affect tight junction integrity or barrier function, but it dose-dependently increased acetaldehyde-mediated tight junction disruption and barrier dysfunction. Src kinase and MLCK inhibitors blocked this synergistic effect of ethanol and acetaldehyde on tight junction. Ethanol and acetaldehyde caused a rapid and synergistic elevation of intracellular calcium. Calcium depletion by BAPTA or Ca 2+ -free medium blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. Diltiazem and selective knockdown of TRPV6 or Ca V 1.3 channels, by shRNA blocked ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. Ethanol and acetaldehyde induced a rapid and synergistic increase in reactive oxygen species by a calcium-dependent mechanism. N-acetyl-L-cysteine and cyclosporine A, blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. These results demonstrate that ethanol and acetaldehyde synergistically disrupt tight junctions by a mechanism involving calcium, oxidative stress, Src kinase and MLCK.

An analysis and reduction of disruptive behavior on school buses.

PubMed Central

Greene, B F; Bailey, J S; Barber, F

1981-01-01

Thousands of children are injured or killed each year in school bus accidents. A significant number of these tragic incidents is precipitated by disruptive child behavior that distracts the drivers from their difficult task. Two experiments were conducted which addressed this problem. For both experiments an automated sound recording device (referred to as a Noise Guard) selectively responsive to frequencies above 500 Hz (i.e., unresponsive to bus drone) recorded both the duration and frequency of noise outbursts above a tolerable threshold. Additionally, an observer made in situ measurements of other disruptions including roughhousing and getting-out-of-seat. In the first experiment, following baseline measurements of these behaviors, middle-school students received feedback for noise outbursts. That is, when "Noise Guard" was activated, it in turn operated one of several lights on a panel visible to all passengers. Each day students were allowed to listen to high-appeal taped music while riding the bus and to participate in a raffle for prizes, provided the number of outbursts on the preceding day remained below a specified criterion indicated on the light panel. This intervention resulted in drastic reductions of noise outbursts with a concomitant reduction in other disruptive behaviors. Comparable results were obtained in the second experiment which eliminated the raffle from the intervention. PMID:7287600

Social causes of correlational selection and the resolution of a heritable throat color polymorphism in a lizard.

PubMed

Sinervo, B; Bleay, C; Adamopoulou, C

2001-10-01

When selection acts on social or behavioral traits, the fitness of an individual depends on the phenotypes of its competitors. Here, we describe methods and statistical inference for measuring natural selection in small social groups. We measured selection on throat color alleles that arises from microgeographic variation in allele frequency at natal sites of side-blotched lizards (Uta stansburiana). Previous game-theoretic analysis indicates that two color morphs of female side-blotched lizards are engaged in an offspring quantity-quality game that promotes a density- and frequency-dependent cycle. Orange-throated females are r-strategists. They lay large clutches of small progeny, which have poor survival at high density, but good survival at low density. In contrast, yellow-throated females are K-strategists. They lay small clutches of large progeny, which have good survival at high density. We tested three predictions of the female game: (1) orange progeny should have a fitness advantage at low density; (2) correlational selection acts to couple color alleles and progeny size; and (3) this correlational selection arises from frequency-dependent selection in which large hatchling size confers an advantage, but only when yellow alleles are rare. We also confirmed the heritability of color, and therefore its genetic basis, by producing progeny from controlled matings. A parsimonious cause of the high heritability is that three alleles (o, b, y) segregate as one genetic factor. We review the physiology of color formation to explain the possible genetic architecture of the throat color trait. Heritability of color was nearly additive in our breeding study, allowing us to compute a genotypic value for each individual and thus predict the frequency of progeny alleles released on 116 plots. Rather than study the fitness of individual progeny, we studied how the fitness of their color alleles varied with allele frequency on plots. We confirmed prediction 1: When orange alleles are present in female progeny, they have higher fitness at low density when compared to other alleles. Even though the difference in egg size of the female morphs was small (0.02 g), it led to knife-edged survival effects for their progeny depending on local social context. Selection on hatchling survival was not only dependent on color alleles, but on a fitness interaction between color alleles and hatchling size, which confirmed prediction 2. Sire effects, which are not confounded by maternal phenotype, allowed us to resolve the frequency dependence of correlational selection on egg size and color alleles and thereby confirmed prediction 3. Selection favored large size when yellow sire alleles were rare, but small size when they were common. Correlational selection promotes the formation of a self-reinforcing genetic correlation between the morphs and life-history variation, which causes selection in the next density and frequency cycle to be exacerbated. We discuss general conditions for the evolution of self-reinforcing genetic correlations that arise from social selection associated with frequency-dependent sexual and natural selection.

Classroom discipline skills and disruption rate: A correlational study

NASA Astrophysics Data System (ADS)

Dropik, Melonie Jane

Very little has been done to quantify the relationship between the frequency with which teachers use discipline skills and disruption rate in high school settings. Most of the available research that examined this relationship empirically was done in elementary schools, while a few studies examined the junior high school setting. The present research examined whether the use of ten specific discipline skills were related to the rate of disruption in suburban high school science classrooms. The ten skills were selected based on their prevalence in the theoretical literature and the strength of the relationships reported in empirical studies of elementary and junior high classrooms. Each relationship was tested directionally at alpha = .01. The maximum experimentwise Type I error rate was .10. Disruption rate was measured by trained observers over five class periods in the Fall of the school year. The frequency of performing the ten skills was assessed using a student survey developed for this study. The ten skills were: (1) beginning class on time, (2) using routines, (3) waiting for student attention before speaking, (4) giving clear directions, (5) presenting material fast enough to hold students' attention, (6) requiring students to remain seated, (7) appearing confident, (8) stopping misbehavior quickly, (9) checking for student attentiveness, and (10) teaching to the bell. Appearing confident (r = --.697, p = .004) and quickly stopping misbehavior (r = --.709, p = .003) were significantly negatively related to disruption rate. The effect sizes for the confidence and stopping misbehavior variables were .49 and .50, respectively. At least half of the variation in disruption rate was attributable to the difference in the frequency of appearing confident and stopping misbehavior quickly. The eight other relationships produced nonsignificant results. The results raise questions about whether theories developed from observational and anecdotal evidence gathered in elementary or junior high school classrooms can be applied to high school classrooms and indicate that further investigation into the high school setting is necessary.

Non-thermal X-ray emission from tidal disruption flares

NASA Astrophysics Data System (ADS)

Stone, Nicholas

2016-09-01

A star that passes too close to a supermassive black hole will be disrupted by the black hole's tidal gravity. The result is a flare of thermal emission at optical and X-ray frequencies. The return rate of stellar debris decreases from highly super-Eddington to sub-Eddington in a few years, making stellar tidal disruptions flares (TDFs) a unique laboratory to study accretion physics. In one class of models, the optical emission is due to reprocessing of the X-ray photons, thus explaining the lack of X-ray detections from optically selected TDFs. After a few years, the outer reprocessing regions will dilute, allowing us to observe any non-thermal emission from the inner disk. Here we propose Chandra observations to measure the luminosity of newly formed accretion disks in two known TDFs.

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

Mating System Evolution under Strong Pollen Limitation: Evidence of Disruptive Selection through Male and Female Fitness in Clarkia xantiana.

PubMed

Briscoe Runquist, Ryan D; Geber, Monica A; Pickett-Leonard, Michael; Moeller, David A

2017-05-01

Selection on floral traits in hermaphroditic plants is determined by both male and female reproductive success. However, predictions regarding floral trait and mating system evolution are often based solely on female fitness. Selection via male fitness has the potential to affect the outcomes of floral evolution. In this study, we used paternity analysis to assess individual selfing rates and selection on floral traits via male and female fitness in an experimental population of Clarkia xantiana where pollen limitation of seed set was strong. We detected selection through both female and male fitness with reinforcing or noninterfering patterns of selection through the two sex functions. For female fitness, selection favored reduced herkogamy and protandry, traits that promote increased autonomous selfing. For male fitness, selection on petal area was disruptive, with higher trait values conferring greater pollinator attraction and outcross siring success and smaller trait values leading to higher selfed siring success. Combining both female and male fitness, selection on petal area and protandry was disruptive because intermediate phenotypes were less successful as both males and females. Finally, functional relationships among male and female fertility components indicated that selfing resulted in seed discounting and pollen discounting. Under these functional relationships, the evolutionarily stable selfing rate can be intermediate or predominantly selfing or outcrossing, depending on the segregating load of deleterious mutations.

The dynamics of integrate-and-fire: mean versus variance modulations and dependence on baseline parameters.

PubMed

Pressley, Joanna; Troyer, Todd W

2011-05-01

The leaky integrate-and-fire (LIF) is the simplest neuron model that captures the essential properties of neuronal signaling. Yet common intuitions are inadequate to explain basic properties of LIF responses to sinusoidal modulations of the input. Here we examine responses to low and moderate frequency modulations of both the mean and variance of the input current and quantify how these responses depend on baseline parameters. Across parameters, responses to modulations in the mean current are low pass, approaching zero in the limit of high frequencies. For very low baseline firing rates, the response cutoff frequency matches that expected from membrane integration. However, the cutoff shows a rapid, supralinear increase with firing rate, with a steeper increase in the case of lower noise. For modulations of the input variance, the gain at high frequency remains finite. Here, we show that the low-frequency responses depend strongly on baseline parameters and derive an analytic condition specifying the parameters at which responses switch from being dominated by low versus high frequencies. Additionally, we show that the resonant responses for variance modulations have properties not expected for common oscillatory resonances: they peak at frequencies higher than the baseline firing rate and persist when oscillatory spiking is disrupted by high noise. Finally, the responses to mean and variance modulations are shown to have a complementary dependence on baseline parameters at higher frequencies, resulting in responses to modulations of Poisson input rates that are independent of baseline input statistics.

Complexity and diversity.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2010-04-23

The mechanisms for the origin and maintenance of biological diversity are not fully understood. It is known that frequency-dependent selection, generating advantages for rare types, can maintain genetic variation and lead to speciation, but in models with simple phenotypes (that is, low-dimensional phenotype spaces), frequency dependence needs to be strong to generate diversity. However, we show that if the ecological properties of an organism are determined by multiple traits with complex interactions, the conditions needed for frequency-dependent selection to generate diversity are relaxed to the point where they are easily satisfied in high-dimensional phenotype spaces. Mathematically, this phenomenon is reflected in properties of eigenvalues of quadratic forms. Because all living organisms have at least hundreds of phenotypes, this casts the potential importance of frequency dependence for the origin and maintenance of diversity in a new light.

Processing Complex Sounds Passing through the Rostral Brainstem: The New Early Filter Model

PubMed Central

Marsh, John E.; Campbell, Tom A.

2016-01-01

The rostral brainstem receives both “bottom-up” input from the ascending auditory system and “top-down” descending corticofugal connections. Speech information passing through the inferior colliculus of elderly listeners reflects the periodicity envelope of a speech syllable. This information arguably also reflects a composite of temporal-fine-structure (TFS) information from the higher frequency vowel harmonics of that repeated syllable. The amplitude of those higher frequency harmonics, bearing even higher frequency TFS information, correlates positively with the word recognition ability of elderly listeners under reverberatory conditions. Also relevant is that working memory capacity (WMC), which is subject to age-related decline, constrains the processing of sounds at the level of the brainstem. Turning to the effects of a visually presented sensory or memory load on auditory processes, there is a load-dependent reduction of that processing, as manifest in the auditory brainstem responses (ABR) evoked by to-be-ignored clicks. Wave V decreases in amplitude with increases in the visually presented memory load. A visually presented sensory load also produces a load-dependent reduction of a slightly different sort: The sensory load of visually presented information limits the disruptive effects of background sound upon working memory performance. A new early filter model is thus advanced whereby systems within the frontal lobe (affected by sensory or memory load) cholinergically influence top-down corticofugal connections. Those corticofugal connections constrain the processing of complex sounds such as speech at the level of the brainstem. Selective attention thereby limits the distracting effects of background sound entering the higher auditory system via the inferior colliculus. Processing TFS in the brainstem relates to perception of speech under adverse conditions. Attentional selectivity is crucial when the signal heard is degraded or masked: e.g., speech in noise, speech in reverberatory environments. The assumptions of a new early filter model are consistent with these findings: A subcortical early filter, with a predictive selectivity based on acoustical (linguistic) context and foreknowledge, is under cholinergic top-down control. A prefrontal capacity limitation constrains this top-down control as is guided by the cholinergic processing of contextual information in working memory. PMID:27242396

Processing Complex Sounds Passing through the Rostral Brainstem: The New Early Filter Model.

PubMed

Marsh, John E; Campbell, Tom A

2016-01-01

The rostral brainstem receives both "bottom-up" input from the ascending auditory system and "top-down" descending corticofugal connections. Speech information passing through the inferior colliculus of elderly listeners reflects the periodicity envelope of a speech syllable. This information arguably also reflects a composite of temporal-fine-structure (TFS) information from the higher frequency vowel harmonics of that repeated syllable. The amplitude of those higher frequency harmonics, bearing even higher frequency TFS information, correlates positively with the word recognition ability of elderly listeners under reverberatory conditions. Also relevant is that working memory capacity (WMC), which is subject to age-related decline, constrains the processing of sounds at the level of the brainstem. Turning to the effects of a visually presented sensory or memory load on auditory processes, there is a load-dependent reduction of that processing, as manifest in the auditory brainstem responses (ABR) evoked by to-be-ignored clicks. Wave V decreases in amplitude with increases in the visually presented memory load. A visually presented sensory load also produces a load-dependent reduction of a slightly different sort: The sensory load of visually presented information limits the disruptive effects of background sound upon working memory performance. A new early filter model is thus advanced whereby systems within the frontal lobe (affected by sensory or memory load) cholinergically influence top-down corticofugal connections. Those corticofugal connections constrain the processing of complex sounds such as speech at the level of the brainstem. Selective attention thereby limits the distracting effects of background sound entering the higher auditory system via the inferior colliculus. Processing TFS in the brainstem relates to perception of speech under adverse conditions. Attentional selectivity is crucial when the signal heard is degraded or masked: e.g., speech in noise, speech in reverberatory environments. The assumptions of a new early filter model are consistent with these findings: A subcortical early filter, with a predictive selectivity based on acoustical (linguistic) context and foreknowledge, is under cholinergic top-down control. A prefrontal capacity limitation constrains this top-down control as is guided by the cholinergic processing of contextual information in working memory.

A phase transition induces chaos in a predator-prey ecosystem with a dynamic fitness landscape.

PubMed

Gilpin, William; Feldman, Marcus W

2017-07-01

In many ecosystems, natural selection can occur quickly enough to influence the population dynamics and thus future selection. This suggests the importance of extending classical population dynamics models to include such eco-evolutionary processes. Here, we describe a predator-prey model in which the prey population growth depends on a prey density-dependent fitness landscape. We show that this two-species ecosystem is capable of exhibiting chaos even in the absence of external environmental variation or noise, and that the onset of chaotic dynamics is the result of the fitness landscape reversibly alternating between epochs of stabilizing and disruptive selection. We draw an analogy between the fitness function and the free energy in statistical mechanics, allowing us to use the physical theory of first-order phase transitions to understand the onset of rapid cycling in the chaotic predator-prey dynamics. We use quantitative techniques to study the relevance of our model to observational studies of complex ecosystems, finding that the evolution-driven chaotic dynamics confer community stability at the "edge of chaos" while creating a wide distribution of opportunities for speciation during epochs of disruptive selection-a potential observable signature of chaotic eco-evolutionary dynamics in experimental studies.

Spelling ability selectively predicts the magnitude of disruption in unspaced text reading.

PubMed

Veldre, Aaron; Drieghe, Denis; Andrews, Sally

2017-09-01

We examined the effect of individual differences in written language proficiency on unspaced text reading in a large sample of skilled adult readers who were assessed on reading comprehension and spelling ability. Participants' eye movements were recorded as they read sentences containing a low or high frequency target word, presented with standard interword spacing, or in one of three unsegmented text conditions that either preserved or eliminated word boundary information. The average data replicated previous studies: unspaced text reading was associated with increased fixation durations, a higher number of fixations, more regressions, reduced saccade length, and an inflation of the word frequency effect. The individual differences results provided insight into the mechanisms contributing to these effects. Higher reading ability was associated with greater overall reading speed and fluency in all conditions. In contrast, spelling ability selectively modulated the effect of interword spacing with poorer spelling ability predicting greater difficulty across the majority of sentence- and word-level measures. These results suggest that high quality lexical representations allowed better spellers to extract lexical units from unfamiliar text forms, inoculating them against the disruptive effects of being deprived of spacing information. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Emotion Causes Targeted Forgetting of Established Memories

PubMed Central

Strange, Bryan A.; Kroes, Marijn C. W.; Fan, Judith E.; Dolan, Raymond J.

2010-01-01

Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval. PMID:21191439

Emotion causes targeted forgetting of established memories.

PubMed

Strange, Bryan A; Kroes, Marijn C W; Fan, Judith E; Dolan, Raymond J

2010-01-01

Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT(1A) and 5-HT(2A) receptors.

PubMed

Riga, Maurizio S; Bortolozzi, Analia; Campa, Letizia; Artigas, Francesc; Celada, Pau

2016-02-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT(1A)/5-HT(2A)-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (S1) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT(1A)-R and 5-HT(2A)-R, using wild type (WT) and 5-HT(2A)-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT(1A)-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 5-HT(1A)-R. Moreover, 5-MeO-DMT reduced LFCO in S1, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT(1A)-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (S1, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT(1A)-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT(2A)-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lack of dependence on resonant error field of locked mode island size in ohmic plasmas in DIII-D

DOE PAGES

Haye, R. J. La; Paz-Soldan, C.; Strait, E. J.

2015-01-23

DIII-D experiments show that fully penetrated resonant n=1 error field locked modes in Ohmic plasmas with safety factor q 95≳3 grow to similar large disruptive size, independent of resonant error field correction. Relatively small resonant (m/n=2/1) static error fields are shielded in Ohmic plasmas by the natural rotation at the electron diamagnetic drift frequency. However, the drag from error fields can lower rotation such that a bifurcation results, from nearly complete shielding to full penetration, i.e., to a driven locked mode island that can induce disruption.

Impaired Midline Theta Power and Connectivity During Proactive Cognitive Control in Schizophrenia.

PubMed

Ryman, Sephira G; Cavanagh, James F; Wertz, Christopher J; Shaff, Nicholas A; Dodd, Andrew B; Stevens, Brigitte; Ling, Josef; Yeo, Ronald A; Hanlon, Faith M; Bustillo, Juan; Stromberg, Shannon F; Lin, Denise S; Abrams, Swala; Mayer, Andrew R

2018-05-25

Disrupted proactive cognitive control, a form of early selection and active goal maintenance, is hypothesized to underlie the broad cognitive deficits observed in patients with schizophrenia (SPs). Current research suggests that the disrupted activation within and connectivity between regions of the cognitive control network contribute to disrupted proactive cognitive control; however, no study has examined these mechanisms using an AX Continuous Performance Test task in schizophrenia. Twenty-six SPs (17 male subjects; mean age 34.46 ± 8.77 years) and 28 healthy control participants (HCs; 16 male subjects; mean age 31.43 ± 7.23 years) underwent an electroencephalogram while performing the AX Continuous Performance Test. To examine the extent of activation and level of connectivity within the cognitive control network, power, intertrial phase clustering, and intersite phase clustering metrics were calculated and analyzed. SPs exhibited expected general decrements in behavioral performance relative to HCs and a more selective deficit in conditions requiring proactive cognitive control. Additionally, SPs exhibited deficits in midline theta power and connectivity during proactive cognitive control trials. Specifically, HCs exhibited significantly greater theta power for B cues relative to A cues, whereas SPs exhibited no significant differences between A- and B-cue theta power. Additionally, differential theta connectivity patterns were observed in SPs and HCs. Behavioral measures of proactive cognitive control predicted functional outcomes in SPs. This study suggests that low-frequency midline theta activity is selectively disrupted during proactive cognitive control in SPs. The disrupted midline theta activity may reflect a failure of SPs to proactively recruit cognitive control processes. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Frequency-dependent selection acting on the widely fluctuating sex ratio of the aphid Prociphilus oriens.

PubMed

Li, Y; Akimoto, S

2017-07-01

Frequency-dependent selection is a fundamental principle of adaptive sex ratio evolution in all sex ratio theories but has rarely been detected in the wild. Through long-term censuses, we confirmed large fluctuations in the population sex ratio of the aphid Prociphilus oriens and detected frequency-dependent selection acting on these fluctuations. Fluctuations in the population sex ratio were partly attributable to climatic factors during the growing season. Climatic factors likely affected the growth conditions of host plants, which in turn led to yearly fluctuations in maternal conditions and sex ratios. In the process of frequency-dependent selection, female proportion higher or lower than ca. 60% was associated with a reduction or increase in female proportion, respectively, the next year. The rearing of aphid clones in the laboratory indicated that mothers of each clone produced an increasing number of females as maternal size increased. However, the mean male number was not related to maternal size, but varied largely among clones. Given genetic variance in the ability to produce males among clones, selection should favour clones that can produce more numerous males in years with a high female proportion. Population-level sex allocation to females was on average 71%-73% for three localities and more female-biased when maternal conditions were better. This tendency was accounted for by the hypothesis of competition among foundresses rather than the hypothesis of local mate competition. We conclude that despite consistent operation of frequency-dependent selection, the sex ratio continues to fluctuate because environmental conditions always push it away from equilibrium. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Selective, retrieval-independent disruption of methamphetamine-associated memory by actin depolymerization.

PubMed

Young, Erica J; Aceti, Massimiliano; Griggs, Erica M; Fuchs, Rita A; Zigmond, Zachary; Rumbaugh, Gavin; Miller, Courtney A

2014-01-15

Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder. There is a growing consensus that memory is supported by structural and functional plasticity driven by F-actin polymerization in postsynaptic dendritic spines at excitatory synapses. However, the mechanisms responsible for the long-term maintenance of memories, after consolidation has occurred, are largely unknown. Conditioned place preference (n = 112) and context-induced reinstatement of self-administration (n = 19) were used to assess the role of F-actin polymerization and myosin II, a molecular motor that drives memory-promoting dendritic spine actin polymerization, in the maintenance of METH-associated memories and related structural plasticity. Memories formed through association with METH but not associations with foot shock or food reward were disrupted by a highly-specific actin cycling inhibitor when infused into the amygdala during the postconsolidation maintenance phase. This selective effect of depolymerization on METH-associated memory was immediate, persistent, and did not depend upon retrieval or strength of the association. Inhibition of non-muscle myosin II also resulted in a disruption of METH-associated memory. Thus, drug-associated memories seem to be actively maintained by a unique form of cycling F-actin driven by myosin II. This finding provides a potential therapeutic approach for the selective treatment of unwanted memories associated with psychiatric disorders that is both selective and does not rely on retrieval of the memory. The results further suggest that memory maintenance depends upon the preservation of polymerized actin. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein.

PubMed

Klinman, Eva; Holzbaur, Erika L F

2015-07-21

Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Mechanisms underlying intensity-dependent changes in cortical selectivity for frequency-modulated sweeps.

PubMed

Razak, K A

2012-04-01

Frequency-modulated (FM) sweeps are common components of species-specific vocalizations. The intensity of FM sweeps can cover a wide range in the natural environment, but whether intensity affects neural selectivity for FM sweeps is unclear. Bats, such as the pallid bat, which use FM sweeps for echolocation, are suited to address this issue, because the intensity of echoes will vary with target distance. In this study, FM sweep rate selectivity of pallid bat auditory cortex neurons was measured using downward sweeps at different intensities. Neurons became more selective for FM sweep rates present in the bat's echolocation calls as intensity increased. Increased selectivity resulted from stronger inhibition of responses to slower sweep rates. The timing and bandwidth of inhibition generated by frequencies on the high side of the excitatory tuning curve [sideband high-frequency inhibition (HFI)] shape rate selectivity in cortical neurons in the pallid bat. To determine whether intensity-dependent changes in FM rate selectivity were due to altered inhibition, the timing and bandwidth of HFI were quantified at multiple intensities using the two-tone inhibition paradigm. HFI arrived faster relative to excitation as sound intensity increased. The bandwidth of HFI also increased with intensity. The changes in HFI predicted intensity-dependent changes in FM rate selectivity. These data suggest that neural selectivity for a sweep parameter is not static but shifts with intensity due to changes in properties of sideband inhibition.

Resistance to change and frequency of response-dependent stimuli uncorrelated with reinforcement.

PubMed

Podlesnik, Christopher A; Jimenez-Gomez, Corina; Ward, Ryan D; Shahan, Timothy A

2009-09-01

Stimuli uncorrelated with reinforcement have been shown to enhance response rates and resistance to disruption; however, the effects of different rates of stimulus presentations have not been assessed. In two experiments, we assessed the effects of adding different rates of response-dependent brief stimuli uncorrelated with primary reinforcement on relative response rates and resistance to change. In both experiments, pigeons responded on variable-interval 60-s schedules of food reinforcement in two components of a multiple schedule, and brief response-dependent keylight-color changes were added to one or both components. Although relative response rates were not systematically affected in either experiment, relative resistance to presession feeding and extinction were. In Experiment 1, adding stimuli on a variable-interval schedule to one component of a multiple schedule either at a low rate (1 per min) for one group or at a high rate (4 per min) for another group similarly increased resistance to disruption in the components with added stimuli. When high and low rates of stimuli were presented across components (i.e., within subjects) in Experiment 2, however, relative resistance to disruption was greater in the component presenting stimuli at a lower rate. These results suggest that stimuli uncorrelated with food reinforcement do not strengthen responding in the same way as primary reinforcers.

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

PubMed Central

Sakata, Kazuko; Martinowich, Keri; Woo, Newton H.; Schloesser, Robert J.; Jimenez, Dennisse V.; Ji, Yuanyuan; Shen, Liya; Lu, Bai

2013-01-01

Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal–PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders. PMID:23980178

Mutation rate evolution in replicator dynamics.

PubMed

Allen, Benjamin; Rosenbloom, Daniel I Scholes

2012-11-01

The mutation rate of an organism is itself evolvable. In stable environments, if faithful replication is costless, theory predicts that mutation rates will evolve to zero. However, positive mutation rates can evolve in novel or fluctuating environments, as analytical and empirical studies have shown. Previous work on this question has focused on environments that fluctuate independently of the evolving population. Here we consider fluctuations that arise from frequency-dependent selection in the evolving population itself. We investigate how the dynamics of competing traits can induce selective pressure on the rates of mutation between these traits. To address this question, we introduce a theoretical framework combining replicator dynamics and adaptive dynamics. We suppose that changes in mutation rates are rare, compared to changes in the traits under direct selection, so that the expected evolutionary trajectories of mutation rates can be obtained from analysis of pairwise competition between strains of different rates. Depending on the nature of frequency-dependent trait dynamics, we demonstrate three possible outcomes of this competition. First, if trait frequencies are at a mutation-selection equilibrium, lower mutation rates can displace higher ones. Second, if trait dynamics converge to a heteroclinic cycle-arising, for example, from "rock-paper-scissors" interactions-mutator strains succeed against non-mutators. Third, in cases where selection alone maintains all traits at positive frequencies, zero and nonzero mutation rates can coexist indefinitely. Our second result suggests that relatively high mutation rates may be observed for traits subject to cyclical frequency-dependent dynamics.

Negative frequency-dependent selection or alternative reproductive tactics: maintenance of female polymorphism in natural populations

PubMed Central

2013-01-01

Background Sex-limited polymorphisms have long intrigued evolutionary biologists and have been the subject of long-standing debates. The coexistence of multiple male and/or female morphs is widely believed to be maintained through negative frequency-dependent selection imposed by social interactions. However, remarkably few empirical studies have evaluated how social interactions, morph frequencies and fitness parameters relate to one another under natural conditions. Here, we test two hypotheses proposed to explain the maintenance of a female polymorphism in a species with extreme geographical variation in morph frequencies. We first elucidate how fecundity traits of the morphs vary in relation to the frequencies and densities of males and female morphs in multiple sites over multiple years. Second, we evaluate whether the two female morphs differ in resource allocation among fecundity traits, indicating alternative tactics to maximize reproductive output. Results We present some of the first empirical evidence collected under natural conditions that egg number and clutch mass was higher in the rarer female morph. This morph-specific fecundity advantage gradually switched with the population morph frequency. Our results further indicate that all investigated fecundity traits are negatively affected by relative male density (i.e. operational sex ratio), which confirms male harassment as selective agent. Finally, we show a clear trade-off between qualitative (egg mass) and quantitative (egg number) fecundity traits. This trade-off, however, is not morph-specific. Conclusion Our reported frequency- and density-dependent fecundity patterns are consistent with the hypothesis that the polymorphism is driven by a conflict between sexes over optimal mating rate, with costly male sexual harassment driving negative frequency-dependent selection on morph fecundity. PMID:23822745

Stimulation of the human medial temporal lobe between learning and recall selectively enhances forgetting

PubMed Central

Merkow, Maxwell B.; Burke, John F.; Ramayya, Ashwin G.; Sharan, Ashwini D.; Sperling, Michael R.; Kahana, Michael J.

2017-01-01

Background Direct electrical stimulation applied to the human medial temporal lobe (MTL) typically disrupts performance on memory tasks, however, the mechanism underlying this effect is not known. Objective To study the effects of MTL stimulation on memory performance Methods We studied the effects of MTL stimulation on memory in five patients undergoing invasive electrocorticographic monitoring during various phases of a memory task (encoding, distractor, recall). Results We found that MTL stimulation disrupted memory performance in a timing-dependent manner; we observed greater forgetting when applying stimulation during the delay between encoding and recall, compared to when it was applied during encoding or recall. Conclusions The results suggest that recall is most dependent on the MTL between learning and retrieval. PMID:28073638

A multislice gradient echo pulse sequence for CEST imaging.

PubMed

Dixon, W Thomas; Hancu, Ileana; Ratnakar, S James; Sherry, A Dean; Lenkinski, Robert E; Alsop, David C

2010-01-01

Chemical exchange-dependent saturation transfer and paramagnetic chemical exchange-dependent saturation transfer are agent-mediated contrast mechanisms that depend on saturating spins at the resonant frequency of the exchangeable protons on the agent, thereby indirectly saturating the bulk water. In general, longer saturating pulses produce stronger chemical and paramagnetic exchange-dependent saturation transfer effects, with returns diminishing for pulses longer than T1. This could make imaging slow, so one approach to chemical exchange-dependent saturation transfer imaging has been to follow a long, frequency-selective saturation period by a fast imaging method. A new approach is to insert a short frequency-selective saturation pulse before each spatially selective observation pulse in a standard, two-dimensional, gradient-echo pulse sequence. Being much less than T1 apart, the saturation pulses have a cumulative effect. Interleaved, multislice imaging is straightforward. Observation pulses directed at one slice did not produce observable, unintended chemical exchange-dependent saturation transfer effects in another slice. Pulse repetition time and signal-to noise ratio increase in the normal way as more slices are imaged simultaneously. Copyright (c) 2009 Wiley-Liss, Inc.

Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.

PubMed

Betterton, Ruth T; Broad, Lisa M; Tsaneva-Atanasova, Krasimira; Mellor, Jack R

2017-06-01

Modulation of gamma oscillations is important for the processing of information and the disruption of gamma oscillations is a prominent feature of schizophrenia and Alzheimer's disease. Gamma oscillations are generated by the interaction of excitatory and inhibitory neurons where their precise frequency and amplitude are controlled by the balance of excitation and inhibition. Acetylcholine enhances the intrinsic excitability of pyramidal neurons and suppresses both excitatory and inhibitory synaptic transmission, but the net modulatory effect on gamma oscillations is not known. Here, we find that the power, but not frequency, of optogenetically induced gamma oscillations in the CA3 region of mouse hippocampal slices is enhanced by low concentrations of the broad-spectrum cholinergic agonist carbachol but reduced at higher concentrations. This bidirectional modulation of gamma oscillations is replicated within a mathematical model by neuronal depolarisation, but not by reducing synaptic conductances, mimicking the effects of muscarinic M1 receptor activation. The predicted role for M1 receptors was supported experimentally; bidirectional modulation of gamma oscillations by acetylcholine was replicated by a selective M1 receptor agonist and prevented by genetic deletion of M1 receptors. These results reveal that acetylcholine release in CA3 of the hippocampus modulates gamma oscillation power but not frequency in a bidirectional and dose-dependent manner by acting primarily through muscarinic M1 receptors. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Disruption of DNA methylation-dependent long gene repression in Rett syndrome

PubMed Central

Gabel, Harrison W.; Kinde, Benyam Z.; Stroud, Hume; Gilbert, Caitlin S.; Harmin, David A.; Kastan, Nathaniel R.; Hemberg, Martin; Ebert, Daniel H.; Greenberg, Michael E.

2015-01-01

Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism1. MECP2 encodes a methyl-DNA-binding protein2 that has been proposed to function as a transcriptional repressor, but despite numerous studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 regulates transcription3–9. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain. PMID:25762136

Understanding your supply chain to reduce the risk of supply chain disruption.

PubMed

Wildgoose, Nick; Brennan, Patrick; Thompson, Simon

2012-01-01

Supply chains are at the heart of the way in which organisations operate and compete today; they also play a critical role in overall organisation performance. In the context of increasingly complex and global supply chains, the actions taken to drive down costs are likely to drive risk into the supply chain. The frequency of supply chain disruptions is high and this paper offers practical advice to help reduce the frequency and cost associated with these. There is advice to help with the understanding of how to identify critical suppliers. The reader is guided through comprehensive risk assessment and mitigation approaches and a selection of practical risk solutions and tools that you can use is described. There is a section on the 'dos and don'ts' relating to supplier due diligence. For those organisations facing the challenge of drawing up a business case relating to investment in improving supply chain resiliency, there is also a section outlining some of the business benefits of improving supply chain resiliency.

High temperatures disrupt Artemia franciscana mating patterns and impact sexual selection intensity

NASA Astrophysics Data System (ADS)

Santos, Maria R.; Vieira, Natividade; Monteiro, Nuno M.

2018-07-01

Temperature plays a critical role in survival and reproduction, especially in ectotherms. Therefore, it is important to understand the mechanisms influencing life history traits and reproductive behaviours in order to predict climate change impacts on species' occurrence and performance. Here, we used the crustacean Artemia franciscana to investigate the potential impacts of temperature on life history traits, mating patterns and intensity of sexual selection. We reared A. franciscana at three temperatures 20 °C, 25 °C, and 30 °C and measured life history traits such as growth, mortality or development of sexual traits. Our observations confirmed a clear link between life history traits and temperature, with advanced sexual maturity and increased mortality rates following temperature rises. Also, we found that mating is size assortative close to the ideal developmental temperature. Nevertheless, when temperatures deviate from the optimum, mating patterns were altered. Although selection intensity for females remained similar at all tested temperatures, as males preferentially mated with the larger females, size assortative mating disappeared at the highest temperature. Overall, our results highlight the potential for a temperature-dependent disruption of A. franciscana mating patterns. This disruption is especially pronounced under high temperatures as reproduction becomes progressively more random, thus entailing a relaxation of sexual selection intensity.

Sibutramine-induced anorexia: potent, dose-dependent and behaviourally-selective profile in male rats.

PubMed

Tallett, A J; Blundell, J E; Rodgers, R J

2009-03-17

The serotonin and noradrenaline reuptake inhibitor sibutramine has been licensed as an anti-obesity treatment for more than a decade. However, while inhibitory effects on food intake and weight gain are well documented, surprisingly little published detail exists regarding its influence on feeding and related behaviours. The present study was therefore designed to assess the effects of acute sibutramine treatment on food intake, the behavioural satiety sequence (BSS) and post-treatment weight gain. Subjects were 10 non-deprived adult male Lister hooded rats, tested with 0.5-3.0 mg/kg sibutramine hydrochloride during 1-h DVD-recorded test sessions with palatable mash. Our results show that sibutramine dose-dependently reduced food intake, an effect significant at all doses tested. Ethological analysis revealed very few behavioural effects, except for a dose-dependent reduction in time spent feeding and an increase in the frequency of resting. Behavioural specificity was further supported by time-bin analysis which confirmed both the structural integrity and dose-dependent acceleration of the BSS. Single dosing with sibutramine (3.0 mg/kg) also suppressed daily weight gain over the 24-72 h period post-dosing. Current data support the conclusion that the acute anorectic and weight loss efficacy of sibutramine in adult male rats is not secondary to behavioural disruption but, instead, is due largely to an acceleration in behavioural satiety.

Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.

PubMed

Cohen, Samuel M; Suutari, Benjamin; He, Xingzhi; Wang, Yang; Sanchez, Sandrine; Tirko, Natasha N; Mandelberg, Nataniel J; Mullins, Caitlin; Zhou, Guangjun; Wang, Shuqi; Kats, Ilona; Salah, Alejandro; Tsien, Richard W; Ma, Huan

2018-06-22

Learning and memory depend on neuronal plasticity originating at the synapse and requiring nuclear gene expression to persist. However, how synapse-to-nucleus communication supports long-term plasticity and behavior has remained elusive. Among cytonuclear signaling proteins, γCaMKII stands out in its ability to rapidly shuttle Ca 2+ /CaM to the nucleus and thus activate CREB-dependent transcription. Here we show that elimination of γCaMKII prevents activity-dependent expression of key genes (BDNF, c-Fos, Arc), inhibits persistent synaptic strengthening, and impairs spatial memory in vivo. Deletion of γCaMKII in adult excitatory neurons exerts similar effects. A point mutation in γCaMKII, previously uncovered in a case of intellectual disability, selectively disrupts CaM sequestration and CaM shuttling. Remarkably, this mutation is sufficient to disrupt gene expression and spatial learning in vivo. Thus, this specific form of cytonuclear signaling plays a key role in learning and memory and contributes to neuropsychiatric disease.

Mutational jackpot events generate effective frequency-dependent selection in adapting populations

NASA Astrophysics Data System (ADS)

Hallatschek, Oskar

The site-frequency spectrum is one the most easily measurable quantities that characterize the genetic diversity of a population. While most neutral models predict that site frequency spectra should decay with increasing frequency, a high-frequency uptick has been reported in many populations. Anomalies in the high-frequency tail are particularly unsettling because the highest frequencies can be measured with greatest accuracy. Here, we show that an uptick in the spectrum of neutral mutations generally arises when mutant frequencies are dominated by rare jackpot events, mutational events with large descendant numbers. This leads to an effective pattern of frequency-dependent selection (or unstable internal equilibrium at one half frequency) that causes an accumulation of high-frequency polymorphic sites. We reproduce the known uptick occurring for recurrent hitchhiking (genetic draft) as well as rapid adaptation, and (in the future) generalize the shape of the high-frequency tail to other scenarios that are dominated by jackpot events, such as frequent range expansions. We also tackle (in the future) the inverse approach to use the high-frequency uptick for learning about the tail of the offspring number distribution. Positively selected alleles need to surpass, typically, an u NSF Career Award (PoLS), NIH NIGMS R01, Simons Foundation.

Development process of an assessment tool for disruptive behavior problems in cross-cultural settings: the Disruptive Behavior International Scale – Nepal version (DBIS-N)

PubMed Central

Burkey, Matthew D.; Ghimire, Lajina; Adhikari, Ramesh P.; Kohrt, Brandon A.; Jordans, Mark J. D.; Haroz, Emily; Wissow, Lawrence

2017-01-01

Systematic processes are needed to develop valid measurement instruments for disruptive behavior disorders (DBDs) in cross-cultural settings. We employed a four-step process in Nepal to identify and select items for a culturally valid assessment instrument: 1) We extracted items from validated scales and local free-list interviews. 2) Parents, teachers, and peers (n=30) rated the perceived relevance and importance of behavior problems. 3) Highly rated items were piloted with children (n=60) in Nepal. 4) We evaluated internal consistency of the final scale. We identified 49 symptoms from 11 scales, and 39 behavior problems from free-list interviews (n=72). After dropping items for low ratings of relevance and severity and for poor item-test correlation, low frequency, and/or poor acceptability in pilot testing, 16 items remained for the Disruptive Behavior International Scale—Nepali version (DBIS-N). The final scale had good internal consistency (α=0.86). A 4-step systematic approach to scale development including local participation yielded an internally consistent scale that included culturally relevant behavior problems. PMID:28093575

Improved photoacoustic dosimetry for retinal laser surgery

NASA Astrophysics Data System (ADS)

Dufour, Suzie; Brown, Robert B.; Gallant, Pascal; Mermut, Ozzy

2018-02-01

Lasers are employed for numerous medical interventions by exploiting ablative, disruptive or thermal effects. In ocular procedures, lasers have been used for decades to treat diseases such as diabetic retinopathy, macular edema and aged related macular degeneration via photocoagulation of retinal tissues. Although laser photocoagulation is well established in today's practice, efforts to improve clinical outcomes by reducing the collateral damage from thermal diffusion is leading to novel treatments using shorter (μs) laser pulses (e.g. selective retinal therapy) which result in physical rather than thermal damage. However, for these new techniques to be widely utilized, a method is required to ensure safe but sufficient dosage has been applied, since no visible effects can be seen by ophthalmoscopy directly post treatment. Photoacoustic feedback presents an attractive solution, as the signal is dependent directly on absorbed dosage. Here, we present a method that takes advantage of temporal pulse formatting technology to minimize variation in absorbed dose in ophthalmic laser treatment and provide intelligent dosimetry feedback based on photoacoustic (PA) response. This method tailors the pulse to match the frequency response of the sample and/or detection chain. Depending on the system, this may include the absorbing particle size, the laser beam diameter, the laser pulse duration, tissue acoustic properties and the acoustic detector frequency response. A significant improvement (<7x) of photoacoustic signal-to-noise ratio over equivalent traditional pulse formats have been achieved, while spectral analysis of the detected signal provides indications of cavitation events and other sample properties.

How Listening to Music Affects Reading: Evidence From Eye Tracking.

PubMed

Zhang, Han; Miller, Kevin; Cleveland, Raymond; Cortina, Kai

2018-02-01

The current research looked at how listening to music affects eye movements when college students read natural passages for comprehension. Two studies found that effects of music depend on both frequency of the word and dynamics of the music. Study 1 showed that lexical and linguistic features of the text remained highly robust predictors of looking times, even in the music condition. However, under music exposure, (a) readers produced more rereading, and (b) gaze duration on words with very low frequency were less predicted by word length, suggesting disrupted sublexical processing. Study 2 showed that these effects were exacerbated for a short period as soon as a new song came into play. Our results suggested that word recognition generally stayed on track despite music exposure and that extensive rereading can, to some extent, compensate for disruption. However, an irrelevant auditory signal may impair sublexical processing of low-frequency words during first-pass reading, especially when the auditory signal changes dramatically. These eye movement patterns are different from those observed in some other scenarios in which reading comprehension is impaired, including mindless reading. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Frequency control using a complex effective reflectivity in laterally coupled semiconductor laser arrays.

PubMed

Griffel, G; Marshall, W K; Gravé, I; Yariv, A; Nabiev, R

1991-08-01

Frequency selectivity of a novel type of multielement, multisection laterally coupled semiconductor laser array is studied using the round-trip method. It is found that such a structure should lead to a strong frequency selectivity owing to a periodic dependency of the threshold gain on the frequency. A gain-guided two-coupledcavity device was fabricated. The experimental results show excellent agreement with the theoretical prediction.

Stimulation of the human medial temporal lobe between learning and recall selectively enhances forgetting.

PubMed

Merkow, Maxwell B; Burke, John F; Ramayya, Ashwin G; Sharan, Ashwini D; Sperling, Michael R; Kahana, Michael J

Direct electrical stimulation applied to the human medial temporal lobe (MTL) typically disrupts performance on memory tasks, however, the mechanism underlying this effect is not known. To study the effects of MTL stimulation on memory performance. We studied the effects of MTL stimulation on memory in five patients undergoing invasive electrocorticographic monitoring during various phases of a memory task (encoding, distractor, recall). We found that MTL stimulation disrupted memory performance in a timing-dependent manner; we observed greater forgetting when applying stimulation during the delay between encoding and recall, compared to when it was applied during encoding or recall. The results suggest that recall is most dependent on the MTL between learning and retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

Frequency-selective fading statistics of shallow-water acoustic communication channel with a few multipaths

NASA Astrophysics Data System (ADS)

Bae, Minja; Park, Jihyun; Kim, Jongju; Xue, Dandan; Park, Kyu-Chil; Yoon, Jong Rak

2016-07-01

The bit error rate of an underwater acoustic communication system is related to multipath fading statistics, which determine the signal-to-noise ratio. The amplitude and delay of each path depend on sea surface roughness, propagation medium properties, and source-to-receiver range as a function of frequency. Therefore, received signals will show frequency-dependent fading. A shallow-water acoustic communication channel generally shows a few strong multipaths that interfere with each other and the resulting interference affects the fading statistics model. In this study, frequency-selective fading statistics are modeled on the basis of the phasor representation of the complex path amplitude. The fading statistics distribution is parameterized by the frequency-dependent constructive or destructive interference of multipaths. At a 16 m depth with a muddy bottom, a wave height of 0.2 m, and source-to-receiver ranges of 100 and 400 m, fading statistics tend to show a Rayleigh distribution at a destructive interference frequency, but a Rice distribution at a constructive interference frequency. The theoretical fading statistics well matched the experimental ones.

Neutron diffraction reveals hydrogen bonds critical for cGMP-selective activation: Insights for cGMP-dependent protein kinase agonist design

DOE PAGES

Huang, Gilbert Y.; Gerlits, Oksana O.; Blakeley, Matthew P.; ...

2014-10-01

High selectivity of cyclic-nucleotide binding (CNB) domains for cAMP and cGMP are required for segregating signaling pathways; however, the mechanism of selectivity remains unclear. To investigate the mechanism of high selectivity in cGMP-dependent protein kinase (PKG), we determined a room-temperature joint X-ray/neutron (XN) structure of PKG Iβ CNB-B, a domain 200-fold selective for cGMP over cAMP, bound to cGMP (2.2 Å), and a low-temperature X-ray structure of CNB-B with cAMP (1.3 Å). Finally, the XN structure directly describes the hydrogen bonding interactions that modulate high selectivity for cGMP, while the structure with cAMP reveals that all these contacts are disrupted,more » explaining its low affinity for cAMP.« less

Pulse Width Dependence Of Pigment Cell Damage At 694 nm In Guinea Pig Skin

NASA Astrophysics Data System (ADS)

Dover, Jeffrey S.; Polla, Luigi L.; Margolis, Randall J.; Whitaker, Diana; Watanabe, Schinichi; Murphy, George F.; Parrish, John A.; Anderson, R. R.

1987-03-01

351 nm, 20-nsec XeF excimer laser irradiation has previously been shown to selectively target and damage melanosomes in human skin. In the following studies selective targeting with melanosomal photodisruption has been demonstrated in pigmented guinea pig skin with a Q-switched 40-nsec ruby laser, and a 750-nsec pulsed dye laser but not with a 400-usec pulsed dye laser. The pulse width dependence of melanosomal disruption, occurring only at pulsewidths shorter than the thermal relaxation time of the melanosome (0.5 - 1.0 usec), is in accordance with the theory of selective photothermolysis. Possible mechanisms of melanosomal photodisruption include development of sudden thermal gradients leading to cavitation or shock wave production.

Optogenetic stimulation of adrenergic C1 neurons causes sleep state-dependent cardiorespiratory stimulation and arousal with sighs in rats.

PubMed

Burke, Peter G R; Abbott, Stephen B G; Coates, Melissa B; Viar, Kenneth E; Stornetta, Ruth L; Guyenet, Patrice G

2014-12-01

The rostral ventrolateral medulla (RVLM) contains central respiratory chemoreceptors (retrotrapezoid nucleus, RTN) and the sympathoexcitatory, hypoxia-responsive C1 neurons. Simultaneous optogenetic stimulation of these neurons produces vigorous cardiorespiratory stimulation, sighing, and arousal from non-REM sleep. To identify the effects that result from selectively stimulating C1 cells. A Cre-dependent vector expressing channelrhodopsin 2 (ChR2) fused with enhanced yellow fluorescent protein or mCherry was injected into the RVLM of tyrosine hydroxylase (TH)-Cre rats. The response of ChR2-transduced neurons to light was examined in anesthetized rats. ChR2-transduced C1 neurons were photoactivated in conscious rats while EEG, neck muscle EMG, blood pressure (BP), and breathing were recorded. Most ChR2-expressing neurons (95%) contained C1 neuron markers and innervated the spinal cord. RTN neurons were not transduced. While the rats were under anesthesia, the C1 cells were faithfully activated by each light pulse up to 40 Hz. During quiet resting and non-REM sleep, C1 cell stimulation (20 s, 2-20 Hz) increased BP and respiratory frequency and produced sighs and arousal from non-REM sleep. Arousal was frequency-dependent (85% probability at 20 Hz). Stimulation during REM sleep increased BP, but had no effect on EEG or breathing. C1 cell-mediated breathing stimulation was occluded by hypoxia (12% FIO2), but was unchanged by 6% FiCO2. C1 cell stimulation reproduces most effects of acute hypoxia, specifically cardiorespiratory stimulation, sighs, and arousal. C1 cell activation likely contributes to the sleep disruption and adverse autonomic consequences of sleep apnea. During hypoxia (awake) or REM sleep, C1 cell stimulation increases BP but no longer stimulates breathing.

Selective impairment of hippocampus and posterior hub areas in Alzheimer's disease: an MEG-based multiplex network study.

PubMed

Yu, Meichen; Engels, Marjolein M A; Hillebrand, Arjan; van Straaten, Elisabeth C W; Gouw, Alida A; Teunissen, Charlotte; van der Flier, Wiesje M; Scheltens, Philip; Stam, Cornelis J

2017-05-01

Although frequency-specific network analyses have shown that functional brain networks are altered in patients with Alzheimer's disease, the relationships between these frequency-specific network alterations remain largely unknown. Multiplex network analysis is a novel network approach to study complex systems consisting of subsystems with different types of connectivity patterns. In this study, we used magnetoencephalography to integrate five frequency-band specific brain networks in a multiplex framework. Previous structural and functional brain network studies have consistently shown that hub brain areas are selectively disrupted in Alzheimer's disease. Accordingly, we hypothesized that hub regions in the multiplex brain networks are selectively targeted in patients with Alzheimer's disease in comparison to healthy control subjects. Eyes-closed resting-state magnetoencephalography recordings from 27 patients with Alzheimer's disease (60.6 ± 5.4 years, 12 females) and 26 controls (61.8 ± 5.5 years, 14 females) were projected onto atlas-based regions of interest using beamforming. Subsequently, source-space time series for both 78 cortical and 12 subcortical regions were reconstructed in five frequency bands (delta, theta, alpha 1, alpha 2 and beta band). Multiplex brain networks were constructed by integrating frequency-specific magnetoencephalography networks. Functional connections between all pairs of regions of interests were quantified using a phase-based coupling metric, the phase lag index. Several multiplex hub and heterogeneity metrics were computed to capture both overall importance of each brain area and heterogeneity of the connectivity patterns across frequency-specific layers. Different nodal centrality metrics showed consistently that several hub regions, particularly left hippocampus, posterior parts of the default mode network and occipital regions, were vulnerable in patients with Alzheimer's disease compared to control subjects. Of note, these detected vulnerable hubs in Alzheimer's disease were absent in each individual frequency-specific network, thus showing the value of integrating the networks. The connectivity patterns of these vulnerable hub regions in the patients were heterogeneously distributed across layers. Perturbed cognitive function and abnormal cerebrospinal fluid amyloid-β42 levels correlated positively with the vulnerability of the hub regions in patients with Alzheimer's disease. Our analysis therefore demonstrates that the magnetoencephalography-based multiplex brain networks contain important information that cannot be revealed by frequency-specific brain networks. Furthermore, this indicates that functional networks obtained in different frequency bands do not act as independent entities. Overall, our multiplex network study provides an effective framework to integrate the frequency-specific networks with different frequency patterns and reveal neuropathological mechanism of hub disruption in Alzheimer's disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cholinergic Blockade Reduces Theta-Gamma Phase Amplitude Coupling and Speed Modulation of Theta Frequency Consistent with Behavioral Effects on Encoding

PubMed Central

Gillet, Shea N.; Climer, Jason R.; Hasselmo, Michael E.

2013-01-01

Large-scale neural activation dynamics in the hippocampal-entorhinal circuit local field potential, observable as theta and gamma rhythms and coupling between these rhythms, is predictive of encoding success. Behavioral studies show that systemic administration of muscarinic acetylcholine receptor antagonists selectively impairs encoding, suggesting that they may also disrupt the coupling between the theta and gamma bands. Here, we tested the hypothesis that muscarinic antagonists selectively disrupt coupling between theta and gamma. Specifically, we characterized the effects of systemically administered scopolamine on movement-induced theta and gamma rhythms recorded in the superficial layers of the medial entorhinal cortex (MEC) of freely moving rats. We report the novel result that gamma power at the peak of theta was most reduced following muscarinic blockade, significantly shifting the phase of maximal gamma power to occur at later phases of theta. We also characterize the existence of multiple distinct gamma bands in the superficial layers of the MEC. Further, we observed that theta frequency was significantly less modulated by movement speed following muscarinic blockade. Finally, the slope relating speed to theta frequency, a correlate of familiarity with a testing enclosure, increased significantly less between the preinjection and recovery trials when scopolamine was administered during the intervening injection session than when saline was administered, suggesting that scopolamine reduced encoding of the testing enclosure. These data are consistent with computational models suggesting that encoding and retrieval occur during the peak and trough of theta, respectively, and support the theory that acetylcholine regulates the balance between encoding versus retrieval. PMID:24336727

Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8/19.

PubMed

Park, Min Ju; Shen, Hailian; Spaeth, Jason M; Tolvanen, Jaana H; Failor, Courtney; Knudtson, Jennifer F; McLaughlin, Jessica; Halder, Sunil K; Yang, Qiwei; Bulun, Serdar E; Al-Hendy, Ayman; Schenken, Robert S; Aaltonen, Lauri A; Boyer, Thomas G

2018-03-30

Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at high frequency in uterine fibroids (UFs) and breast fibroepithelial tumors as well as recurrently, albeit less frequently, in malignant uterine leimyosarcomas, chronic lymphocytic leukemias, and colorectal cancers. Previously, we reported that UF-linked mutations in MED12 disrupt its ability to activate cyclin C (CycC)-dependent kinase 8 (CDK8) in Mediator, implicating impaired Mediator-associated CDK8 activity in the molecular pathogenesis of these clinically significant lesions. Notably, the CDK8 paralog CDK19 is also expressed in myometrium, and both CDK8 and CDK19 assemble into Mediator in a mutually exclusive manner, suggesting that CDK19 activity may also be germane to the pathogenesis of MED12 mutation-induced UFs. However, whether and how UF-linked mutations in MED12 affect CDK19 activation is unknown. Herein, we show that MED12 allosterically activates CDK19 and that UF-linked exon 2 mutations in MED12 disrupt its CDK19 stimulatory activity. Furthermore, we find that within the Mediator kinase module, MED13 directly binds to the MED12 C terminus, thereby suppressing an apparent UF mutation-induced conformational change in MED12 that otherwise disrupts its association with CycC-CDK8/19. Thus, in the presence of MED13, mutant MED12 can bind, but cannot activate, CycC-CDK8/19. These findings indicate that MED12 binding is necessary but not sufficient for CycC-CDK8/19 activation and reveal an additional step in the MED12-dependent activation process, one critically dependent on MED12 residues altered by UF-linked exon 2 mutations. These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in UFs. © 2018 Park et al.

Multivariate sexual selection on male tegmina in wild populations of sagebrush crickets, Cyphoderris strepitans (Orthoptera: Haglidae).

PubMed

Ower, G D; Hunt, J; Sakaluk, S K

2017-02-01

Although the strength and form of sexual selection on song in male crickets have been studied extensively, few studies have examined selection on the morphological structures that underlie variation in males' song, particularly in wild populations. Geometric morphometric techniques were used to measure sexual selection on the shape, size and symmetry of both top and bottom tegmina in wild populations of sagebrush crickets, a species in which nuptial feeding by females imposes an unambiguous phenotypic marker on males. The size of the tegmina negatively covaried with song dominant frequency and positively covaried with song pulse duration. Sexual selection was more intense on the bottom tegmen, conceivably because it interacts more freely with the subtegminal airspace, which may play a role in song amplification. An expanded coastal/subcostal region was one of the phenotypes strongly favoured by disruptive selection on the bottom tegmen, an adaptation that may form a more effective seal with the thorax to prevent noise cancellation. Directional selection also favoured increased symmetry in tegminal shape. Assuming more symmetrical males are better able to buffer against developmental noise, the song produced by these males may make them more attractive to females. Despite the strong stabilizing selection documented previously on the dominant frequency of the song, stabilizing selection on the resonator that regulates dominant frequency was surprisingly absent. Nonetheless, wing morphology had an important influence on song structure and appears to be subject to significant linear and nonlinear sexual selection through female mate choice. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Interspecific competition alters natural selection on shade avoidance phenotypes in Impatiens capensis.

PubMed

McGoey, Brechann V; Stinchcombe, John R

2009-08-01

Shade avoidance syndrome is a known adaptive response for Impatiens capensis growing in dense intraspecific competition. However, I. capensis also grow with dominant interspecific competitors in marshes. Here, we compare the I. capensis shade-avoidance phenotypes produced in the absence and presence of heterospecific competitors, as well as selection on those traits. Two treatments were established in a marsh; in one treatment all heterospecifics were removed, while in the other, all competitors remained. We compared morphological traits, light parameters, seed output and, using phenotypic selection analysis, examined directional and nonlinear selection operating in the different competitive treatments. Average phenotypes, light parameters and seed production all varied depending on competitive treatment. Phenotypic selection analyses revealed different directional, disruptive, stabilizing and correlational selection. The disparities seen in both phenotypes and selection between the treatments related to the important differences in elongation timing depending on the presence of heterospecifics, although environmental covariances between traits and fitness could also contribute. Phenotypes produced by I. capensis depend on their competitive environment, and differing selection on shade-avoidance traits between competitive environments could indirectly select for increased plasticity given gene flow between populations in different competitive contexts.

Sprayable microencapsulated sex pheromone formulations for mating disruption of four tortricid species: effects of application height, rate, frequency, and sticker adjuvant.

PubMed

Stelinski, L L; McGhee, P; Haas, M; Il'ichev, A L; Gut, L J

2007-08-01

Several application parameters of microencapsulated (MEC) sex pheromone formulations were manipulated to determine their impact on efficacy of disruption for codling moth, Cydia pomonella (L.); oriental fruit moth, Grapholita molesta (Busck); obliquebanded leafroller, Choristoneura rosaceana (Harris); and redbanded leafroller, Argyrotaenia velutinana (Walker). Depending on the experiment, the formulations evaluated were those formerly manufactured by 3M Canada (London, ON, Canada) or those that are currently available from Suterra LLC (Bend, OR). The efficacy of MEC formulations applied by air-blast sprayer evenly throughout the entire canopy of 2-3-m-tall apple (Malus spp.) trees was equivalent to treatments in which targeted applications of MECs were made to the lower or upper 1.5 m of the canopy (at equivalent overall rates) for oriental fruit moth and both leafroller species. The realized distribution of deposited microcapsules within the tree canopy corresponded well with the intended heights of application within the canopy. The additional coapplication of the pine resin sticker Nu-Film 17 increased efficacy but not longevity of MEC formulations for oriental fruit moth; this adjuvant had no added effects for codling moth or leafroller formulations. Increasing the rate of active ingredient (AI) per hectare by 20-30-fold (range 2.5-75.0 g/ha) did not improve the disruption efficacy of MECs for codling moth or either leafroller species when both low and high rates were applied at equivalent frequencies per season. A low-rate, high-frequency (nine applications per season) application protocol was compared with a standard protocol in which two to three applications were made per season, once before each moth generation for each species. The low-rate, high-frequency protocol resulted in equivalent or better disruption efficacy for each moth species, despite using two-fold less total AI per hectare per season with the former treatment. The low-rate, frequent-application protocol should make the use of MEC formulations of synthetic pheromone more economical and perhaps more effective.

Athletes with inguinal disruption benefit from endoscopic totally extraperitoneal (TEP) repair.

PubMed

Roos, M M; Bakker, W J; Goedhart, E A; Verleisdonk, E J M M; Clevers, G J; Voorbrood, C E H; Sanders, F B M; Naafs, D B; Burgmans, J P J

2018-06-01

Inguinal disruption, a common condition in athletes, is a diagnostic and therapeutic challenge. The aim of this study was to evaluate the effect of endoscopic totally extraperitoneal (TEP) repair in athletes with inguinal disruption, selected through a multidisciplinary, systematic work-up. An observational, prospective cohort study was conducted in 32 athletes with inguinal disruption. Athletes were assessed by a sports medicine physician, radiologist and hernia surgeon and underwent subsequent endoscopic TEP repair with placement of polypropylene mesh. The primary outcome was pain reduction during exercise on the numeric rating scale (NRS) 3 months postoperatively. Secondary outcomes were sports resumption, physical functioning and long-term pain intensity. Patients were assessed preoperatively, 3 months postoperatively and after a median follow-up of 19 months. Follow-up was completed in 30 patients (94%). The median pain score decreased from 8 [interquartile range (IQR) 7-8] preoperatively to 2 (IQR 0-5) 3 months postoperatively (p < 0.001). At long-term follow-up, the median pain score was 0 (IQR 0-3) (p < 0.001). At 3 months, 60% of patients were able to complete a full training and match. The median intensity of sport was 50% (IQR 20-70) preoperatively, 95% (IQR 70-100) 3 months postoperatively (p < 0.001), and 100% (IQR 90-100) at long-term follow-up (p < 0.001). The median frequency of sport was 4 (IQR 3-5) times per week before development of symptoms and 3 (IQR 3-4) times per week 3 months postoperatively (p = 0.025). Three months postoperatively, improvement was shown on all physical functioning subscales. Athletes with inguinal disruption, selected through a multidisciplinary, systematic work-up, benefit from TEP repair.

A phase transition induces chaos in a predator-prey ecosystem with a dynamic fitness landscape

PubMed Central

2017-01-01

In many ecosystems, natural selection can occur quickly enough to influence the population dynamics and thus future selection. This suggests the importance of extending classical population dynamics models to include such eco-evolutionary processes. Here, we describe a predator-prey model in which the prey population growth depends on a prey density-dependent fitness landscape. We show that this two-species ecosystem is capable of exhibiting chaos even in the absence of external environmental variation or noise, and that the onset of chaotic dynamics is the result of the fitness landscape reversibly alternating between epochs of stabilizing and disruptive selection. We draw an analogy between the fitness function and the free energy in statistical mechanics, allowing us to use the physical theory of first-order phase transitions to understand the onset of rapid cycling in the chaotic predator-prey dynamics. We use quantitative techniques to study the relevance of our model to observational studies of complex ecosystems, finding that the evolution-driven chaotic dynamics confer community stability at the “edge of chaos” while creating a wide distribution of opportunities for speciation during epochs of disruptive selection—a potential observable signature of chaotic eco-evolutionary dynamics in experimental studies. PMID:28678792

Epistasis can accelerate adaptive diversification in haploid asexual populations.

PubMed

Griswold, Cortland K

2015-03-07

A fundamental goal of the biological sciences is to determine processes that facilitate the evolution of diversity. These processes can be separated into ecological, physiological, developmental and genetic. An ecological process that facilitates diversification is frequency-dependent selection caused by competition. Models of frequency-dependent adaptive diversification have generally assumed a genetic basis of phenotype that is non-epistatic. Here, we present a model that indicates diversification is accelerated by an epistatic basis of phenotype in combination with a competition model that invokes frequency-dependent selection. Our model makes use of a genealogical model of epistasis and insights into the effects of balancing selection on the genealogical structure of a population to understand how epistasis can facilitate diversification. The finding that epistasis facilitates diversification may be informative with respect to empirical results that indicate an epistatic basis of phenotype in experimental bacterial populations that experienced adaptive diversification. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Behavioral toxicity of selected radioprotectors

NASA Astrophysics Data System (ADS)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

The effects of extra-low-frequency atmospheric pressure oscillations on human mental activity

NASA Astrophysics Data System (ADS)

Delyukov, A. A.; Didyk, L.

Slight atmospheric pressure oscillations (APO) in the extra-low-frequency range below 0.1 Hz, which frequently occur naturally, can influence human mental activity. This phenomenon has been observed in experiments with a group of 12 healthy volunteers exposed to experimentally created APO with amplitudes 30-50 Pa in the frequency band 0.011-0.17 Hz. Exposure of the subjects to APO for 15-30 min caused significant changes in attention and short-term memory functions, performance rate, and mental processing flexibility. The character of the response depended on the APO frequency and coherence. Periodic APO promoted purposeful mental activity, accompanied by an increase in breath-holding duration and a slower heart rate. On the other hand, quasi-chaotic APO, similar to the natural perturbations of atmospheric pressure, disrupted mental activity. These observations suggest that APO could be partly responsible for meteorosensitivity in humans.

Similar patterns of frequency-dependent selection on animal personalities emerge in three species of social spiders.

PubMed

Lichtenstein, J L L; Pruitt, J N

2015-06-01

Frequency-dependent selection is thought to be a major contributor to the maintenance of phenotypic variation. We tested for frequency-dependent selection on contrasting behavioural strategies, termed here 'personalities', in three species of social spiders, each thought to represent an independent evolutionary origin of sociality. The evolution of sociality in the spider genus Anelosimus is consistently met with the emergence of two temporally stable discrete personality types: an 'aggressive' or 'docile' form. We assessed how the foraging success of each phenotype changes as a function of its representation within a colony. We did this by creating experimental colonies of various compositions (six aggressives, three aggressives and three dociles, one aggressive and five dociles, six dociles), maintaining them in a common garden for 3 weeks, and tracking the mass gained by individuals of either phenotype. We found that both the docile and aggressive phenotypes experienced their greatest mass gain in mixed colonies of mostly docile individuals. However, the performance of both phenotypes decreased as the frequency of the aggressive phenotype increased. Nearly identical patterns of phenotype-specific frequency dependence were recovered in all three species. Naturally occurring colonies of these spiders exhibit mixtures dominated by the docile phenotype, suggesting that these spiders may have evolved mechanisms to maintain the compositions that maximize the success of the colony without compromising the expected reproductive output of either phenotype. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Human Commercial Models' Eye Colour Shows Negative Frequency-Dependent Selection.

PubMed

Forti, Isabela Rodrigues Nogueira; Young, Robert John

2016-01-01

In this study we investigated the eye colour of human commercial models registered in the UK (400 female and 400 male) and Brazil (400 female and 400 male) to test the hypothesis that model eye colour frequency was the result of negative frequency-dependent selection. The eye colours of the models were classified as: blue, brown or intermediate. Chi-square analyses of data for countries separated by sex showed that in the United Kingdom brown eyes and intermediate colours were significantly more frequent than expected in comparison to the general United Kingdom population (P<0.001). In Brazil, the most frequent eye colour brown was significantly less frequent than expected in comparison to the general Brazilian population. These results support the hypothesis that model eye colour is the result of negative frequency-dependent selection. This could be the result of people using eye colour as a marker of genetic diversity and finding rarer eye colours more attractive because of the potential advantage more genetically diverse offspring that could result from such a choice. Eye colour may be important because in comparison to many other physical traits (e.g., hair colour) it is hard to modify, hide or disguise, and it is highly polymorphic.

Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.

PubMed

Ryan, Benedict K; Vollmayr, Barbara; Klyubin, Igor; Gass, Peter; Rowan, Michael J

2010-06-01

The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (<3 h), inhibited induction of both NMDA receptor-dependent LTP induced by a standard high frequency (200 Hz) conditioning stimulus and an additional LTP that required voltage-dependent Ca(2+) channel activation triggered by strong (400 Hz) conditioning stimulation. In contrast, acute inescapable footshock stress, used to study learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.

Selection, subdivision and extinction and recolonization.

PubMed Central

Cherry, Joshua L

2004-01-01

In a subdivided population, the interaction between natural selection and stochastic change in allele frequency is affected by the occurrence of local extinction and subsequent recolonization. The relative importance of selection can be diminished by this additional source of stochastic change in allele frequency. Results are presented for subdivided populations with extinction and recolonization where there is more than one founding allele after extinction, where these may tend to come from the same source deme, where the number of founding alleles is variable or the founders make unequal contributions, and where there is dominance for fitness or local frequency dependence. The behavior of a selected allele in a subdivided population is in all these situations approximately the same as that of an allele with different selection parameters in an unstructured population with a different size. The magnitude of the quantity N(e)s(e), which determines fixation probability in the case of genic selection, is always decreased by extinction and recolonization, so that deleterious alleles are more likely to fix and advantageous alleles less likely to do so. The importance of dominance or frequency dependence is also altered by extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations. PMID:15020490

Selection, subdivision and extinction and recolonization.

PubMed

Cherry, Joshua L

2004-02-01

In a subdivided population, the interaction between natural selection and stochastic change in allele frequency is affected by the occurrence of local extinction and subsequent recolonization. The relative importance of selection can be diminished by this additional source of stochastic change in allele frequency. Results are presented for subdivided populations with extinction and recolonization where there is more than one founding allele after extinction, where these may tend to come from the same source deme, where the number of founding alleles is variable or the founders make unequal contributions, and where there is dominance for fitness or local frequency dependence. The behavior of a selected allele in a subdivided population is in all these situations approximately the same as that of an allele with different selection parameters in an unstructured population with a different size. The magnitude of the quantity N(e)s(e), which determines fixation probability in the case of genic selection, is always decreased by extinction and recolonization, so that deleterious alleles are more likely to fix and advantageous alleles less likely to do so. The importance of dominance or frequency dependence is also altered by extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations.

Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia*

PubMed Central

Dong, Qian; Ernst, Sarah E.; Ostedgaard, Lynda S.; Shah, Viral S.; Ver Heul, Amanda R.; Welsh, Michael J.; Randak, Christoph O.

2015-01-01

The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P1,P5-di(adenosine-5′) pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5′-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5′-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl− channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. PMID:25887396

Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

PubMed

Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

2015-05-29

The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory

PubMed Central

Fang, Qin; Chai, Ning; Zhao, Li-Yan; Xue, Yan-Xue; Luo, Yi-Xiao; Jian, Min; Han, Ying; Shi, Hai-Shui; Lu, Lin; Wu, Ping; Wang, Ji-Shi

2013-01-01

The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM) formation (tested 24 h later), but the effects of stress on the persistence of LTM (tested at least 1 week later) are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress) during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h) after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h) after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system. PMID:23544051

Influence of Plasma Unsteadiness on the Spectrum and Shape of Microwave Pulses in a Plasma Relativistic Microwave Amplifier

NASA Astrophysics Data System (ADS)

Kartashov, I. N.; Kuzelev, M. V.; Strelkov, P. S.; Tarakanov, V. P.

2018-02-01

Dependence of the shape of a microwave pulse in a plasma relativistic microwave amplifier (PRMA) on the initial plasma electron density in the system is detected experimentally. Depending on the plasma density, fast disruption of amplification, stable operation of the amplifier during the relativistic electron beam (REB) pulse, and its delayed actuation can take place. A reduction in the output signal frequency relative to the input frequency is observed experimentally. The change in the shape of the microwave signal and the reduction in its frequency are explained by a decrease in the plasma density in the system. The dynamics of the plasma density during the REB pulse is determined qualitatively from the experimental data by using the linear theory of a PRMA with a thin-wall hollow electron beam. The processes in a PRMA are analyzed by means of the KARAT particle-in-cell code. It is shown that REB injection is accompanied by an increase in the mean energy of plasma electrons and a significant decrease in their density.

Abnormal frequency discrimination in children with SLI as indexed by mismatch negativity (MMN).

PubMed

Rinker, Tanja; Kohls, Gregor; Richter, Cathrin; Maas, Verena; Schulz, Eberhard; Schecker, Michael

2007-02-14

For several decades, the aetiology of specific language impairment (SLI) has been associated with a central auditory processing deficit disrupting the normal language development of affected children. One important aspect for language acquisition is the discrimination of different acoustic features, such as frequency information. Concerning SLI, studies to date that examined frequency discrimination abilities have been contradictory. We hypothesized that an auditory processing deficit in children with SLI depends on the frequency range and the difference between the tones used. Using a passive mismatch negativity (MMN)-design, 13 boys with SLI and 13 age- and IQ-matched controls (7-11 years) were tested with two sine tones of different frequency (700Hz versus 750Hz). Reversed hemispheric activity between groups indicated abnormal processing in SLI. In a second time window, MMN2 was absent for the children with SLI. It can therefore be assumed that a frequency discrimination deficit in children with SLI becomes particularly apparent for tones below 750Hz and for a frequency difference of 50Hz. This finding may have important implications for future research and integration of various research approaches.

Different roles of axon guidance cues and patterned spontaneous activity in establishing receptive fields in the mouse superior colliculus.

PubMed

Liu, Mingna; Wang, Lupeng; Cang, Jianhua

2014-01-01

Visual neurons in the superior colliculus (SC) respond to both bright (On) and dark (Off) stimuli in their receptive fields. This receptive field property is due to proper convergence of On- and Off-centered retinal ganglion cells to their target cells in the SC. In this study, we have compared the receptive field structure of individual SC neurons in two lines of mutant mice that are deficient in retinotopic mapping: the ephrin-A knockouts that lack important retinocollicular axonal guidance cues and the nAChR-β2 knockouts that have altered activity-dependent refinement of retinocollicular projections. We find that even though the receptive fields are much larger in the ephrin-A knockouts, their On-Off overlap remains unchanged. These neurons also display normal level of selectivity for stimulus direction and orientation. In contrast, the On-Off overlap is disrupted in the β2 knockouts. Together with the previous finding of disrupted direction and orientation selectivity in the β2 knockout mice, our results indicate that molecular guidance cues and activity-dependent processes play different roles in the development of receptive field properties in the SC.

Motor impairment: a new ethanol withdrawal phenotype in mice

PubMed Central

Philibin, Scott D.; Cameron, Andy J.; Metten, Pamela; Crabbe, John C.

2015-01-01

Alcoholism is a complex disorder with genetic and environmental risk factors. The presence of withdrawal symptoms is one criterion for alcohol dependence. Genetic animal models have followed a reductionist approach by quantifying various effects of ethanol withdrawal separately. Different ethanol withdrawal symptoms may have distinct genetic etiologies, and therefore differentiating distinct neurobiological mechanisms related to separate signs of withdrawal would increase our understanding of various aspects of the complex phenotype. This study establishes motor incoordination as a new phenotype of alcohol withdrawal in mice. Mice were made physically dependent on ethanol by exposure to ethanol vapor for 72 h. The effects of ethanol withdrawal in mice from different genetic backgrounds were measured on the accelerating rotarod, a simple motor task. Ethanol withdrawal disrupted accelerating rotarod behavior in mice. The disruptive effects of withdrawal suggest a performance rather than a learning deficit. Inbred strain comparisons suggest genetic differences in magnitude of this withdrawal phenotype. The withdrawal-induced deficits were not correlated with the selection response difference in handling convulsion severity in selectively bred Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant lines. The accelerating rotarod seems to be a simple behavioral measure of ethanol withdrawal that is suitable for comparing genotypes. PMID:18690115

Optimizing Aerosol Dispensers for Mating Disruption of Codling Moth, Cydia pomonella L.

PubMed

McGhee, Peter S; Miller, James R; Thomson, Donald R; Gut, Larry J

2016-07-01

Experiments were conducted in commercial apple orchards to determine if improved efficiencies in pheromone delivery may be realized by using aerosol pheromone dispensers for codling moth (CM), Cydia pomonella L., mating disruption. Specifically, we tested how reducing: pheromone concentration, period of dispenser operation, and frequency of pheromone emission from aerosol dispensers affected orientational disruption of male CM to pheromone-baited monitoring traps. Isomate® CM MIST formulated with 50 % less codlemone (3.5 mg/ emission) provided orientation disruption equal to the standard commercial formulation (7 mg / emission). Decreased periods of dispenser operation (3 and 6 h) and frequency of pheromone emission (30 and 60 min) provided a level of orientational disruption similar to the current standard protocol of releasing pheromone over a 12 h period on a 15 min cycle, respectively. These three modifications provide a means of substantially reducing the amount of pheromone necessary for CM disruption. The savings accompanying pheromone conservation could lead to increased adoption of CM mating disruption and, moreover, provide an opportunity for achieving higher levels of disruption by increasing dispenser densities.

Intra-aneurysmal flow disruption after implantation of the Medina® Embolization Device depends on aneurysm neck coverage.

PubMed

Frölich, Andreas Maximilian; Nawka, Marie Teresa; Ernst, Marielle; Frischmuth, Isabell; Fiehler, Jens; Buhk, Jan-Hendrik

2018-01-01

Flow disruption achieved by braided intrasaccular implants is a novel treatment strategy for cerebrovascular aneurysms. We hypothesized that the degree of intra-aneurysmal flow disruption can be quantified in vitro and is influenced by device position across the aneurysm neck. We tested this hypothesis using the Medina® Embolization Device (MED). Ten different patient-specific elastic vascular models were manufactured. Models were connected to a pulsatile flow circuit, filled with a blood-mimicking fluid and treated by two operators using a single MED. Intra-aneurysmal flow velocity was measured using conventional and high-frequency digital subtraction angiography (HF-DSA) before and after each deployment. Aneurysm neck coverage by the implanted devices was assessed with flat detector computed tomography on a three-point Likert scale. A total of 80 individual MED deployments were performed by the two operators. The mean intra-aneurysmal flow velocity reduction after MED implantation was 33.6% (27.5-39.7%). No significant differences in neck coverage (p = 0.99) or flow disruption (p = 0.84) were observed between operators. The degree of flow disruption significantly correlated with neck coverage (ρ = 0.42, 95% CI: 0.21-0.59, p = 0.002) as well as with neck area (ρ = -0,35, 95% CI: -0.54 --0.13, p = 0.024). On multiple regression analysis, both neck coverage and total neck area were independent predictors of flow disruption. The degree of intra-aneurysmal flow disruption after MED implantation can be quantified in vitro and varies considerably between different aneurysms and different device configurations. Optimal device coverage across the aneurysm neck improves flow disruption and may thus contribute to aneurysm occlusion.

Compensatory Evolution of Intrinsic Transcription Terminators in Bacillus Cereus

PubMed Central

Safina, Ksenia R.; Mironov, Andrey A.

2017-01-01

Many RNA molecules possess complicated secondary structure critical to their function. Mutations in double-helical regions of RNA may disrupt Watson–Crick (WC) interactions causing structure destabilization or even complete loss of function. Such disruption can be compensated by another mutation restoring base pairing, as has been shown for mRNA, rRNA and tRNA. Here, we investigate the evolution of intrinsic transcription terminators between closely related strains of Bacillus cereus. While the terminator structure is maintained by strong natural selection, as evidenced by the low frequency of disrupting mutations, we observe multiple instances of pairs of disrupting-compensating mutations in RNA structure stems. Such two-step switches between different WC pairs occur very fast, consistent with the low fitness conferred by the intermediate non-WC variant. Still, they are not instantaneous, and probably involve transient fixation of the intermediate variant. The GU wobble pair is the most frequent intermediate, and remains fixed longer than other intermediates, consistent with its less disruptive effect on the RNA structure. Double switches involving non-GU intermediates are more frequent at the ends of RNA stems, probably because they are associated with smaller fitness loss. Together, these results show that the fitness landscape of bacterial transcription terminators is rather rugged, but that the fitness valleys associated with unpaired stem nucleotides are rather shallow, facilitating evolution. PMID:28201729

Combined effect of attrition and ultrasound on the disruption of Pseudomonas putida for the efficient release of arginine deiminase.

PubMed

Patil, Mahesh D; Shinde, Ashok S; Dev, Manoj J; Patel, Gopal; Bhilare, Kiran D; Banerjee, Uttam Chand

2018-06-08

Disruption of Pseudomonas putida KT2440 by ultrasound treatment in a bath sonicator, in presence of the glass beads, was carried out for the release of arginine deiminase (ADI) and the results were compared with that of by Dyno-mill. The release of ADI depended mainly on the bead size and cellmass concentration being disrupted in bead mill. Nearly 23 U/mL ADI was released when slurry with a cell-mass concentration of 250 g/L was disintegrated for 9 min with 80% bead loading (0.25 mm) in Dyno-mill. Marginally higher amount of ADI (24.1 U/mL) was released by the bath sonication of 250 g/L cellmass slurry for 30 min with the beads (0.1 mm) and a sonication power of 170 W. The glass beads, suspended along with the cellmass slurry in bath sonicator, efficiently disrupted the microbial cells to release ADI. Variation in the kinetic constants for the performance parameters implied that ADI release and cell disruption kinetics is a function of disruption technique used and the process variables thereof. Estimation of location factor suggested that selective release of ADI can be achieved. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.

[Speech fluency developmental profile in Brazilian Portuguese speakers].

PubMed

Martins, Vanessa de Oliveira; Andrade, Claudia Regina Furquim de

2008-01-01

speech fluency varies from one individual to the next, fluent or stutterer, depending on several factors. Studies that investigate the influence of age on fluency patterns have been identified; however these differences were investigated in isolated age groups. Studies about life span fluency variations were not found. to verify the speech fluency developmental profile. speech samples of 594 fluent participants of both genders, with ages between 2:0 and 99:11 years, speakers of the Brazilian Portuguese language, were analyzed. Participants were grouped as follows: pre-scholars, scholars, early adolescence, late adolescence, adults and elderlies. Speech samples were analyzed according to the Speech Fluency Profile variables and were compared regarding: typology of speech disruptions (typical and less typical), speech rate (words and syllables per minute) and frequency of speech disruptions (percentage of speech discontinuity). although isolated variations were identified, overall there was no significant difference between the age groups for the speech disruption indexes (typical and less typical speech disruptions and percentage of speech discontinuity). Significant differences were observed between the groups when considering speech rate. the development of the neurolinguistic system for speech fluency, in terms of speech disruptions, seems to stabilize itself during the first years of life, presenting no alterations during the life span. Indexes of speech rate present variations in the age groups, indicating patterns of acquisition, development, stabilization and degeneration.

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes

PubMed Central

Petit, Emilie I; Michalak, Zuzanna; Cox, Rachel; O'Tuathaigh, Colm M P; Clarke, Niamh; Tighe, Orna; Talbot, Konrad; Blake, Derek; Joel, Josephine; Shaw, Alexander; Sheardown, Steven A; Morrison, Alastair D; Wilson, Stephen; Shapland, Ellen M; Henshall, David C; Kew, James N; Kirby, Brian P; Waddington, John L

2017-01-01

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A−/−, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A−/− showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A−/− provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects. PMID:27986973

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes.

PubMed

Petit, Emilie I; Michalak, Zuzanna; Cox, Rachel; O'Tuathaigh, Colm M P; Clarke, Niamh; Tighe, Orna; Talbot, Konrad; Blake, Derek; Joel, Josephine; Shaw, Alexander; Sheardown, Steven A; Morrison, Alastair D; Wilson, Stephen; Shapland, Ellen M; Henshall, David C; Kew, James N; Kirby, Brian P; Waddington, John L

2017-05-01

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/- , with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/- showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/- provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects.

Chaos and unpredictability in evolution.

PubMed

Doebeli, Michael; Ispolatov, Iaroslav

2014-05-01

The possibility of complicated dynamic behavior driven by nonlinear feedbacks in dynamical systems has revolutionized science in the latter part of the last century. Yet despite examples of complicated frequency dynamics, the possibility of long-term evolutionary chaos is rarely considered. The concept of "survival of the fittest" is central to much evolutionary thinking and embodies a perspective of evolution as a directional optimization process exhibiting simple, predictable dynamics. This perspective is adequate for simple scenarios, when frequency-independent selection acts on scalar phenotypes. However, in most organisms many phenotypic properties combine in complicated ways to determine ecological interactions, and hence frequency-dependent selection. Therefore, it is natural to consider models for evolutionary dynamics generated by frequency-dependent selection acting simultaneously on many different phenotypes. Here we show that complicated, chaotic dynamics of long-term evolutionary trajectories in phenotype space is very common in a large class of such models when the dimension of phenotype space is large, and when there are selective interactions between the phenotypic components. Our results suggest that the perspective of evolution as a process with simple, predictable dynamics covers only a small fragment of long-term evolution. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Anger, anxiety, and depressive affect as predictors of stress-induced cortisol production in khat and tobacco users.

PubMed

Lemieux, Andrine M; Nakajima, Motohiro; Saif-Ali, Riyadh; Al-Habori, Molham; Dokam, Anisa; al'Absi, Mustafa

2018-07-01

Glucocorticoid activity is disrupted in substance users including khat chewers who also use tobacco. Anger, dysphoria, and anxiety can mediate this relationship. The aim of this study was to contrast emotion dysregulation and substance use variables as predictors of post-stress cortisol output. Comparable numbers of males (n = 90) and females (n = 85) including controls, khat only, and concurrent khat and tobacco users participated in a stress study. Depressive affect, anxiety, anger, substance use patterns, and saliva samples were collected following a standardized laboratory stress manipulation. Regression analysis showed that high depression and low anxiety was associated with high post-stress cortisol, but only in co-users of tobacco and khat. Males, but not females, showed a significant association between co-use of khat and tobacco and cortisol, which appears to be mediated by frequency of use. The link between anxiety and post-stress cortisol in the co-users remained significant after controlling for nicotine dependence and substance use frequency. Anxiety predicted the neuroendocrine consequences of concurrent use of tobacco and khat above and beyond sex, nicotine dependence, anger, and substance use frequency. Sex differences, however, are related to differences in nicotine dependence. Copyright © 2018. Published by Elsevier Ltd.

The nature of selection on the major histocompatibility complex.

PubMed

Apanius, V; Penn, D; Slev, P R; Ruff, L R; Potts, W K

1997-01-01

Only natural selection can account for the extreme genetic diversity of genes of the major histocompatibility complex (MHC). Although the structure and function of classic MHC genes is well understood at the molecular and cellular levels, there is controversy about how MHC diversity is selectively maintained. The diversifying selection can be driven by pathogen interactions and inbreeding avoidance mechanisms. Pathogen-driven selection can maintain MHC polymorphism based on heterozygote advantage or frequency-dependent selection due to pathogen evasion of MHC-dependent immune recognition. Empirical evidence demonstrates that specific MHC haplotypes are resistant to certain infectious agents, while susceptible to others. These data are consistent with both heterozygote advantage and frequency-dependent models. Additional research is needed to discriminate between these mechanisms. Infectious agents can precipitate autoimmunity and can potentially contribute to MHC diversity through molecular mimicry and by favoring immunodominance. MHC-dependent abortion and mate choice, based on olfaction, can also maintain MHC diversity and probably functions both to avoid genome-wide inbreeding and produce MHC-heterozygous offspring with increased immune responsiveness. Although this diverse set of hypotheses are often treated as competing alternatives, we believe that they all fit into a coherent, internally consistent thesis. It is likely that at least in some species, all of these mechanisms operate, leading to the extreme diversification found in MHC genes.

Frequency-Selective Attention in Auditory Scenes Recruits Frequency Representations Throughout Human Superior Temporal Cortex.

PubMed

Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

2017-05-01

A sound of interest may be tracked amid other salient sounds by focusing attention on its characteristic features including its frequency. Functional magnetic resonance imaging findings have indicated that frequency representations in human primary auditory cortex (AC) contribute to this feat. However, attentional modulations were examined at relatively low spatial and spectral resolutions, and frequency-selective contributions outside the primary AC could not be established. To address these issues, we compared blood oxygenation level-dependent (BOLD) responses in the superior temporal cortex of human listeners while they identified single frequencies versus listened selectively for various frequencies within a multifrequency scene. Using best-frequency mapping, we observed that the detailed spatial layout of attention-induced BOLD response enhancements in primary AC follows the tonotopy of stimulus-driven frequency representations-analogous to the "spotlight" of attention enhancing visuospatial representations in retinotopic visual cortex. Moreover, using an algorithm trained to discriminate stimulus-driven frequency representations, we could successfully decode the focus of frequency-selective attention from listeners' BOLD response patterns in nonprimary AC. Our results indicate that the human brain facilitates selective listening to a frequency of interest in a scene by reinforcing the fine-grained activity pattern throughout the entire superior temporal cortex that would be evoked if that frequency was present alone. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

NASA Astrophysics Data System (ADS)

Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

Transducer design and characterization for dorsal-based ultrasound exposure and two-photon imaging of in vivo blood-brain barrier disruption in a rat model.

PubMed

Nhan, Tam; Burgess, Alison; Hynynen, Kullervo

2013-07-01

Focused ultrasound (FUS) and microbubbles have been used effectively for transient, noninvasive blood¿ brain barrier disruption (BBBD). The use of two-photon microscopy (2PM) imaging of BBBD can provide valuable insights into the associated cellular mechanisms and fundamental biological effects. Coupling a thin ring-shaped transducer to a coverslip offers a robust solution for simultaneous dorsal application of FUS for BBBD and in vivo 2PM imaging of the cerebral microvasculature under treatment conditions. Two modes of vibration (thickness and height) from the transducer configuration were investigated for BBBD in an animal model. With the transducer operating in the thickness mode at 1.2 MHz frequency, shallow and localized BBBD near the cortical surface of animal brain was detected via 2PM and confirmed by Evans blue (EB) extravasation. Acoustic pressures ranging from 0.2 to 0.8 MPa were tested and the probability for successful BBBD was identified. Two distinct types of disruption characterized by different leakage kinetics were observed and appeared to be dependent on acoustic pressure.

Changes in predator community structure shifts the efficacy of two warning signals in Arctiid moths.

PubMed

Nokelainen, Ossi; Valkonen, Janne; Lindstedt, Carita; Mappes, Johanna

2014-05-01

Polymorphism in warning coloration is puzzling because positive frequency-dependent selection by predators is expected to promote monomorphic warning signals in defended prey. We studied predation on the warning-coloured wood tiger moth (Parasemia plantaginis) by using artificial prey resembling white and yellow male colour morphs in five separate populations with different naturally occurring morph frequencies. We tested whether predation favours one of the colour morphs over the other and whether that is influenced either by local, natural colour morph frequencies or predator community composition. We found that yellow specimens were attacked less than white ones regardless of the local frequency of the morphs indicating frequency-independent selection, but predation did depend on predator community composition: yellows suffered less attacks when Paridae were abundant, whereas whites suffered less attacks when Prunellidae were abundant. Our results suggest that spatial heterogeneity in predator community composition can generate a geographical mosaic of selection facilitating the evolution of polymorphic warning signals. This is the first time this mechanism gains experimental support. Altogether, this study sheds light on the evolution of adaptive coloration in heterogeneous environments. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

Adolescent and Adult Rats Differ in the Amnesic Effects of Acute Ethanol in Two Hippocampus-Dependent Tasks: Trace and Contextual Fear Conditioning

PubMed Central

Hunt, Pamela S.; Barnet, Robert C.

2015-01-01

Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiments 2a and 2b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed. PMID:26192910

Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.

PubMed

Byrne, Susan M; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M

2015-02-18

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Roles of cell-cell adhesion-dependent tyrosine phosphorylation of Gab-1.

PubMed

Shinohara, M; Kodama, A; Matozaki, T; Fukuhara, A; Tachibana, K; Nakanishi, H; Takai, Y

2001-06-01

Gab-1 is a multiple docking protein that is tyrosine phosphorylated by receptor tyrosine kinases such as c-Met, hepatocyte growth factor/scatter factor receptor, and epidermal growth factor receptor. We have now demonstrated that cell-cell adhesion also induces marked tyrosine phosphorylation of Gab-1 and that disruption of cell-cell adhesion results in its dephosphorylation. An anti-E-cadherin antibody decreased cell-cell adhesion-dependent tyrosine phosphorylation of Gab-1, whereas the expression of E-cadherin specifically induced tyrosine phosphorylation of Gab-1. A relatively selective inhibitor of Src family kinases reduced cell-cell adhesion-dependent tyrosine phosphorylation of Gab-1, whereas expression of a dominant-negative mutant of Csk increased it. Disruption of cell-cell adhesion, which reduced tyrosine phosphorylation of Gab-1, also reduced the activation of mitogen-activated protein kinase and Akt in response to cell-cell adhesion. These results indicate that E-cadherin-mediated cell-cell adhesion induces tyrosine phosphorylation by a Src family kinase of Gab-1, thereby regulating the activation of Ras/MAP kinase and phosphatidylinositol 3-kinase/Akt cascades.

Results on asymptotic behaviour for discrete, two-patch metapopulations with density-dependent selection

Treesearch

James F. Selgrade; James H. Roberds

2005-01-01

A 4-dimensional system of nonlinear difference equations tracking allele frequencies and population sizes for a two-patch metapopulation model is studied. This system describes intergenerational changes brought about by density-dependent selection within patches and moderated by the effects of migration between patches. To determine conditions which result in similar...

Development of an efficient genetic manipulation strategy for sequential gene disruption and expression of different heterologous GFP genes in Candida tropicalis.

PubMed

Zhang, Lihua; Chen, Xianzhong; Chen, Zhen; Wang, Zezheng; Jiang, Shan; Li, Li; Pötter, Markus; Shen, Wei; Fan, You

2016-11-01

The diploid yeast Candida tropicalis, which can utilize n-alkane as a carbon and energy source, is an attractive strain for both physiological studies and practical applications. However, it presents some characteristics, such as rare codon usage, difficulty in sequential gene disruption, and inefficiency in foreign gene expression, that hamper strain improvement through genetic engineering. In this work, we present a simple and effective method for sequential gene disruption in C. tropicalis based on the use of an auxotrophic mutant host defective in orotidine monophosphate decarboxylase (URA3). The disruption cassette, which consists of a functional yeast URA3 gene flanked by a 0.3 kb gene disruption auxiliary sequence (gda) direct repeat derived from downstream or upstream of the URA3 gene and of homologous arms of the target gene, was constructed and introduced into the yeast genome by integrative transformation. Stable integrants were isolated by selection for Ura + and identified by PCR and sequencing. The important feature of this construct, which makes it very attractive, is that recombination between the flanking direct gda repeats occurs at a high frequency (10 -8 ) during mitosis. After excision of the URA3 marker, only one copy of the gda sequence remains at the recombinant locus. Thus, the resulting ura3 strain can be used again to disrupt a second allelic gene in a similar manner. In addition to this effective sequential gene disruption method, a codon-optimized green fluorescent protein-encoding gene (GFP) was functionally expressed in C. tropicalis. Thus, we propose a simple and reliable method to improve C. tropicalis by genetic manipulation.

The Experiences of Sleep Disruption in Families of Technology-Dependent Children Living at Home

ERIC Educational Resources Information Center

Heaton, Janet; Noyes, Jane; Sloper, Patricia; Shah, Robina

2006-01-01

This paper examines the sleep disruption experienced by 36 families of technology-dependent children living at home in the United Kingdom. The paper begins with an overview of the qualitative study in which parents' experiences of sleep disruption emerged as a major theme. We then describe the nature of and reasons for the sleep disruption, the…

Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties.

PubMed

Troeira Henriques, Sónia; Lawrence, Nicole; Chaousis, Stephanie; Ravipati, Anjaneya S; Cheneval, Olivier; Benfield, Aurélie H; Elliott, Alysha G; Kavanagh, Angela Maria; Cooper, Matthew A; Chan, Lai Yue; Huang, Yen-Hua; Craik, David J

2017-09-15

Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by ∼10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development.

Defect-mediated phonon dynamics in TaS2 and WSe2

PubMed Central

Cremons, Daniel R.; Plemmons, Dayne A.; Flannigan, David J.

2017-01-01

We report correlative crystallographic and morphological studies of defect-dependent phonon dynamics in single flakes of 1T-TaS2 and 2H-WSe2 using selected-area diffraction and bright-field imaging in an ultrafast electron microscope. In both materials, we observe in-plane speed-of-sound acoustic-phonon wave trains, the dynamics of which (i.e., emergence, propagation, and interference) are strongly dependent upon discrete interfacial features (e.g., vacuum/crystal and crystal/crystal interfaces). In TaS2, we observe cross-propagating in-plane acoustic-phonon wave trains of differing frequencies that undergo coherent interference approximately 200 ps after initial emergence from distinct interfacial regions. With ultrafast bright-field imaging, the properties of the interfering wave trains are observed to correspond to the beat frequency of the individual oscillations, while intensity oscillations of Bragg spots generated from selected areas within the region of interest match well with the real-space dynamics. In WSe2, distinct acoustic-phonon dynamics are observed emanating and propagating away from structurally dissimilar morphological discontinuities (vacuum/crystal interface and crystal terrace), and results of ultrafast selected-area diffraction reveal thickness-dependent phonon frequencies. The overall observed dynamics are well-described using finite element analysis and time-dependent linear-elastic continuum mechanics. PMID:28503630

The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat.

PubMed

Kanoski, Scott E; Zhang, Yanshu; Zheng, Wei; Davidson, Terry L

2010-01-01

Cognitive impairment and Alzheimer's disease are linked with intake of a Western diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-day consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. These results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity.

Universal distribution of component frequencies in biological and technological systems

PubMed Central

Pang, Tin Yau; Maslov, Sergei

2013-01-01

Bacterial genomes and large-scale computer software projects both consist of a large number of components (genes or software packages) connected via a network of mutual dependencies. Components can be easily added or removed from individual systems, and their use frequencies vary over many orders of magnitude. We study this frequency distribution in genomes of ∼500 bacterial species and in over 2 million Linux computers and find that in both cases it is described by the same scale-free power-law distribution with an additional peak near the tail of the distribution corresponding to nearly universal components. We argue that the existence of a power law distribution of frequencies of components is a general property of any modular system with a multilayered dependency network. We demonstrate that the frequency of a component is positively correlated with its dependency degree given by the total number of upstream components whose operation directly or indirectly depends on the selected component. The observed frequency/dependency degree distributions are reproduced in a simple mathematically tractable model introduced and analyzed in this study. PMID:23530195

Warning signals are under positive frequency-dependent selection in nature

PubMed Central

Chouteau, Mathieu; Arias, Mónica; Joron, Mathieu

2016-01-01

Positive frequency-dependent selection (FDS) is a selection regime where the fitness of a phenotype increases with its frequency, and it is thought to underlie important adaptive strategies resting on signaling and communication. However, whether and how positive FDS truly operates in nature remains unknown, which hampers our understanding of signal diversity. Here, we test for positive FDS operating on the warning color patterns of chemically defended butterflies forming multiple coexisting mimicry assemblages in the Amazon. Using malleable prey models placed in localities showing differences in the relative frequencies of warningly colored prey, we demonstrate that the efficiency of a warning signal increases steadily with its local frequency in the natural community, up to a threshold where protection stabilizes. The shape of this relationship is consistent with the direct effect of the local abundance of each warning signal on the corresponding avoidance knowledge of the local predator community. This relationship, which differs from purifying selection acting on each mimetic pattern, indicates that predator knowledge, integrated over the entire community, is saturated only for the most common warning signals. In contrast, among the well-established warning signals present in local prey assemblages, most are incompletely known to local predators and enjoy incomplete protection. This incomplete predator knowledge should generate strong benefits to life history traits that enhance warning efficiency by increasing the effective frequency of prey visible to predators. Strategies such as gregariousness or niche convergence between comimics may therefore readily evolve through their effects on predator knowledge and warning efficiency. PMID:26858416

Neural processing of high and low spatial frequency information in faces changes across development: qualitative changes in face processing during adolescence.

PubMed

Peters, Judith C; Vlamings, Petra; Kemner, Chantal

2013-05-01

Face perception in adults depends on skilled processing of interattribute distances ('configural' processing), which is disrupted for faces presented in inverted orientation (face inversion effect or FIE). Children are not proficient in configural processing, and this might relate to an underlying immaturity to use facial information in low spatial frequency (SF) ranges, which capture the coarse information needed for configural processing. We hypothesized that during adolescence a shift from use of high to low SF information takes place. Therefore, we studied the influence of SF content on neural face processing in groups of children (9-10 years), adolescents (14-15 years) and young adults (21-29 years) by measuring event-related potentials (ERPs) to upright and inverted faces which varied in SF content. Results revealed that children show a neural FIE in early processing stages (i.e. P1; generated in early visual areas), suggesting a superficial, global facial analysis. In contrast, ERPs of adults revealed an FIE at later processing stages (i.e. N170; generated in face-selective, higher visual areas). Interestingly, adolescents showed FIEs in both processing stages, suggesting a hybrid developmental stage. Furthermore, adolescents and adults showed FIEs for stimuli containing low SF information, whereas such effects were driven by both low and high SF information in children. These results indicate that face processing has a protracted maturational course into adolescence, and is dependent on changes in SF processing. During adolescence, sensitivity to configural cues is developed, which aids the fast and holistic processing that is so special for faces. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The evolution of conditional dispersal and reproductive isolation along environmental gradients

PubMed Central

Payne, Joshua L.; Mazzucco, Rupert; Dieckmann, Ulf

2011-01-01

Dispersal modulates gene flow throughout a population’s spatial range. Gene flow affects adaptation at local spatial scales, and consequently impacts the evolution of reproductive isolation. A recent theoretical investigation has demonstrated that local adaptation along an environmental gradient, facilitated by the evolution of limited dispersal, can lead to parapatric speciation even in the absence of assortative mating. This and other studies assumed unconditional dispersal, so individuals start dispersing without regard to local environmental conditions. However, many species disperse conditionally; their propensity to disperse is contingent upon environmental cues, such as the degree of local crowding or the availability of suitable mates. Here, we use an individual-based model in continuous space to investigate by numerical simulation the relationship between the evolution of threshold-based conditional dispersal and parapatric speciation driven by frequency-dependent competition along environmental gradients. We find that, as with unconditional dispersal, parapatric speciation occurs under a broad range of conditions when reproduction is asexual, and under a more restricted range of conditions when reproduction is sexual. In both the asexual and sexual cases, the evolution of conditional dispersal is strongly influenced by the slope of the environmental gradient: shallow environmental gradients result in low dispersal thresholds and high dispersal distances, while steep environmental gradients result in high dispersal thresholds and low dispersal distances. The latter, however, remain higher than under unconditional dispersal, thus undermining isolation by distance, and hindering speciation in sexual populations. Consequently, the speciation of sexual populations under conditional dispersal is triggered by a steeper gradient than under unconditional dispersal. Enhancing the disruptiveness of frequency-dependent selection, more box-shaped competition kernels dramatically lower the speciation-enabling slope of the environmental gradient. PMID:21194533

Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression.

PubMed

Choi, Soon Gang; Wang, Qian; Jia, Jingjing; Chikina, Maria; Pincas, Hanna; Dolios, Georgia; Sasaki, Kazuki; Wang, Rong; Minamino, Naoto; Salton, Stephen R J; Sealfon, Stuart C

2016-09-30

Reproductive function is controlled by the pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates the expression of the gonadotropins luteinizing hormone and FSH in pituitary gonadotropes. Paradoxically, Fshb gene expression is maximally induced at lower frequency GnRH pulses, which provide a very low average concentration of GnRH stimulation. We studied the role of secreted factors in modulating gonadotropin gene expression. Inhibition of secretion specifically disrupted gonadotropin subunit gene regulation but left early gene induction intact. We characterized the gonadotrope secretoproteome and global mRNA expression at baseline and after Gα s knockdown, which has been found to increase Fshb gene expression (1). We identified 1077 secreted proteins or peptides, 19 of which showed mRNA regulation by GnRH or/and Gα s knockdown. Among several novel secreted factors implicated in Fshb gene regulation, we focused on the neurosecretory protein VGF. Vgf mRNA, whose gene has been implicated in fertility (2), exhibited high induction by GnRH and depended on Gα s In contrast with Fshb induction, Vgf induction occurred preferentially at high GnRH pulse frequency. We hypothesized that a VGF-derived peptide might regulate Fshb gene induction. siRNA knockdown or extracellular immunoneutralization of VGF augmented Fshb mRNA induction by GnRH. GnRH stimulated the secretion of the VGF-derived peptide NERP1. NERP1 caused a concentration-dependent decrease in Fshb gene induction. These findings implicate a VGF-derived peptide in selective regulation of the Fshb gene. Our results support the concept that signaling specificity from the cell membrane GnRH receptor to the nuclear Fshb gene involves integration of intracellular signaling and exosignaling regulatory motifs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression*

PubMed Central

Wang, Qian; Jia, Jingjing; Chikina, Maria; Pincas, Hanna; Dolios, Georgia; Sasaki, Kazuki; Wang, Rong; Minamino, Naoto; Sealfon, Stuart C.

2016-01-01

Reproductive function is controlled by the pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates the expression of the gonadotropins luteinizing hormone and FSH in pituitary gonadotropes. Paradoxically, Fshb gene expression is maximally induced at lower frequency GnRH pulses, which provide a very low average concentration of GnRH stimulation. We studied the role of secreted factors in modulating gonadotropin gene expression. Inhibition of secretion specifically disrupted gonadotropin subunit gene regulation but left early gene induction intact. We characterized the gonadotrope secretoproteome and global mRNA expression at baseline and after Gαs knockdown, which has been found to increase Fshb gene expression (1). We identified 1077 secreted proteins or peptides, 19 of which showed mRNA regulation by GnRH or/and Gαs knockdown. Among several novel secreted factors implicated in Fshb gene regulation, we focused on the neurosecretory protein VGF. Vgf mRNA, whose gene has been implicated in fertility (2), exhibited high induction by GnRH and depended on Gαs. In contrast with Fshb induction, Vgf induction occurred preferentially at high GnRH pulse frequency. We hypothesized that a VGF-derived peptide might regulate Fshb gene induction. siRNA knockdown or extracellular immunoneutralization of VGF augmented Fshb mRNA induction by GnRH. GnRH stimulated the secretion of the VGF-derived peptide NERP1. NERP1 caused a concentration-dependent decrease in Fshb gene induction. These findings implicate a VGF-derived peptide in selective regulation of the Fshb gene. Our results support the concept that signaling specificity from the cell membrane GnRH receptor to the nuclear Fshb gene involves integration of intracellular signaling and exosignaling regulatory motifs. PMID:27466366

The evolution of conditional dispersal and reproductive isolation along environmental gradients.

PubMed

Payne, Joshua L; Mazzucco, Rupert; Dieckmann, Ulf

2011-03-21

Dispersal modulates gene flow throughout a population's spatial range. Gene flow affects adaptation at local spatial scales, and consequently impacts the evolution of reproductive isolation. A recent theoretical investigation has demonstrated that local adaptation along an environmental gradient, facilitated by the evolution of limited dispersal, can lead to parapatric speciation even in the absence of assortative mating. This and other studies assumed unconditional dispersal, so individuals start dispersing without regard to local environmental conditions. However, many species disperse conditionally; their propensity to disperse is contingent upon environmental cues, such as the degree of local crowding or the availability of suitable mates. Here, we use an individual-based model in continuous space to investigate by numerical simulation the relationship between the evolution of threshold-based conditional dispersal and parapatric speciation driven by frequency-dependent competition along environmental gradients. We find that, as with unconditional dispersal, parapatric speciation occurs under a broad range of conditions when reproduction is asexual, and under a more restricted range of conditions when reproduction is sexual. In both the asexual and sexual cases, the evolution of conditional dispersal is strongly influenced by the slope of the environmental gradient: shallow environmental gradients result in low dispersal thresholds and high dispersal distances, while steep environmental gradients result in high dispersal thresholds and low dispersal distances. The latter, however, remain higher than under unconditional dispersal, thus undermining isolation by distance, and hindering speciation in sexual populations. Consequently, the speciation of sexual populations under conditional dispersal is triggered by a steeper gradient than under unconditional dispersal. Enhancing the disruptiveness of frequency-dependent selection, more box-shaped competition kernels dramatically lower the speciation-enabling slope of the environmental gradient. Copyright © 2010 Elsevier Ltd. All rights reserved.

Soldier-Robot Team Communication: An Investigation of Exogenous Orienting Visual Display Cues and Robot Reporting Preferences

DTIC Science & Technology

2018-02-12

usability preference. Results under the second focus showed that the frequency with which participants expected status updates differed depending upon the...assistance requests for both navigational route and building selection depending on the type of exogenous visual cues displayed? 3) Is there a difference...in response time to visual reports for both navigational route and building selection depending on the type of exogenous visual cues displayed? 4

Moderating effect of self-efficacy on the relation between behavior problems in persons with dementia and the distress they cause in caregivers.

PubMed

Nogales-González, C; Romero-Moreno, R; Losada, A; Márquez-González, M; Zarit, S H

2015-01-01

Behavioral and psychological symptoms in dementia (BPSD) are the principal sources of stress in caregivers. The aim of the present work is to analyze the moderating effect of self-efficacy for managing BPSD on the distress these problems generate in family caregivers. The participants were 231 family caregivers of people with dementia. We assessed the frequency and caregiver distress associated with three dimensions of BPSD (depressive, disruptive and memory problems). In addition, we assessed the moderating effect of self-efficacy for dealing with BPSD in the relationship between the dementia patient's frequency of BPSD and caregiver distress through hierarchical regression analyses, one for each of the dimensions of BPSD. We found a moderating effect of self-efficacy on the relation between the frequency of BPSD and the distress in caregivers for the dimensions of depressive and disruptive behaviors. Caregivers having to deal with a high frequency of behavior problems but with high levels of self-efficacy presented significantly lower levels of distress associated with depressive and disruptive behavior problems compared to those caregivers with low levels of self-efficacy. No differences in the effects of self-efficacy were found for distress levels of caregivers who dealt with low frequency of BPSD. Also, we did not find a moderating effect of self-efficacy on the relation between the frequency of memory problems and caregivers' distress. The results suggest that self-efficacy for managing BPSD attenuates the relation between the frequency of behavior problems – both disruptive and depressive – and the distress they cause in caregivers.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

PubMed Central

Scheffzük, Claudia; Kukushka, Valeriy I.; Vyssotski, Alexei L.; Draguhn, Andreas

2011-01-01

Background The mammalian brain expresses a wide range of state-dependent network oscillations which vary in frequency and spatial extension. Such rhythms can entrain multiple neurons into coherent patterns of activity, consistent with a role in behaviour, cognition and memory formation. Recent evidence suggests that locally generated fast network oscillations can be systematically aligned to long-range slow oscillations. It is likely that such cross-frequency coupling supports specific tasks including behavioural choice and working memory. Principal Findings We analyzed temporal coupling between high-frequency oscillations and EEG theta activity (4–12 Hz) in recordings from mouse parietal neocortex. Theta was exclusively present during active wakefulness and REM-sleep. Fast oscillations occurred in two separate frequency bands: gamma (40–100 Hz) and fast gamma (120–160 Hz). Theta, gamma and fast gamma were more prominent during active wakefulness as compared to REM-sleep. Coupling between theta and the two types of fast oscillations, however, was more pronounced during REM-sleep. This state-dependent cross-frequency coupling was particularly strong for theta-fast gamma interaction which increased 9-fold during REM as compared to active wakefulness. Theta-gamma coupling increased only by 1.5-fold. Significance State-dependent cross-frequency-coupling provides a new functional characteristic of REM-sleep and establishes a unique property of neocortical fast gamma oscillations. Interactions between defined patterns of slow and fast network oscillations may serve selective functions in sleep-dependent information processing. PMID:22163023

The Stability of Radiatively Cooling Jets. 2: Nonlinear Evolution

NASA Technical Reports Server (NTRS)

Stone, James M.; Xu, Jianjun; Hardee, Philip

1997-01-01

We use two-dimensional time-dependent hydrodynamical simulations to follow the growth of the Kelvin-Helmholtz (K-H) instability in cooling jets into the nonlinear regime. We focus primarily on asymmetric modes that give rise to transverse displacements of the jet beam. A variety of Mach numbers and two different cooling curves are studied. The growth rates of waves in the linear regime measured from the numerical simulations are in excellent agreement with the predictions of the linear stability analysis presented in the first paper in this series. In the nonlinear regime, the simulations show that asymmetric modes of the K-H instability can affect the structure and evolution of cooling jets in a number of ways. We find that jets in which the growth rate of the sinusoidal surface wave has a maximum at a so-called resonant frequency can be dominated by large-amplitude sinusoidal oscillations near this frequency. Eventually, growth of this wave can disrupt the jet. On the other hand, nonlinear body waves tend to produce low-amplitude wiggles in the shape of the jet but can result in strong shocks in the jet beam. In cooling jets, these shocks can produce dense knots and filaments of cooling gas within the jet. Ripples in the surface of the jet beam caused by both surface and body waves generate oblique shock "spurs" driven into the ambient gas. Our simulations show these shock "spurs" can accelerate ambient gas at large distances from the jet beam to low velocities, which represents a new mechanism by which low-velocity bipolar outflows may be driven by high-velocity jets. Rapid entrainment and acceleration of ambient gas may also occur if the jet is disrupted. For parameters typical of protostellar jets, the frequency at which K-H growth is a maximum (or highest frequency to which the entire jet can respond dynamically) will be associated with perturbations with a period of - 200 yr. Higher frequency (shorter period) perturbations excite waves associated with body modes that produce internal shocks and only small-amplitude wiggles within the jet. The fact that most observed systems show no evidence for large-amplitude sinusoidal oscillation leading to disruption is indicative that the perturbation frequencies are generally large, consistent with the suggestion that pro- tostellar jets arise from the inner regions (r less than 1 AU) of accretion disks.

Doing better by getting worse: posthypnotic amnesia improves random number generation.

PubMed

Terhune, Devin Blair; Brugger, Peter

2011-01-01

Although forgetting is often regarded as a deficit that we need to control to optimize cognitive functioning, it can have beneficial effects in a number of contexts. We examined whether disrupting memory for previous numerical responses would attenuate repetition avoidance (the tendency to avoid repeating the same number) during random number generation and thereby improve the randomness of responses. Low suggestible and low dissociative and high dissociative highly suggestible individuals completed a random number generation task in a control condition, following a posthypnotic amnesia suggestion to forget previous numerical responses, and in a second control condition following the cancellation of the suggestion. High dissociative highly suggestible participants displayed a selective increase in repetitions during posthypnotic amnesia, with equivalent repetition frequency to a random system, whereas the other two groups exhibited repetition avoidance across conditions. Our results demonstrate that temporarily disrupting memory for previous numerical responses improves random number generation.

Doing Better by Getting Worse: Posthypnotic Amnesia Improves Random Number Generation

PubMed Central

Terhune, Devin Blair; Brugger, Peter

2011-01-01

Although forgetting is often regarded as a deficit that we need to control to optimize cognitive functioning, it can have beneficial effects in a number of contexts. We examined whether disrupting memory for previous numerical responses would attenuate repetition avoidance (the tendency to avoid repeating the same number) during random number generation and thereby improve the randomness of responses. Low suggestible and low dissociative and high dissociative highly suggestible individuals completed a random number generation task in a control condition, following a posthypnotic amnesia suggestion to forget previous numerical responses, and in a second control condition following the cancellation of the suggestion. High dissociative highly suggestible participants displayed a selective increase in repetitions during posthypnotic amnesia, with equivalent repetition frequency to a random system, whereas the other two groups exhibited repetition avoidance across conditions. Our results demonstrate that temporarily disrupting memory for previous numerical responses improves random number generation. PMID:22195022

Mercury Trapped Ion Frequency Standard for Ultra-Stable Reference Applications

NASA Technical Reports Server (NTRS)

Larsen, Kameron (Inventor); Burt, Eric A. (Inventor); Tjoelker, Robert L. (Inventor); Hamell, Robert L. (Inventor); Tucker, Blake C. (Inventor)

2017-01-01

An atomic clock including an ion trap assembly, a C-field coil positioned for generating a first magnetic field in the interrogation region of the ion trap assembly, a compensation coil positioned for generating a second magnetic field in the interrogation region, wherein the combination of the first and second magnetic fields produces an ion number-dependent second order Zeeman shift (Zeeman shift) in the resonance frequency that is opposite in sign to an ion number-dependent second order Doppler shift (Doppler shift) in the resonance frequency, the C-field coil has a radius selected using data indicating how changes in the radius affect an ion-number-dependent shift in the resonance frequency, such that a difference in magnitude between the Doppler shift and the Zeeman shift is controlled or reduced, and the resonance frequency, including the adjustment by the Zeeman shift, is used to obtain the frequency standard.

The Coalescent Process in Models with Selection

PubMed Central

Kaplan, N. L.; Darden, T.; Hudson, R. R.

1988-01-01

Statistical properties of the process describing the genealogical history of a random sample of genes are obtained for a class of population genetics models with selection. For models with selection, in contrast to models without selection, the distribution of this process, the coalescent process, depends on the distribution of the frequencies of alleles in the ancestral generations. If the ancestral frequency process can be approximated by a diffusion, then the mean and the variance of the number of segregating sites due to selectively neutral mutations in random samples can be numerically calculated. The calculations are greatly simplified if the frequencies of the alleles are tightly regulated. If the mutation rates between alleles maintained by balancing selection are low, then the number of selectively neutral segregating sites in a random sample of genes is expected to substantially exceed the number predicted under a neutral model. PMID:3066685

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

PubMed

Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

2014-08-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

A CIT Investigation of Disruptive Student Behaviors: The Students' Perspective

ERIC Educational Resources Information Center

Hoffman, K. Douglas; Lee, Seung Hwan

2014-01-01

This research focuses on gaining a better understanding of how students negatively impact other students' classroom experience. More specifically, this research develops a typology of disruptive student behavior, including frequency of occurrence and the perceived magnitude of the disruption from a student perspective. Students also provide…

An integrated map of genetic variation from 1,092 human genomes

PubMed Central

2012-01-01

Summary Through characterising the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help understand the genetic contribution to disease. We describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methodologies to integrate information across multiple algorithms and diverse data sources we provide a validated haplotype map of 38 million SNPs, 1.4 million indels and over 14 thousand larger deletions. We show that individuals from different populations carry different profiles of rare and common variants and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways and that each individual harbours hundreds of rare non-coding variants at conserved sites, such as transcription-factor-motif disrupting changes. This resource, which captures up to 98% of accessible SNPs at a frequency of 1% in populations of medical genetics focus, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. PMID:23128226

Regulation of GABAergic Inputs to CA1 Pyramidal Neurons by Nicotinic Receptors and Kynurenic Acid

PubMed Central

Banerjee, Jyotirmoy; Alkondon, Manickavasagom; Pereira, Edna F. R.

2012-01-01

Impaired α7 nicotinic acetylcholine receptor (nAChR) function and GABAergic transmission in the hippocampus and elevated brain levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the kynurenine pathway, are key features of schizophrenia. KYNA acts as a noncompetitive antagonist with respect to agonists at both α7 nAChRs and N-methyl-d-aspartate receptors. Here, we tested the hypothesis that in hippocampal slices tonically active α7 nAChRs control GABAergic transmission to CA1 pyramidal neurons and are sensitive to inhibition by rising levels of KYNA. The α7 nAChR-selective antagonist α-bungarotoxin (α-BGT; 100 nM) and methyllycaconitine (MLA; 10 nM), an antagonist at α7 and other nAChRs, reduced by 51.3 ± 1.3 and 65.2 ± 1.5%, respectively, the frequency of GABAergic postsynaptic currents (PSCs) recorded from CA1 pyramidal neurons. MLA had no effect on miniature GABAergic PSCs. Thus, GABAergic synaptic activity in CA1 pyramidal neurons is maintained, in part, by tonically active α7 nAChRs located on the preterminal region of axons and/or the somatodendritic region of interneurons that synapse onto the neurons under study. l-Kynurenine (20 or 200 μM) or KYNA (20–200 μM) suppressed concentration-dependently the frequency of GABAergic PSCs; the inhibitory effect of 20 μM l-kynurenine had an onset time of approximately 35 min and could not be detected in the presence of 100 nM α-BGT. These results suggest that KYNA levels generated from 20 μM kynurenine inhibit tonically active α7 nAChR-dependent GABAergic transmission to the pyramidal neurons. Disruption of nAChR-dependent GABAergic transmission by mildly elevated levels of KYNA can be an important determinant of the cognitive deficits presented by patients with schizophrenia. PMID:22344459

Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis lyrata.

PubMed

Bechsgaard, J; Bataillon, T; Schierup, M H

2004-05-01

Self-incompatibility in Arabidopsis lyrata is sporophytically controlled by the multi-allelic S-locus. Self-incompatibility alleles (S-alleles) are under strong negative frequency dependent selection because pollen carrying common S-alleles have fewer mating opportunities. Population genetics theory predicts that deleterious alleles can accumulate if linked to the S-locus. This was tested by studying segregation of S-alleles in 11 large full sib families in A. lyrata. Significant segregation distortion leading to an up to fourfold difference in transmission rates was found in six families. Differences in transmission rates were not significantly different in reciprocal crosses and the distortions observed were compatible with selection acting at the gametic stage alone. The S-allele with the largest segregation advantage is also the most recessive, and is very common in natural populations concordant with its apparent segregation advantage. These results imply that frequencies of S-alleles in populations of A. lyrata cannot be predicted based on simple models of frequency-dependent selection alone.

Inhibiting Mitochondrial DNA Ligase IIIα Activates Caspase 1-Dependent Apoptosis in Cancer Cells.

PubMed

Sallmyr, Annahita; Matsumoto, Yoshihiro; Roginskaya, Vera; Van Houten, Bennett; Tomkinson, Alan E

2016-09-15

Elevated levels of DNA ligase IIIα (LigIIIα) have been identified as a biomarker of an alteration in DNA repair in cancer cells that confers hypersensitivity to a LigIIIα inhibitor, L67, in combination with a poly (ADP-ribose) polymerase inhibitor. Because LigIIIα functions in the nucleus and mitochondria, we examined the effect of L67 on these organelles. Here, we show that, although the DNA ligase inhibitor selectively targets mitochondria, cancer and nonmalignant cells respond differently to disruption of mitochondrial DNA metabolism. Inhibition of mitochondrial LigIIIα in cancer cells resulted in abnormal mitochondrial morphology, reduced levels of mitochondrial DNA, and increased levels of mitochondrially generated reactive oxygen species that caused nuclear DNA damage. In contrast, these effects did not occur in nonmalignant cells. Furthermore, inhibition of mitochondrial LigIIIα activated a caspase 1-dependent apoptotic pathway, which is known to be part of inflammatory responses induced by pathogenic microorganisms in cancer, but not nonmalignant cells. These results demonstrate that the disruption of mitochondrial DNA metabolism elicits different responses in nonmalignant and cancer cells and suggests that the abnormal response in cancer cells may be exploited in the development of novel therapeutic strategies that selectively target cancer cells. Cancer Res; 76(18); 5431-41. ©2016 AACR. ©2016 American Association for Cancer Research.

Bistability in a complementary metal oxide semiconductor inverter circuit.

PubMed

Carroll, Thomas L

2005-09-01

Radiofrequency signals can disrupt the operation of low frequency circuits. A digital inverter circuit would seem to be immune to such disruption, because its output state usually jumps abruptly between 0 and 5 V. Nevertheless, when driven with a high frequency signal, the inverter can have two coexisting stable states (which are not at 0 and 5 V). Slow switching between these states (by changing the rf signal) will produce a low frequency signal. I demonstrate the bistability in a circuit experiment and in a simple model of the circuit.

Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

PubMed

Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

2017-02-01

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

Actionable exomic incidental findings in 6503 participants: challenges of variant classification

PubMed Central

Amendola, Laura M.; Dorschner, Michael O.; Robertson, Peggy D.; Salama, Joseph S.; Hart, Ragan; Shirts, Brian H.; Murray, Mitzi L.; Tokita, Mari J.; Gallego, Carlos J.; Kim, Daniel Seung; Bennett, James T.; Crosslin, David R.; Ranchalis, Jane; Jones, Kelly L.; Rosenthal, Elisabeth A.; Jarvik, Ella R.; Itsara, Andy; Turner, Emily H.; Herman, Daniel S.; Schleit, Jennifer; Burt, Amber; Jamal, Seema M.; Abrudan, Jenica L.; Johnson, Andrew D.; Conlin, Laura K.; Dulik, Matthew C.; Santani, Avni; Metterville, Danielle R.; Kelly, Melissa; Foreman, Ann Katherine M.; Lee, Kristy; Taylor, Kent D.; Guo, Xiuqing; Crooks, Kristy; Kiedrowski, Lesli A.; Raffel, Leslie J.; Gordon, Ora; Machini, Kalotina; Desnick, Robert J.; Biesecker, Leslie G.; Lubitz, Steven A.; Mulchandani, Surabhi; Cooper, Greg M.; Joffe, Steven; Richards, C. Sue; Yang, Yaoping; Rotter, Jerome I.; Rich, Stephen S.; O’Donnell, Christopher J.; Berg, Jonathan S.; Spinner, Nancy B.; Evans, James P.; Fullerton, Stephanie M.; Leppig, Kathleen A.; Bennett, Robin L.; Bird, Thomas; Sybert, Virginia P.; Grady, William M.; Tabor, Holly K.; Kim, Jerry H.; Bamshad, Michael J.; Wilfond, Benjamin; Motulsky, Arno G.; Scott, C. Ronald; Pritchard, Colin C.; Walsh, Tom D.; Burke, Wylie; Raskind, Wendy H.; Byers, Peter; Hisama, Fuki M.; Rehm, Heidi; Nickerson, Debbie A.; Jarvik, Gail P.

2015-01-01

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. PMID:25637381

Low-frequency electroacupuncture suppresses focal epilepsy and improves epilepsy-induced sleep disruptions.

PubMed

Yi, Pei-Lu; Lu, Chin-Yu; Jou, Shuo-Bin; Chang, Fang-Chia

2015-07-07

The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high-frequency (100 Hz) electroacupuncture (EA) at Feng-Chi acupoints deteriorates both pilocarpine-induced focal epilepsy and sleep disruptions. This study investigated the effects of low-frequency (10 Hz) EA on epileptic activities and epilepsy-induced sleep disruptions. In rats, the Feng-Chi acupoint is located 3 mm away from the center of a line between the two ears. Rats received 30 min of 10 Hz EA stimuli per day before each day's dark period for three consecutive days. Our results indicated that administration of pilocarpine into the left CeA at the beginning of the dark period induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep during the consequent light period. Low-frequency (10 Hz) EA at Feng-Chi acupoints suppressed pilocarpine-induced epileptiform EEGs, and this effect was in turn blocked by naloxone (a broad-spectrum opioid receptor antagonist), but not by naloxonazine (a μ-receptor antagonist), naltrindole (a δ-receptor antagonist) and nor-binaltorphimine (a κ-receptor antagonist). Ten Hz EA enhanced NREM sleep during the dark period, and this enhancement was blocked by all of the opioid receptor antagonists. On the other hand, 10 Hz EA reversed pilocarpine-induced NREM suppression during the light period, and the EA's effect on the sleep disruption was only blocked by naloxonazine. These results indicate that low-frequency EA stimulation of Feng-Chi acupoints is beneficial in improving epilepsy and epilepsy-induced sleep disruptions, and that opioid receptors in the CeA mediate EA's therapeutic effects.

The effect of polyandry on a distorter system with differential viabilities in the sexes.

PubMed

Manser, Andri; Lindholm, Anna K; König, Barbara; Bagheri, Homayoun C

2012-11-01

The presence of selfish genetic elements can have fatal consequences for populations that harbor them. In the well known t haplotype in wild house mice, large proportions of the population die from t/t recessive lethal effects. Due to strong advantages at the gamete level (drive), t haplotypes nevertheless occur at substantial frequencies. The stable presence of a lethal is not the only effect of the t. It also distorts the fate of mutations that differentially affect male and female survival and reproduction (such as in sexual conflict), by giving male selective effects a strong advantage over female selective effects. In a recent study, we proposed polyandry as a potential counterstrategy against t deleterious effects. Here, we show that (1) the efficiency of polyandry in reducing the t frequency strongly depends on the selective context and (2) polyandry helps to reduce male-biased leverage in sex dependent selection.

Context-dependent female mate choice maintains variation in male sexual activity

PubMed Central

Plath, Martin; Gismann, Jakob; Helfrich, Claudia; Bierbach, David

2017-01-01

The existence of individual variation in males' motivation to mate remains a conundrum as directional selection should favour high mating frequencies. Balancing selection resulting from (context-dependent) female mate choice could contribute to the maintenance of this behavioural polymorphism. In dichotomous choice tests, mosquitofish (Gambusia holbrooki) females preferred virtual males showing intermediate mating frequencies, reflecting females' tendencies to avoid harassment by highly sexually active males. When tested in the presence of a female shoal—which protects females from male harassment—focal females showed significantly stronger preferences for high sexual activity. A trade-off between (indirect) benefits and (direct) costs of mating with sexually active males probably explains context-dependent female mate choice, as costs depend on the social environment in which females choose their mates. No preference was observed when we tested virgin females, suggesting that the behavioural pattern described here is part of the learned behavioural repertoire of G. holbrooki females. PMID:28791157

Low Frequency Vibrations Disrupt Left-Right Patterning in the Xenopus Embryo

PubMed Central

Vandenberg, Laura N.; Pennarola, Brian W.; Levin, Michael

2011-01-01

The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs. PMID:21826245

Synchronous oscillation prior to disruption caused by kink modes in HL-2A tokamak plasmas

NASA Astrophysics Data System (ADS)

Jiang, M.; Hu, D.; Wang, X. G.; Shi, Z. B.; Xu, Y.; Chen, W.; Ding, X. T.; Zhong, W. L.; Dong, Y. B.; Ji, X. Q.; Zhang, Y. P.; Gao, J. M.; Li, J. X.; Yang, Z. C.; Li, Y. G.; Liu, Y.

2015-08-01

A class of evident MHD activities prior to major disruption has been observed during recent radiation induced disruptions of the HL-2A tokamak discharges. It can be named SOD, synchronous oscillations prior to disruption, characterized by synchronous oscillation of electron cyclotron emission (ECE), core soft x-ray, Mirnov coil, and {{D}α} radiation signals at the divertor plate. The SOD activity is mostly observed in a parametric regime where the poloidal beta is low enough before disruption, typically corresponding to those radiation-induced disruptions. It has been found that the m/n = 2/1 mode is dominant during the SODs, and consequently it is the drop of the mode frequency and the final mode locking that lead to thermal quench. The mode frequency before the mode locking corresponds to the toroidal rotation frequency of the edge plasma. It is also found that during SODs, the location of the q = 2 surface is moving outward, and most of the plasma current is enclosed within the surface. This demonstrates that the current channel lies inside the rational surface during SOD, and thus the resistive kink mode is unstable. Further analysis of the electron temperature perturbation structure shows that the plasma is indeed dominated by the resistive kink mode, with kink-like perturbation in the core plasma region. It suggests that it is the nonlinear growth of the m/n = 2/1 resistive kink mode and its higher order harmonics, rather than the spontaneous overlapping of multiple neighboring islands, that ultimately triggered the disruption.

Short-duration stimulation of the supplementary eye fields perturbs anti-saccade performance while potentiating contralateral head orienting.

PubMed

Chapman, Brendan B; Corneil, Brian D

2014-01-01

Many forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro- and anti-saccades, we show a surprising diversity of state-dependent effects of ICMS-SEF. Short-duration ICMS-SEF passed around cue presentation selectively disrupted anti-saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti-saccade trials. These results are consistent with the functional relevance of the SEF for anti-saccades. The multiplicity of stimulation-evoked effects, with ICMS-SEF simultaneously disrupting anti-saccade performance and facilitating contralateral head orienting, probably reflects both the diversity of cortical and subcortical targets of SEF projections, and the response of this oculomotor network to stimulation. We speculate that the bilateral disruption of anti-saccades arises via feedback loops that may include the thalamus, whereas neck muscle recruitment arises via feedforward polysynaptic pathways to the motor periphery. Consideration of both sets of results reveals a more complete picture of the highly complex and multiphasic response to ICMS-SEF that can play out differently in different effector systems.

The Evolutionary Consequences of Disrupted Male Mating Signals: An Agent-Based Modelling Exploration of Endocrine Disrupting Chemicals in the Guppy

PubMed Central

Senior, Alistair McNair; Nakagawa, Shinichi; Grimm, Volker

2014-01-01

Females may select a mate based on signalling traits that are believed to accurately correlate with heritable aspects of male quality. Anthropogenic actions, in particular chemicals released into the environment, are now disrupting the accuracy of mating signals to convey information about male quality. The long-term prediction for disrupted mating signals is most commonly loss of female preference. Yet, this prediction has rarely been tested using quantitative models. We use agent-based models to explore the effects of rapid disruption of mating signals. In our model, a gene determines survival. Males signal their level of genetic quality via a signal trait, which females use to select a mate. We allowed this system of sexual selection to become established, before introducing a disruption between the male signal trait and quality, which was similar in nature to that induced by exogenous chemicals. Finally, we assessed the capacity of the system to recover from this disruption. We found that within a relatively short time frame, disruption of mating signals led to a lasting loss of female preference. Decreases in mean viability at the population-level were also observed, because sexual-selection acting against newly arising deleterious mutations was relaxed. The ability of the population to recover from disrupted mating signals was strongly influenced by the mechanisms that promoted or maintained genetic diversity in traits under sexual selection. Our simple model demonstrates that environmental perturbations to the accuracy of male mating signals can result in a long-term loss of female preference for those signals within a few generations. What is more, the loss of this preference can have knock-on consequences for mean population fitness. PMID:25047080

Disruption in neural phase synchrony is related to identification of inattentional deafness in real-world setting.

PubMed

Callan, Daniel E; Gateau, Thibault; Durantin, Gautier; Gonthier, Nicolas; Dehais, Frédéric

2018-06-01

Individuals often have reduced ability to hear alarms in real world situations (e.g., anesthesia monitoring, flying airplanes) when attention is focused on another task, sometimes with devastating consequences. This phenomenon is called inattentional deafness and usually occurs under critical high workload conditions. It is difficult to simulate the critical nature of these tasks in the laboratory. In this study, dry electroencephalography is used to investigate inattentional deafness in real flight while piloting an airplane. The pilots participating in the experiment responded to audio alarms while experiencing critical high workload situations. It was found that missed relative to detected alarms were marked by reduced stimulus evoked phase synchrony in theta and alpha frequencies (6-14 Hz) from 120 to 230 ms poststimulus onset. Correlation of alarm detection performance with intertrial coherence measures of neural phase synchrony showed different frequency and time ranges for detected and missed alarms. These results are consistent with selective attentional processes actively disrupting oscillatory coherence in sensory networks not involved with the primary task (piloting in this case) under critical high load conditions. This hypothesis is corroborated by analyses of flight parameters showing greater maneuvering associated with difficult phases of flight occurring during missed alarms. Our results suggest modulation of neural oscillation is a general mechanism of attention utilizing enhancement of phase synchrony to sharpen alarm perception during successful divided attention, and disruption of phase synchrony in brain networks when attentional demands of the primary task are great, such as in the case of inattentional deafness. © 2018 Wiley Periodicals, Inc.

Locomotor effects of a low-frequency fire alarm on C57BL/6 male mice: a preliminary study.

PubMed

Povroznik, Jessica M; Faith, Robert E; Kessler, Matthew J; Ali, Frank N; Kosik, James; Prince, Stephen; Engler-Chiurazzi, Elizabeth B

2017-12-01

Maintaining appropriate acoustic conditions for animal welfare and data collection are crucial in biomedical research facilities. Negative impacts of disruptive sound are known and can include auditory damage, immune function changes, and behavioral alterations. One type of disruptive sound occurring in research facilities is that of fire alarms. To ameliorate this problem, many facilities have incorporated the use of low-frequency fire alarms that emit tones outside the rodent audible range. The impact of these devices has been assumed to be negligible. However, this has yet to be evaluated with controlled behavioral experiments. Thus, our objective was to investigate the impact of low-frequency fire alarm exposure on locomotor behavior in the open field, a test sensitive to acoustic stimuli disruption. Male mice were randomized to three alarm exposure groups (No-Alarm; Alarm-During; and Alarm-After) and placed in individual photobeam-activated locomotor chambers. The Alarm-During group displayed significantly reduced horizontal locomotion, with a trend towards reduced vertical locomotion. These data suggest that a low-frequency brief alarm tone can temporarily disrupt movement, a valuable insight should an alarm be deployed. Further, findings support close collaboration between researchers and institutional facility staff to ensure appropriate acoustic conditions are maintained, whenever possible, for research animals.

High-frequency ultrasound-responsive block copolymer micelle.

PubMed

Wang, Jie; Pelletier, Maxime; Zhang, Hongji; Xia, Hesheng; Zhao, Yue

2009-11-17

Micelles of a diblock copolymer composed of poly(ethylene oxide) and poly(2-tetrahydropyranyl methacrylate) (PEO-b-PTHPMA) in aqueous solution could be disrupted by high-frequency ultrasound (1.1 MHz). It was found that, upon exposure to a high-intensity focused ultrasound (HIFU) beam at room temperature, the pH value of the micellar solution decreased over irradiation time. The infrared spectroscopic analysis of solid block copolymer samples collected from the ultrasound irradiated micellar solution revealed the formation of carboxylic acid dimers and hydroxyl groups. These characterization results suggest that the high-frequency HIFU beam could induce the hydrolysis reaction of THPMA at room temperature resulting in the cleavage of THP groups. The disruption of PEO-b-PTHPMA micelles by ultrasound was investigated by using dynamic light scattering, atomic force microscopy, and fluorescence spectroscopy. On the basis of the pH change, it was found that the disruption process was determined by a number of factors such as the ultrasound power, the micellar solution volume and the location of the focal spot of the ultrasound beam. This study shows the potential to develop ultrasound-sensitive block copolymer micelles by having labile chemical bonds in the polymer structure, and to use the high-frequency HIFU to trigger a chemical reaction for the disruption of micelles.

Frequency-dependent selection at rough expanding fronts

NASA Astrophysics Data System (ADS)

Kuhr, Jan-Timm; Stark, Holger

2015-10-01

Microbial colonies are experimental model systems for studying the colonization of new territory by biological species through range expansion. We study a generalization of the two-species Eden model, which incorporates local frequency-dependent selection, in order to analyze how social interactions between two species influence surface roughness of growing microbial colonies. The model includes several classical scenarios from game theory. We then concentrate on an expanding public goods game, where either cooperators or defectors take over the front depending on the system parameters. We analyze in detail the critical behavior of the nonequilibrium phase transition between global cooperation and defection and thereby identify a new universality class of phase transitions dealing with absorbing states. At the transition, the number of boundaries separating sectors decays with a novel power law in time and their superdiffusive motion crosses over from Eden scaling to a nearly ballistic regime. In parallel, the width of the front initially obeys Eden roughening and, at later times, passes over to selective roughening.

Incorrect evaluation of the frequency of malnutrition and of its screening in hospitalized children by health care professionals.

PubMed

Restier, Lioara; Duclos, Antoine; Jarri, Laura; Touzet, Sandrine; Denis, Angelique; Occelli, Pauline; Kassai-Koupai, Behrouz; Lachaux, Alain; Loras-Duclaux, Irene; Colin, Cyrille; Peretti, Noel

2015-10-01

Malnutrition screening is essential to detect and to treat patients with stunting or wasting. The aim was to evaluate the subjective perception of frequency and assessment of malnutrition by health care professionals. In a paediatric university hospital, a cross-sectional survey was conducted with a Likert scale approach to health care professionals and compared with objective measurements on a given day of frequency of malnutrition and of its screening. 279 health care professionals participated. The malnutrition rate, estimated versus measured, was 16.8% and 34.8%, respectively. Conversely, the estimated frequency of malnutrition screening versus measured frequency was 80.6% versus 43.1%, respectively. Furthermore, the perception of health care professionals did not differ depending on their professional category or speciality. In conclusion, health care staff underestimates the prevalence of malnutrition in children by half and overestimates the frequency of appropriate screening practices for detection of malnutrition. This flawed/unreliable perception may disrupt both screening and the management of malnourished children. There is an urgent need to find out the reasons behind these errors caused by subjective perception in order to develop appropriate educational training to remedy the situation. © 2015 John Wiley & Sons, Ltd.

Coalescence with Background and Balancing Selection in Systems with Bi- and Uniparental Reproduction: Contrasting Partial Asexuality and Selfing

PubMed Central

Agrawal, Aneil F.; Hartfield, Matthew

2016-01-01

Uniparental reproduction in diploids, via asexual reproduction or selfing, reduces the independence with which separate loci are transmitted across generations. This is expected to increase the extent to which a neutral marker is affected by selection elsewhere in the genome. Such effects have previously been quantified in coalescent models involving selfing. Here we examine the effects of background selection and balancing selection in diploids capable of both sexual and asexual reproduction (i.e., partial asexuality). We find that the effect of background selection on reducing coalescent time (and effective population size) can be orders of magnitude greater when rates of sex are low than when sex is common. This is because asexuality enhances the effects of background selection through both a recombination effect and a segregation effect. We show that there are several reasons that the strength of background selection differs between systems with partial asexuality and those with comparable levels of uniparental reproduction via selfing. Expectations for reductions in Ne via background selection have been verified using stochastic simulations. In contrast to background selection, balancing selection increases the coalescence time for a linked neutral site. With partial asexuality, the effect of balancing selection is somewhat dependent upon the mode of selection (e.g., heterozygote advantage vs. negative frequency-dependent selection) in a manner that does not apply to selfing. This is because the frequency of heterozygotes, which are required for recombination onto alternative genetic backgrounds, is more dependent on the pattern of selection with partial asexuality than with selfing. PMID:26584901

Coalescence with Background and Balancing Selection in Systems with Bi- and Uniparental Reproduction: Contrasting Partial Asexuality and Selfing.

PubMed

Agrawal, Aneil F; Hartfield, Matthew

2016-01-01

Uniparental reproduction in diploids, via asexual reproduction or selfing, reduces the independence with which separate loci are transmitted across generations. This is expected to increase the extent to which a neutral marker is affected by selection elsewhere in the genome. Such effects have previously been quantified in coalescent models involving selfing. Here we examine the effects of background selection and balancing selection in diploids capable of both sexual and asexual reproduction (i.e., partial asexuality). We find that the effect of background selection on reducing coalescent time (and effective population size) can be orders of magnitude greater when rates of sex are low than when sex is common. This is because asexuality enhances the effects of background selection through both a recombination effect and a segregation effect. We show that there are several reasons that the strength of background selection differs between systems with partial asexuality and those with comparable levels of uniparental reproduction via selfing. Expectations for reductions in Ne via background selection have been verified using stochastic simulations. In contrast to background selection, balancing selection increases the coalescence time for a linked neutral site. With partial asexuality, the effect of balancing selection is somewhat dependent upon the mode of selection (e.g., heterozygote advantage vs. negative frequency-dependent selection) in a manner that does not apply to selfing. This is because the frequency of heterozygotes, which are required for recombination onto alternative genetic backgrounds, is more dependent on the pattern of selection with partial asexuality than with selfing. Copyright © 2016 by the Genetics Society of America.

Bubble measuring instrument and method

NASA Technical Reports Server (NTRS)

Magari, Patrick J. (Inventor); Kline-Schoder, Robert (Inventor)

2003-01-01

Method and apparatus are provided for a non-invasive bubble measuring instrument operable for detecting, distinguishing, and counting gaseous embolisms such as bubbles over a selectable range of bubble sizes of interest. A selected measurement volume in which bubbles may be detected is insonified by two distinct frequencies from a pump transducer and an image transducer, respectively. The image transducer frequency is much higher than the pump transducer frequency. The relatively low-frequency pump signal is used to excite bubbles to resonate at a frequency related to their diameter. The image transducer is operated in a pulse-echo mode at a controllable repetition rate that transmits bursts of high-frequency ultrasonic signal to the measurement volume in which bubbles may be detected and then receives the echo. From the echo or received signal, a beat signal related to the repetition rate may be extracted and used to indicate the presence or absence of a resonant bubble. In a preferred embodiment, software control maintains the beat signal at a preselected frequency while varying the pump transducer frequency to excite bubbles of different diameters to resonate depending on the range of bubble diameters selected for investigation.

Bubble Measuring Instrument and Method

NASA Technical Reports Server (NTRS)

Kline-Schoder, Robert (Inventor); Magari, Patrick J. (Inventor)

2002-01-01

Method and apparatus are provided for a non-invasive bubble measuring instrument operable for detecting, distinguishing, and counting gaseous embolisms such as bubbles over a selectable range of bubble sizes of interest. A selected measurement volume in which bubbles may be detected is insonified by two distinct frequencies from a pump transducer and an image transducer. respectively. The image transducer frequency is much higher than the pump transducer frequency. The relatively low-frequency pump signal is used to excite bubbles to resonate at a frequency related to their diameter. The image transducer is operated in a pulse-echo mode at a controllable repetition rate that transmits bursts of high-frequency ultrasonic signal to the measurement volume in which bubbles may be detected and then receives the echo. From the echo or received signal, a beat signal related to the repetition rate may be extracted and used to indicate the presence or absence of a resonant bubble. In a preferred embodiment, software control maintains the beat signal at a preselected frequency while varying the pump transducer frequency to excite bubbles of different diameters to resonate depending on the range of bubble diameters selected for investigation.

Adaptive responses and disruptive effects: how major wildfire influences kinship-based social interactions in a forest marsupial.

PubMed

Banks, Sam C; Blyton, Michaela D J; Blair, David; McBurney, Lachlan; Lindenmayer, David B

2012-02-01

Environmental disturbance is predicted to play a key role in the evolution of animal social behaviour. This is because disturbance affects key factors underlying social systems, such as demography, resource availability and genetic structure. However, because natural disturbances are unpredictable there is little information on their effects on social behaviour in wild populations. Here, we investigated how a major wildfire affected cooperation (sharing of hollow trees) by a hollow-dependent marsupial. We based two alternative social predictions on the impacts of fire on population density, genetic structure and resources. We predicted an adaptive social response from previous work showing that kin selection in den-sharing develops as competition for den resources increases. Thus, kin selection should occur in burnt areas because the fire caused loss of the majority of hollow-bearing trees, but no detectable mortality. Alternatively, fire may have a disruptive social effect, whereby postfire home range-shifts 'neutralize' fine-scale genetic structure, thereby removing opportunities for kin selection between neighbours. Both predictions occurred: the disruptive social effect in burnt habitat and the adaptive social response in adjacent unburnt habitat. The latter followed a massive demographic influx to unburnt 'refuge' habitat that increased competition for dens, leading to a density-related kin selection response. Our results show remarkable short-term plasticity of animal social behaviour and demonstrate how the social effects of disturbance extend into undisturbed habitat owing to landscape-scale demographic shifts. We predicted long-term changes in kinship-based cooperative behaviour resulting from the genetic and resource impacts of forecast changes to fire regimes in these forests. © 2011 Blackwell Publishing Ltd.

Embedding resilience in the design of the electricity supply for industrial clients

PubMed Central

Moura, Márcio das Chagas; Diniz, Helder Henrique Lima; da Cunha, Beatriz Sales; Lins, Isis Didier; Simoni, Vicente Ribeiro

2017-01-01

This paper proposes an optimization model, using Mixed-Integer Linear Programming (MILP), to support decisions related to making investments in the design of power grids serving industrial clients that experience interruptions to their energy supply due to disruptive events. In this approach, by considering the probabilities of the occurrence of a set of such disruptive events, the model is used to minimize the overall expected cost by determining an optimal strategy involving pre- and post-event actions. The pre-event actions, which are considered during the design phase, evaluate the resilience capacity (absorption, adaptation and restoration) and are tailored to the context of industrial clients dependent on a power grid. Four cases are analysed to explore the results of different probabilities of the occurrence of disruptions. Moreover, two scenarios, in which the probability of occurrence is lowest but the consequences are most serious, are selected to illustrate the model’s applicability. The results indicate that investments in pre-event actions, if implemented, can enhance the resilience of power grids serving industrial clients because the impacts of disruptions either are experienced only for a short time period or are completely avoided. PMID:29190777

Embedding resilience in the design of the electricity supply for industrial clients.

PubMed

Moura, Márcio das Chagas; Diniz, Helder Henrique Lima; Droguett, Enrique López; da Cunha, Beatriz Sales; Lins, Isis Didier; Simoni, Vicente Ribeiro

2017-01-01

This paper proposes an optimization model, using Mixed-Integer Linear Programming (MILP), to support decisions related to making investments in the design of power grids serving industrial clients that experience interruptions to their energy supply due to disruptive events. In this approach, by considering the probabilities of the occurrence of a set of such disruptive events, the model is used to minimize the overall expected cost by determining an optimal strategy involving pre- and post-event actions. The pre-event actions, which are considered during the design phase, evaluate the resilience capacity (absorption, adaptation and restoration) and are tailored to the context of industrial clients dependent on a power grid. Four cases are analysed to explore the results of different probabilities of the occurrence of disruptions. Moreover, two scenarios, in which the probability of occurrence is lowest but the consequences are most serious, are selected to illustrate the model's applicability. The results indicate that investments in pre-event actions, if implemented, can enhance the resilience of power grids serving industrial clients because the impacts of disruptions either are experienced only for a short time period or are completely avoided.

Nonspinning black hole-neutron star mergers: A model for the amplitude of gravitational waveforms

NASA Astrophysics Data System (ADS)

Pannarale, Francesco; Berti, Emanuele; Kyutoku, Koutarou; Shibata, Masaru

2013-10-01

Black hole-neutron star binary mergers display a much richer phenomenology than black hole-black hole mergers, even in the relatively simple case—considered in this paper—in which both the black hole and the neutron star are nonspinning. When the neutron star is tidally disrupted, the gravitational wave emission is radically different from the black hole-black hole case and it can be broadly classified in two groups, depending on the spatial extent of the disrupted material. We present a phenomenological model for the gravitational waveform amplitude in the frequency domain that encompasses the three possible outcomes of the merger: no tidal disruption, “mild,” and “strong” tidal disruption. The model is calibrated to general relativistic numerical simulations using piecewise polytropic neutron star equations of state. It should prove useful to extract information on the nuclear equation of state from future gravitational-wave observations, and also to obtain more accurate estimates of black hole-neutron star merger event rates in second- and third-generation interferometric gravitational-wave detectors. We plan to extend and improve the model as longer and more accurate gravitational waveforms become available, and we will make it publicly available online as a Mathematica package. We also present in the Appendix analytical fits of the projected KAGRA noise spectral density, which should be useful in data analysis applications.

Stress dependence of the Raman spectrum of polycrystalline barium titanate in presence of localized domain texture

NASA Astrophysics Data System (ADS)

Sakashita, Tatsuo; Deluca, Marco; Yamamoto, Shinsuke; Chazono, Hirokazu; Pezzotti, Giuseppe

2007-06-01

The stress dependence of the Raman spectrum of polycrystalline barium titanate (BaTiO3, BT) ceramics has been examined with microprobe polarized Raman spectroscopy. The angular dependence of the Raman spectrum of the tetragonal BT crystal has been theoretically established, enabling us to assess the stress dependence of selected spectral modes without the influence of crystallographic domain orientation. Upon considering the frequency shift of selected Raman modes as a function of orientation between the crystallographic axis and the polarization vector of incident and scattered light, a suitable instrumental configuration has been selected, which allowed a direct residual stress measurement according to a modified piezospectroscopic procedure. The analysis is based on the selection of mixed photostimulated spectral modes in two perpendicular angular orientations.

The burden of disrupting gastro-oesophageal reflux disease: a database study in US and European cohorts.

PubMed

Toghanian, Samira; Wahlqvist, Peter; Johnson, David A; Bolge, Susan C; Liljas, Bengt

2010-01-01

Recent data indicate that among patients with gastro-oesophageal reflux disease (GORD) there is a subgroup with a higher disrupting burden of illness in terms of symptom frequency and overall impact. The aim of this study was to evaluate the burden of disrupting versus non-disrupting GORD on individuals, healthcare providers and society. Data were obtained from European (France, Germany, Italy, Spain and the UK) and US respondents in the 2007 National Health and Wellness Survey (NHWS). Respondents with GORD were classified as having disrupting or non-disrupting GORD based on self-reported symptom frequency, presence of night-time symptoms and medication usage. Disrupting GORD was defined as the presence of GORD symptoms on at least 2 days/week in addition to either night-time symptoms or use of prescribed/over-the-counter medication at least twice a week during the past month. Of 116 536 respondents included in the 2007 NHWS, 23% reported GORD symptoms; 39% of these were acknowledged as having disrupting GORD. These patients had higher healthcare resource utilization than those with non-disrupting disease. Respondents with disrupting GORD also had poorer health-related quality of life, greater impairments in health-related work productivity and absenteeism (all p < 0.05 vs non-disrupting GORD), and higher associated total medical costs. Overall, patients with physician-diagnosed GORD also had significantly lower health-related quality of life than self-diagnosed respondents (p < 0.05). GORD is a common disease that places a substantial burden on affected individuals and society. A high proportion of patients have disrupting GORD, which has significant adverse potential from both a clinical and an economic perspective.

Parasite-mediated selection drives an immunogenetic trade-off in plains zebras (Equus quagga)

PubMed Central

Kamath, Pauline L.; Turner, Wendy C.; Küsters, Martina; Getz, Wayne M.

2014-01-01

Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite ‘susceptibility alleles’ were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation. PMID:24718761

Parasite-mediated selection drives an immunogenetic tradeoff in plains zebra (Equus quagga)

USGS Publications Warehouse

Kamath, Pauline L.; Turner, Wendy C.; Küsters, Martina; Getz, Wayne M.

2014-01-01

Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite ‘susceptibility alleles’ were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation.

Natural selection and the predictability of evolution in Timema stick insects.

PubMed

Nosil, Patrik; Villoutreix, Romain; de Carvalho, Clarissa F; Farkas, Timothy E; Soria-Carrasco, Víctor; Feder, Jeffrey L; Crespi, Bernard J; Gompert, Zach

2018-02-16

Predicting evolution remains difficult. We studied the evolution of cryptic body coloration and pattern in a stick insect using 25 years of field data, experiments, and genomics. We found that evolution is more difficult to predict when it involves a balance between multiple selective factors and uncertainty in environmental conditions than when it involves feedback loops that cause consistent back-and-forth fluctuations. Specifically, changes in color-morph frequencies are modestly predictable through time ( r 2 = 0.14) and driven by complex selective regimes and yearly fluctuations in climate. In contrast, temporal changes in pattern-morph frequencies are highly predictable due to negative frequency-dependent selection ( r 2 = 0.86). For both traits, however, natural selection drives evolution around a dynamic equilibrium, providing some predictability to the process. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Microalgal cell disruption via ultrasonic nozzle spraying.

PubMed

Wang, M; Yuan, W

2015-01-01

The objective of this study was to understand the effect of operating parameters, including ultrasound amplitude, spraying pressure, nozzle orifice diameter, and initial cell concentration on microalgal cell disruption and lipid extraction in an ultrasonic nozzle spraying system (UNSS). Two algal species including Scenedesmus dimorphus and Nannochloropsis oculata were evaluated. Experimental results demonstrated that the UNSS was effective in the disruption of microalgal cells indicated by significant changes in cell concentration and Nile red-stained lipid fluorescence density between all treatments and the control. It was found that increasing ultrasound amplitude generally enhanced cell disruption and lipid recovery although excessive input energy was not necessary for best results. The effect of spraying pressure and nozzle orifice diameter on cell disruption and lipid recovery was believed to be dependent on the competition between ultrasound-induced cavitation and spraying-generated shear forces. Optimal cell disruption was not always achieved at the highest spraying pressure or biggest nozzle orifice diameter; instead, they appeared at moderate levels depending on the algal strain and specific settings. Increasing initial algal cell concentration significantly reduced cell disruption efficiency. In all UNSS treatments, the effectiveness of cell disruption and lipid recovery was found to be dependent on the algal species treated.

Prevalence of disruptive selection predicts extent of species differentiation in Lake Victoria cichlids.

PubMed

van Rijssel, Jacco C; Moser, Florian N; Frei, David; Seehausen, Ole

2018-01-31

Theory suggests that speciation with gene flow is most likely when both sexual and ecological selection are divergent or disruptive. Divergent sexual and natural selection on the visual system have been demonstrated before in sympatric, morphologically similar sister species of Lake Victoria cichlids, but this does not explain the subtle morphological differences between them. To investigate the significance of natural selection on morphology during speciation, we here ask whether the prevalence of disruptive ecological selection differs between sympatric sister species that are at different stages of speciation. Some of our species pairs do ( Pundamilia ) and others do not ( Neochromis ) differ distinctively in sexually selected male nuptial coloration. We find that (i) evidence for disruptive selection, and for evolutionary response to it, is prevalent in traits that are differentiated between sister species; (ii) prevalence of both predicts the extent of genetic differentiation; and (iii) genetic differentiation is weaker in species pairs with conserved male nuptial coloration. Our results speak to the existence of two different mechanisms of speciation with gene flow: speciation mainly by sexual selection tightly followed by ecological character displacement in some cases and speciation mainly by divergent ecological selection in others. © 2018 The Author(s).

Amygdala lesions in rhesus monkeys fail to disrupt object choices based on internal context

PubMed Central

Rhodes, Sarah E. V.; Charles, David P.; Howland, Emily J.; Murray, Elisabeth A.

2012-01-01

We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context. PMID:22352788

NEW CONSTRAINTS ON MASS-DEPENDENT DISRUPTION OF STAR CLUSTERS IN M51

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chandar, Rupali; Whitmore, Bradley C.; Regan, Michael

2011-02-01

We use UBVI H{alpha} images of the Whirlpool galaxy, M51, taken with the Advanced Camera for Surveys and WFPC2 cameras on the Hubble Space Telescope (HST) to select star clusters, and to estimate their masses and ages by comparing their observed colors with predictions from population synthesis models. We construct the mass function of intermediate-age (1-4 x 10{sup 8} yr) clusters, and find that it is well described by a power law, {psi}(M) {proportional_to} M{sup {beta}}, with {beta} = -2.1 {+-} 0.2, for clusters more massive than M {approx} 6 x 10{sup 3} M{sub sun}. This extends the mass functionmore » of intermediate-age clusters in M51 to masses lower by nearly a factor of five over previous determinations. The mass function does not show evidence for curvature at either the high or low mass end. This shape indicates that there is no evidence for the earlier disruption of lower mass clusters compared with their higher mass counterparts (i.e., no mass-dependent disruption) over the observed range of masses and ages, or for a physical upper mass limit M{sub C} with which clusters in M51 can form. These conclusions differ from previous suggestions based on poorer-quality HST observations. We discuss their implications for the formation and disruption of the clusters. Ages of clusters in two 'feathers', stellar features extending from the outer portion of a spiral arm, show that the feather with a larger pitch angle formed earlier, and over a longer period, than the other.« less

Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease.

PubMed

Giles, E M; Sanders, T J; McCarthy, N E; Lung, J; Pathak, M; MacDonald, T T; Lindsay, J O; Stagg, A J

2017-01-01

Type 1 interferon (IFN-1) promotes regulatory T-cell function to suppress inflammation in the mouse intestine, but little is known about IFN-1 in the human gut. We therefore assessed the influence of IFN-1 on CD4+ T-cells isolated from human colon tissue obtained from healthy controls or patients with inflammatory bowel disease (IBD). Immunofluorescent imaging revealed constitutive expression of IFNβ in human intestinal tissue, and colonic T-cells were responsive to exogenous IFN-1 as assessed by phosphorylation of signal transduction and activator of transcription 1 (pSTAT1) and induction of interferon stimulated genes (ISGs). Unlike their blood counterparts, intestinal T-cells from non-inflamed regions of IBD colon displayed enhanced responsiveness to IFN-1, increased frequency of pSTAT1+ cells, and greater induction of ISGs upon IFN-1 exposure in vitro. In healthy tissue, antibody neutralization of IFNβ selectively reduced T-cell production of the pro-regulatory cytokine interleukin-10 (IL-10) and increased IFNγ synthesis. In contrast, neutralization of IFNβ in IBD tissue cultures increased the frequency of T-cells producing inflammatory cytokines but did not alter IL-10 expression. These data support a role for endogenous IFN-1 as a context-dependent modulator of T-cell function that promotes regulatory activity in healthy human intestine, but indicate that the IFN-1/STAT1 pathway is dysregulated in inflammatory bowel disease.

Influence of White and Gray Matter Connections on Endogenous Human Cortical Oscillations

PubMed Central

Hawasli, Ammar H.; Kim, DoHyun; Ledbetter, Noah M.; Dahiya, Sonika; Barbour, Dennis L.; Leuthardt, Eric C.

2016-01-01

Brain oscillations reflect changes in electrical potentials summated across neuronal populations. Low- and high-frequency rhythms have different modulation patterns. Slower rhythms are spatially broad, while faster rhythms are more local. From this observation, we hypothesized that low- and high-frequency oscillations reflect white- and gray-matter communications, respectively, and synchronization between low-frequency phase with high-frequency amplitude represents a mechanism enabling distributed brain-networks to coordinate local processing. Testing this common understanding, we selectively disrupted white or gray matter connections to human cortex while recording surface field potentials. Counter to our original hypotheses, we found that cortex consists of independent oscillatory-units (IOUs) that maintain their own complex endogenous rhythm structure. IOUs are differentially modulated by white and gray matter connections. White-matter connections maintain topographical anatomic heterogeneity (i.e., separable processing in cortical space) and gray-matter connections segregate cortical synchronization patterns (i.e., separable temporal processing through phase-power coupling). Modulation of distinct oscillatory modules enables the functional diversity necessary for complex processing in the human brain. PMID:27445767

Calcium-dependent control of temporal processing in an auditory interneuron: a computational analysis

PubMed Central

Ponnath, Abhilash

2010-01-01

Sensitivity to acoustic amplitude modulation in crickets differs between species and depends on carrier frequency (e.g., calling song vs. bat-ultrasound bands). Using computational tools, we explore how Ca2+-dependent mechanisms underlying selective attention can contribute to such differences in amplitude modulation sensitivity. For omega neuron 1 (ON1), selective attention is mediated by Ca2+-dependent feedback: [Ca2+]internal increases with excitation, activating a Ca2+-dependent after-hyperpolarizing current. We propose that Ca2+ removal rate and the size of the after-hyperpolarizing current can determine ON1’s temporal modulation transfer function (TMTF). This is tested using a conductance-based simulation calibrated to responses in vivo. The model shows that parameter values that simulate responses to single pulses are sufficient in simulating responses to modulated stimuli: no special modulation-sensitive mechanisms are necessary, as high and low-pass portions of the TMTF are due to Ca2+-dependent spike frequency adaptation and post-synaptic potential depression, respectively. Furthermore, variance in the two biophysical parameters is sufficient to produce TMTFs of varying bandwidth, shifting amplitude modulation sensitivity like that in different species and in response to different carrier frequencies. Thus, the hypothesis that the size of after-hyperpolarizing current and the rate of Ca2+ removal can affect amplitude modulation sensitivity is computationally validated. PMID:20559640

Amblyopia in Astigmatic Children: Patterns of Deficits

PubMed Central

Harvey, Erin M.; Dobson, Velma; Miller, Joseph M.; Clifford-Donaldson, Candice E.

2007-01-01

Neural changes that result from disruption of normal visual experience during development are termed amblyopia. To characterize visual deficits specific to astigmatism-related amblyopia, we compared best-corrected visual performance in 330 astigmatic and 475 non-astigmatic kindergarten through 6th grade children. Astigmatism was associated with deficits in letter, grating and vernier acuity, high and middle spatial frequency contrast sensitivity, and stereoacuity. Although grating acuity, vernier acuity, and contrast sensitivity were reduced across stimulus orientation, astigmats demonstrated orientation-dependent deficits (meridional amblyopia) only for grating acuity. Astigmatic children are at risk for deficits across a range of visual functions. PMID:17184807

Classification and Surgical Repair of Ramp Lesions of the Medial Meniscus.

PubMed

Thaunat, Mathieu; Fayard, Jean Marie; Guimaraes, Tales M; Jan, Nicolas; Murphy, Colin G; Sonnery-Cottet, Bertrand

2016-08-01

Ramp lesions of the medial meniscus are commonly associated with anterior cruciate ligament ruptures and consist of longitudinal peripheral tears of the posterior horn of the medial meniscus. Given the frequency of partial-thickness tears, they can be difficult to diagnose arthroscopically from the anterior compartment. We describe a classification of the different types of ramp lesions depending on both tear pattern (partial- or full-thickness tear) and associated meniscotibial ligament disruption. An original technique of arthroscopic suture placement through a single posteromedial portal with a 25° curved suture hook device is described.

The relative effect of citral on mitotic microtubules in wheat roots and BY2 cells.

PubMed

Chaimovitsh, D; Rogovoy Stelmakh, O; Altshuler, O; Belausov, E; Abu-Abied, M; Rubin, B; Sadot, E; Dudai, N

2012-03-01

The plant volatile monoterpene citral is a highly active compound with suggested allelopathic traits. Seed germination and seedling development are inhibited in the presence of citral, and it disrupts microtubules in both plant and animal cells in interphase. We addressed the following additional questions: can citral interfere with cell division; what is the relative effect of citral on mitotic microtubules compared to interphase cortical microtubules; what is its effect on newly formed cell plates; and how does it affect the association of microtubules with γ-tubulin? In wheat seedlings, citral led to inhibition of root elongation, curvature of newly formed cell walls and deformation of microtubule arrays. Citral's effect on microtubules was both dose- and time-dependent, with mitotic microtubules appearing to be more sensitive to citral than cortical microtubules. Association of γ-tubulin with microtubules was more sensitive to citral than were the microtubules themselves. To reveal the role of disrupted mitotic microtubules in dictating aberrations in cell plates in the presence of citral, we used tobacco BY2 cells expressing GFP-Tua6. Citral disrupted mitotic microtubules, inhibited the cell cycle and increased the frequency of asymmetric cell plates in these cells. The time scale of citral's effect in BY2 cells suggested a direct influence on cell plates during their formation. Taken together, we suggest that at lower concentrations, citral interferes with cell division by disrupting mitotic microtubules and cell plates, and at higher concentrations it inhibits cell elongation by disrupting cortical microtubules. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Alternative surgical approaches in epilepsy.

PubMed

Gigante, Paul R; Goodman, Robert R

2011-08-01

The mainstay of epilepsy surgery is the resection of a presumed seizure focus or disruption of seizure propagation pathways. These approaches cannot be applied to all patients with medically refractory epilepsy (MRE). Since 1997, vagus nerve stimulation has been a palliative adjunct to the care of MRE patients. Deep brain stimulation (DBS) in select locations has been reported to reduce seizure frequency in small studies over the past three decades. Recently published results from the SANTE (Stimulation of the Anterior Nuclei of Thalamus for Epilepsy) trial-the first large-scale, randomized, double-blind trial of bilateral anterior thalamus DBS for MRE-demonstrate a significant reduction in seizure frequency with programmed stimulation. Another surgical alternative is the RNS™ System (NeuroPace, Mountain View, CA), which uses a closed-loop system termed responsive neurostimulation to both detect apparent seizure onsets and deliver stimulation. Recently presented results from the RNS™ pivotal trial demonstrate a sustained reduction in seizure frequency with stimulation, although comprehensive trial results are pending.

Microfluidic cell disruption system employing a magnetically actuated diaphragm.

PubMed

Huh, Yun Suk; Choi, Jong Hyun; Huh, Kyoung Ae Kim; Kim, Kyoung Ae; Park, Tae Jung; Hong, Yeon Ki; Kim, Do Hyun; Hong, Won Hi; Lee, Sang Yup

2007-12-01

A microfluidic cell lysis chip equipped with a micromixer and SPE unit was developed and used for quantitative analysis of intracellular proteins. This miniaturized sample preparation system can be employed for any purpose where cell disruption is needed to obtain intracellular constituents for the subsequent analysis. This system comprises a magnetically actuated micromixer to disrupt cells, a hydrophobic valve to manipulate the cell lysate, and a packed porous polymerized monolith chamber for SPE and filtering debris from the cell lysate. Using recombinant Escherichia coli expressing intracellular enhanced green fluorescent protein (EGFP) and lipase as model bacteria, we optimized the cell disruption condition with respect to the lysis buffer composition, mixing time, and the frequency of the diaphragm in the micromixer, which was magnetically actuated by an external magnetic stirrer in the micromixer chamber. The lysed sample prepared under the optimal condition was purified by the packed SPE in the microfluidic chip. At a frequency of 1.96 Hz, the final cell lysis efficiency and relative fluorescence intensity of EGFP after the cell disruption process were greater than 90 and 94%, respectively. Thus, this microfluidic cell disruption chip can be used for the efficient lysis of cells for further analysis of intracellular contents in many applications.

How Does a Modern Field Artillery Cannon Battalion Operate in a Degraded, Denied, and Disrupted Space Operating Environment

DTIC Science & Technology

2017-06-09

reports, a potential solution to communication shortfalls was the use of high frequency (HF) Harris radios that possess complex encryption... communications , positioning, and navigation do not properly function, is known as a Degraded, Denied, Disrupted Space Operating Environment (D3SOE).7...battalion operates in a D3SOE. This was a very relevant question for a force increasingly reliant on frequency modulated (FM) radio communication systems

Information Operations

DTIC Science & Technology

2006-02-13

restricted frequency list (JRFL). This list specifies protected, guarded, and taboo frequencies that should not normally be disrupted without prior... frequency list JROC Joint Requirement Oversight Council JSC Joint Spectrum Center JTCB joint targeting coordination board JTF joint task force JWAC joint

BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells

PubMed Central

Lagadinou, Eleni D.; Sach, Alexander; Callahan, Kevin; Rossi, Randall M.; Neering, Sarah J.; Minhajuddin, Mohammad; Ashton, John M.; Pei, Shanshan; Grose, Valerie; O’Dwyer, Kristen M.; Liesveld, Jane L.; Brookes, Paul S.; Becker, Michael W.; Jordan, Craig T.

2013-01-01

Summary Most forms of chemotherapy employ mechanisms involving induction of oxidative stress, a strategy that can be effective due to the elevated oxidative state commonly observed in cancer cells. However, recent studies have shown that relative redox levels in primary tumors can be heterogeneous, suggesting that regimens dependent on differential oxidative state may not be uniformly effective. To investigate this issue in hematological malignancies, we evaluated mechanisms controlling oxidative state in primary specimens derived from acute myelogenous leukemia (AML) patients. Our studies demonstrate three striking findings. First, the majority of functionally-defined leukemia stem cells (LSCs) are characterized by relatively low levels of reactive oxygen species (termed “ROS-low”). Second, ROS-low LSCs aberrantly over-express BCL-2. Third, BCL-2 inhibition reduced oxidative phosphorylation and selectively eradicated quiescent LSCs. Based on these findings, we propose a model wherein the unique physiology of ROS-low LSCs provides an opportunity for selective targeting via disruption of BCL-2-dependent oxidative phosphorylation. PMID:23333149

Effect of electrode biasing on m/n  =  2/1 tearing modes in J-TEXT experiments

NASA Astrophysics Data System (ADS)

Liu, Hai; Hu, Qiming; Chen, Zhipeng; Yu, Q.; Zhu, Lizhi; Cheng, Zhifeng; Zhuang, Ge; Chen, Zhongyong

2017-01-01

The effects of electrode biasing (EB) on the m/n  =  2/1 tearing mode have been experimentally studied in J-TEXT tokamak discharges, where m and n are the poloidal and toroidal mode numbers. It is found that for a negative bias voltage, the mode amplitude is reduced, and the mode frequency is increased accompanied by the increased toroidal plasma rotation speed in the counter-I p direction. For a positive bias voltage, the mode frequency is decreased together with the change of the rotation velocity towards the co-I p direction, and the mode amplitude is increased. Statistic results show that the variations in the toroidal rotation speed, the 2/1 mode frequency and its amplitude linearly depend on the bias voltage. The threshold voltages for complete suppression and locking of the mode are found. The experimental results suggest that applied electrode biasing is a possible method for the avoidance of mode locking and disruption.

Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

PubMed Central

Williams, Sarah K; Lauder, Jean M; Johns, Josephine M

2011-01-01

Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine’s effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure. PMID:22379462

Mode perturbation method for optimal guided wave mode and frequency selection.

PubMed

Philtron, J H; Rose, J L

2014-09-01

With a thorough understanding of guided wave mechanics, researchers can predict which guided wave modes will have a high probability of success in a particular nondestructive evaluation application. However, work continues to find optimal mode and frequency selection for a given application. This "optimal" mode could give the highest sensitivity to defects or the greatest penetration power, increasing inspection efficiency. Since material properties used for modeling work may be estimates, in many cases guided wave mode and frequency selection can be adjusted for increased inspection efficiency in the field. In this paper, a novel mode and frequency perturbation method is described and used to identify optimal mode points based on quantifiable wave characteristics. The technique uses an ultrasonic phased array comb transducer to sweep in phase velocity and frequency space. It is demonstrated using guided interface waves for bond evaluation. After searching nearby mode points, an optimal mode and frequency can be selected which has the highest sensitivity to a defect, or gives the greatest penetration power. The optimal mode choice for a given application depends on the requirements of the inspection. Copyright © 2014 Elsevier B.V. All rights reserved.

Waveform selectivity at the same frequency.

PubMed

Wakatsuchi, Hiroki; Anzai, Daisuke; Rushton, Jeremiah J; Gao, Fei; Kim, Sanghoon; Sievenpiper, Daniel F

2015-04-13

Electromagnetic properties depend on the composition of materials, i.e. either angstrom scales of molecules or, for metamaterials, subwavelength periodic structures. Each material behaves differently in accordance with the frequency of an incoming electromagnetic wave due to the frequency dispersion or the resonance of the periodic structures. This indicates that if the frequency is fixed, the material always responds in the same manner unless it has nonlinearity. However, such nonlinearity is controlled by the magnitude of the incoming wave or other bias. Therefore, it is difficult to distinguish different incoming waves at the same frequency. Here we present a new concept of circuit-based metasurfaces to selectively absorb or transmit specific types of waveforms even at the same frequency. The metasurfaces, integrated with schottky diodes as well as either capacitors or inductors, selectively absorb short or long pulses, respectively. The two types of circuit elements are then combined to absorb or transmit specific waveforms in between. This waveform selectivity gives us another degree of freedom to control electromagnetic waves in various fields including wireless communications, as our simulation reveals that the metasurfaces are capable of varying bit error rates in response to different waveforms.

Humans have already increased the risk of major disruption to Pacific rainfall

NASA Astrophysics Data System (ADS)

Power, Scott; Delage, Francois; Chung, Christine; Ye, Harvey; Murphy, Brad

2017-04-01

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to approximately one year have major impacts on severe weather, agricultural production, ecosystems, and disease within the Pacific, and in many countries beyond. These disruptions are primarily driven by the El Niño/La Niña cycle, which is a naturally occurring phenomenon centered in the tropical Pacific. Recent research concluded that global warming under scenarios with further large increases in global greenhouse gas emissions will increase the frequency of disruptions to Pacific rainfall over the 21st century. Fortunately governments from around the world recently agreed to markedly reduce emissions over coming decades. But will these cuts be sufficient to prevent a human-forced increase in the risk of major disruption? And has the risk (i.e., likelihood) of major disruption driven by year-to-year rainfall variability already increased relative to pre-industrial times? These issues are addressed here (Power et al., Nature Communications, in press). We examined disruption in CMIP5 models under climatic conditions corresponding to the pre-industrial era, the historical period and the remainder of the 21st century under the RCP2.6, RCP4.5 and RCP8.5 scenarios. RCP2.6 results in global warming in the late 21st century that is likely to be in the range of approximately 0.9-2.3°C (relative to the latter half of the 19th century). The equivalent figures for RCP8.5 are 3.2-5.4°C (IPCC 2014). We use a simple measure of disruption or volatility: the time evolving RMS difference in seasonal rainfall over the Pacific relative to a changing climatological value of seasonal rainfall. The CMIP5 models, the observations and an SST-forced AGCM all indicate that while both El Nino and La Nina can cause major disruptions, the largest disruptions occur during El Nino years. We also show that there is a 26% increase in the frequency of major disruptions in the models by the early twentieth century and a 28% increase by the end of the twentieth century, relative to the pre-idustrial value of approximately one major disruption every nine years. Under RCP8.5 there is a 90% increase in the early 21st century and a 126% increase during the late 21st century, again relative to the pre-industrial value. The increase in the frequency of disruption arises from an increase in the frequency of El Niño and La Niña events in some models, and a non-linear boost in precipitation anomalies during El Niño and La Niña events caused by the associated global warming. This boost occurs even if the underlying sea-surface temperature anomalies during El Niño and La Niña events are unchanged from pre-industrial times. The non-linear boost increases the likelihood that a given El Niño or La Niña event will cause major disruption to rainfall. Unfortunately, even the stringent mitigation represented in RCP2.6 does not prevent further increases in the frequency of disruption: there is a 56% increase in the early twenty first century, and a 61% increase in the late 21st century. Four important conclusions can be drawn from these climate model results. First, the risk of major disruption to Pacific rainfall had already increased by the end of the 20th century and the early 21st century. This means, for example, that some of the disruption actually witnessed in the real world might have been partially due to anthropogenic increases in greenhouse gas concentrations that had already occurred by that time. Second, the risk is elevated today relative to pre-industrial times, and will remain elevated over coming years. Third, further increases in the risk of major disruption during the remainder of the 21st century can be strongly moderated if major and sustained cuts to global emissions of GHGs are made, but elevated risk for at least the remainder of the 21st century might arise, even if global action is successful in restricting emissions to RCP2.6 levels.

Delay selection by spike-timing-dependent plasticity in recurrent networks of spiking neurons receiving oscillatory inputs.

PubMed

Kerr, Robert R; Burkitt, Anthony N; Thomas, Doreen A; Gilson, Matthieu; Grayden, David B

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem.

Delay Selection by Spike-Timing-Dependent Plasticity in Recurrent Networks of Spiking Neurons Receiving Oscillatory Inputs

PubMed Central

Kerr, Robert R.; Burkitt, Anthony N.; Thomas, Doreen A.; Gilson, Matthieu; Grayden, David B.

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem. PMID:23408878

Global attractors for a discrete selection model with periodic immigration

Treesearch

James F. Selgrade; James H. Roberds

2007-01-01

A one-island selection-migration model is used to study the periodic immigration of a population of fixed allele frequency into a natural population. Density-dependent selection and immigration are the primary factors affecting the demographic genetic change in the island population. With the assumptions of complete dominance (CD) or no dominance (ND) and homozygote...

A time domain frequency-selective multivariate Granger causality approach.

PubMed

Leistritz, Lutz; Witte, Herbert

2016-08-01

The investigation of effective connectivity is one of the major topics in computational neuroscience to understand the interaction between spatially distributed neuronal units of the brain. Thus, a wide variety of methods has been developed during the last decades to investigate functional and effective connectivity in multivariate systems. Their spectrum ranges from model-based to model-free approaches with a clear separation into time and frequency range methods. We present in this simulation study a novel time domain approach based on Granger's principle of predictability, which allows frequency-selective considerations of directed interactions. It is based on a comparison of prediction errors of multivariate autoregressive models fitted to systematically modified time series. These modifications are based on signal decompositions, which enable a targeted cancellation of specific signal components with specific spectral properties. Depending on the embedded signal decomposition method, a frequency-selective or data-driven signal-adaptive Granger Causality Index may be derived.

The association between e-cigarette use characteristics and combustible cigarette consumption and dependence symptoms: Results from a national longitudinal study.

PubMed

Buu, Anne; Hu, Yi-Han; Piper, Megan E; Lin, Hsien-Chang

2018-09-01

Existing longitudinal surveys focused on the association between ever use of e-cigarettes and combustible cigarette consumption, making it difficult to infer what characteristics of e-cigarette use could potentially change combustible cigarette use behavior, which may have long-term health consequences. Although e-cigarettes' efficacy of alleviating dependence symptoms was supported by studies conducted in laboratory settings, whether the results can be translated into symptom reduction in the real world and over time is an open question. This study conducted secondary analysis on the Waves 1-2 data of the Population Assessment of Tobacco and Health (PATH) Study to examine the association between e-cigarette use characteristics (frequency, flavoring, and voltage adjustment) and combustible cigarette use outcomes (frequency, quantity, and symptoms), using the Heckman 2-step selection procedure with the selection bias controlled. The inclusion criteria ensured that we followed an adult cohort of exclusive combustible cigarette users at Wave 1. The result shows that higher frequency of e-cigarette use was associated with lower combustible cigarette consumption and dependence symptoms, controlling for the corresponding baseline cigarette use variable and other confounders. Given the frequency of e-cigarette use, the feature of voltage adjustment was not significantly associated with any of the cigarette use outcomes. Flavoring, on the other hand, was associated with lower quantity of cigarette use. Exclusive smokers who start using e-cigarettes do indeed change the frequency and quantity with which they smoke cigarettes. E-cigarette use may also help reduce dependence symptoms. Copyright © 2018 Elsevier Ltd. All rights reserved.

A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism

PubMed Central

Villanea, Fernando A.; Safi, Kristin N.; Busch, Jeremiah W.

2015-01-01

The ABO locus in humans is characterized by elevated heterozygosity and very similar allele frequencies among populations scattered across the globe. Using knowledge of ABO protein function, we generated a simple model of asymmetric negative frequency dependent selection and genetic drift to explain the maintenance of ABO polymorphism and its loss in human populations. In our models, regardless of the strength of selection, models with large effective population sizes result in ABO allele frequencies that closely match those observed in most continental populations. Populations must be moderately small to fall out of equilibrium and lose either the A or B allele (Ne ≤ 50) and much smaller (N e ≤ 25) for the complete loss of diversity, which nearly always involved the fixation of the O allele. A pattern of low heterozygosity at the ABO locus where loss of polymorphism occurs in our model is consistent with small populations, such as Native American populations. This study provides a general evolutionary model to explain the observed global patterns of polymorphism at the ABO locus and the pattern of allele loss in small populations. Moreover, these results inform the range of population sizes associated with the recent human colonization of the Americas. PMID:25946124

Alcohol and aldehyde dehydrogenase polymorphisms in Chinese and Indian populations.

PubMed

Tan, Ene-Choo; Lim, Leslie; Leong, Jern-Yi; Lim, Jing-Yan; Lee, Arthur; Yang, Jun; Tan, Chay-Hoon; Winslow, Munidasa

2010-01-01

The association between two functional polymorphisms in alcohol dehydrogenase (ADH2/ADH1B) and aldehyde dehydrogenase (ALDH2) genes and alcohol dependence was examined in 182 Chinese and Indian patients undergoing treatment for alcohol dependence and 184 screened control subjects from Singapore. All subjects were screened by the Alcohol Use Disorders Identification Test (AUDIT). Patients were also administered the Severity of Alcohol Dependence Questionnaire (SADQ). Polymorphisms were genotyped by allele-specific polymerase chain reaction and selected genotypes confirmed by DNA sequencing or restriction fragment length polymorphism. Our results showed that frequencies of ADH1B*2 and ALDH2*2 were higher in controls compared to alcohol-dependent subjects for both Chinese and Indians. Frequencies of these two alleles were also higher in the 104 Chinese controls compared to the 80 Indian controls. None of the eight Chinese who were homozygous for both protective alleles was alcohol dependent. The higher frequencies of the protective alleles could explain the lower rate of alcohol dependence in Chinese.

Frequency dependence of p-mode frequency shifts induced by magnetic activity in Kepler solar-like stars

NASA Astrophysics Data System (ADS)

Salabert, D.; Régulo, C.; Pérez Hernández, F.; García, R. A.

2018-04-01

The variations of the frequencies of the low-degree acoustic oscillations in the Sun induced by magnetic activity show a dependence on radial order. The frequency shifts are observed to increase towards higher-order modes to reach a maximum of about 0.8 μHz over the 11-yr solar cycle. A comparable frequency dependence is also measured in two other main sequence solar-like stars, the F-star HD 49933, and the young 1 Gyr-old solar analog KIC 10644253, although with different amplitudes of the shifts of about 2 μHz and 0.5 μHz, respectively. Our objective here is to extend this analysis to stars with different masses, metallicities, and evolutionary stages. From an initial set of 87 Kepler solar-like oscillating stars with known individual p-mode frequencies, we identify five stars showing frequency shifts that can be considered reliable using selection criteria based on Monte Carlo simulations and on the photospheric magnetic activity proxy Sph. The frequency dependence of the frequency shifts of four of these stars could be measured for the l = 0 and l = 1 modes individually. Given the quality of the data, the results could indicate that a physical source of perturbation different from that in the Sun is dominating in this sample of solar-like stars.

Kinship as a frequency dependent strategy

PubMed Central

Ji, Ting; Zheng, Xiu-Deng; He, Qiao-Qiao; Wu, Jia-Jia; Tao, Yi

2016-01-01

Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction. PMID:26998333

Small-molecule inhibitors directly target CARD9 and mimic its protective variant in inflammatory bowel disease.

PubMed

Leshchiner, Elizaveta S; Rush, Jason S; Durney, Michael A; Cao, Zhifang; Dančík, Vlado; Chittick, Benjamin; Wu, Huixian; Petrone, Adam; Bittker, Joshua A; Phillips, Andrew; Perez, Jose R; Shamji, Alykhan F; Kaushik, Virendar K; Daly, Mark J; Graham, Daniel B; Schreiber, Stuart L; Xavier, Ramnik J

2017-10-24

Advances in human genetics have dramatically expanded our understanding of complex heritable diseases. Genome-wide association studies have identified an allelic series of CARD9 variants associated with increased risk of or protection from inflammatory bowel disease (IBD). The predisposing variant of CARD9 is associated with increased NF-κB-mediated cytokine production. Conversely, the protective variant lacks a functional C-terminal domain and is unable to recruit the E3 ubiquitin ligase TRIM62. Here, we used biochemical insights into CARD9 variant proteins to create a blueprint for IBD therapeutics and recapitulated the mechanism of the CARD9 protective variant using small molecules. We developed a multiplexed bead-based technology to screen compounds for disruption of the CARD9-TRIM62 interaction. We identified compounds that directly and selectively bind CARD9, disrupt TRIM62 recruitment, inhibit TRIM62-mediated ubiquitinylation of CARD9, and demonstrate cellular activity and selectivity in CARD9-dependent pathways. Taken together, small molecules targeting CARD9 illustrate a path toward improved IBD therapeutics. Published under the PNAS license.

Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

PubMed

Amendola, Laura M; Dorschner, Michael O; Robertson, Peggy D; Salama, Joseph S; Hart, Ragan; Shirts, Brian H; Murray, Mitzi L; Tokita, Mari J; Gallego, Carlos J; Kim, Daniel Seung; Bennett, James T; Crosslin, David R; Ranchalis, Jane; Jones, Kelly L; Rosenthal, Elisabeth A; Jarvik, Ella R; Itsara, Andy; Turner, Emily H; Herman, Daniel S; Schleit, Jennifer; Burt, Amber; Jamal, Seema M; Abrudan, Jenica L; Johnson, Andrew D; Conlin, Laura K; Dulik, Matthew C; Santani, Avni; Metterville, Danielle R; Kelly, Melissa; Foreman, Ann Katherine M; Lee, Kristy; Taylor, Kent D; Guo, Xiuqing; Crooks, Kristy; Kiedrowski, Lesli A; Raffel, Leslie J; Gordon, Ora; Machini, Kalotina; Desnick, Robert J; Biesecker, Leslie G; Lubitz, Steven A; Mulchandani, Surabhi; Cooper, Greg M; Joffe, Steven; Richards, C Sue; Yang, Yaoping; Rotter, Jerome I; Rich, Stephen S; O'Donnell, Christopher J; Berg, Jonathan S; Spinner, Nancy B; Evans, James P; Fullerton, Stephanie M; Leppig, Kathleen A; Bennett, Robin L; Bird, Thomas; Sybert, Virginia P; Grady, William M; Tabor, Holly K; Kim, Jerry H; Bamshad, Michael J; Wilfond, Benjamin; Motulsky, Arno G; Scott, C Ronald; Pritchard, Colin C; Walsh, Tom D; Burke, Wylie; Raskind, Wendy H; Byers, Peter; Hisama, Fuki M; Rehm, Heidi; Nickerson, Debbie A; Jarvik, Gail P

2015-03-01

Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. © 2015 Amendola et al.; Published by Cold Spring Harbor Laboratory Press.

The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents

PubMed Central

Sławińska, Anna; Wierońska, Joanna M; Stachowicz, Katarzyna; Marciniak, Marcin; Łasoń-Tyburkiewicz, Magdalena; Gruca, Piotr; Papp, Mariusz; Kusek, Magdalena; Tokarski, Krzysztof; Doller, Darío; Pilc, Andrzej

2013-01-01

Background and Purpose Because agonists at metabotropic glutamate receptors exert beneficial effects in schizophrenia, we have assessed the actions of Lu AF21934 and Lu AF32615, two chemically distinct, selective and brain-penetrant positive allosteric modulators (PAMs) of the mGlu4 receptor, in several tests reflecting positive, negative and cognitive symptoms of schizophrenia in rodents. Experimental Approach Hyperactivity induced by MK-801 or amphetamine and head twitches induced by 2,5-dimethoxy-4-iodoamphetamine (DOI) in mice were used as models for positive symptoms. Disruption of social interaction and spatial delayed alternation tests induced by MK-801 in rats were used as models for negative and cognitive symptoms of schizophrenia, respectively. Key Results Lu AF21934 (0.1–5 mg·kg−1) and Lu AF32615 (2–10 mg·kg−1) dose-dependently inhibited hyperactivity induced by MK-801 or amphetamine. They also antagonized head twitches and increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in brain slices, induced by DOI. In mice lacking the mGlu4 receptor (mGlu4−/−) mice, Lu AF21934 did not antagonize DOI-induced head twitches. MK-801-induced disruption in the social interaction test was decreased by Lu AF21934 at 0.5 mg·kg−1 and by Lu AF32615 at 10 mg·kg−1. In the delayed spatial alternation test, Lu AF21934 was active at 1 and 2 mg·kg−1, while Lu AF32615 was active at 10 mg·kg−1. Conclusions and Implications We propose that activation by PAMs of the mGlu4 receptor is a promising approach to the discovery of novel antipsychotic drugs. PMID:23714045

Voltage and frequency dependence of prestin-associated charge transfer

PubMed Central

Sun, Sean X.; Farrell, Brenda; Chana, Matthew S.; Oster, George; Brownell, William E.; Spector, Alexander A.

2009-01-01

Membrane protein prestin is a critical component of the motor complex that generates forces and dimensional changes in cells in response to changes in the cell membrane potential. In its native cochlear outer hair cell, prestin is crucial to the amplification and frequency selectivity of the mammalian ear up to frequencies of tens of kHz. Other cells transfected with prestin acquire voltage-dependent properties similar to those of the native cell. The protein performance is critically dependent on chloride ions, and intrinsic protein charges also play a role. We propose an electro-diffusion model to reveal the frequency and voltage dependence of electric charge transfer by prestin. The movement of the combined charge (i.e., anion and protein charges) across the membrane is described with a Fokker-Planck equation coupled to a kinetic equation that describes the binding of chloride ions to prestin. We found a voltage-and frequency-dependent phase shift between the transferred charge and the applied electric field that determines capacitive and resistive components of the transferred charge. The phase shift monotonically decreases from zero to -90 degree as a function of frequency. The capacitive component as a function of voltage is bell-shaped, and decreases with frequency. The resistive component is bell-shaped for both voltage and frequency. The capacitive and resistive components are similar to experimental measurements of charge transfer at high frequencies. The revealed nature of the transferred charge can help reconcile the high-frequency electrical and mechanical observations associated with prestin, and it is important for further analysis of the structure and function of this protein. PMID:19490917

Sound absorption of metallic sound absorbers fabricated via the selective laser melting process

NASA Astrophysics Data System (ADS)

Cheng, Li-Wei; Cheng, Chung-Wei; Chung, Kuo-Chun; Kam, Tai-Yan

2017-01-01

The sound absorption capability of metallic sound absorbers fabricated using the additive manufacturing (selective laser melting) method is investigated via both the experimental and theoretical approaches. The metallic sound absorption structures composed of periodic cubic cells were made of laser-melted Ti6Al4 V powder. The acoustic impedance equations with different frequency-independent and frequency-dependent end corrections factors are employed to calculate the theoretical sound absorption coefficients of the metallic sound absorption structures. The calculated sound absorption coefficients are in close agreement with the experimental results for the frequencies ranging from 2 to 13 kHz.

An organizational assessment of disruptive clinician behavior: findings and implications.

PubMed

Walrath, Jo M; Dang, Deborah; Nyberg, Dorothy

2013-01-01

This study investigated registered nurses' (RNs) and physicians' (MD) experiences with disruptive behavior, triggers, responses, and impacts on clinicians, patients, and the organization. Using the Disruptive Clinician Behavior Survey for Hospital Settings, it was found that RNs experienced a significantly higher frequency of disruptive behaviors and triggers than MDs; MDs (45% of 295) and RNs (37% of 689) reported that their peer's disruptive behavior affected them most negatively. The most frequently occurring trigger was pressure from high census, volume, and patient flow; 189 incidences of harm to patients as a result of disruptive behavior were reported. Findings provide organizational leaders with evidence to customize interventions to strengthen the culture of safety.

Power Analysis of Artificial Selection Experiments Using Efficient Whole Genome Simulation of Quantitative Traits

PubMed Central

Kessner, Darren; Novembre, John

2015-01-01

Evolve and resequence studies combine artificial selection experiments with massively parallel sequencing technology to study the genetic basis for complex traits. In these experiments, individuals are selected for extreme values of a trait, causing alleles at quantitative trait loci (QTL) to increase or decrease in frequency in the experimental population. We present a new analysis of the power of artificial selection experiments to detect and localize quantitative trait loci. This analysis uses a simulation framework that explicitly models whole genomes of individuals, quantitative traits, and selection based on individual trait values. We find that explicitly modeling QTL provides qualitatively different insights than considering independent loci with constant selection coefficients. Specifically, we observe how interference between QTL under selection affects the trajectories and lengthens the fixation times of selected alleles. We also show that a substantial portion of the genetic variance of the trait (50–100%) can be explained by detected QTL in as little as 20 generations of selection, depending on the trait architecture and experimental design. Furthermore, we show that power depends crucially on the opportunity for recombination during the experiment. Finally, we show that an increase in power is obtained by leveraging founder haplotype information to obtain allele frequency estimates. PMID:25672748

Tissue–selective effects of nucleolar stress and rDNA damage in developmental disorders

PubMed Central

Calo, Eliezer; Gu, Bo; Bowen, Margot E.; Aryan, Fardin; Zalc, Antoine; Liang, Jialiang; Flynn, Ryan A.; Swigut, Tomek; Chang, Howard Y.; Attardi, Laura D.; Wysocka, Joanna

2018-01-01

Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis1,2. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis3,4, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis5, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Taken together, our findings illustrate how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations. PMID:29364875

Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.

PubMed

Calo, Eliezer; Gu, Bo; Bowen, Margot E; Aryan, Fardin; Zalc, Antoine; Liang, Jialiang; Flynn, Ryan A; Swigut, Tomek; Chang, Howard Y; Attardi, Laura D; Wysocka, Joanna

2018-02-01

Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Taken together, our findings illustrate how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations.

Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

PubMed Central

Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G.; Schweitzer, Paul; Parsons, Loren H.; Roberto, Marisa

2015-01-01

The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and type 1 cannabinoid receptor (CB1) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naïve rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not type 2 cannabinoid receptor (CB2) antagonism. After 2–3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naïve CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naïve and ethanol exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling. PMID:25940135

Fire occurence (2004)

Treesearch

John W. Coulston

2007-01-01

Why Is Fire Important? Fire is a powerful, selective regulatory mechanism in forest ecosystems. It is a natural part of the environment, and fireaffected ecosystems depend on a particular frequency and intensity of fire. These ecosystems will remain in their natural state only if the fire regime to which they are adapted is present (Kimmins 1987). The frequency and...

Temperature and frequency dependence of ultrasonic attenuation in selected tissues

NASA Technical Reports Server (NTRS)

Gammell, P. M.; Croissette, D. H. L.; Heyser, R. C.

1979-01-01

Ultrasonic attenuation over the frequency range of 1.5-10 MHz has been measured as a function of temperature for porcine liver, backfat, kidney and spleen as well as for a single specimen of human liver. The attenuation in these excised specimens increases nearly linearly with frequency. Over the temperature range of approximately 4-37 C the attenuation decreases with increasing temperature for most soft tissue studied.

PSIDD3: Post-Scan Ultrasonic Data Display System for the Windows-Based PC Including Fuzzy Logic Analysis

NASA Technical Reports Server (NTRS)

Lovelace, Jeffrey J.; Cios, Krzysztof J.; Roth, Don J.; Cao, Wei

2000-01-01

Post-Scan Interactive Data Display (PSIDD) III is a user-oriented Windows-based system that facilitates the display and comparison of ultrasonic contact data. The system is optimized to compare ultrasonic measurements made at different locations within a material or at different stages of material degradation. PSIDD III provides complete analysis of the primary wave forms in the time and frequency domains along with the calculation of several frequency dependent properties including Phase Velocity and Attenuation Coefficient and several frequency independent properties, like the Cross Correlation Velocity. The system allows image generation on all of the frequency dependent properties at any available frequency (limited by the bandwidth used in the scans) and on any of the frequency independent properties. From ultrasonic contact scans, areas of interest on an image can be studied with regard to underlying raw waveforms and derived ultrasonic properties by simply selecting the point on the image. The system offers various modes of in-depth comparison between scan points. Up to five scan points can be selected for comparative analysis at once. The system was developed with Borland Delphi software (Visual Pascal) and is based on a SQL database. It is ideal for classification of material properties, or location of microstructure variations in materials.

CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

PubMed Central

Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

2014-01-01

CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

Stay tuned: active amplification tunes tree cricket ears to track temperature-dependent song frequency.

PubMed

Mhatre, Natasha; Pollack, Gerald; Mason, Andrew

2016-04-01

Tree cricket males produce tonal songs, used for mate attraction and male-male interactions. Active mechanics tunes hearing to conspecific song frequency. However, tree cricket song frequency increases with temperature, presenting a problem for tuned listeners. We show that the actively amplified frequency increases with temperature, thus shifting mechanical and neuronal auditory tuning to maintain a match with conspecific song frequency. Active auditory processes are known from several taxa, but their adaptive function has rarely been demonstrated. We show that tree crickets harness active processes to ensure that auditory tuning remains matched to conspecific song frequency, despite changing environmental conditions and signal characteristics. Adaptive tuning allows tree crickets to selectively detect potential mates or rivals over large distances and is likely to bestow a strong selective advantage by reducing mate-finding effort and facilitating intermale interactions. © 2016 The Author(s).

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

PubMed Central

Chesler, Elissa J.; Gatti, Daniel M.; Morgan, Andrew P.; Strobel, Marge; Trepanier, Laura; Oberbeck, Denesa; McWeeney, Shannon; Hitzemann, Robert; Ferris, Martin; McMullan, Rachel; Clayshultle, Amelia; Bell, Timothy A.; de Villena, Fernando Pardo-Manuel; Churchill, Gary A.

2016-01-01

Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility. PMID:27694113

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection.

PubMed

Chesler, Elissa J; Gatti, Daniel M; Morgan, Andrew P; Strobel, Marge; Trepanier, Laura; Oberbeck, Denesa; McWeeney, Shannon; Hitzemann, Robert; Ferris, Martin; McMullan, Rachel; Clayshultle, Amelia; Bell, Timothy A; Manuel de Villena, Fernando Pardo; Churchill, Gary A

2016-12-07

Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility. Copyright © 2016 by the Genetics Society of America.

Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain-related working memory deficits in neuropathic pain rats.

PubMed

Cardoso-Cruz, H; Dourado, M; Monteiro, C; Galhardo, V

2018-05-01

Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity. To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task. Within-subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model. Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta-oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level. Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions. This study provides new insights into the role of D2r in the manifestation of pain-related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta-oscillations, and amplifies pain-related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions. © 2018 European Pain Federation - EFIC®.

Amygdala lesions in rhesus monkeys fail to disrupt object choices based on internal context.

PubMed

Rhodes, Sarah E V; Charles, David P; Howland, Emily J; Murray, Elisabeth A

2012-04-01

We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task, monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context. (c) 2012 APA, all rights reserved

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

DOE PAGES

Blundon, Jay A.; Roy, Noah C.; Teubner, Brett J. W.; ...

2017-06-30

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. We show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase–dependent adenosine production or A1–adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement ofmore » tone-discrimination abilities. We determined that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.« less

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blundon, Jay A.; Roy, Noah C.; Teubner, Brett J. W.

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. We show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase–dependent adenosine production or A1–adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement ofmore » tone-discrimination abilities. We determined that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.« less

A Visual-Cue-Dependent Memory Circuit for Place Navigation.

PubMed

Qin, Han; Fu, Ling; Hu, Bo; Liao, Xiang; Lu, Jian; He, Wenjing; Liang, Shanshan; Zhang, Kuan; Li, Ruijie; Yao, Jiwei; Yan, Junan; Chen, Hao; Jia, Hongbo; Zott, Benedikt; Konnerth, Arthur; Chen, Xiaowei

2018-06-05

The ability to remember and to navigate to safe places is necessary for survival. Place navigation is known to involve medial entorhinal cortex (MEC)-hippocampal connections. However, learning-dependent changes in neuronal activity in the distinct circuits remain unknown. Here, by using optic fiber photometry in freely behaving mice, we discovered the experience-dependent induction of a persistent-task-associated (PTA) activity. This PTA activity critically depends on learned visual cues and builds up selectively in the MEC layer II-dentate gyrus, but not in the MEC layer III-CA1 pathway, and its optogenetic suppression disrupts navigation to the target location. The findings suggest that the visual system, the MEC layer II, and the dentate gyrus are essential hubs of a memory circuit for visually guided navigation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas

PubMed Central

Brooks, Joseph L.; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

2012-01-01

Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG. PMID:22947116

An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

PubMed

Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

2018-05-15

BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

CRISPR-Mediated Base Editing Enables Efficient Disruption of Eukaryotic Genes through Induction of STOP Codons.

PubMed

Billon, Pierre; Bryant, Eric E; Joseph, Sarah A; Nambiar, Tarun S; Hayward, Samuel B; Rothstein, Rodney; Ciccia, Alberto

2017-09-21

Standard CRISPR-mediated gene disruption strategies rely on Cas9-induced DNA double-strand breaks (DSBs). Here, we show that CRISPR-dependent base editing efficiently inactivates genes by precisely converting four codons (CAA, CAG, CGA, and TGG) into STOP codons without DSB formation. To facilitate gene inactivation by induction of STOP codons (iSTOP), we provide access to a database of over 3.4 million single guide RNAs (sgRNAs) for iSTOP (sgSTOPs) targeting 97%-99% of genes in eight eukaryotic species, and we describe a restriction fragment length polymorphism (RFLP) assay that allows the rapid detection of iSTOP-mediated editing in cell populations and clones. To simplify the selection of sgSTOPs, our resource includes annotations for off-target propensity, percentage of isoforms targeted, prediction of nonsense-mediated decay, and restriction enzymes for RFLP analysis. Additionally, our database includes sgSTOPs that could be employed to precisely model over 32,000 cancer-associated nonsense mutations. Altogether, this work provides a comprehensive resource for DSB-free gene disruption by iSTOP. Copyright © 2017 Elsevier Inc. All rights reserved.

Life history variation is maintained by fitness trade-offs and negative frequency-dependent selection.

PubMed

Christie, Mark R; McNickle, Gordon G; French, Rod A; Blouin, Michael S

2018-04-24

The maintenance of diverse life history strategies within and among species remains a fundamental question in ecology and evolutionary biology. By using a near-complete 16-year pedigree of 12,579 winter-run steelhead ( Oncorhynchus mykiss ) from the Hood River, Oregon, we examined the continued maintenance of two life history traits: the number of lifetime spawning events (semelparous vs. iteroparous) and age at first spawning (2-5 years). We found that repeat-spawning fish had more than 2.5 times the lifetime reproductive success of single-spawning fish. However, first-time repeat-spawning fish had significantly lower reproductive success than single-spawning fish of the same age, suggesting that repeat-spawning fish forego early reproduction to devote additional energy to continued survival. For single-spawning fish, we also found evidence for a fitness trade-off for age at spawning: older, larger males had higher reproductive success than younger, smaller males. For females, in contrast, we found that 3-year-old fish had the highest mean lifetime reproductive success despite the observation that 4- and 5-year-old fish were both longer and heavier. This phenomenon was explained by negative frequency-dependent selection: as 4- and 5-year-old fish decreased in frequency on the spawning grounds, their lifetime reproductive success became greater than that of the 3-year-old fish. Using a combination of mathematical and individual-based models parameterized with our empirical estimates, we demonstrate that both fitness trade-offs and negative frequency-dependent selection observed in the empirical data can theoretically maintain the diverse life history strategies found in this population.

Targeting Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Prostate Cancer

DTIC Science & Technology

2013-10-01

that disrupt more selective classes of LxxLL motifs: for example, we have compounds that can block AR-PELP1 and AR- hsp27 interaction through the LxxLL...motif as well as compounds that only block AR-PELP1 (and not AR- hsp27 ). We believe that these compounds will be critical for ascertaining the...IP: AR Input PELP1 PELP1 AR AR Hsp27 hsp27 10 Planned structural modifications of D2-derived peptidomimetics by docking

Irreversible Electroporation of Human Primary Uveal Melanoma in Enucleated Eyes

PubMed Central

Mandel, Yossi; Laufer, Shlomi; Belkin, Michael; Rubinsky, Boris; Pe'er, Jacob; Frenkel, Shahar

2013-01-01

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is characterized by high rates of metastatic disease. Although brachytherapy is the most common globe-sparing treatment option for small- and medium-sized tumors, the treatment is associated with severe adverse reactions and does not lead to increased survival rates as compared to enucleation. The use of irreversible electroporation (IRE) for tumor ablation has potential advantages in the treatment of tumors in complex organs such as the eye. Following previous theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were treated with short electric pulses (50–100 µs, 1000–2000 V/cm) using a customized electrode design. Tumor bioimpedance was measured before and after treatment and was followed by histopathological evaluation. We found that IRE caused tumor ablation characterized by cell membrane disruption while sparing the non-cellular sclera. Membrane disruption and loss of cellular capacitance were also associated with significant reduction in total tumor impedance and loss of impedance frequency dependence. The effect was more pronounced near the pulsing electrodes and was dependent on time from treatment to fixation. Future studies should further evaluate the potential of IRE as an alternative method of uveal melanoma treatment. PMID:24039721

Perceptual consequences of disrupted auditory nerve activity.

PubMed

Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders.

Effects of aberrant gamma frequency oscillations on prepulse inhibition.

PubMed

Jones, Nigel C; Anderson, Paul; Rind, Gil; Sullivan, Caley; van den Buuse, Maarten; O'Brien, Terence J

2014-10-01

Emerging literature implicates abnormalities in gamma frequency oscillations in the pathophysiology of schizophrenia, with hypofunction of N-methyl-D-aspartate (NMDA) receptors implicated as a key factor. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating, which is disrupted in schizophrenia. We studied relationships between ongoing and sensory-evoked gamma oscillations and PPI using pharmacological interventions designed to increase gamma oscillations (ketamine, MK-801); reduce gamma oscillations (LY379268); or disrupt PPI (amphetamine). We predicted that elevating ongoing gamma power would lead to increased 'neural noise' in cortical circuits, dampened sensory-evoked gamma responses and disrupted behaviour. Wistar rats were implanted with EEG recording electrodes. They received ketamine (5 mg/kg), MK-801 (0.16 mg/kg), amphetamine (0.5 mg/kg), LY379268 (3 mg/kg) or vehicle and underwent PPI sessions with concurrent EEG recording. Ketamine and MK-801 increased the power of ongoing gamma oscillations and caused time-matched disruptions of PPI, while amphetamine marginally affected ongoing gamma power. In contrast, LY379268 reduced ongoing gamma power, but had no effect on PPI. The sensory gamma response evoked by the prepulse was reduced following treatment with all psychotomimetics, associating with disruptions in PPI. This was most noticeable following treatment with NMDA receptor antagonists. We found that ketamine and MK-801 increase ongoing gamma power and reduce evoked gamma power, both of which are related to disruptions in sensorimotor gating. This appears to be due to antagonism of NMDA receptors, since amphetamine and LY379268 differentially impacted these outcomes and possess different neuropharmacological substrates. Aberrant gamma frequency oscillations caused by NMDA receptor hypofunction may mediate the sensory processing deficits observed in schizophrenia.

Pulse evolution and mode selection characteristics in a TEA-CO2 laser perturbed by injection of external radiation

NASA Technical Reports Server (NTRS)

Flamant, P. H.; Menzies, R. T.; Kavaya, M. J.; Oppenheim, U. P.

1983-01-01

A grating-tunable TEA-CO2 laser with an unstable resonator cavity, modified to allow injection of CW CO2 laser radiation at the resonant transition line by means of an intracavity NaCl window, has been used to study the coupling requirements for generation of single frequency pulses. The width and shape of the mode selection region, and the dependence of the gain-switched spike buildup time and the pulse shapes on the intensity and detuning frequency of the injected radiation are reported. Comparisons of the experimental results with previously reported mode selection behavior are discussed.

Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation: A case report.

PubMed

Lai, Jian-Bo; Han, Mao-Mao; Xu, Yi; Hu, Shao-Hua

2017-11-01

Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic.

Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation

PubMed Central

Lai, Jian-bo; Han, Mao-mao; Xu, Yi; Hu, Shao-hua

2017-01-01

Abstract Rationale: Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. Patient concerns: In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. Diagnoses: After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. Interventions: The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). Outcomes: The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. Lessons: This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic. PMID:29145290

Activity-induced synaptic delivery of the GluN2A-containing NMDA receptor is dependent on endoplasmic reticulum chaperone Bip and involved in fear memory

PubMed Central

Zhang, Xiao-min; Yan, Xun-yi; Zhang, Bin; Yang, Qian; Ye, Mao; Cao, Wei; Qiang, Wen-bin; Zhu, Li-jun; Du, Yong-lan; Xu, Xing-xing; Wang, Jia-sheng; Xu, Fei; Lu, Wei; Qiu, Shuang; Yang, Wei; Luo, Jian-hong

2015-01-01

The N-methyl-D-aspartate receptor (NMDAR) in adult forebrain is a heterotetramer mainly composed of two GluN1 subunits and two GluN2A and/or GluN2B subunits. The synaptic expression and relative numbers of GluN2A- and GluN2B-containing NMDARs play critical roles in controlling Ca2+-dependent signaling and synaptic plasticity. Previous studies have suggested that the synaptic trafficking of NMDAR subtypes is differentially regulated, but the precise molecular mechanism is not yet clear. In this study, we demonstrated that Bip, an endoplasmic reticulum (ER) chaperone, selectively interacted with GluN2A and mediated the neuronal activity-induced assembly and synaptic incorporation of the GluN2A-containing NMDAR from dendritic ER. Furthermore, the GluN2A-specific synaptic trafficking was effectively disrupted by peptides interrupting the interaction between Bip and GluN2A. Interestingly, fear conditioning in mice was disrupted by intraperitoneal injection of the interfering peptide before training. In summary, we have uncovered a novel mechanism for the activity-dependent supply of synaptic GluN2A-containing NMDARs, and demonstrated its relevance to memory formation. PMID:26088419

Locality and Word Order in Active Dependency Formation in Bangla.

PubMed

Chacón, Dustin A; Imtiaz, Mashrur; Dasgupta, Shirsho; Murshed, Sikder M; Dan, Mina; Phillips, Colin

2016-01-01

Research on filler-gap dependencies has revealed that there are constraints on possible gap sites, and that real-time sentence processing is sensitive to these constraints. This work has shown that comprehenders have preferences for potential gap sites, and immediately detect when these preferences are not met. However, neither the mechanisms that select preferred gap sites nor the mechanisms used to detect whether these preferences are met are well-understood. In this paper, we report on three experiments in Bangla, a language in which gaps may occur in either a pre-verbal embedded clause or a post-verbal embedded clause. This word order variation allows us to manipulate whether the first gap linearly available is contained in the same clause as the filler, which allows us to dissociate structural locality from linear locality. In Experiment 1, an untimed ambiguity resolution task, we found a global bias to resolve a filler-gap dependency with the first gap linearly available, regardless of structural hierarchy. In Experiments 2 and 3, which use the filled-gap paradigm, we found sensitivity to disruption only when the blocked gap site is both structurally and linearly local, i.e., the filler and the gap site are contained in the same clause. This suggests that comprehenders may not show sensitivity to the disruption of all preferred gap resolutions.

Robustness and Recovery of Lifeline Infrastructure and Ecosystem Networks

NASA Astrophysics Data System (ADS)

Bhatia, U.; Ganguly, A. R.

2015-12-01

Disruptive events, both natural and man-made, can have widespread impacts on both natural systems and lifeline infrastructure networks leading to the loss of biodiversity and essential functionality, respectively. Projected sea-level rise and climate change can further increase the frequency and severity of large-scale floods on urban-coastal megacities. Nevertheless, Failure in infrastructure systems can trigger cascading impacts on dependent ecosystems, and vice-versa. An important consideration in the behavior of the isolated networks and inter-connected networks following disruptive events is their resilience, or the ability of the network to "bounce back" to a pre-disaster state. Conventional risk analysis and subsequent risk management frameworks have focused on identifying the components' vulnerability and strengthening of the isolated components to withstand these disruptions. But high interconnectedness of these systems, and evolving nature of hazards, particularly in the context of climate extremes, make the component level analysis unrealistic. In this study, we discuss the complex network-based resilience framework to understand fragility and recovery strategies for infrastructure systems impacted by climate-related hazards. We extend the proposed framework to assess the response of ecological networks to multiple species loss and design the restoration management framework to identify the most efficient restoration sequence of species, which can potentially lead to disproportionate gains in biodiversity.

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current

PubMed Central

Liu, Pin W.; Blair, Nathaniel T.

2017-01-01

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. PMID:28877968

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

PubMed

Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

2017-10-04

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

Reducing Sweeping Frequencies in Microwave NDT Employing Machine Learning Feature Selection

PubMed Central

Moomen, Abdelniser; Ali, Abdulbaset; Ramahi, Omar M.

2016-01-01

Nondestructive Testing (NDT) assessment of materials’ health condition is useful for classifying healthy from unhealthy structures or detecting flaws in metallic or dielectric structures. Performing structural health testing for coated/uncoated metallic or dielectric materials with the same testing equipment requires a testing method that can work on metallics and dielectrics such as microwave testing. Reducing complexity and expenses associated with current diagnostic practices of microwave NDT of structural health requires an effective and intelligent approach based on feature selection and classification techniques of machine learning. Current microwave NDT methods in general based on measuring variation in the S-matrix over the entire operating frequency ranges of the sensors. For instance, assessing the health of metallic structures using a microwave sensor depends on the reflection or/and transmission coefficient measurements as a function of the sweeping frequencies of the operating band. The aim of this work is reducing sweeping frequencies using machine learning feature selection techniques. By treating sweeping frequencies as features, the number of top important features can be identified, then only the most influential features (frequencies) are considered when building the microwave NDT equipment. The proposed method of reducing sweeping frequencies was validated experimentally using a waveguide sensor and a metallic plate with different cracks. Among the investigated feature selection techniques are information gain, gain ratio, relief, chi-squared. The effectiveness of the selected features were validated through performance evaluations of various classification models; namely, Nearest Neighbor, Neural Networks, Random Forest, and Support Vector Machine. Results showed good crack classification accuracy rates after employing feature selection algorithms. PMID:27104533

Quantifying light-dependent circadian disruption in humans and animal models.

PubMed

Rea, Mark S; Figueiro, Mariana G

2014-12-01

Although circadian disruption is an accepted term, little has been done to develop methods to quantify the degree of disruption or entrainment individual organisms actually exhibit in the field. A variety of behavioral, physiological and hormonal responses vary in amplitude over a 24-h period and the degree to which these circadian rhythms are synchronized to the daily light-dark cycle can be quantified with a technique known as phasor analysis. Several studies have been carried out using phasor analysis in an attempt to measure circadian disruption exhibited by animals and by humans. To perform these studies, species-specific light measurement and light delivery technologies had to be developed based upon a fundamental understanding of circadian phototransduction mechanisms in the different species. When both nocturnal rodents and diurnal humans, experienced different species-specific light-dark shift schedules, they showed, based upon phasor analysis of the light-dark and activity-rest patterns, similar levels of light-dependent circadian disruption. Indeed, both rodents and humans show monotonically increasing and quantitatively similar levels of light-dependent circadian disruption with increasing shift-nights per week. Thus, phasor analysis provides a method for quantifying circadian disruption in the field and in the laboratory as well as a bridge between ecological measurements of circadian entrainment in humans and parametric studies of circadian disruption in animal models, including nocturnal rodents.

Consequences of Family Disruption on Children’s Educational Outcomes in Norway

PubMed Central

STEELE, FIONA; SIGLE-RUSHTON, WENDY; KRAVDAL, ØYSTEIN

2009-01-01

Using high-quality data from Norwegian population registers, we examine the relationship between family disruption and children’s educational outcomes. We distinguish between disruptions caused by parental divorce and paternal death and, using a simultaneous equation model, pay particular attention to selection bias in the effect of divorce. We also allow for the possibility that disruption may have different effects at different stages of a child’s educational career. Our results suggest that selection on time-invariant maternal characteristics is important and works to overstate the effects of divorce on a child’s chances of continuing in education. Nevertheless, the experience of marital breakdown during childhood is associated with lower levels of education, and the effect weakens with the child’s age at disruption. The effects of divorce are most pronounced for the transitions during or just beyond the high school level. In models that do not allow for selection, children who experienced a father’s death appear less disadvantaged than children whose parents divorced. After we control for selection, however, differences in the educational qualifications of children from divorced and bereaved families narrow substantially and, at mean ages of divorce, are almost non-existent. PMID:19771944

Distinct frequency dependent effects of whole-body vibration on non-fractured bone and fracture healing in mice.

PubMed

Wehrle, Esther; Wehner, Tim; Heilmann, Aline; Bindl, Ronny; Claes, Lutz; Jakob, Franz; Amling, Michael; Ignatius, Anita

2014-08-01

Low-magnitude high-frequency vibration (LMHFV) provokes anabolic effects in non-fractured bone; however, in fracture healing, inconsistent results were reported and optimum vibration conditions remain unidentified. Here, we investigated frequency dependent effects of LMHFV on fracture healing. Twelve-week-old, female C57BL/6 mice received a femur osteotomy stabilized using an external fixator. The mice received whole-body vibrations (20 min/day) with 0.3g peak-to-peak acceleration and a frequency of either 35 or 45 Hz. After 10 and 21 days, the osteotomized femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, µ-computed tomography, and histomorphometry. In non-fractured trabecular bone, vibration with 35 Hz significantly increased the relative amount of bone (+28%) and the trabecular number (+29%), whereas cortical bone was not influenced. LMHFV with 45 Hz failed to provoke anabolic effects in trabecular or cortical bone. Fracture healing was not significantly influenced by whole-body vibration with 35 Hz, whereas 45 Hz significantly reduced bone formation (-64%) and flexural rigidity (-34%) of the callus. Although the exact mechanisms remain open, our results suggest that small vibration setting changes could considerably influence LMHFV effects on bone formation in remodeling and repair, and even disrupt fracture healing, implicating caution when treating patients with impaired fracture healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Medial Prefrontal Cortex Is Selectively Involved in Response Selection Using Visual Context in the Background

ERIC Educational Resources Information Center

Lee, Inah; Shin, Ji Yun

2012-01-01

The exact roles of the medial prefrontal cortex (mPFC) in conditional choice behavior are unknown and a visual contextual response selection task was used for examining the issue. Inactivation of the mPFC severely disrupted performance in the task. mPFC inactivations, however, did not disrupt the capability of perceptual discrimination for visual…

Negative frequency-dependent selection maintains a dramatic flower color polymorphism in the rewardless orchid Dactylorhiza sambucina (L.) Soò

PubMed Central

Gigord, Luc D. B.; Macnair, Mark R.; Smithson, Ann

2001-01-01

The orchid Dactylorhiza sambucina shows a stable and dramatic flower-color polymorphism, with both yellow- and purple-flowered individuals present in natural populations throughout the range of the species in Europe. The evolutionary significance of flower-color polymorphisms found in many rewardless orchid species has been discussed at length, but the mechanisms responsible for their maintenance remain unclear. Laboratory experiments have suggested that behavioral responses by pollinators to lack of reward availability might result in a reproductive advantage for rare-color morphs. Consequently, we performed an experiment varying the relative frequency of the two color morphs of D. sambucina to test whether rare morph advantage acted in the natural habitat of the species. We show here clear evidence from this manipulative experiment that rare-color morphs have reproductive advantage through male and female components. This is the first demonstration, to our knowledge, that negative frequency-dependent selection through pollinator preference for rare morphs can cause the maintenance of a flower-color polymorphism. PMID:11353863

Frequency-dependent selection can lead to evolution of high mutation rates.

PubMed

Rosenbloom, Daniel I S; Allen, Benjamin

2014-05-01

Theoretical and experimental studies have shown that high mutation rates can be advantageous, especially in novel or fluctuating environments. Here we examine how frequency-dependent competition may lead to fluctuations in trait frequencies that exert upward selective pressure on mutation rates. We use a mathematical model to show that cyclical trait dynamics generated by "rock-paper-scissors" competition can cause the mutation rate in a population to converge to a high evolutionarily stable mutation rate, reflecting a trade-off between generating novelty and reproducing past success. Introducing recombination lowers the evolutionarily stable mutation rate but allows stable coexistence between mutation rates above and below the evolutionarily stable rate. Even considering strong mutational load and ignoring the costs of faithful replication, evolution favors positive mutation rates if the selective advantage of prevailing in competition exceeds the ratio of recombining to nonrecombining offspring. We discuss a number of genomic mechanisms that may meet our theoretical requirements for the adaptive evolution of mutation. Overall, our results suggest that local mutation rates may be higher on genes influencing cyclical competition and that global mutation rates in asexual species may be higher in populations subject to strong cyclical competition.

Numerical model study of radio frequency vessel sealing thermodynamics

NASA Astrophysics Data System (ADS)

Pearce, John

2015-03-01

Several clinically successful clinical radio frequency vessel-sealing devices are currently available. The dominant thermodynamic principles at work involve tissue water vaporization processes. It is necessary to thermally denature vessel collagen, elastin and their adherent proteins to achieve a successful fusion. Collagens denature at middle temperatures, between about 60 and 90 C depending on heating time and rate. Elastin, and its adherent proteins, are more thermally robust, and require temperatures in excess of the boiling point of water at atmospheric pressure to thermally fuse. Rapid boiling at low apposition pressures leads to steam vacuole formation, brittle tissue remnants and frequently to substantial disruption in the vessel wall, particularly in high elastin-content arteries. High apposition pressures substantially increase the equilibrium boiling point of tissue water and are necessary to ensure a high probability of a successful seal. The FDM numerical models illustrate the beneficial effects of high apposition pressures.

When Disruptive Approaches Meet Disruptive Technologies: Learning at a Distance.

ERIC Educational Resources Information Center

Gibson, Chere Campbell

2000-01-01

Reviews research on constructivism in learning and selection of learning strategies. Suggests linking constructivism with instructional technologies for continuing medical education in order to "disrupt" reactive, habitual ways of learning and encourage active engagement. (SK)

Antarctic climate change: extreme events disrupt plastic phenotypic response in Adélie penguins.

PubMed

Lescroël, Amélie; Ballard, Grant; Grémillet, David; Authier, Matthieu; Ainley, David G

2014-01-01

In the context of predicted alteration of sea ice cover and increased frequency of extreme events, it is especially timely to investigate plasticity within Antarctic species responding to a key environmental aspect of their ecology: sea ice variability. Using 13 years of longitudinal data, we investigated the effect of sea ice concentration (SIC) on the foraging efficiency of Adélie penguins (Pygoscelis adeliae) breeding in the Ross Sea. A 'natural experiment' brought by the exceptional presence of giant icebergs during 5 consecutive years provided unprecedented habitat variation for testing the effects of extreme events on the relationship between SIC and foraging efficiency in this sea-ice dependent species. Significant levels of phenotypic plasticity were evident in response to changes in SIC in normal environmental conditions. Maximum foraging efficiency occurred at relatively low SIC, peaking at 6.1% and decreasing with higher SIC. The 'natural experiment' uncoupled efficiency levels from SIC variations. Our study suggests that lower summer SIC than currently observed would benefit the foraging performance of Adélie penguins in their southernmost breeding area. Importantly, it also provides evidence that extreme climatic events can disrupt response plasticity in a wild seabird population. This questions the predictive power of relationships built on past observations, when not only the average climatic conditions are changing but the frequency of extreme climatic anomalies is also on the rise.

Antarctic Climate Change: Extreme Events Disrupt Plastic Phenotypic Response in Adélie Penguins

PubMed Central

Lescroël, Amélie; Ballard, Grant; Grémillet, David; Authier, Matthieu; Ainley, David G.

2014-01-01

In the context of predicted alteration of sea ice cover and increased frequency of extreme events, it is especially timely to investigate plasticity within Antarctic species responding to a key environmental aspect of their ecology: sea ice variability. Using 13 years of longitudinal data, we investigated the effect of sea ice concentration (SIC) on the foraging efficiency of Adélie penguins (Pygoscelis adeliae) breeding in the Ross Sea. A ‘natural experiment’ brought by the exceptional presence of giant icebergs during 5 consecutive years provided unprecedented habitat variation for testing the effects of extreme events on the relationship between SIC and foraging efficiency in this sea-ice dependent species. Significant levels of phenotypic plasticity were evident in response to changes in SIC in normal environmental conditions. Maximum foraging efficiency occurred at relatively low SIC, peaking at 6.1% and decreasing with higher SIC. The ‘natural experiment’ uncoupled efficiency levels from SIC variations. Our study suggests that lower summer SIC than currently observed would benefit the foraging performance of Adélie penguins in their southernmost breeding area. Importantly, it also provides evidence that extreme climatic events can disrupt response plasticity in a wild seabird population. This questions the predictive power of relationships built on past observations, when not only the average climatic conditions are changing but the frequency of extreme climatic anomalies is also on the rise. PMID:24489657

Frequency dependence in matings with water-borne sperm.

PubMed

Pemberton, A J; Noble, L R; Bishop, J D D

2003-03-01

Negative frequency-dependent mating success--the rare male effect--is a potentially powerful evolutionary force, but disagreement exists as to whether previous work, focusing on copulating species, has robustly demonstrated this phenomenon. Noncopulating sessile organisms that release male gametes into the environment but retain their eggs for fertilization may routinely receive unequal mixtures of sperm. Although promiscuity seems unavoidable it does not follow that the resulting paternity obeys 'fair raffle' expectations. This study investigates frequency dependence in the mating of one such species, the colonial ascidian Diplosoma listerianum. In competition with an alternative sperm source males fathered more progeny if previously mated to a particular female than if no mating history existed. This suggests positive frequency-dependent selection, but may simply result from a mate order effect involving sperm storage. With fewer acclimation matings, separated by longer intervals, this pattern was not found. When, in a different experimental design, virgin females were given simultaneous mixtures of gametes at widely divergent concentrations, sperm at the lower frequency consistently achieved a greater than expected share of paternity--a rare male effect. A convincing argument as to why D. listerianum should favour rare sperm has not been identified, as sperm rarity is expected to correlate very poorly with ecological or genetic male characteristics in this pattern of mating. The existence of nongenetic female preferences at the level of colony modules, analogous in effect to fixed female preferences, is proposed. If visible to selection, indirect benefits from increasing the genetic diversity of a sibship appear the only likely explanation of the rare male effect in this system as the life history presents virtually no costs to multiple mating, and a near absence of direct (resource) benefits, whereas less controversial hypotheses of female promiscuity (e.g. trade up, genetic incompatibility) do not seem appropriate.

Effects of repeated light-dark phase shifts on voluntary ethanol and water intake in male and female Fischer and Lewis rats.

PubMed

Rosenwasser, Alan M; Clark, James W; Fixaris, Michael C; Belanger, Gabriel V; Foster, James A

2010-05-01

Several lines of evidence implicate reciprocal interactions between excessive alcohol (ethanol) intake and dysregulation of circadian biological rhythms. Thus, chronic alcohol intake leads to widespread circadian disruption in both humans and experimental animals, while in turn, chronobiological disruption has been hypothesized to promote or sustain excessive alcohol intake. Nevertheless, the effects of circadian disruption on voluntary ethanol intake have not been investigated extensively, and prior studies have reported both increased and decreased ethanol intake in rats maintained under "shift-lag" lighting regimens mimicking those experienced by shift workers and transmeridian travelers. In the present study, male and female inbred Fischer and Lewis rats were housed in running wheel cages with continuous free-choice access to both water and 10% (vol/vol) ethanol solution and exposed to repeated 6-h phase advances of the daily light-dark (LD) cycle, whereas controls were kept under standard LD 12:12 conditions. Shift-lag lighting reduced overall ethanol and water intake, and reduced ethanol preference in Fischer rats. Although contrary to the hypothesis that circadian disruption would increase voluntary ethanol intake, these results are consistent with our previous report of reduced ethanol intake in selectively bred high-alcohol-drinking (HAD1) rats housed under a similar lighting regimen. We conclude that chronic circadian disruption is a form of chronobiological stressor that, like other stressors, can either increase or decrease ethanol intake, depending on a variety of poorly understood variables. 2010 Elsevier Inc. All rights reserved.

Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.

PubMed

Moerke, Megan J; Banks, Matthew L; Cheng, Kejun; Rice, Kenner C; Negus, S Stevens

2017-12-01

Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0-0.1mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents.

PubMed

Qi, Yingjie; Klyubin, Igor; Harney, Sarah C; Hu, NengWei; Cullen, William K; Grant, Marianne K; Steffen, Julia; Wilson, Edward N; Do Carmo, Sonia; Remy, Stefan; Fuhrmann, Martin; Ashe, Karen H; Cuello, A Claudio; Rowan, Michael J

2014-12-24

Long before synaptic loss occurs in Alzheimer's disease significant harbingers of disease may be detected at the functional level. Here we examined if synaptic long-term potentiation is selectively disrupted prior to extracellular deposition of Aß in a very complete model of Alzheimer's disease amyloidosis, the McGill-R-Thy1-APP transgenic rat. Longitudinal studies in freely behaving animals revealed an age-dependent, relatively rapid-onset and persistent inhibition of long-term potentiation without a change in baseline synaptic transmission in the CA1 area of the hippocampus. Thus the ability of a standard 200 Hz conditioning protocol to induce significant NMDA receptor-dependent short- and long-term potentiation was lost at about 3.5 months of age and this deficit persisted for at least another 2-3 months, when plaques start to appear. Consistent with in vitro evidence for a causal role of a selective reduction in NMDA receptor-mediated synaptic currents, the deficit in synaptic plasticity in vivo was associated with a reduction in the synaptic burst response to the conditioning stimulation and was overcome using stronger 400 Hz stimulation. Moreover, intracerebroventricular treatment for 3 days with an N-terminally directed monoclonal anti- human Aß antibody, McSA1, transiently reversed the impairment of synaptic plasticity. Similar brief treatment with the BACE1 inhibitor LY2886721 or the γ-secretase inhibitor MRK-560 was found to have a comparable short-lived ameliorative effect when tracked in individual rats. These findings provide strong evidence that endogenously generated human Aß selectively disrupts the induction of long-term potentiation in a manner that enables potential therapeutic options to be assessed longitudinally at the pre-plaque stage of Alzheimer's disease amyloidosis.

A new method to evaluate the unfolding activity of chaperone unit ClpA based on Fe-S cluster disruption.

PubMed

Ohgita, Takashi; Okuno, Takashi; Hama, Susumu; Tsuchiya, Hiroyuki; Kogure, Kentaro

2011-01-01

ATP-dependent proteases unfold their substrates and then refold (via chaperone activity) or degrade (via protease activity) them. The proteases choose between these two activities by selecting their substrates; however, little is known about their substrate selection mechanism. The present study attempts to clarify this mechanism by investigating the role of the Escherichia coli (E. coli) ATP-dependent protease ClpAP. To address this, a reaction system that can measure both chaperone and protease activities simultaneously must be constructed. However, the chaperone activities cannot be evaluated in the presence of protease units. Green fluorescent protein (GFP) is usually used as a model substrate of ClpAP; the fluorescence decrease reflects the degradation of substrates. However, it is difficult to evaluate the chaperone activity of ClpAP using this system, because it cannot distinguish between intact and refolded substrates. Therefore, it is necessary to evaluate the exact unfolding activity while avoiding restoration of substrate spectroscopic characteristics due to chaperone activity. In this study, E. coli Ferredoxin (Fd) was used as a new model substrate for ClpAP to evaluate its unfolding activity. Intact and refolded substrates may be distinguished by the existence of an Fd Fe-S cluster. To verify this hypothesis, the absorption spectrum of Fd complexed with ClpA, the chaperone unit of ClpAP, was measured. A decrease in two peaks derived from the Fe-S cluster was observed, indicating that the Fe-S cluster of Fd was disrupted by the ClpA chaperone. This reaction system should prove useful to evaluate the exact unfolding activity of ATP-dependent proteases.

Traveling-Wave Tube Amplifier Model to Predict High-Order Modulation Intersymbol Interference

NASA Technical Reports Server (NTRS)

Kory, Carol L.; Andro, Monty; Williams, W. D. (Technical Monitor)

2001-01-01

Demands for increased data rates in satellite communications necessitate higher order modulation schemes, larger system bandwidth, and minimum distortion of the modulated signal as it is passed through the traveling wave tube amplifier (TWTA). One type of distortion that the TWTA contributes to is intersymbol interference (ISI), and this becomes particularly disruptive with wide-band, complex modulation schemes. It is suspected that in addition to the dispersion of the TWT, frequency dependent reflections due to mismatches within the TWT are a significant contributor to ISI. To experimentally investigate the effect of these mismatches within the physical TWT on ISI would be prohibitively expensive, as it would require manufacturing numerous amplifiers in addition to the acquisition of the required digital hardware. In an attempt to develop a more accurate model to correlate IS1 with the TWTA and the operational signal, a fully three-dimensional (3D), time-dependent, TWT interaction model has been developed using the electromagnetic particle-in-cell (PIC) code MAFIA (solution of Maxwell's equations by the Finite-Integration-Algorithm). The model includes a user defined slow-wave circuit with a spatially tapered region of loss to implement a sever, and spatially varied geometry (such as helical pitch) to implement a phase velocity taper. The model also includes user defined input/output coupling and an electron beam contained by solenoidal, electrostatic, or periodic permanent magnet (PPM) focusing allowing standard or novel TWTs to be investigated. This model comprehensively takes into account the effects of frequency dependent nonlinear distortions (MAM and AMPM); gain ripple due to frequency dependent reflections at the input/output coupling, severs, and mismatches from dynamic pitch variations; drive induced oscillations; harmonic generation; intermodulation products; and backward waves.

Sleep Disruption is Associated with Increased Ventricular Ectopy and Cardiac Arrest in Hospitalized Adults

PubMed Central

Miner, Steven Edward Stuart; Pahal, Dev; Nichols, Laurel; Darwood, Amanda; Nield, Lynne Elizabeth; Wulffhart, Zaev

2016-01-01

Study Objectives: To determine whether sleep disruption increases ventricular ectopy and the risk of cardiac arrest in hospitalized patients. Methods: Hospital emergency codes (HEC) trigger multiple hospital-wide overhead announcements. In 2014 an electronic “code white” program was instituted to protect staff from violent patients. This resulted in an increase in nocturnal HEC. Telemetry data was examined between September 14 and October 2, 2014. The frequency of nocturnal announcements was correlated with changes in frequency of premature ventricular complexes per hour (PVC/h). Cardiac arrest data were examined over a 3-y period. All HEC were assumed to have triggered announcements. The relationship between nocturnal HEC and the incidence of subsequent cardiac arrest was examined. Results: 2,603 hours of telemetry were analyzed in 87 patients. During nights with two or fewer announcements, PVC/h decreased 33% and remained 30% lower the next day. On nights with four or more announcements, PVC/h increased 23% (P < 0.001) and further increased 85% the next day (P = 0.001). In 2014, following the introduction of the code white program, the frequency of all HEC increased from 1.1/day to 6.2/day (P < 0.05). The frequency of cardiac arrest/24 h rose from 0.46/day in 2012–2013 to 0.62/day in 2014 (P = 0.001). During daytime hours (06:00–22:00), from 2012 through 2014, the frequency of cardiac arrest following zero, one or at least two nocturnal HEC were 0.331 ± 0.03, 0.396 ± 0.04 and 0.471 ± 0.09 respectively (R2 = 0.99, P = 0.03). Conclusions: Sleep disruption is associated with increased ventricular ectopy and increased frequency of cardiac arrest. Citation: Miner SE, Pahal D, Nichols L, Darwood A, Nield LE, Wulffart Z. Sleep disruption is associated with increased ventricular ectopy and cardiac arrest in hospitalized adults. SLEEP 2016;39(4):927–935. PMID:26715226

Aberrant Network Activity in Schizophrenia.

PubMed

Hunt, Mark J; Kopell, Nancy J; Traub, Roger D; Whittington, Miles A

2017-06-01

Brain dynamic changes associated with schizophrenia are largely equivocal, with interpretation complicated by many factors, such as the presence of therapeutic agents and the complex nature of the syndrome itself. Evidence for a brain-wide change in individual network oscillations, shared by all patients, is largely equivocal, but stronger for lower (delta) than for higher (gamma) bands. However, region-specific changes in rhythms across multiple, interdependent, nested frequencies may correlate better with pathology. Changes in synaptic excitation and inhibition in schizophrenia disrupt delta rhythm-mediated cortico-cortical communication, while enhancing thalamocortical communication in this frequency band. The contrasting relationships between delta and higher frequencies in thalamus and cortex generate frequency mismatches in inter-regional connectivity, leading to a disruption in temporal communication between higher-order brain regions associated with mental time travel. Copyright © 2017 Elsevier Ltd. All rights reserved.

RIPK3 regulates p62-LC3 complex formation via the caspase-8-dependent cleavage of p62.

PubMed

Matsuzawa, Yu; Oshima, Shigeru; Nibe, Yoichi; Kobayashi, Masanori; Maeyashiki, Chiaki; Nemoto, Yasuhiro; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Watanabe, Mamoru

2015-01-02

RIPK3 is a key molecule for necroptosis, initially characterized by necrotic cell death morphology and the activation of autophagy. Cell death and autophagic signaling are believed to tightly regulate each other. However, the associated recruitment of signaling proteins remains poorly understood. p62/sequestosome-1 is a selective autophagy substrate and a selective receptor for ubiquitinated proteins. In this study, we illustrated that both mouse and human RIPK3 mediate p62 cleavage and that RIPK3 interacts with p62, resulting in complex formation. In addition, RIPK3-dependent p62 cleavage is restricted by the inhibition of caspases, especially caspase-8. Moreover, overexpression of A20, a ubiquitin-editing enzyme and an inhibitor of caspase-8 activity, inhibits RIPK3-dependent p62 cleavage. To further investigate the potential role of RIPK3 in selective autophagy, we analyzed p62-LC3 complex formation, revealing that RIPK3 prevents the localization of LC3 and ubiquitinated proteins to the p62 complex. In addition, RIPK3-dependent p62-LC3 complex disruption is regulated by caspase inhibition. Taken together, these results demonstrated that RIPK3 interacts with p62 and regulates p62-LC3 complex formation. These findings suggested that RIPK3 serves as a negative regulator of selective autophagy and provides new insights into the mechanism by which RIPK3 regulates autophagic signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

Sideways wall force produced during tokamak disruptions

NASA Astrophysics Data System (ADS)

Strauss, H.; Paccagnella, R.; Breslau, J.; Sugiyama, L.; Jardin, S.

2013-07-01

A critical issue for ITER is to evaluate the forces produced on the surrounding conducting structures during plasma disruptions. We calculate the non-axisymmetric ‘sideways’ wall force Fx, produced in disruptions. Simulations were carried out of disruptions produced by destabilization of n = 1 modes by a vertical displacement event (VDE). The force depends strongly on γτwall, where γ is the mode growth rate and τwall is the wall penetration time, and is largest for γτwall = constant, which depends on initial conditions. Simulations of disruptions caused by a model of massive gas injection were also performed. It was found that the wall force increases approximately offset linearly with the displacement from the magnetic axis produced by a VDE. These results are also obtained with an analytical model. Disruptions are accompanied by toroidal variation of the plasma current Iφ. This is caused by toroidal variation of the halo current, as verified computationally and analytically.

The effect of pollen versus seed flow on the maintenance of nuclear-cytoplasmic gynodioecy.

PubMed

Dufay, Mathilde; Pannell, John R

2010-03-01

Gynodioecy, where females co-occur with hermaphrodites, is a relatively common sexual system in plants that is often the result of a genetic conflict between maternally inherited male sterility genes in the mitochondrial genome and the biparentally inherited male fertility restorer genes in the nucleus. Previous models have shown that nuclear-cytoplasmic gynodioecy can be maintained under certain conditions by negative frequency-dependent selection, but the effect of other evolutionary processes such as genetic drift and population subdivision is only partially understood. Here, we investigate the joint effects of frequency-dependent selection, drift, and migration through either pollen or seeds on the maintenance of nuclear-cytoplasmic gynodioecy in a subdivided population. We find that the combination of drift and selection causes the loss of gynodioecy under scenarios that would maintain it under the influence of selection alone, and that both seed and, more surprisingly, pollen flow can maintain the polymorphism. In particular, although pollen flow could not avoid the loss of cytoplasmic polymorphism within demes, it allowed the maintenance of nuclear-cytoplasmic polymorphism at the metapopulation level.

Controller for controlling operation of at least one electrical load operating on an AC supply, and a method thereof

DOEpatents

Cantin, Luc; Deschenes, Mario; D'Amours, Mario

1995-08-15

A controller is provided for controlling operation of at least one electrical load operating on an AC supply having a typical frequency, the AC supply being provided via power transformers by an electrical power distribution grid. The controller is associated with the load and comprises an input interface for coupling the controller to the grid, a frequency detector for detecting the frequency of the AC supply and producing a signal indicative of the frequency, memory modules for storing preprogrammed commands, a frequency monitor for reading the signal indicative of the frequency and producing frequency data derived thereof, a selector for selecting at least one of the preprogrammed commands with respect to the frequency data, a control unit for producing at least one command signal representative of the selected preprogrammed commands, and an output interface including a device responsive to the command signal for controlling the load. Therefore, the load can be controlled by means of the controller depending on the frequency of the AC supply.

Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons

PubMed Central

Powrozek, Teresa A.; Olson, Eric C.

2012-01-01

Prenatal ethanol exposure disrupts cortical neurite initiation and outgrowth, but prior studies have reported both ethanol-dependent growth promotion and inhibition. To resolve this ambiguity and better approximate in vivo conditions, we quantitatively analyzed neuronal morphology using a new, whole hemisphere explant model. In this model, Layer 6 (L6) cortical neurons migrate, laminate and extend neurites in an organotypic fashion. To selectively label L6 neurons we performed ex utero electroporation of a GFP expression construct at embryonic day 13 and allowed the explants to develop for 2 days in vitro. Explants were exposed to (400mg/dL) ethanol for either 4 or 24 hrs prior to fixation. Complete 3-D reconstructions were made of >80 GFP-positive neurons in each experimental condition. Acute responses to ethanol exposure included compaction of the Golgi apparatus accompanied by elaboration of supernumerary primary apical neurites, as well as a modest (~15%) increase in higher order apical neurite length. With longer exposure time, ethanol exposure leads to a consistent, significant disorientation of the cell (cell body, primary apical neurite, and Golgi) with respect to the pial surface. The effects on cellular orientation were accompanied by decreased expression of cytoskeletal elements, microtubule associated protein 2 and F-actin. These findings indicate that upon exposure to ethanol, developing L6 neurons manifest disruptions in Golgi apparatus and cytoskeletal elements which may in turn trigger selective and significant perturbations to primary neurite formation and neuronal polarity. PMID:22840816

Obesity-related hypertension: is there a role for selective leptin resistance?

PubMed

Correia, Marcelo L G; Haynes, William G

2004-06-01

Obesity is a risk factor for cardiovascular diseases, in particular for hypertension. Serum leptin levels and sympathetic nerve activity are both increased in obesity. Leptin has been demonstrated to increase sympathetic nerve activity. Thus, leptin-dependent sympathoactivation might contribute to obesity-related hypertension. However, leptin resistance occurs in obesity. One possibility is that leptin resistance is selective to the metabolic effects of leptin, sparing its sympathoexcitatory actions. In this article, we review experimental evidence supporting the novel concept of selective leptin resistance. We also discuss the sympathetic actions of leptin that are relevant to blood pressure modulation and potential mechanisms of leptin resistance. Disruption of leptin intracellular signaling pathways and resistance of specific leptin-responsive neural networks provide theoretic models of selective leptin resistance. However, most information about leptin-sympathetic actions and leptin-resistance mechanisms derive from in vitro and animal studies. Future research in humans is widely awaited.

Evolution of frequency-dependent mate choice: keeping up with fashion trends

PubMed Central

Kokko, Hanna; Jennions, Michael D; Houde, Anne

2007-01-01

The diversity of sexual traits favoured by females is enormous and, curiously, includes preferences for males with rare or novel phenotypes. We modelled the evolution of a preference for rarity that yielded two surprising results. First, a Fisherian ‘sexy son’ effect can boost female preferences to a frequency well above that predicted by mutation–selection balance, even if there are significant mortality costs for females. Preferences do not reach fixation, however, as they are subject to frequency-dependent selection: if choosy females are too common, then rare genotypes in one generation become common, and thus unattractive, in the offspring generation. Nevertheless, even at relatively low frequency, preferences maintain polymorphism in male traits. The second unexpected result is that the preferences can evolve to much higher frequencies if choice is hindered, such that females cannot always express their preferences. Our results emphasize the need to consider feedback where preferences determine the dynamics of male genotypes and vice versa. They also highlight the similarity between the arbitrariness of behavioural norms in models of social evolution with punishment (the so-called ‘folk theorem’) and the diversity of sexual traits that can be preferred simply because deviating from the norm produces unattractive offspring and is, in this sense, ‘punished’. PMID:17360285

cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice

PubMed Central

Blake, Camille B.

2014-01-01

Pathologies in which insulin is dysregulated, including diabetes, can disrupt central vagal circuitry, leading to gastrointestinal and other autonomic dysfunction. Insulin affects whole body metabolism through central mechanisms and is transported into the brain stem dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarius (NTS), which mediate parasympathetic visceral regulation. The NTS receives viscerosensory vagal input and projects heavily to the DMV, which supplies parasympathetic vagal motor output. Normally, insulin inhibits synaptic excitation of DMV neurons, with no effect on synaptic inhibition. Modulation of synaptic inhibition in DMV, however, is often sensitive to cAMP-dependent mechanisms. We hypothesized that an effect of insulin on GABAergic synaptic transmission may be uncovered by elevating resting cAMP levels in GABAergic terminals. We used whole cell patch-clamp recordings in brain stem slices from control and diabetic mice to identify insulin effects on inhibitory neurotransmission in the DMV in the presence of forskolin to elevate cAMP levels. In the presence of forskolin, insulin decreased the frequency of inhibitory postsynaptic currents (IPSCs) and the paired-pulse ratio of evoked IPSCs in DMV neurons from control mice. This effect was blocked by brefeldin-A, a Golgi-disrupting agent, or indinavir, a GLUT4 blocker, indicating that protein trafficking and glucose transport were involved. In streptozotocin-treated, diabetic mice, insulin did not affect IPSCs in DMV neurons in the presence of forskolin. Results suggest an impairment of cAMP-induced insulin effects on GABA release in the DMV, which likely involves disrupted protein trafficking in diabetic mice. These findings provide insight into mechanisms underlying vagal dysregulation associated with diabetes. PMID:24990858

MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy.

PubMed

Zimowski, Janusz G; Massalska, Diana; Holding, Mariola; Jadczak, Sylwia; Fidziańska, Elżbieta; Lusakowska, Anna; Kostera-Pruszczyk, Anna; Kamińska, Anna; Zaremba, Jacek

2014-01-01

Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60-65% of mutations, duplications for 5-10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009-2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45-54 and 3-21, whereas most duplications involved exons 3-18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots - different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10.

PubMed

Nickols, Jordan; Obiako, Boniface; Ramila, K C; Putinta, Kevin; Schilling, Sarah; Sayner, Sarah L

2015-12-15

Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. Copyright © 2015 the American Physiological Society.

Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10

PubMed Central

Nickols, Jordan; Obiako, Boniface; Ramila, K. C.; Putinta, Kevin; Schilling, Sarah

2015-01-01

Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. PMID:26475732

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenson, Justin M.; Ryan, Jeremy A.; Grant, Robert A.

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry,more » relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors.« less

Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1

PubMed Central

Jenson, Justin M; Ryan, Jeremy A; Grant, Robert A; Letai, Anthony; Keating, Amy E

2017-01-01

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry, relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors. DOI: http://dx.doi.org/10.7554/eLife.25541.001 PMID:28594323

Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms

PubMed Central

Schimizzi, Gregory V.; Maher, Meghan T.; Loza, Andrew J.; Longmore, Gregory D.

2016-01-01

The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin. PMID:27454609

Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms.

PubMed

Schimizzi, Gregory V; Maher, Meghan T; Loza, Andrew J; Longmore, Gregory D

2016-01-01

The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin.

Mapping of the stochastic Lotka-Volterra model to models of population genetics and game theory

NASA Astrophysics Data System (ADS)

Constable, George W. A.; McKane, Alan J.

2017-08-01

The relationship between the M -species stochastic Lotka-Volterra competition (SLVC) model and the M -allele Moran model of population genetics is explored via timescale separation arguments. When selection for species is weak and the population size is large but finite, precise conditions are determined for the stochastic dynamics of the SLVC model to be mappable to the neutral Moran model, the Moran model with frequency-independent selection, and the Moran model with frequency-dependent selection (equivalently a game-theoretic formulation of the Moran model). We demonstrate how these mappings can be used to calculate extinction probabilities and the times until a species' extinction in the SLVC model.

Effects of eddy currents on selective spectral editing experiments at 3T.

PubMed

Oeltzschner, Georg; Snoussi, Karim; Puts, Nicolaas A; Mikkelsen, Mark; Harris, Ashley D; Pradhan, Subechhya; Tsapkini, Kyrana; Schär, Michael; Barker, Peter B; Edden, Richard A E

2018-03-01

To investigate frequency-offset effects in edited magnetic resonance spectroscopy (MRS) experiments arising from B 0 eddy currents. Macromolecule-suppressed (MM-suppressed) γ-aminobutyric acid (GABA)-edited experiments were performed at 3T. Saturation-offset series of MEGA-PRESS experiments were performed in phantoms, in order to investigate different aspects of the relationship between the effective editing frequencies and eddy currents associated with gradient pulses in the sequence. Difference integrals were quantified for each series, and the offset dependence of the integrals was analyzed to quantify the difference in frequency (Δf) between the actual vs. nominal expected saturation frequency. Saturation-offset N-acetyl-aspartate-phantom experiments show that Δf varied with voxel orientation, ranging from 10.4 Hz (unrotated) to 6.4 Hz (45° rotation about the caudal-cranial axis) and 0.4 Hz (45° rotation about left-right axis), indicating that gradient-related B 0 eddy currents vary with crusher-gradient orientation. Fixing the crusher-gradient coordinate-frame substantially reduced the orientation dependence of Δf (to ∼2 Hz). Water-suppression crusher gradients also introduced a frequency offset, with Δf = 0.6 Hz ("excitation" water suppression), compared to 10.2 Hz (no water suppression). In vivo spectra showed a negative edited "GABA" signal, suggesting Δf on the order of 10 Hz; with fixed crusher-gradient coordinate-frame, the expected positive edited "GABA" signal was observed. Eddy currents associated with pulsed field gradients may have a considerable impact on highly frequency-selective spectral-editing experiments, such as MM-suppressed GABA editing at 3T. Careful selection of crusher gradient orientation may ameliorate these effects. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:673-681. © 2017 International Society for Magnetic Resonance in Medicine.

Fast-Spiking Interneurons Supply Feedforward Control of Bursting, Calcium, and Plasticity for Efficient Learning.

PubMed

Owen, Scott F; Berke, Joshua D; Kreitzer, Anatol C

2018-02-08

Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrophysiology, imaging, and behavior to describe a unified mechanism by which striatal FSIs control burst firing, calcium influx, and synaptic plasticity in neighboring medium spiny projection neurons (MSNs). In vivo silencing of FSIs increased bursting, calcium transients, and AMPA/NMDA ratios in MSNs. In a motor sequence task, FSI silencing increased the frequency of calcium transients but reduced the specificity with which transients aligned to individual task events. Consistent with this, ablation of FSIs disrupted the acquisition of striatum-dependent egocentric learning strategies. Together, our data support a model in which feedforward inhibition from FSIs temporally restricts MSN bursting and calcium-dependent synaptic plasticity to facilitate striatum-dependent sequence learning. Copyright © 2018 Elsevier Inc. All rights reserved.

Disruptive Civil Technologies: Six Technologies With Potential Impacts on US Interests Out to 2025

DTIC Science & Technology

2008-04-01

power (geopolitical, military, economic, or social cohesion). The six disruptive technologies were identified through a process carried out by...clustering, development of technology descriptors, screening, and prioritizing, analysts down-selected from 102 potentially disruptive technologies . They

Cognitive and motor functioning in a patient with selective infarction of the left basal ganglia: evidence for decreased non-routine response selection and performance.

PubMed

Troyer, Angela K; Black, Sandra E; Armilio, Maria L; Moscovitch, Morris

2004-01-01

Focal damage to the basal ganglia is relatively rare, and little is known about the cognitive effects of damage to specific basal ganglia structures. A 28-year-old, highly educated male (patient RI) sustained a unilateral left ischemic infarction involving primarily the putamen and secondarily the head of the caudate and the anterior internal capsule. Two detailed neuropsychological assessments, at 3 and 16 months post-infarction, revealed that a majority of cognitive abilities were spared. RI's general intelligence, simple attention, concept formation, cognitive flexibility, and explicit memory were unaffected. Select cognitive abilities were affected, and these appeared to be related to direct involvement of the putamen and/or to indirect disruption of circuits between the basal ganglia and frontal lobes. Consistent with involvement of the left putamen, RI showed micrographia with his right hand. Interestingly, his micrographia was context-dependent, appearing only when verbal expression was involved (e.g., present when writing spontaneously, but not when copying sentences or when drawing). Evidence of disruption to frontal systems included variably decreased sustained attention, mildly decreased ability to generate words and to generate ideas, and significantly impaired abstraction ability in both verbal and visual modalities. Although there are several possible interpretations for these findings, this pattern of cognitive and motor functioning is consistent with neuroimaging research suggesting that the frontal/subcortical circuit between the putamen and frontal motor areas plays a role in non-routine response selection and performance.

Aggressive Marital Conflict, Maternal Harsh Punishment, and Child Aggressive-Disruptive Behavior: Evidence for Direct and Mediated Relations

PubMed Central

Erath, Stephen A.; Bierman, Karen L.

2009-01-01

Direct associations between aggressive marital conflict and child aggressive-disruptive behavior at home and school were explored in this cross-sectional study of 360 kindergarten children. In addition, mediated pathways linking aggressive marital conflict to maternal harsh punishment to child aggressive-disruptive behavior were examined. Moderation analyses explored how the overall frequency of marital disagreement might buffer or exacerbate the impact of aggressive marital conflict on maternal harsh punishment and child aggressive-disruptive behavior. Hierarchical regressions revealed direct pathways linking aggressive marital conflict to child aggressive-disruptive behavior at home and school and a partially mediated pathway linking aggressive marital conflict to child aggressive-disruptive behavior at home. Further analyses revealed that rates of marital disagreement moderated the association between aggressive marital conflict and child aggressive-disruptive behavior at home, with an attenuated association at high rates of marital disagreement as compared with low rates of marital disagreement. PMID:16756397

Two-photon direct frequency comb spectroscopy of alkali atoms

NASA Astrophysics Data System (ADS)

Palm, Christopher; Pradhananga, Trinity; Nguyen, Khoa; Montcrieffe, Caitlin; Kimball, Derek

2012-11-01

We have studied transition frequencies and excited state hyperfine structure in rubidium using 2-photon transitions excited directly with the frequency-doubled output of a erbium fiber optical frequency comb. The frequency comb output is directed in two counterpropagating directions through a vapor cell containing the rubidium vapor. A pair of optical filters is used to select teeth of the comb in order to identify the transition wavelengths. A photomultiplier tube (PMT) measures fluorescence from a decay channel wavelength selected with another optical filter. Using different combinations of filters enables a wide range of transitions to be investigated. By scanning the repetition rate, a Doppler-free spectrum can be obtained enabling kHz-resolution spectral measurements. An interesting dependence of the 2-photon spectrum on the energy of the intermediate state of the 2-photon transition is discussed. Our investigations are laying the groundwork for a long-term research program to use direct frequency comb spectroscopy to understand the complex spectra of rare-earth atoms.

The evolution of social learning rules: payoff-biased and frequency-dependent biased transmission.

PubMed

Kendal, Jeremy; Giraldeau, Luc-Alain; Laland, Kevin

2009-09-21

Humans and other animals do not use social learning indiscriminately, rather, natural selection has favoured the evolution of social learning rules that make selective use of social learning to acquire relevant information in a changing environment. We present a gene-culture coevolutionary analysis of a small selection of such rules (unbiased social learning, payoff-biased social learning and frequency-dependent biased social learning, including conformism and anti-conformism) in a population of asocial learners where the environment is subject to a constant probability of change to a novel state. We define conditions under which each rule evolves to a genetically polymorphic equilibrium. We find that payoff-biased social learning may evolve under high levels of environmental variation if the fitness benefit associated with the acquired behaviour is either high or low but not of intermediate value. In contrast, both conformist and anti-conformist biases can become fixed when environment variation is low, whereupon the mean fitness in the population is higher than for a population of asocial learners. Our examination of the population dynamics reveals stable limit cycles under conformist and anti-conformist biases and some highly complex dynamics including chaos. Anti-conformists can out-compete conformists when conditions favour a low equilibrium frequency of the learned behaviour. We conclude that evolution, punctuated by the repeated successful invasion of different social learning rules, should continuously favour a reduction in the equilibrium frequency of asocial learning, and propose that, among competing social learning rules, the dominant rule will be the one that can persist with the lowest frequency of asocial learning.

Observation and theory of reorientation-induced spectral diffusion in polarization-selective 2D IR spectroscopy.

PubMed

Kramer, Patrick L; Nishida, Jun; Giammanco, Chiara H; Tamimi, Amr; Fayer, Michael D

2015-05-14

In nearly all applications of ultrafast multidimensional infrared spectroscopy, the spectral degrees of freedom (e.g., transition frequency) and the orientation of the transition dipole are assumed to be decoupled. We present experimental results which confirm that frequency fluctuations can be caused by rotational motion and observed under appropriate conditions. A theory of the frequency-frequency correlation function (FFCF) observable under various polarization conditions is introduced, and model calculations are found to reproduce the qualitative trends in FFCF rates. The FFCF determined with polarization-selective two-dimensional infrared (2D IR) spectroscopy is a direct reporter of the frequency-rotational coupling. For the solute methanol in a room temperature ionic liquid, the FFCF of the hydroxyl (O-D) stretch decays due to spectral diffusion with different rates depending on the polarization of the excitation pulses. The 2D IR vibrational echo pulse sequence consists of three excitation pulses that generate the vibrational echo, a fourth pulse. A faster FFCF decay is observed when the first two excitation pulses are polarized perpendicular to the third pulse and the echo, 〈XXY Y〉, than in the standard all parallel configuration, 〈XXXX〉, in which all four pulses have the same polarization. The 2D IR experiment with polarizations 〈XY XY〉 ("polarization grating" configuration) gives a FFCF that decays even more slowly than in the 〈XXXX〉 configuration. Polarization-selective 2D IR spectra of bulk water do not exhibit polarization-dependent FFCF decays; spectral diffusion is effectively decoupled from reorientation in the water system.

Observation and theory of reorientation-induced spectral diffusion in polarization-selective 2D IR spectroscopy

NASA Astrophysics Data System (ADS)

Kramer, Patrick L.; Nishida, Jun; Giammanco, Chiara H.; Tamimi, Amr; Fayer, Michael D.

2015-05-01

In nearly all applications of ultrafast multidimensional infrared spectroscopy, the spectral degrees of freedom (e.g., transition frequency) and the orientation of the transition dipole are assumed to be decoupled. We present experimental results which confirm that frequency fluctuations can be caused by rotational motion and observed under appropriate conditions. A theory of the frequency-frequency correlation function (FFCF) observable under various polarization conditions is introduced, and model calculations are found to reproduce the qualitative trends in FFCF rates. The FFCF determined with polarization-selective two-dimensional infrared (2D IR) spectroscopy is a direct reporter of the frequency-rotational coupling. For the solute methanol in a room temperature ionic liquid, the FFCF of the hydroxyl (O-D) stretch decays due to spectral diffusion with different rates depending on the polarization of the excitation pulses. The 2D IR vibrational echo pulse sequence consists of three excitation pulses that generate the vibrational echo, a fourth pulse. A faster FFCF decay is observed when the first two excitation pulses are polarized perpendicular to the third pulse and the echo, , than in the standard all parallel configuration, , in which all four pulses have the same polarization. The 2D IR experiment with polarizations ("polarization grating" configuration) gives a FFCF that decays even more slowly than in the configuration. Polarization-selective 2D IR spectra of bulk water do not exhibit polarization-dependent FFCF decays; spectral diffusion is effectively decoupled from reorientation in the water system.

Roles for the yeast RAD18 and RAD52 DNA repair genes in UV mutagenesis.

PubMed

Armstrong, J D; Chadee, D N; Kunz, B A

1994-11-01

Experimental evidence indicates that although the Saccharomyces cerevisiae RAD18 and RAD52 genes are not required for nucleotide excision repair, they function in the processing of UV-induced DNA damage in yeast. Conflicting statements regarding the UV mutability of strains deleted for RAD18 prompted us to re-examine the influence of RAD18, and RAD52, on UV mutagenesis. To do so, we characterized mutations induced by UV in SUP4-o, a yeast suppressor tRNA gene. SUP4-o was maintained on a plasmid in isogenic strains that either carried one of two different rad18 deletions (rad18 delta) or had RAD52 disrupted. Both rad18 deletions decreased the frequency of UV-induced SUP4-o mutations to levels close to those for spontaneous mutagenesis in the rad18 delta backgrounds, and prevented a net increase in mutant yield. A detailed analysis of mutations isolated after UV irradiation of one of the rad18 delta strains uncovered little evidence of the specificity features typical for UV mutagenesis in the isogenic repair-proficient (RAD) parent (e.g., predominance of G.C-->A.T transitions). Evidently, UV induction of SUP4-o mutations is highly dependent on the RAD18 gene. Compared to the RAD strain, disruption of RAD52 reduced the frequency and yield of UV mutagenesis by about two-thirds. Closer inspection revealed that 80% of this reduction was due to a decrease in the frequency of G.C-->A.T transitions. In addition, there were differences in the distributions and site specificities of single base-pair substitutions. Thus, RAD52 also participates in UV mutagenesis of a plasmid-borne gene in yeast, but to a lesser extent than RAD18.

DNA-damage response during mitosis induces whole-chromosome missegregation.

PubMed

Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

2014-11-01

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

Low-frequency oscillations in default mode subnetworks are associated with episodic memory impairments in Alzheimer's disease.

PubMed

Veldsman, Michele; Egorova, Natalia; Singh, Baljeet; Mungas, Dan; DeCarli, Charles; Brodtmann, Amy

2017-11-01

Disruptions to functional connectivity in subsystems of the default mode network are evident in Alzheimer's disease (AD). Functional connectivity estimates correlations in the time course of low-frequency activity. Much less is known about other potential perturbations to this activity, such as changes in the amplitude of oscillations and how this relates to cognition. We examined the amplitude of low-frequency fluctuations in 44 AD patients and 128 cognitively normal participants and related this to episodic memory, the core deficit in AD. We show higher amplitudes of low-frequency oscillations in AD patients. Rather than being compensatory, this appears to be maladaptive, with greater amplitude in the ventral default mode subnetwork associated with poorer episodic memory. Perturbations to default mode subnetworks in AD are evident in the amplitude of low-frequency oscillations in the resting brain. These disruptions are associated with episodic memory demonstrating their behavioral and clinical relevance in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

The fighting hypothesis as an evolutionary explanation for the handedness polymorphism in humans: where are we?

PubMed

Faurie, Charlotte; Raymond, Michel

2013-06-01

The ubiquitous and persistent handedness polymorphism in humans requires an evolutionary explanation. It has been suggested that left-handers have a frequency-dependent advantage during a fight, such that this advantage decreases when their frequency increases. Many independent studies are providing data from interactive sports (a specific class of fights), and are very supportive of the fighting hypothesis. The only intercultural study on traditional societies is also consistent with the fighting hypothesis, although it has not yet been replicated. The frequencies of left-handers in the few remaining violent societies are likely to be rapidly decreasing, due to Western colonization (long-range weapons, religion, and money market) dramatically affecting the frequency-dependent selection associated with handedness. Clearly, more data are urgently needed outside the Western influence. © 2013 New York Academy of Sciences.

The impact of developmental dyslexia and dysgraphia on movement production during word writing.

PubMed

Kandel, Sonia; Lassus-Sangosse, Delphine; Grosjacques, Géraldine; Perret, Cyril

This study investigated how deficits in orthographic processing affect movement production during word writing. Children with dyslexia and dysgraphia wrote words and pseudo-words on a digitizer. The words were orthographically regular and irregular of varying frequency. The group analysis revealed that writing irregular words and pseudo-words increased movement duration and dysfluency. This indicates that the spelling processes were active while the children were writing the words. The impact of these spelling processes was stronger for the children with dyslexia and dysgraphia. The analysis of individual performance revealed that most dyslexic/dysgraphic children presented similar writing patterns. However, selective lexical processing deficits affected irregular word writing but not pseudo-word writing. Selective poor sublexical processing affected pseudo-word writing more than irregular word writing. This study suggests that the interaction between orthographic and motor processing constitutes an important cognitive load that may disrupt the graphic outcome of the children with dyslexia/dysgraphia.

Dynamical behaviour of a discrete selection-migration model with arbitrary dominance

Treesearch

James F. Selgrade; Jordan West Bostic; James H. Roberds

2009-01-01

To study the effects of immigration of genes (possibly transgenic) into a natural population, a one-island selection-migration model with density-dependent regulation is used to track allele frequency and population size. The existence and uniqueness of a polymorphic genetic equilibrium is proved under a general assumption about dominance in fitnesses. Also, conditions...

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.

PubMed

Fahrion, Jennifer K; Komuro, Yutaro; Li, Ying; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

2012-03-27

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca(2+) spikes through alterations in Ca(2+), cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca(2+) spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca(2+) spike frequency by stimulating internal Ca(2+) release and Ca(2+) influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca(2+) spike frequency and Ca(2+), cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication.

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency

PubMed Central

Fahrion, Jennifer K.; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

2012-01-01

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca2+ spikes through alterations in Ca2+, cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca2+ spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca2+ spike frequency by stimulating internal Ca2+ release and Ca2+ influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca2+ spike frequency and Ca2+, cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication. PMID:22411806

Masking disrupts reentrant processing in human visual cortex.

PubMed

Fahrenfort, J J; Scholte, H S; Lamme, V A F

2007-09-01

In masking, a stimulus is rendered invisible through the presentation of a second stimulus shortly after the first. Over the years, authors have typically explained masking by postulating some early disruption process. In these feedforward-type explanations, the mask somehow "catches up" with the target stimulus, disrupting its processing either through lateral or interchannel inhibition. However, studies from recent years indicate that visual perception--and most notably visual awareness itself--may depend strongly on cortico-cortical feedback connections from higher to lower visual areas. This has led some researchers to propose that masking derives its effectiveness from selectively interrupting these reentrant processes. In this experiment, we used electroencephalogram measurements to determine what happens in the human visual cortex during detection of a texture-defined square under nonmasked (seen) and masked (unseen) conditions. Electro-encephalogram derivatives that are typically associated with reentrant processing turn out to be absent in the masked condition. Moreover, extrastriate visual areas are still activated early on by both seen and unseen stimuli, as shown by scalp surface Laplacian current source-density maps. This conclusively shows that feedforward processing is preserved, even when subject performance is at chance as determined by objective measures. From these results, we conclude that masking derives its effectiveness, at least partly, from disrupting reentrant processing, thereby interfering with the neural mechanisms of figure-ground segmentation and visual awareness itself.

Mapping alternating current electroosmotic flow at the dielectrophoresis crossover frequency of a colloidal probe.

PubMed

Wang, Jingyu; Wei, Ming-Tzo; Cohen, Joel A; Ou-Yang, H Daniel

2013-07-01

AC electroosmotic (ACEO) flow above the gap between coplanar electrodes is mapped by the measurement of Stokes forces on an optically trapped polystyrene colloidal particle. E²-dependent forces on the probe particle are selected by amplitude modulation (AM) of the ACEO electric field (E) and lock-in detection at twice the AM frequency. E²-dependent DEP of the probe is eliminated by driving the ACEO at the probe's DEP crossover frequency. The location-independent DEP crossover frequency is determined, in a separate experiment, as the limiting frequency of zero horizontal force as the probe is moved toward the midpoint between the electrodes. The ACEO velocity field, uncoupled from probe DEP effects, was mapped in the region 1-9 μm above a 28 μm gap between the electrodes. By use of variously sized probes, each at its DEP crossover frequency, the frequency dependence of the ACEO flow was determined at a point 3 μm above the electrode gap and 4 μm from an electrode tip. At this location the ACEO flow was maximal at ∼117 kHz for a low salt solution. This optical trapping method, by eliminating DEP forces on the probe, provides unambiguous mapping of the ACEO velocity field. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of CYP3A4 genetic polymorphisms in Han Chinese.

PubMed

Zhou, Qing; Yu, Xiaomin; Shu, Chang; Cai, Yimei; Gong, Wei; Wang, Xumin; Wang, Duen-mei; Hu, Songnian

2011-06-01

Our study aimed to comprehensively investigate the genetic polymorphisms of CYP3A4 in Han Chinese. We sequenced the gene regions of CYP3A4, including its promoter, exons, surrounding introns and 3' untranslated region (3'UTR), from 100 unrelated-healthy Han Chinese individuals. We detected 11 SNPs, three of which are novel. According to in silico functional prediction of novel variants, 20148 A>G in exon 10, resulting in substitution of Tyr319 with Cys (CYP3A4*21), may induce dramatic alteration of protein conformation, and 26908 G>A in 3'UTR may disrupt post-transcriptional regulation. We identified five alleles in Han Chinese, the allele frequencies of CYP3A4*1, *5, *6, *18 and *21 are 97, 0.5, 1, 1 and 0.5%, respectively. Haplotype inference revealed 14 haplotypes, of which the major haplotype CYP3A4*1A constitutes 59% of the total chromosomes. We also examined the possible role of natural selection in shaping the variation of CYP3A4 and confirmed a trend, consistent with the action of positive selection. We systematically screened the genetic polymorphisms of CYP3A4 in Han Chinese, highlighted possible functional impairment of the novel allele and summarized the distinct allele and haplotype frequency distribution, with an emphasis on detecting the footprint of recent positive selection on the CYP3A4 gene in Han Chinese.

Scaling behavior of EEG amplitude and frequency time series across sleep stages

NASA Astrophysics Data System (ADS)

Kantelhardt, Jan W.; Tismer, Sebastian; Gans, Fabian; Schumann, Aicko Y.; Penzel, Thomas

2015-10-01

We study short-term and long-term persistence properties (related with auto-correlations) of amplitudes and frequencies of EEG oscillations in 176 healthy subjects and 40 patients during nocturnal sleep. The amplitudes show scaling from 2 to 500 seconds (depending on the considered band) with large fluctuation exponents during (nocturnal) wakefulness (0.73-0.83) and small ones during deep sleep (0.50-0.69). Light sleep is similar to deep sleep, while REM sleep (0.64-0.76) is closer to wakefulness except for the EEG γ band. Some of the frequency time series also show long-term scaling, depending on the selected bands and stages. Only minor deviations are seen for patients with depression, anxiety, or Parkinson's disease.

A type IV burst associated with a coronal streamer disruption event

NASA Technical Reports Server (NTRS)

Kundu, M. R.

1987-01-01

A type IV burst was observed on February 17, 1985 with the Clark Lake Radio Observatory multifrequency radioheliograph operating in the frequency range 20-125 MHz. This burst was associated with a coronal streamer disruption event. From two-dimensional images produced at 50 MHz, evidence of a type II burst and a slow moving type IV burst are shown. The observations of the moving type IV burst suggests that a plasmoid containing energetic electrons can result from the disruption of a coronal streamer.

Activated Macrophages Destroy Intracellular Leishmania Major Amastigotes by an l-Arginine-Dependent Killing Mechanism

DTIC Science & Technology

1990-01-01

atom of L-arginine and a precursor of the nitrite measured, may disrupt Fe- dependent enzymatic pathways vital to the survival of amastigotes within...geneti- a precursor of the nitrite measured, may disrupt Fe- cally susceptible BALB/c mice. The exact role of IFN-1 in dependent enzymatic pathways vital...induces the heme - dependent activation of 0 6 ± 4 89 80 guanylate cyclase. with the subsequent stimulation of 0.01 8 ± 3 85 67 the secondary messenger

New tools for targeted disruption of cholinergic synaptic transmission in Drosophila melanogaster.

PubMed

Mejia, Monica; Heghinian, Mari D; Marí, Frank; Godenschwege, Tanja A

2013-01-01

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The α7 subtype of nAChRs is involved in neurological pathologies such as Parkinson's disease, Alzheimer's disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster α7 (Dα7) has the closest sequence homology to the vertebrate α7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Dα7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the Dα7 nAChR's ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a Dα7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in Dα7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of Dα7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type Dα7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the Dα7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of Dα7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the circuits without affecting other cellular signaling.

New Tools for Targeted Disruption of Cholinergic Synaptic Transmission in Drosophila melanogaster

PubMed Central

Mejia, Monica; Heghinian, Mari D.; Marí, Frank; Godenschwege, Tanja A.

2013-01-01

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The α7 subtype of nAChRs is involved in neurological pathologies such as Parkinson’s disease, Alzheimer’s disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster α7 (Dα7) has the closest sequence homology to the vertebrate α7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Dα7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the Dα7 nAChR’s ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a Dα7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in Dα7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of Dα7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type Dα7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the Dα7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of Dα7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the circuits without affecting other cellular signaling. PMID:23737994

Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

PubMed Central

Tomkins, Oren; Feintuch, Akiva; Benifla, Moni; Cohen, Avi; Friedman, Alon; Shelef, Ilan

2011-01-01

Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE. PMID:21436875

Angular dependence of Raman scattering selection rules for long-wavelength optical phonons in short-period GaAs/AlAs superlattices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volodin, V. A., E-mail: volodin@isp.nsc.ru; Sachkov, V. A.; Sinyukov, M. P.

2016-07-15

The angular dependence of Raman scattering selection rules for optical phonons in short-period (001) GaAs/AlAs superlattices is calculated and experimentally studied. Experiments are performed using a micro-Raman setup, in the scattering geometry with the wavevectors of the incident and scattered light lying in the plane of superlattices (so-called in-plane geometry). Phonon frequencies are calculated using the Born model taking the Coulomb interaction into account in the rigid-ion approximation. Raman scattering spectra are calculated in the framework of the deformation potential and electro-optical mechanisms. Calculations show an angular dependence of the selection rules for optical phonons with different directions of themore » wavevectors. Drastic differences in the selection rules are found for experimental and calculated spectra. Presumably, these differences are due to the Fröhlich mechanism in Raman scattering for short-period superlattices.« less

20170312 - Adverse Outcome Pathway (AOP) framework for ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Adverse Outcome Pathway (AOP) framework for embryonic ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Locality and Word Order in Active Dependency Formation in Bangla

PubMed Central

Chacón, Dustin A.; Imtiaz, Mashrur; Dasgupta, Shirsho; Murshed, Sikder M.; Dan, Mina; Phillips, Colin

2016-01-01

Research on filler-gap dependencies has revealed that there are constraints on possible gap sites, and that real-time sentence processing is sensitive to these constraints. This work has shown that comprehenders have preferences for potential gap sites, and immediately detect when these preferences are not met. However, neither the mechanisms that select preferred gap sites nor the mechanisms used to detect whether these preferences are met are well-understood. In this paper, we report on three experiments in Bangla, a language in which gaps may occur in either a pre-verbal embedded clause or a post-verbal embedded clause. This word order variation allows us to manipulate whether the first gap linearly available is contained in the same clause as the filler, which allows us to dissociate structural locality from linear locality. In Experiment 1, an untimed ambiguity resolution task, we found a global bias to resolve a filler-gap dependency with the first gap linearly available, regardless of structural hierarchy. In Experiments 2 and 3, which use the filled-gap paradigm, we found sensitivity to disruption only when the blocked gap site is both structurally and linearly local, i.e., the filler and the gap site are contained in the same clause. This suggests that comprehenders may not show sensitivity to the disruption of all preferred gap resolutions. PMID:27610090

Pediatric genetic disease of the cornea

PubMed Central

Fecarotta, Christopher M.; Huang, Wendy W.

2014-01-01

Our objective is to evaluate the literature regarding selected genetic diseases of the cornea, including megalocornea, keratoglobus, keratoconus, cystinosis, the mucopolysaccharidoses, sclerocornea, Peters' anomaly, familial dysautonomia, and various corneal dystrophies. The transparency of the cornea is a consequence of uniformity in both size and spacing of the collagen lamellae. The cornea's clarity depends on a delicate biochemical and structural balance; consequently, genetic disorders that disrupt either its metabolic or anatomic function can cause opacity and vision loss. Many childhood corneal diseases have a genetic etiology and are associated with known syndromes. Each disorder has unique associated set of possible complications. Prognosis often depends on the extent of opacity and disorganization of the anterior segment. Corneal transplantation has been performed for these disorders with variable success. PMID:27625877

A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption.

PubMed

Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Mardor, Yael; Miklavcic, Damijan

2016-03-01

Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r(2) = 0.79; p < 0.008, r(2) = 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup.

The Role of piRNA-Mediated Epigenetic Silencing in the Population Dynamics of Transposable Elements in Drosophila melanogaster

PubMed Central

Lee, Yuh Chwen G.

2015-01-01

The piwi-interacting RNAs (piRNA) are small RNAs that target selfish transposable elements (TEs) in many animal genomes. Until now, piRNAs’ role in TE population dynamics has only been discussed in the context of their suppression of TE transposition, which alone is not sufficient to account for the skewed frequency spectrum and stable containment of TEs. On the other hand, euchromatic TEs can be epigenetically silenced via piRNA-dependent heterochromatin formation and, similar to the widely known “Position-effect variegation”, heterochromatin induced by TEs can “spread” into nearby genes. We hypothesized that the piRNA-mediated spread of heterochromatin from TEs into adjacent genes has deleterious functional effects and leads to selection against individual TEs. Unlike previously identified deleterious effects of TEs due to the physical disruption of DNA, the functional effect we investigated here is mediated through the epigenetic influences of TEs. We found that the repressive chromatin mark, H3K9me, is elevated in sequences adjacent to euchromatic TEs at multiple developmental stages in Drosophila melanogaster. Furthermore, the heterochromatic states of genes depend not only on the number of and distance from adjacent TEs, but also on the likelihood that their nearest TEs are targeted by piRNAs. These variations in chromatin status probably have functional consequences, causing genes near TEs to have lower expression. Importantly, we found stronger selection against TEs that lead to higher H3K9me enrichment of adjacent genes, demonstrating the pervasive evolutionary consequences of TE-induced epigenetic silencing. Because of the intrinsic biological mechanism of piRNA amplification, spread of TE heterochromatin could result in the theoretically required synergistic deleterious effects of TE insertions for stable containment of TE copy number. The indirect deleterious impact of piRNA-mediated epigenetic silencing of TEs is a previously unexplored, yet important, element for the evolutionary dynamics of TEs. PMID:26042931

Frequency-dependent acceleration of relaxation in mammalian heart: a property not relying on phospholamban and SERCA2a phosphorylation

PubMed Central

Valverde, Carlos A; Mundiña-Weilenmann, Cecilia; Said, Matilde; Ferrero, Paola; Vittone, Leticia; Salas, Margarita; Palomeque, Julieta; Petroff, Martín Vila; Mattiazzi, Alicia

2005-01-01

An increase in stimulation frequency causes an acceleration of myocardial relaxation (FDAR). Several mechanisms have been postulated to explain this effect, among which is the Ca2+–calmodulin-dependent protein kinase (CaMKII)-dependent phosphorylation of the Thr17 site of phospholamban (PLN). To gain further insights into the mechanisms of FDAR, we studied the FDAR and the phosphorylation of PLN residues in perfused rat hearts, cat papillary muscles and isolated cat myocytes. This allowed us to sweep over a wide range of frequencies, in species with either positive or negative force–frequency relationships, as well as to explore the FDAR under isometric (or isovolumic) and isotonic conditions. Results were compared with those produced by isoprenaline, an intervention known to accelerate relaxation (IDAR) via PLN phosphorylation. While IDAR occurs tightly associated with a significant increase in the phosphorylation of Ser16 and Thr17 of PLN, FDAR occurs without significant changes in the phosphorylation of PLN residues in the intact heart and cat papillary muscles. Moreover, in intact hearts, FDAR was not associated with any significant change in the CaMKII-dependent phosphorylation of sarcoplasmic/endoplasmic Ca2+ ATPase (SERCA2a), and was not affected by the presence of the CaMKII inhibitor, KN-93. In isolated myocytes, FDAR occurred associated with an increase in Thr17 phosphorylation. However, for a similar relaxant effect produced by isoprenaline, the phosphorylation of PLN (Ser16 and Thr17) was significantly higher in the presence of the β-agonist. Moreover, the time course of Thr17 phosphorylation was significantly delayed with respect to the onset of FDAR. In contrast, the time course of Ser16 phosphorylation, the first residue that becomes phosphorylated with isoprenaline, was temporally associated with IDAR. Furthermore, KN-93 significantly decreased the phosphorylation of Thr17 that was evoked by increasing the stimulation frequency, but failed to affect FDAR. Taken together, the results provide direct evidence indicating that CaMKII phosphorylation pathways are not involved in FDAR and that FDAR and IDAR do not share a common underlying mechanism. More likely, a CaMKII-independent mechanism could be involved, whereby increasing stimulation frequency would disrupt the SERCA2a–PLN interaction, leading to an increase in SR Ca2+ uptake and myocardial relaxation. PMID:15528241

Spin Dependence in Tidal Disruption Events

NASA Astrophysics Data System (ADS)

Kesden, Michael; Stone, Nicholas; van Velzen, Sjoert

2018-01-01

A supermassive black hole (SBH) can tidally disrupt stars when its tidal field overwhelms the stars’ self-gravity. The stellar debris produced in such tidal disruption events (TDEs) evolves into tidal streams that can self-intersect. These inelastic stream collisions dissipate orbital energy, both circularizing the tidal stream and contributing to the emission observed during the TDE. Once circularized into a disk, the stellar debris can be viscously accreted by the SBH powering additional luminous emission. We explore how SBH spin can affect the tidal disruption process. Tidal forces are spin dependent, as is the minimum orbital angular momentum below which stars are directly captured by the SBH. This implies that the TDE rate will be spin dependent, particularly for more massive SBHs for which relativistic effects are more significant. SBH spin also affects TDE light curves through the initial debris orbits, the nature of the stream collisions, the viscous evolution of the accretion disk, and the possibility of launching jets. We explore the spin dependence of these phenomena to identify promising signatures for upcoming surveys expected to discover hundreds of TDE candidates in the next decade.

Variable Temperature Infrared Spectroscopy Investigations of Benzoic Acid Desorption from Sodium and Calcium Montmorillonite Clays.

PubMed

Nickels, Tara M; Ingram, Audrey L; Maraoulaite, Dalia K; White, Robert L

2015-12-01

Processes involved in thermal desorption of benzoic acid from sodium and calcium montmorillonite clays are investigated by using variable temperature diffuse reflection Fourier transform infrared spectroscopy (DRIFTS). By monitoring the temperature dependence of infrared absorbance bands while heating samples, subtle changes in molecular vibrations are detected and employed to characterize specific benzoic acid adsorption sites. Abrupt changes in benzoic acid adsorption site properties occur for both clay samples at about 125 °C. Difference spectra absorbance band frequency variations indicate that adsorbed benzoic acid interacts with interlayer cations through water bridges and that these interactions can be disrupted by the presence of organic anions, in particular, benzoate.

Predictors of burden among lower socioeconomic status caregivers of persons with chronic mental illness.

PubMed

Biegel, D E; Milligan, S E; Putnam, P L; Song, L Y

1994-10-01

This study uses a stress-coping-support framework to examine the predictors of caregiver burden with a sample of 103 lower social class family caregivers of persons with chronic mental illness. Results of multiple regression analyses show that the greater the frequency of client behavioral symptoms and the lower the amount of perceived support from family members, the higher the level of overall caregiver burden. Examination of the predictors of specific types of burden-family disruption, stigma, strain, and dependency-reveal that different constellations of variables predict different types of burden. The need for mental health agencies to address caregiver and client concerns is addressed. Implications are presented for practice and future research.

Frequency selective detection of nuclear quadrupole resonance (NQR) spin echoes

NASA Astrophysics Data System (ADS)

Somasundaram, Samuel D.; Jakobsson, Andreas; Smith, John A. S.; Althoefer, Kaspar A.

2006-05-01

Nuclear Quadrupole Resonance (NQR) is a radio frequency (RF) technique that can be used to detect the presence of quadrupolar nuclei, such as the 14N nucleus prevalent in many explosives and narcotics. The technique has been hampered by low signal-to-noise ratios and is further aggravated by the presence of RF interference (RFI). To ensure accurate detection, proposed detectors should exploit the rich form of the NQR signal. Furthermore, the detectors should also be robust to any remaining residual interference, left after suitable RFI mitigation has been employed. In this paper, we propose a new NQR data model, particularly for the realistic case where multiple pulse sequences are used to generate trains of spin echoes. Furthermore, we refine two recently proposed approximative maximum likelihood (AML) detectors, enabling the algorithm to optimally exploit the data model of the entire echo train and also incorporate knowledge of the temperature dependent spin-echo decay time. The AML-based detectors ensure accurate detection and robustness against residual RFI, even when the temperature of the sample is not precisely known, by exploiting the dependencies of the NQR resonant lines on temperature. Further robustness against residual interference is gained as the proposed detector is frequency selective; exploiting only those regions of the spectrum where the NQR signal is expected. Extensive numerical evaluations based on both simulated and measured NQR data indicate that the proposed Frequency selective Echo Train AML (FETAML) detector offers a significant improvement as compared to other existing detectors.

Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome.

PubMed

McIntyre, Rebecca E; Lakshminarasimhan Chavali, Pavithra; Ismail, Ozama; Carragher, Damian M; Sanchez-Andrade, Gabriela; Forment, Josep V; Fu, Beiyuan; Del Castillo Velasco-Herrera, Martin; Edwards, Andrew; van der Weyden, Louise; Yang, Fengtang; Ramirez-Solis, Ramiro; Estabel, Jeanne; Gallagher, Ferdia A; Logan, Darren W; Arends, Mark J; Tsang, Stephen H; Mahajan, Vinit B; Scudamore, Cheryl L; White, Jacqueline K; Jackson, Stephen P; Gergely, Fanni; Adams, David J

2012-01-01

Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm)) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm) embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm) embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.

Disruption of Mouse Cenpj, a Regulator of Centriole Biogenesis, Phenocopies Seckel Syndrome

PubMed Central

McIntyre, Rebecca E.; Lakshminarasimhan Chavali, Pavithra; Forment, Josep V.; Fu, Beiyuan; Del Castillo Velasco-Herrera, Martin; Edwards, Andrew; van der Weyden, Louise; Yang, Fengtang; Ramirez-Solis, Ramiro; Estabel, Jeanne; Gallagher, Ferdia A.; Logan, Darren W.; Arends, Mark J.; Tsang, Stephen H.; Mahajan, Vinit B.; Scudamore, Cheryl L.; White, Jacqueline K.; Jackson, Stephen P.; Gergely, Fanni; Adams, David J.

2012-01-01

Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpjtm/tm) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpjtm/tm embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpjtm/tm embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome. PMID:23166506

Distinguishing the central drive to tremor in Parkinson's disease and essential tremor.

PubMed

Brittain, John-Stuart; Cagnan, Hayriye; Mehta, Arpan R; Saifee, Tabish A; Edwards, Mark J; Brown, Peter

2015-01-14

Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N = 24) and ET (N = 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology. Copyright © 2015 Brittain et al.

Distinguishing the Central Drive to Tremor in Parkinson's Disease and Essential Tremor

PubMed Central

Brittain, John-Stuart; Cagnan, Hayriye; Mehta, Arpan R.; Saifee, Tabish A.; Edwards, Mark J.

2015-01-01

Parkinson's disease (PD) and essential tremor (ET) are the two most common movement disorders. Both have been associated with similar patterns of network activation leading to the suggestion that they may result from similar network dysfunction, specifically involving the cerebellum. Here, we demonstrate that parkinsonian tremors and ETs result from distinct patterns of interactions between neural oscillators. These patterns are reflected in the tremors' derived frequency tolerance, a novel measure readily attainable from bedside accelerometry. Frequency tolerance characterizes the temporal evolution of tremor by quantifying the range of frequencies over which the tremor may be considered stable. We found that patients with PD (N = 24) and ET (N = 21) were separable based on their frequency tolerance, with PD associated with a broad range of stable frequencies whereas ET displayed characteristics consistent with a more finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by transcranial alternating current stimulation applied over cerebellum. Narrow frequency tolerances predicted stronger entrainment of tremor by stimulation, providing good evidence that the cerebellum plays an important role in pacing those tremors. The different patterns of frequency tolerance could be captured with a simple model based on a broadly coupled set of neural oscillators for PD, but a more finely tuned set of oscillators in ET. Together, these results reveal a potential organizational principle of the human motor system, whose disruption in PD and ET dictates how patients respond to empirical, and potentially therapeutic, interventions that interact with their underlying pathophysiology. PMID:25589772

Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors

PubMed Central

Mori, Munemasa; Mahoney, John E.; Stupnikov, Maria R.; Paez-Cortez, Jesus R.; Szymaniak, Aleksander D.; Varelas, Xaralabos; Herrick, Dan B.; Schwob, James; Zhang, Hong; Cardoso, Wellington V.

2015-01-01

Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection. Disruption of this mechanism resulted in aberrant expansion of basal cells and altered pseudostratification. Analysis of human lungs showing similar abnormalities and decreased NOTCH3 expression in subjects with chronic obstructive pulmonary disease suggests an involvement of NOTCH3-dependent events in the pathogenesis of this condition. PMID:25564622

Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort

PubMed Central

Silver, Matt J.; Corbin, Karen D.; Hellenthal, Garrett; da Costa, Kerry-Ann; Dominguez-Salas, Paula; Moore, Sophie E.; Owen, Jennifer; Prentice, Andrew M.; Hennig, Branwen J.; Zeisel, Steven H.

2015-01-01

Choline is an essential nutrient, and the amount needed in the diet is modulated by several factors. Given geographical differences in dietary choline intake and disparate frequencies of single-nucleotide polymorphisms (SNPs) in choline metabolism genes between ethnic groups, we tested the hypothesis that 3 SNPs that increase dependence on dietary choline would be under negative selection pressure in settings where choline intake is low: choline dehydrogenase (CHDH) rs12676, methylenetetrahydrofolate reductase 1 (MTHFD1) rs2236225, and phosphatidylethanolamine-N-methyltransferase (PEMT) rs12325817. Evidence of negative selection was assessed in 2 populations: one in The Gambia, West Africa, where there is historic evidence of a choline-poor diet, and the other in the United States, with a comparatively choline-rich diet. We used 2 independent methods, and confirmation of our hypothesis was sought via a comparison with SNP data from the Maasai, an East African population with a genetic background similar to that of Gambians but with a traditional diet that is higher in choline. Our results show that frequencies of SNPs known to increase dependence on dietary choline are significantly reduced in the low-choline setting of The Gambia. Our findings suggest that adequate intake levels of choline may have to be reevaluated in different ethnic groups and highlight a possible approach for identifying novel functional SNPs under the influence of dietary selective pressure.—Silver, M. J., Corbin, K. D., Hellenthal, G., da Costa, K.-A., Dominguez-Salas, P., Moore, S. E., Owen, J., Prentice, A. M., Hennig, B. J., Zeisel, S. H. Evidence for negative selection of gene variants that increase dependence on dietary choline in a Gambian cohort. PMID:25921832

Disruption of the vacuolar calcium-ATPases in Arabidopsis results in the activation of a salicylic acid-dependent programmed cell death pathway.

PubMed

Boursiac, Yann; Lee, Sang Min; Romanowsky, Shawn; Blank, Robert; Sladek, Chris; Chung, Woo Sik; Harper, Jeffrey F

2010-11-01

Calcium (Ca(2+)) signals regulate many aspects of plant development, including a programmed cell death pathway that protects plants from pathogens (hypersensitive response). Cytosolic Ca(2+) signals result from a combined action of Ca(2+) influx through channels and Ca(2+) efflux through pumps and cotransporters. Plants utilize calmodulin-activated Ca(2+) pumps (autoinhibited Ca(2+)-ATPase [ACA]) at the plasma membrane, endoplasmic reticulum, and vacuole. Here, we show that a double knockout mutation of the vacuolar Ca(2+) pumps ACA4 and ACA11 in Arabidopsis (Arabidopsis thaliana) results in a high frequency of hypersensitive response-like lesions. The appearance of macrolesions could be suppressed by growing plants with increased levels (greater than 15 mm) of various anions, providing a method for conditional suppression. By removing plants from a conditional suppression, lesion initials were found to originate primarily in leaf mesophyll cells, as detected by aniline blue staining. Initiation and spread of lesions could also be suppressed by disrupting the production or accumulation of salicylic acid (SA), as shown by combining aca4/11 mutations with a sid 2 (for salicylic acid induction-deficient2) mutation or expression of the SA degradation enzyme NahG. This indicates that the loss of the vacuolar Ca(2+) pumps by itself does not cause a catastrophic defect in ion homeostasis but rather potentiates the activation of a SA-dependent programmed cell death pathway. Together, these results provide evidence linking the activity of the vacuolar Ca(2+) pumps to the control of a SA-dependent programmed cell death pathway in plants.

Examining Hippocampal Mossy Fiber Synapses by 3D Electron Microscopy in Wildtype and Kirrel3 Knockout Mice

PubMed Central

Rawson, Randi L.

2017-01-01

Neural circuits balance excitatory and inhibitory activity and disruptions in this balance are commonly found in neurodevelopmental disorders. Mice lacking the intellectual disability and autism-associated gene Kirrel3 have an excitation-inhibition imbalance in the hippocampus but the precise synaptic changes underlying this functional defect are unknown. Kirrel3 is a homophilic adhesion molecule expressed in dentate gyrus (DG) and GABA neurons. It was suggested that the excitation-inhibition imbalance of hippocampal neurons in Kirrel3 knockout mice is due to loss of mossy fiber (MF) filopodia, which are DG axon protrusions thought to excite GABA neurons and thereby provide feed-forward inhibition to CA3 pyramidal neurons. Fewer filopodial structures were observed in Kirrel3 knockout mice but neither filopodial synapses nor DG en passant synapses, which also excite GABA neurons, were examined. Here, we used serial block-face scanning electron microscopy (SBEM) with 3D reconstruction to define the precise connectivity of MF filopodia and elucidate synaptic changes induced by Kirrel3 loss. Surprisingly, we discovered wildtype MF filopodia do not synapse exclusively onto GABA neurons as previously thought, but instead synapse with similar frequency onto GABA neurons and CA3 neurons. Moreover, Kirrel3 loss selectively reduces MF filopodial synapses onto GABA neurons but not those made onto CA3 neurons or en passant synapses. In sum, the selective loss of MF filopodial synapses with GABA neurons likely underlies the hippocampal activity imbalance observed in Kirrel3 knockout mice and may impact neural function in patients with Kirrel3-dependent neurodevelopmental disorders. PMID:28670619

Polarization-independent tunable spectral slicing filter in Ti:LiNbO3.

PubMed

Rabelo, Renato C; Eknoyan, Ohannes; Taylor, Henry F

2011-02-01

A two-port polarization-independent tunable spectral slicing filter at the 1530 nm wavelength regime is presented. The design utilizes an asymmetric interferometer with a sparse index grating along its arms. The sparse grating makes it possible to select equally spaced frequency channels from an incident WDM signal and to place nulls between them to coincide with the signal comb frequency. The number of selected channels and nulls between them depends on the number of coupling regions used in the sparse grating. The free spectral range depends on the spacing between the coupling regions. The Z-transform method is used to synthesize the filter and determine the spectral response. The operation of a device with six coupling regions is demonstrated, and good agreement with theoretical predictions is obtained. A 3 dB bandwidth of ∼1 nm and thermal tuning over a range of ∼13 nm are measured.

Sibling genes as environment: Sibling dopamine genotypes and adolescent health support frequency dependent selection.

PubMed

Rauscher, Emily; Conley, Dalton; Siegal, Mark L

2015-11-01

While research consistently suggests siblings matter for individual outcomes, it remains unclear why. At the same time, studies of genetic effects on health typically correlate variants of a gene with the average level of behavioral or health measures, ignoring more complicated genetic dynamics. Using National Longitudinal Study of Adolescent Health data, we investigate whether sibling genes moderate individual genetic expression. We compare twin variation in health-related absences and self-rated health by genetic differences at three locations related to dopamine regulation and transport to test sibship-level cross-person gene-gene interactions. Results suggest effects of variation at these genetic locations are moderated by sibling genes. Although the mechanism remains unclear, this evidence is consistent with frequency dependent selection and suggests much genetic research may violate the stable unit treatment value assumption. Copyright © 2015 Elsevier Inc. All rights reserved.

Ultrasonic Data Display and Analysis System Developed (Including Fuzzy Logic Analysis) for the Windows-Based PC

NASA Technical Reports Server (NTRS)

Lovelace, Jeffrey J.; Cios, Kryzsztof J.; Roth, Don J.; cAO, wEI n.

2001-01-01

Post-Scan Interactive Data Display (PSIDD) III is a user-oriented Windows-based system that facilitates the display and comparison of ultrasonic contact measurement data obtained at NASA Glenn Research Center's Ultrasonic Nondestructive Evaluation measurement facility. The system is optimized to compare ultrasonic measurements made at different locations within a material or at different stages of material degradation. PSIDD III provides complete analysis of the primary waveforms in the time and frequency domains along with the calculation of several frequency-dependent properties including phase velocity and attenuation coefficient and several frequency-independent properties, like the cross correlation velocity. The system allows image generation on all the frequency-dependent properties at any available frequency (limited by the bandwidth used in the scans) and on any of the frequency-independent properties. From ultrasonic contact scans, areas of interest on an image can be studied with regard to underlying raw waveforms and derived ultrasonic properties by simply selecting the point on the image. The system offers various modes of indepth comparison between scan points. Up to five scan points can be selected for comparative analysis at once. The system was developed with Borland Delphi software (Visual Pascal) and is based on an SQL data base. It is ideal for the classification of material properties or the location of microstructure variations in materials. Along with the ultrasonic contact measurement software that it is partnered with, this system is technology ready and can be transferred to users worldwide.

Robustness of non-interdependent and interdependent networks against dependent and adaptive attacks

NASA Astrophysics Data System (ADS)

Tyra, Adam; Li, Jingtao; Shang, Yilun; Jiang, Shuo; Zhao, Yanjun; Xu, Shouhuai

2017-09-01

Robustness of complex networks has been extensively studied via the notion of site percolation, which typically models independent and non-adaptive attacks (or disruptions). However, real-life attacks are often dependent and/or adaptive. This motivates us to characterize the robustness of complex networks, including non-interdependent and interdependent ones, against dependent and adaptive attacks. For this purpose, dependent attacks are accommodated by L-hop percolation where the nodes within some L-hop (L ≥ 0) distance of a chosen node are all deleted during one attack (with L = 0 degenerating to site percolation). Whereas, adaptive attacks are launched by attackers who can make node-selection decisions based on the network state in the beginning of each attack. The resulting characterization enriches the body of knowledge with new insights, such as: (i) the Achilles' Heel phenomenon is only valid for independent attacks, but not for dependent attacks; (ii) powerful attack strategies (e.g., targeted attacks and dependent attacks, dependent attacks and adaptive attacks) are not compatible and cannot help the attacker when used collectively. Our results shed some light on the design of robust complex networks.

Speech Disruptions in the Narratives of English-Speaking Children with Specific Language Impairment

ERIC Educational Resources Information Center

Guo, Ling-yu; Tomblin, J. Bruce; Samelson, Vicki

2008-01-01

Purpose: This study examined the types, frequencies, and distribution of speech disruptions in the spoken narratives of children with specific language impairment (SLI) and their age-matched (CA) and language-matched (LA) peers. Method: Twenty 4th-grade children with SLI, 20 typically developing CA children, and 20 younger typically developing LA…

Ripple-Triggered Stimulation of the Locus Coeruleus during Post-Learning Sleep Disrupts Ripple/Spindle Coupling and Impairs Memory Consolidation

ERIC Educational Resources Information Center

Novitskaya, Yulia; Sara, Susan J.; Logothetis, Nikos K.; Eschenko, Oxana

2016-01-01

Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to…

Factors related to frequency of narghile (waterpipe) use: the first insights on tobacco dependence in narghile users.

PubMed

Maziak, W; Ward, K D; Eissenberg, T

2004-10-05

To evaluate factors related to level of narghile (waterpipe) use as a first step towards modeling tobacco dependence among narghile users. Cross sectional survey done in 2003 using interviewer-administered anonymous questionnaires. Cafes/restaurants serving narghiles in Aleppo, Syria. Narghile smokers (161 men and 107 women; mean age, 30.1 +/- 10.2, 161; age range, 18-68 years; response rate, 95.3%) randomly selected from the 17 cafes/restaurants sampled. Frequency of narghile use (daily, weekly, monthly) was assessed as a function of several factors potentially indicative of dependence, including situational characteristics (where, when, and with whom smoking occurs; seasonality of use, and sharing of narghile), attitudes, and experience with quitting narghile use, escalation of use over time, future intentions regarding use, perception of being "hooked" on narghile, and cognitions/behaviors engaged in to support use (carrying one's own narghile; think of narghile when it is not available; considering narghile for selection of cafes/restaurants). Frequency of narghile use was strongly correlated with participant's subjective judgment of how hooked they are on narghile (coefficient, 0.5). Predictors of narghile use frequency according to multinomial logistic regression were: male gender, smoking mainly alone versus with others; smoking mainly at home versus outside; smoking more frequently since initiation, being hooked on narghile, carrying narghile, and considering it for cafe/restaurant choice. Our data reveal two main domains of a tobacco dependence syndrome likely to be relevant to narghile; the first reflects the effects of nicotine contained in narghile tobacco, and is not very different from what is seen with other tobacco products, and the second is unique to narghile and is related mainly to its social dimension, with more intensive smokers showing an increasingly individual pattern of narghile smoking.

Evolution of Resistance to Quorum Quenching in Digital Organisms

PubMed Central

Beckmann, Benjamin E.; Knoester, David B.; Connelly, Brian D.; Waters, Christopher M.

2014-01-01

Quorum sensing (QS) is a collective behavior whereby actions of individuals depend on the density of the surrounding population. Bacteria use QS to trigger secretion of digestive enzymes, formation and destruction of biofilms, and, in the case of pathogenic organisms, expression of virulence factors that cause disease. Investigations of mechanisms that prevent or disrupt QS, referred to as quorum quenching, are of interest because they provide a new alternative to antibiotics for treating bacterial infections. Traditional antibiotics either kill bacteria or inhibit their growth, producing selective pressures that promote resistant strains. In contrast, quorum quenching and other so-called anti-infective strategies focus on altering behavior. In this article we evolve QS in populations of digital organisms, a type of self-replicating computer program, and investigate the effects of quorum quenching on these populations. Specifically, we injected the populations with mutant organisms that were impaired in selected ways to disrupt the QS process. The experimental results indicate that the rate at which these mutants are introduced into a population influences both the evolvability of QS and the persistence of an existing QS behavior. Surprisingly, we also observed resistance to quorum quenching. Effectively, populations evolved resistance by reaching quorum at lower cell densities than did the parent strain. Moreover, the level of resistance was highest when the rate of mutant introduction increased over time. These results show that digital organisms can serve as a model to study the evolution and disruption of QS, potentially informing wet-lab studies aimed at identifying targets for anti-infective development. PMID:22662911

Low level exposure to inorganic mercury interferes with B cell receptor signaling in transitional type 1 B cells.

PubMed

Gill, R; McCabe, M J; Rosenspire, A J

2017-09-01

Mercury (Hg) has been implicated as a factor contributing to autoimmune disease in animal models and humans. However the mechanism by which this occurs has remained elusive. Since the discovery of B cells it has been appreciated by immunologists that during the normal course of B cell development, some immature B cells must be generated that produce immunoglobulin reactive to self-antigens (auto-antibodies). However in the course of normal development, the vast majority of immature auto-reactive B cells are prevented from maturing by processes collectively known as tolerance. Autoimmune disease arises when these mechanisms of tolerance are disrupted. In the B cell compartment, it is firmly established that tolerance depends in part upon negative selection of self-reactive immature (transitional type 1) B cells. In these cells negative selection depends upon signals generated by the B Cell Receptor (BCR), in the sense that those T1 B cells who's BCRs most strongly bind to, and so generate the strongest signals to self-antigens are neutralized. In this report we have utilized multicolor phosphoflow cytometry to show that in immature T1 B cells Hg attenuates signal generation by the BCR through mechanisms that may involve Lyn, a key tyrosine kinase in the BCR signal transduction pathway. We suggest that exposure to low, environmentally relevant levels of Hg, disrupts tolerance by interfering with BCR signaling in immature B cells, potentially leading to the appearance of mature auto-reactive B cells which have the ability to contribute to auto-immune disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Lesions of the rat nucleus basalis magnocellularis disrupt appetitive-to-aversive transfer learning.

PubMed

Butt, A E; Schultz, J A; Arnold, L L; Garman, E E; George, C L; Garraghty, P E

2003-01-01

Rats with selective lesions of the nucleus basalis magnocellularis (NBM) and sham-lesion control animals were tested in an operant appetitive-to-aversive transfer task. We hypothesized that NBM lesions would not affect performance in the appetitive phase, but that performance would be impaired during subsequent transfer to the aversive phase of the task. Additional groups of NBM lesion and control rats were tested in the avoidance condition only, where we hypothesized that NBM lesions would not disrupt performance. These hypotheses were based on the argument that the NBM is not necessary for simple association learning that does not tax attention. Both the appetitive phase of the transfer task and the avoidance only task depend only on simple associative learning and are argued not to tax attention. Consequently, performance in these tasks was predicted to be spared following NBM lesions. Complex, attention-demanding associative learning, however, is argued to depend on the NBM. Performance in the aversive phase of the transfer task is both attentionally demanding and associatively more complex than in either the appetitive or aversive tasks alone; thus, avoidance performance in the NBM lesion group was predicted to be impaired following transfer from prior appetitive conditioning. Results supported our hypotheses, with the NBM lesion group acquiring the appetitive response normally, but showing impaired performance following transfer to the aversive conditioning phase of the transfer task. Impairments were not attributable to disrupted avoidance learning per se, as avoidance behavior was normal in the NBM lesion group tested in the avoidance condition only.

The Dependence on Smokeless Tobacco in the South Asian Communities in East London.

PubMed

Khaja, Amjad Hussain; Ali Zwiad, Abdulsalam; Tarakji, Bassel; Gazal, Giath; Albaba, Feras; KalajI, Nader; Petro, Waleed

2015-05-17

The purpose of the study was to understand the dependency on smokeless tobacco. The major aspect of the interview was to study the type of chewing tobacco used, frequency of purchase of chewing tobacco, change in attitude and behavior after the use of chewing tobacco. This study was done in 2005 in London. Of the 110 respondents interviewed 88 were used for the data analysis. An exploratory study was conducted in East London, United Kingdom. The selected sample was interviewed through a questionnaire, based on the Severson Smokeless Tobacco Dependence Scale. Cross tabulations report that in a sample of 88 South Asian UK resident men 46.6% used leaf (paan), 43.2% used processed form of chewing tobacco and 10.2% used gutka. Older age (67%) respondents were more likely than the younger age (30%) respondents to chew tobacco. The frequency of purchase of chewing tobacco is reported high (67.2%) in the older age group than the younger age group (50%). This current study used an amended form of the Severson Smokeless Tobacco Scale questionnaire to study the dependency on smokeless tobacco. The study could be developed in the selection of the sample, which would include both males and females to study the dependency on smokeless tobacco.

Risky Decision Making in Substance Dependent Adolescents with a Disruptive Behavior Disorder

ERIC Educational Resources Information Center

Schutter, Dennis J. L. G.; van Bokhoven, Irene; Vanderschuren, Louk J. M. J.; Lochman, John E.; Matthys, Walter

2011-01-01

Of all psychiatric disorders, the disruptive behavior disorders (DBDs) are the most likely to predispose to substance dependence (SD). One possible underlying mechanism for this increased vulnerability is risky decision making. The aim of this study was to examine decision making in DBD adolescents with and without SD. Twenty-five DBD adolescents…

Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats.

PubMed

Sanna, Fabrizio; Contini, Andrea; Melis, Maria Rosaria; Argiolas, Antonio

2015-10-01

Dopamine influences the anticipatory and consummatory phases of sexual behavior, by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the D2 subtype, although evidence for a role of D4 receptors in erectile function and copulatory behavior is also available. In order to clarify such a role of D4 receptors, the effect of selective D4 receptor agonists and antagonists on copulatory behavior of sexually potent male rats in classic copulation tests with a receptive female, was compared with that of apomorphine and haloperidol, a classic dopamine receptor agonist and antagonist, respectively. PD-168,077 (0.05-0.2mg/kg) and ABT-724 (0.01-0.04mg/kg), two selective D4 receptor agonists, given subcutaneously, improved dose-dependently copulatory behavior as shown by the decrease of mount frequency and post ejaculatory interval induced by PD-168,077, and of mount frequency, ejaculation latency, post ejaculatory and inter intromission intervals induced by ABT-724, and by the increase of ejaculation frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1-5mg/kg), a selective D4 receptor antagonist, given intraperitoneally, impaired dose-dependently copulatory behavior, as shown by the increase in intromission and ejaculation latencies, mount frequency, post ejaculatory interval and the decrease in ejaculation frequency and copulatory efficacy induced by this drug. L-745,870 (5mg/kg) administered before PD-168,077 (0.2mg/kg) or ABT-724 (0.04mg/kg), also abolished completely the facilitatory effects of both PD-168,077 and ABT-724 on sexual behavior. These results confirm the involvement of D4 receptors in specific aspects of male rat copulatory behavior that overlap only partially with those influenced by apomorphine and haloperidol. Copyright © 2015 Elsevier Inc. All rights reserved.

Formant-Frequency Variation and Informational Masking of Speech by Extraneous Formants: Evidence Against Dynamic and Speech-Specific Acoustical Constraints

PubMed Central

2014-01-01

How speech is separated perceptually from other speech remains poorly understood. Recent research indicates that the ability of an extraneous formant to impair intelligibility depends on the variation of its frequency contour. This study explored the effects of manipulating the depth and pattern of that variation. Three formants (F1+F2+F3) constituting synthetic analogues of natural sentences were distributed across the 2 ears, together with a competitor for F2 (F2C) that listeners must reject to optimize recognition (left = F1+F2C; right = F2+F3). The frequency contours of F1 − F3 were each scaled to 50% of their natural depth, with little effect on intelligibility. Competitors were created either by inverting the frequency contour of F2 about its geometric mean (a plausibly speech-like pattern) or using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Adding a competitor typically reduced intelligibility; this reduction depended on the depth of F2C variation, being greatest for 100%-depth, intermediate for 50%-depth, and least for 0%-depth (constant) F2Cs. This suggests that competitor impact depends on overall depth of frequency variation, not depth relative to that for the target formants. The absence of tuning (i.e., no minimum in intelligibility for the 50% case) suggests that the ability to reject an extraneous formant does not depend on similarity in the depth of formant-frequency variation. Furthermore, triangle-wave competitors were as effective as their more speech-like counterparts, suggesting that the selection of formants from the ensemble also does not depend on speech-specific constraints. PMID:24842068

Information theoretic measures of network coordination in high-frequency scalp EEG reveal dynamic patterns associated with seizure termination

PubMed Central

Stamoulis, Catherine; Schomer, Donald L.; Chang, Bernard S.

2013-01-01

How a seizure terminates is still under-studied and, despite its clinical importance, remains an obscure phase of seizure evolution. Recent studies of seizure-related scalp EEGs at frequencies >100 Hz suggest that neural activity, in the form of oscillations and/or neuronal network interactions, may play an important role in preictal/ictal seizure evolution [2, 31]. However, the role of high-frequency activity in seizure termination, is unknown, if it exists at all. Using information theoretic measures of network coordination, this study investigated ictal and immediate postictal neurodynamic interactions encoded in scalp EEGs from a relatively small sample of 8 patients with focal epilepsy and multiple seizures originating in temporal and/or frontal brain regions, at frequencies ≤100 Hz and >100 Hz, respectively. Despite some heterogeneity in the dynamics of these interactions, consistent patterns were also estimated. Specifically, in several seizures, linear or non-linear increase in high-frequency neuronal coordination during ictal intervals, coincided with a corresponding decrease in coordination at frequencies <100 Hz, suggesting a potential interference role of high-frequency activity, to disrupt abnormal ictal synchrony at lower frequencies. These changes in network synchrony started at least 20–30 sec prior to seizure offset, depending on the seizure duration. Opposite patterns were estimated at frequencies ≤100 Hz in several seizures. These results raise the possibility that high-frequency interference may occur in the form of progressive network coordination during the ictal interval, which continues during the postictal interval. This may be one of several possible mechanisms that facilitate seizure termination. In fact, inhibition of pairwise interactions between EEGs by other signals in their spatial neighborhood, quantified by negative interaction information, was estimated at frequencies ≤100 Hz, at least in some seizures. PMID:23608198

Determination of the electromechanical coupling factor of gallium orthophosphate (GaPO4) and its influence on resonance-frequency temperature dependencies.

PubMed

Nosek, Jaroslav; Pustka, Martin

2006-01-01

The quartz homeotype gallium orthophosphate (GaPO4) is a representative of piezoelectric single crystals of large electromechanical coupling factor. It is known that its coupling factor kappa26 associated with the resonators vibrating in the thickness-shear mode is approximately two times greater than that of quartz. This property increases the spacing between the series and parallel resonance frequencies of resonators, as well as the difference between the resonance frequency temperature dependencies of the fundamental and harmonic resonance frequencies of resonators vibrating in the thickness-shear mode. In this paper, the methods for determination of the coupling factor kappa26 are presented, and the computed values are compared with the measured ones. The influence of the coupling factor to the resonance-frequency temperature dependencies of the fundamental and third harmonics of selected rotated Y-cut GaPO4 resonators vibrating in the thickness-shear mode is presented. The purely elastic case for a laterally unbounded plate, which corresponds closely to the limiting case of high harmonic resonance frequency-temperature behavior was assumed for the calculations. The computed temperature coefficients for the Y-cut orientation and calculated turnover point temperatures TTP for different (YX1) orientations are presented.

Simultaneous Planck , Swift , and Fermi observations of X-ray and γ -ray selected blazars

DOE PAGES

Giommi, P.; Polenta, G.; Lähteenmäki, A.; ...

2012-05-22

We present simultaneous Planck, Swift, Fermi, and ground-based data for 105 blazars belonging to three samples with flux limits in the soft X-ray, hard X-ray, and γ-ray bands, with additional 5GHz flux-density limits to ensure a good probability of a Planck detection. We compare our results to those of a companion paper presenting simultaneous Planck and multi-frequency observations of 104 radio-loud northern active galactic nuclei selected at radio frequencies. While we confirm several previous results, our unique data set allows us to demonstrate that the selection method strongly influences the results, producing biases that cannot be ignored. Almost all themore » BL Lac objects have been detected by the Fermi Large AreaTelescope (LAT), whereas 30% to 40% of the flat-spectrum radio quasars (FSRQs) in the radio, soft X-ray, and hard X-ray selected samples are still below the γ-ray detection limit even after integrating 27 months of Fermi-LAT data. The radio to sub-millimetre spectral slope of blazars is quite flat, with >α> ~ 0 up to about 70GHz, above which it steepens to ~ -0.65. The BL Lacs have significantly flatter spectra than FSRQs at higher frequencies. The distribution of the rest-frame synchrotron peak frequency (ν peak S) in the spectral energy distribution (SED) of FSRQs is the same in all the blazar samples with peak S> = 10 13.1 ± 0.1 Hz, while the mean inverse Compton peak frequency, >ν peak IC>, ranges from 1021 to 1022 Hz. The distributions of ν peak S and ν peak IC of BL Lacs are much broader and are shifted to higher energies than those of FSRQs; their shapes strongly depend on the selection method. The Compton dominance of blazars, defined as the ratio of the inverse Compton to synchrotron peak luminosities, ranges from less than 0.2 to nearly 100, with only FSRQs reaching values larger than about 3. Its distribution is broad and depends strongly on the selection method, with γ-ray selected blazars peaking at ~7 or more, and radio-selected blazars at values close to 1, thus implying that the common assumption that the blazar power budget is largely dominated by high-energy emission is a selection effect. A comparison of our multi-frequency data with theoretical predictions shows that simple homogeneous SSC models cannot explain the simultaneous SEDs of most of the γ-ray detected blazars in all samples. The SED of the blazars that were not detected by Fermi-LAT may instead be consistent with SSC emission. Our data challenge the correlation between bolometric luminosity and ν peak S predicted by the blazar sequence.« less

Invited article: Managing disruptive physician behavior: impact on staff relationships and patient care.

PubMed

Rosenstein, Alan H; O'Daniel, Michelle

2008-04-22

Disruptive behavior can have a significant impact on care delivery, which can adversely affect patient safety and quality outcomes of care. Disruptive behavior occurs across all disciplines but is of particular concern when it involves physicians and nurses who have primary responsibility for patient care. There is a higher frequency of disruptive behavior in neurologists compared to most other nonsurgical specialties. Disruptive behavior causes stress, anxiety, frustration, and anger, which can impede communication and collaboration, which can result in avoidable medical errors, adverse events, and other compromises in quality care. Health care organizations need to be aware of the significance of disruptive behaviors and develop appropriate policies, standards, and procedures to effectively deal with this serious issue and reinforce appropriate standards of behavior. Having a better understanding of what contributes to, incites, or provokes disruptive behaviors will help organizations provide appropriate educational and training programs that can lessen the likelihood of occurrence and improve the overall effectiveness of communication among the health care team.

Electrical and Network Neuronal Properties Are Preferentially Disrupted in Dorsal, But Not Ventral, Medial Entorhinal Cortex in a Mouse Model of Tauopathy

PubMed Central

Booth, Clair A.; Ridler, Thomas; Murray, Tracey K.; Ward, Mark A.; de Groot, Emily; Goodfellow, Marc; Phillips, Keith G.; Randall, Andrew D.

2016-01-01

The entorhinal cortex (EC) is one of the first areas to be disrupted in neurodegenerative diseases such as Alzheimer's disease and frontotemporal dementia. The responsiveness of individual neurons to electrical and environmental stimuli varies along the dorsal–ventral axis of the medial EC (mEC) in a manner that suggests this topographical organization plays a key role in neural encoding of geometric space. We examined the cellular properties of layer II mEC stellate neurons (mEC-SCs) in rTg4510 mice, a rodent model of neurodegeneration. Dorsoventral gradients in certain intrinsic membrane properties, such as membrane capacitance and afterhyperpolarizations, were flattened in rTg4510 mEC-SCs, while other cellular gradients [e.g., input resistance (Ri), action potential properties] remained intact. Specifically, the intrinsic properties of rTg4510 mEC-SCs in dorsal aspects of the mEC were preferentially affected, such that action potential firing patterns in dorsal mEC-SCs were altered, while those in ventral mEC-SCs were unaffected. We also found that neuronal oscillations in the gamma frequency band (30–80 Hz) were preferentially disrupted in the dorsal mEC of rTg4510 slices, while those in ventral regions were comparatively preserved. These alterations corresponded to a flattened dorsoventral gradient in theta-gamma cross-frequency coupling of local field potentials recorded from the mEC of freely moving rTg4510 mice. These differences were not paralleled by changes to the dorsoventral gradient in parvalbumin staining or neurodegeneration. We propose that the selective disruption to dorsal mECs, and the resultant flattening of certain dorsoventral gradients, may contribute to disturbances in spatial information processing observed in this model of dementia. SIGNIFICANCE STATEMENT The medial entorhinal cortex (mEC) plays a key role in spatial memory and is one of the first areas to express the pathological features of dementia. Neurons of the mEC are anatomically arranged to express functional dorsoventral gradients in a variety of neuronal properties, including grid cell firing field spacing, which is thought to encode geometric scale. We have investigated the effects of tau pathology on functional dorsoventral gradients in the mEC. Using electrophysiological approaches, we have shown that, in a transgenic mouse model of dementia, the functional properties of the dorsal mEC are preferentially disrupted, resulting in a flattening of some dorsoventral gradients. Our data suggest that neural signals arising in the mEC will have a reduced spatial content in dementia. PMID:26758825

Effects of Developmental Bisphenol A Exposure on Reproductive-Related Behaviors in California Mice (Peromyscus californicus): A Monogamous Animal Model

PubMed Central

Williams, Scott A.; Jasarevic, Eldin; Vandas, Gregory M.; Warzak, Denise A.; Geary, David C.; Ellersieck, Mark R.; Roberts, R. Michael; Rosenfeld, Cheryl S.

2013-01-01

Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist- antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus), where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight) or ethinyl estradiol (EE) (0.1 part per billion) to provide a “pure” estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a consideration in risk assessment studies. PMID:23405200

Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task

PubMed Central

Martig, Adria K; Mizumori, Sheri JY

2010-01-01

Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicates DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N=9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N=167) and CA3 (N=94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations “rescued” performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps specifically by maintaining place field stability selectively in CA1/CA2. PMID:20082295

Transcranial magnetic stimulation changes response selectivity of neurons in the visual cortex

PubMed Central

Kim, Taekjun; Allen, Elena A.; Pasley, Brian N.; Freeman, Ralph D.

2015-01-01

Background Transcranial magnetic stimulation (TMS) is used to selectively alter neuronal activity of specific regions in the cerebral cortex. TMS is reported to induce either transient disruption or enhancement of different neural functions. However, its effects on tuning properties of sensory neurons have not been studied quantitatively. Objective/Hypothesis Here, we use specific TMS application parameters to determine how they may alter tuning characteristics (orientation, spatial frequency, and contrast sensitivity) of single neurons in the cat’s visual cortex. Methods Single unit spikes were recorded with tungsten microelectrodes from the visual cortex of anesthetized and paralyzed cats (12 males). Repetitive TMS (4Hz, 4sec) was delivered with a 70mm figure-8 coil. We quantified basic tuning parameters of individual neurons for each pre- and post-TMS condition. The statistical significance of changes for each tuning parameter between the two conditions was evaluated with a Wilcoxon signed-rank test. Results We generally find long-lasting suppression which persists well beyond the stimulation period. Pre- and post-TMS orientation tuning curves show constant peak values. However, strong suppression at non-preferred orientations tends to narrow the widths of tuning curves. Spatial frequency tuning exhibits an asymmetric change in overall shape, which results in an emphasis on higher frequencies. Contrast tuning curves show nonlinear changes consistent with a gain control mechanism. Conclusions These findings suggest that TMS causes extended interruption of the balance between sub-cortical and intra-cortical inputs. PMID:25862599

Spatial attention does not require preattentive grouping.

PubMed

Vecera, S P; Behrmann, M

1997-01-01

Does spatial attention follow a full preattentive analysis of the visual field, or can attention select from ungrouped regions of the visual field? We addressed this question by testing an apperceptive agnosic patient, J. W., in tasks involving both spatial selection and preattentive grouping. Results suggest that J.W. had intact spatial attention: He was faster to detect targets appearing at cued location relative to targets appearing at uncued locations. However, his preattentive processes were severely disrupted. Gestalt grouping and symmetry perception, both thought to involve preattentive processes, were impaired in J. W. Also, he could not use gestalt grouping cues to guide spatial attention. These results suggest that spatial attention is not completely dependent on preattentive grouping processes. We argue that preattentive grouping processes and spatial attention may mutually constrain one another in guiding the attentional selection of visual stimuli but that these 2 processes are isolated from one another.

Simultaneous Planck, Swift, and Fermi Observations of X-Ray and gamma-Ray Selected Blazars

NASA Technical Reports Server (NTRS)

Giommi, P.; Polenta, G.; Laehteenmaeki, A.; Thompson, D. J.; Capalbi, M.; Cutini, S.; Gasparrini, D.; Gonzalez-Nuevo, J.; Leon-Tavares, J.; Lopez-Caniego, M.;

Speciation: more likely through a genetic or through a learned habitat preference?

PubMed Central

Beltman, J.B; Metz, J.A.J

2005-01-01

A problem in understanding sympatric speciation is establishing how reproductive isolation can arise when there is disruptive selection on an ecological trait. One of the solutions that has been proposed is that a habitat preference evolves, and that mates are chosen within the preferred habitat. We present a model where the habitat preference can evolve either by means of a genetic mechanism or by means of learning. Employing an adaptive-dynamical analysis, we show that evolution proceeds either to a single population of specialists with a genetic preference for their optimal habitat, or to a population of generalists without a habitat preference. The generalist population subsequently experiences disruptive selection. Learning promotes speciation because it increases the intensity of disruptive selection. An individual-based version of the model shows that, when loci are completely unlinked and learning confers little cost, the presence of disruptive selection most probably leads to speciation via the simultaneous evolution of a learned habitat preference. For high costs of learning, speciation is most likely to occur via the evolution of a genetic habitat preference. However, the latter only happens when the effect of mutations is large, or when there is linkage between genes coding for the different traits. PMID:16011920

A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption

PubMed Central

Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Miklavcic, Damijan

2016-01-01

Background Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Material and methods Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Results Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r2 = 0.79; p < 0.008, r2 = 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. Conclusions The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup. PMID:27069447

Importance of double-pole CFS-PML for broad-band seismic wave simulation and optimal parameters selection

NASA Astrophysics Data System (ADS)

Feng, Haike; Zhang, Wei; Zhang, Jie; Chen, Xiaofei

2017-05-01

The perfectly matched layer (PML) is an efficient absorbing technique for numerical wave simulation. The complex frequency-shifted PML (CFS-PML) introduces two additional parameters in the stretching function to make the absorption frequency dependent. This can help to suppress converted evanescent waves from near grazing incident waves, but does not efficiently absorb low-frequency waves below the cut-off frequency. To absorb both the evanescent wave and the low-frequency wave, the double-pole CFS-PML having two poles in the coordinate stretching function was developed in computational electromagnetism. Several studies have investigated the performance of the double-pole CFS-PML for seismic wave simulations in the case of a narrowband seismic wavelet and did not find significant difference comparing to the CFS-PML. Another difficulty to apply the double-pole CFS-PML for real problems is that a practical strategy to set optimal parameter values has not been established. In this work, we study the performance of the double-pole CFS-PML for broad-band seismic wave simulation. We find that when the maximum to minimum frequency ratio is larger than 16, the CFS-PML will either fail to suppress the converted evanescent waves for grazing incident waves, or produce visible low-frequency reflection, depending on the value of α. In contrast, the double-pole CFS-PML can simultaneously suppress the converted evanescent waves and avoid low-frequency reflections with proper parameter values. We analyse the different roles of the double-pole CFS-PML parameters and propose optimal selections of these parameters. Numerical tests show that the double-pole CFS-PML with the optimal parameters can generate satisfactory results for broad-band seismic wave simulations.

A Method for Search Engine Selection using Thesaurus for Selective Meta-Search Engine

NASA Astrophysics Data System (ADS)

Goto, Shoji; Ozono, Tadachika; Shintani, Toramatsu

In this paper, we propose a new method for selecting search engines on WWW for selective meta-search engine. In selective meta-search engine, a method is needed that would enable selecting appropriate search engines for users' queries. Most existing methods use statistical data such as document frequency. These methods may select inappropriate search engines if a query contains polysemous words. In this paper, we describe an search engine selection method based on thesaurus. In our method, a thesaurus is constructed from documents in a search engine and is used as a source description of the search engine. The form of a particular thesaurus depends on the documents used for its construction. Our method enables search engine selection by considering relationship between terms and overcomes the problems caused by polysemous words. Further, our method does not have a centralized broker maintaining data, such as document frequency for all search engines. As a result, it is easy to add a new search engine, and meta-search engines become more scalable with our method compared to other existing methods.

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

PubMed

Qiu, Ying-Wei; Lv, Xiao-Fei; Jiang, Gui-Hua; Su, Huan-Huan; Ma, Xiao-Fen; Tian, Jun-Zhang; Zhuo, Fu-Zhen

2017-03-01

To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

The behavior and social communication of honey bees (Apis mellifera carnica Poll.) under the influence of alcohol.

PubMed

Mixson, T Andrew; Abramson, Charles I; Bozic, Janko

2010-06-01

In this study, the effects of ethanol on honey bee social communication and behavior within the hive were studied to further investigate the usefulness of honey bees as an ethanol-abuse model. Control (1.5 M sucrose) and experimental (1.5 M sucrose, 2.5% w/v ethanol) solutions were directly administered to individual forager bees via proboscis contact with glass capillary tubes. The duration, frequency, and proportion of time spent performing social and nonsocial behaviors were the dependent variables of interest. No differences in the relative frequency or proportion of time spent performing the target behaviors were observed. However, ethanol consumption significantly decreased bouts of walking, resting, and the duration of trophallactic (i.e., food-exchange) encounters. The results of this study suggest that a low dose of ethanol is sufficient to disrupt both social and nonsocial behaviors in honey bees. In view of these results, future behavioral-genetic investigations of honey bee social behavior are encouraged.

Cannabinoid Receptors Mediate Methamphetamine Induction of High Frequency Gamma Oscillations in the Nucleus Accumbens

PubMed Central

Morra, Joshua T.; Glick, Stanley D.; Cheer, Joseph F.

2012-01-01

Patients suffering from amphetamine---induced psychosis display repetitive behaviors, partially alleviated by antipsychotics, which are reminiscent of rodent stereotypies. Due to recent evidence implicating endocannabinoid involvement in brain disorders, including psychosis, we studied the effects of endocannabinoid signaling on neuronal oscillations of rats exhibiting methamphetamine stereotypy. Neuronal network oscillations were recorded with multiple single electrode arrays aimed at the nucleus accumbens of freely moving rats. During the experiments, animals were dosed intravenously with the CB1 receptor antagonist rimonabant (0.3 mg/kg) or vehicle followed by an ascending dose regimen of methamphetamine (0.01, 0.1, 1, and 3 mg/kg; cumulative dosing). The effects of drug administration on stereotypy and local gamma oscillations were evaluated. Methamphetamine treatment significantly increased high frequency gamma oscillations (~ 80 Hz). Entrainment of a subpopulation of nucleus accumbens neurons to high frequency gamma was associated with stereotypy encoding in putative fast-spiking interneurons, but not in putative medium spiny neurons. The observed ability of methamphetamine to induce both stereotypy and high frequency gamma power was potently disrupted following CB1 receptor blockade. The present data suggest that CB1 receptor-dependent mechanisms are recruited by methamphetamine to modify striatal interneuron oscillations that accompany changes in psychomotor state, further supporting the link between endocannabinoids and schizophrenia spectrum disorders. PMID:22609048

Cre/lox-based multiple markerless gene disruption in the genome of the extreme thermophile Thermus thermophilus.

PubMed

Togawa, Yoichiro; Nunoshiba, Tatsuo; Hiratsu, Keiichiro

2018-02-01

Markerless gene-disruption technology is particularly useful for effective genetic analyses of Thermus thermophilus (T. thermophilus), which have a limited number of selectable markers. In an attempt to develop a novel system for the markerless disruption of genes in T. thermophilus, we applied a Cre/lox system to construct a triple gene disruptant. To achieve this, we constructed two genetic tools, a loxP-htk-loxP cassette and cre-expressing plasmid, pSH-Cre, for gene disruption and removal of the selectable marker by Cre-mediated recombination. We found that the Cre/lox system was compatible with the proliferation of the T. thermophilus HB27 strain at the lowest growth temperature (50 °C), and thus succeeded in establishing a triple gene disruptant, the (∆TTC1454::loxP, ∆TTC1535KpnI::loxP, ∆TTC1576::loxP) strain, without leaving behind a selectable marker. During the process of the sequential disruption of multiple genes, we observed the undesired deletion and inversion of the chromosomal region between multiple loxP sites that were induced by Cre-mediated recombination. Therefore, we examined the effects of a lox66-htk-lox71 cassette by exploiting the mutant lox sites, lox66 and lox71, instead of native loxP sites. We successfully constructed a (∆TTC1535::lox72, ∆TTC1537::lox72) double gene disruptant without inducing the undesired deletion of the 0.7-kbp region between the two directly oriented lox72 sites created by the Cre-mediated recombination of the lox66-htk-lox71 cassette. This is the first demonstration of a Cre/lox system being applicable to extreme thermophiles in a genetic manipulation. Our results indicate that this system is a powerful tool for multiple markerless gene disruption in T. thermophilus.

Stabilizing Effect of Sweep on Low-Frequency STBLI Unsteadiness

NASA Astrophysics Data System (ADS)

Adler, Michael; Gaitonde, Datta

2017-11-01

A Large-Eddy Simulation database is generated to examine unsteady shock/turbulent boundary-layer-interaction (STBLI) mechanisms in a Mach 2 swept-compression-corner. Such interactions exhibit open separation, with separation relief from the sweep, and lack the closed mean recirculation found in spanwise-homogeneous STBLIs. We find that the swept interaction lacks the low-frequency coherent shock unsteadiness, two-decades below incoming turbulent boundary layer scales, that is a principal feature of comparable closed separation STBLIs. Rather, the prominent unsteady content is a mid-frequency regime that develops in the separated shear layer and scales weakly with the local separation length. Additionally, a linear perturbation analysis of the unsteady flow indicates that the feedback pathway (associated with an absolute instability in spanwise-homogeneous interactions) is absent in swept-compression-corner interactions. This suggests that 1) the linear oscillator is an essential component of low-frequency unsteadiness in interactions with closed separation. 2) Low-frequency control efforts should be focused on disrupting this oscillator. 3) Introduction of 3D effects constitute one mechanism to disrupt the oscillator.

Cortical drive of low-frequency oscillations in the human nucleus accumbens during action selection

PubMed Central

Litvak, Vladimir; Rutledge, Robb B.; Zaehle, Tino; Schmitt, Friedhelm C.; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J.

2015-01-01

The nucleus accumbens is thought to contribute to action selection by integrating behaviorally relevant information from multiple regions, including prefrontal cortex. Studies in rodents suggest that information flow to the nucleus accumbens may be regulated via task-dependent oscillatory coupling between regions. During instrumental behavior, local field potentials (LFP) in the rat nucleus accumbens and prefrontal cortex are coupled at delta frequencies (Gruber AJ, Hussain RJ, O'Donnell P. PLoS One 4: e5062, 2009), possibly mediating suppression of afferent input from other areas and thereby supporting cortical control (Calhoon GG, O'Donnell P. Neuron 78: 181–190, 2013). In this report, we demonstrate low-frequency cortico-accumbens coupling in humans, both at rest and during a decision-making task. We recorded LFP from the nucleus accumbens in six epilepsy patients who underwent implantation of deep brain stimulation electrodes. All patients showed significant coherence and phase-synchronization between LFP and surface EEG at delta and low theta frequencies. Although the direction of this coupling as indexed by Granger causality varied between subjects in the resting-state data, all patients showed a cortical drive of the nucleus accumbens during action selection in a decision-making task. In three patients this was accompanied by a significant coherence increase over baseline. Our results suggest that low-frequency cortico-accumbens coupling represents a highly conserved regulatory mechanism for action selection. PMID:25878159

Directional Selectivity for FM Sweeps in the Suprageniculate Nucleus of the Mustached Bat Medial Geniculate Body

PubMed Central

O’NEILL, WILLIAM E.; BRIMIJOIN, W. OWEN

2014-01-01

Mustached bats emit echolocation and communication calls containing both constant frequency (CF) and frequency-modulated (FM) components. Previously we found that 86% of neurons in the ventral division of the external nucleus of the inferior colliculus (ICXv) were directionally selective for linear FM sweeps and that selectivity was dependent on sweep rate. The ICXv projects to the suprageniculate nucleus (Sg) of the medial geniculate body. In this study, we isolated 37 single units in the Sg and measured their responses to best excitatory frequency (BEF) tones and linear 12-kHz upward and downward FM sweeps centered on the BEF. Sweeps were presented at durations of 30, 12, and 4 ms, yielding modulation rates of 400, 1,000, and 3,000 kHz/s. Spike count versus level functions were obtained at each modulation rate and compared with BEF controls. Sg units responded well to both tones and FM sweeps. BEFs clustered at 58 kHz, corresponding to the dominant CF component of the sonar signal. Spike count functions for both tones and sweeps were predominantly non-monotonic. FM directional selectivity was significant in 53–78% of the units, depending on modulation rate and level. Units were classified as up-selective (52%), down-selective (24%), or bi-directional (non-selective, 16%); a few units (8%) showed preferences that were either rate- or level-dependent. Most units showed consistent directional preferences at all SPLs and modulation rates tested, but typically showed stronger selectivity at lower sweep rates. Directional preferences were attributable to suppression of activity by sweeps in the non-preferred direction (~80% of units) and/or facilitation by sweeps in the preferred direction (~20–30%). Latencies for BEF tones ranged from 4.9 to 25.7 ms. Latencies for FM sweeps typically varied linearly with sweep duration. Most FM latency-duration functions had slopes ranging from 0.4 to 0.6, suggesting that the responses were triggered by the BEF. Latencies for BEF tones and FM sweeps were significantly correlated in most Sg units, i.e., the response to FM was temporally related to the occurrence of the BEF in the FM sweep. FM latency declined relative to BEF latency as modulation rate increased, suggesting that at higher rates response is triggered by frequencies in the sweep preceding the BEF. We conclude that Sg and ICXv units have similar, though not identical, response properties. Sg units are predominantly upsweep selective and could respond to either or both the CF and FM components in biosonar signals in a number of echolocation scenarios, as well as to a variety of communication sounds. PMID:12091543

β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation

PubMed Central

Mander, Bryce A.; Marks, Shawn M.; Vogel, Jacob W.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Ancoli-Israel, Sonia; Jagust, William J.; Walker, Matthew P.

2015-01-01

Independent evidence associates β-amyloid pathology with both NREM sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here, we show that β-amyloid burden within medial prefrontal cortex (mPFC) is significantly correlated with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation is not direct, but instead, statistically depends on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a novel mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly. PMID:26030850

Does sex-ratio selection influence nest-site choice in a reptile with temperature-dependent sex determination?

PubMed

Mitchell, Timothy S; Maciel, Jessica A; Janzen, Fredric J

2013-12-07

Evolutionary theory predicts that dioecious species should produce a balanced primary sex ratio maintained by frequency-dependent selection. Organisms with environmental sex determination, however, are vulnerable to maladaptive sex ratios, because environmental conditions vary spatio-temporally. For reptiles with temperature-dependent sex determination, nest-site choice is a behavioural maternal effect that could respond to sex-ratio selection, as mothers could adjust offspring sex ratios by choosing nest sites that will have particular thermal properties. This theoretical prediction has generated decades of empirical research, yet convincing evidence that sex-ratio selection is influencing nesting behaviours remains absent. Here, we provide the first experimental evidence from nature that sex-ratio selection, rather than only viability selection, is probably an important component of nest-site choice in a reptile with temperature-dependent sex determination. We compare painted turtle (Chrysemys picta) neonates from maternally selected nest sites with those from randomly selected nest sites, observing no substantive difference in hatching success or survival, but finding a profound difference in offspring sex ratio in the direction expected based on historical records. Additionally, we leverage long-term data to reconstruct our sex ratio results had the experiment been repeated in multiple years. As predicted by theory, our results suggest that sex-ratio selection has shaped nesting behaviour in ways likely to enhance maternal fitness.

Does sex-ratio selection influence nest-site choice in a reptile with temperature-dependent sex determination?

PubMed Central

Mitchell, Timothy S.; Maciel, Jessica A.; Janzen, Fredric J.

2013-01-01

Evolutionary theory predicts that dioecious species should produce a balanced primary sex ratio maintained by frequency-dependent selection. Organisms with environmental sex determination, however, are vulnerable to maladaptive sex ratios, because environmental conditions vary spatio-temporally. For reptiles with temperature-dependent sex determination, nest-site choice is a behavioural maternal effect that could respond to sex-ratio selection, as mothers could adjust offspring sex ratios by choosing nest sites that will have particular thermal properties. This theoretical prediction has generated decades of empirical research, yet convincing evidence that sex-ratio selection is influencing nesting behaviours remains absent. Here, we provide the first experimental evidence from nature that sex-ratio selection, rather than only viability selection, is probably an important component of nest-site choice in a reptile with temperature-dependent sex determination. We compare painted turtle (Chrysemys picta) neonates from maternally selected nest sites with those from randomly selected nest sites, observing no substantive difference in hatching success or survival, but finding a profound difference in offspring sex ratio in the direction expected based on historical records. Additionally, we leverage long-term data to reconstruct our sex ratio results had the experiment been repeated in multiple years. As predicted by theory, our results suggest that sex-ratio selection has shaped nesting behaviour in ways likely to enhance maternal fitness. PMID:24266033

Size dependence of the disruption threshold: laboratory examination of millimeter-centimeter porous targets

NASA Astrophysics Data System (ADS)

Nakamura, Akiko M.; Yamane, Fumiya; Okamoto, Takaya; Takasawa, Susumu

2015-03-01

The outcome of collision between small solid bodies is characterized by the threshold energy density Q*s, the specific energy to shatter, that is defined as the ratio of projectile kinetic energy to the target mass (or the sum of target and projectile) needed to produce the largest intact fragment that contains one half the target mass. It is indicated theoretically and by numerical simulations that the disruption threshold Q*s decreases with target size in strength-dominated regime. The tendency was confirmed by laboratory impact experiments using non-porous rock targets (Housen and Holsapple, 1999; Nagaoka et al., 2014). In this study, we performed low-velocity impact disruption experiments on porous gypsum targets with porosity of 65-69% and of three different sizes to examine the size dependence of the disruption threshold for porous material. The gypsum specimens were shown to have a weaker volume dependence on static tensile strength than do the non-porous rocks. The disruption threshold had also a weaker dependence on size scale as Q*s ∝D-γ , γ ≤ 0.25 - 0.26, while the previous laboratory studies showed γ=0.40 for the non-porous rocks. The measurements at low-velocity lead to a value of about 100 J kg-1 for Q*s which is roughly one order of magnitude lower than the value of Q*s for the gypsum targets of 65% porosity but impacted by projectiles with higher velocities. Such a clear dependence on the impact velocity was also shown by previous studies of gypsum targets with porosity of 50%.

Inborn and experience-dependent models of categorical brain organization. A position paper

PubMed Central

Gainotti, Guido

2015-01-01

The present review aims to summarize the debate in contemporary neuroscience between inborn and experience-dependent models of conceptual representations that goes back to the description of category-specific semantic disorders for biological and artifact categories. Experience-dependent models suggest that categorical disorders are the by-product of the differential weighting of different sources of knowledge in the representation of biological and artifact categories. These models maintain that semantic disorders are not really category-specific, because they do not respect the boundaries between different categories. They also argue that the brain structures which are disrupted in a given type of category-specific semantic disorder should correspond to the areas of convergence of the sensory-motor information which play a major role in the construction of that category. Furthermore, they provide a simple interpretation of gender-related categorical effects and are supported by studies assessing the importance of prior experience in the cortical representation of objects On the other hand, inborn models maintain that category-specific semantic disorders reflect the disruption of innate brain networks, which are shaped by natural selection to allow rapid identification of objects that are very relevant for survival. From the empirical point of view, these models are mainly supported by observations of blind subjects, which suggest that visual experience is not necessary for the emergence of category-specificity in the ventral stream of visual processing. The weight of the data supporting experience-dependent and inborn models is thoroughly discussed, stressing the fact observations made in blind subjects are still the subject of intense debate. It is concluded that at the present state of knowledge it is not possible to choose between experience-dependent and inborn models of conceptual representations. PMID:25667570

Differential Effectiveness of Interdependent and Dependent Group Contingencies in Reducing Disruptive Classroom Behavior

ERIC Educational Resources Information Center

Hartman, Kelsey; Gresham, Frank

2016-01-01

Disruptive behavior in the classroom negatively affects all students' academic engagement, achievement, and behavior. Group contingencies have been proven effective in reducing disruptive behavior as part of behavior interventions in the classroom. The Good Behavior Game is a Tier 1 classwide intervention that utilizes an interdependent group…

Delayed Auditory Feedback and Movement

ERIC Educational Resources Information Center

Pfordresher, Peter Q.; Dalla Bella, Simone

2011-01-01

It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism.

PubMed

Fasching, Clare L; Cejka, Petr; Kowalczykowski, Stephen C; Heyer, Wolf-Dietrich

2015-02-19

The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII

PubMed Central

Li, Lu; Stefan, Melanie I.; Le Novère, Nicolas

2012-01-01

NMDA receptor dependent long-term potentiation (LTP) and long-term depression (LTD) are two prominent forms of synaptic plasticity, both of which are triggered by post-synaptic calcium elevation. To understand how calcium selectively stimulates two opposing processes, we developed a detailed computational model and performed simulations with different calcium input frequencies, amplitudes, and durations. We show that with a total amount of calcium ions kept constant, high frequencies of calcium pulses stimulate calmodulin more efficiently. Calcium input activates both calcineurin and Ca2+/calmodulin-dependent protein kinase II (CaMKII) at all frequencies, but increased frequencies shift the relative activation from calcineurin to CaMKII. Irrespective of amplitude and duration of the inputs, the total amount of calcium ions injected adjusts the sensitivity of the system to calcium input frequencies. At a given frequency, the quantity of CaMKII activated is proportional to the total amount of calcium. Thus, an input of a small amount of calcium at high frequencies can induce the same activation of CaMKII as a larger amount, at lower frequencies. Finally, the extent of activation of CaMKII signals with high calcium frequency is further controlled by other factors, including the availability of calmodulin, and by the potency of phosphatase inhibitors. PMID:22962589

Uptake of clostridium botulinum C3 exoenzyme into intact HT22 and J774A.1 cells.

PubMed

Rohrbeck, Astrid; von Elsner, Leonie; Hagemann, Sandra; Just, Ingo

2015-02-02

The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high concentration of the C3 enzyme. However, recent work indicates that C3 is selectively endocytosed, suggesting a specific endocytotic pathway, which is not yet understood. In this study, we show that the C3 exoenzyme binds to cell surfaces and is internalized in a time-dependent manner. We show that the intermediate filament, vimentin, is involved in C3 uptake, as indicated by the inhibition of C3 internalization by acrylamide, a known vimentin disruption agent. Inhibition of C3 internalization was not observed by chemical inhibitors, like bafilomycin A, methyl-β-cyclodextrin, nocodazole or latrunculin B. Furthermore, the internalization of C3 exoenzyme was markedly inhibited in dynasore-treated HT22 cells. Our results indicate that C3 internalization depends on vimentin and does not depend strictly on both clathrin and caveolae.

Can we disrupt the sensing of honey bees by the bee parasite Varroa destructor?

PubMed

Eliash, Nurit; Singh, Nitin Kumar; Kamer, Yosef; Pinnelli, Govardhana Reddy; Plettner, Erika; Soroker, Victoria

2014-01-01

The ectoparasitic mite, Varroa destructor, is considered to be one of the most significant threats to apiculture around the world. Chemical cues are known to play a significant role in the host-finding behavior of Varroa. The mites distinguish between bees from different task groups, and prefer nurses over foragers. We examined the possibility of disrupting the Varroa--honey bee interaction by targeting the mite's olfactory system. In particular, we examined the effect of volatile compounds, ethers of cis 5-(2'-hydroxyethyl) cyclopent-2-en-1-ol or of dihydroquinone, resorcinol or catechol. We tested the effect of these compounds on the Varroa chemosensory organ by electrophysiology and on behavior in a choice bioassay. The electrophysiological studies were conducted on the isolated foreleg. In the behavioral bioassay, the mite's preference between a nurse and a forager bee was evaluated. We found that in the presence of some compounds, the response of the Varroa chemosensory organ to honey bee headspace volatiles significantly decreased. This effect was dose dependent and, for some of the compounds, long lasting (>1 min). Furthermore, disruption of the Varroa volatile detection was accompanied by a reversal of the mite's preference from a nurse to a forager bee. Long-term inhibition of the electrophysiological responses of mites to the tested compounds was a good predictor for an alteration in the mite's host preference. These data indicate the potential of the selected compounds to disrupt the Varroa--honey bee associations, thus opening new avenues for Varroa control.

A Randomized Trial of the Self-Management Training and Regulation Strategy (STARS): A Selective Intervention for Students with Disruptive Behaviors

ERIC Educational Resources Information Center

Thompson, Aaron M.

2012-01-01

To attain academic goals, school personnel must effectively manage 20% of students who engage in the disruptive behaviors that interrupt instruction, create teacher stress, and contribute to poor student outcomes. Without effective strategies, school personnel often respond to disruptive students with ineffective authoritarian tactics,…

Molecular genetic techniques for gene manipulation in Candida albicans.

PubMed

Xu, Qiu-Rong; Yan, Lan; Lv, Quan-Zhen; Zhou, Mi; Sui, Xue; Cao, Yong-Bing; Jiang, Yuan-Ying

2014-05-15

Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains.

Smoking, Alcohol, Drug Use, Abuse and Dependence in Narcolepsy and Idiopathic Hypersomnia: A Case-Control Study.

PubMed

Barateau, Lucie; Jaussent, Isabelle; Lopez, Régis; Boutrel, Benjamin; Leu-Semenescu, Smaranda; Arnulf, Isabelle; Dauvilliers, Yves

2016-03-01

Basic experiments support the impact of hypocretin on hyperarousal and motivated state required for increasing drug craving. Our aim was to assess the frequencies of smoking, alcohol and drug use, abuse and dependence in narcolepsy type 1 (NT1, hypocretin-deficient), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH) (non-hypocretin-deficient conditions), in comparison to controls. We hypothesized that NT1 patients would be less vulnerable to drug abuse and addiction compared to other hypersomniac patients and controls from general population. We performed a cross-sectional study in French reference centres for rare hypersomnia diseases and included 450 adult patients (median age 35 years; 41.3% men) with NT1 (n = 243), NT2 (n = 116), IH (n = 91), and 710 adult controls. All participants were evaluated for alcohol consumption, smoking habits, and substance (alcohol and illicit drug) abuse and dependence diagnosis during the past year using the Mini International Neuropsychiatric Interview. An increased proportion of both tobacco and heavy tobacco smokers was found in NT1 compared to controls and other hypersomniacs, despite adjustments for potential confounders. We reported an increased regular and frequent alcohol drinking habit in NT1 versus controls but not compared to other hypersomniacs in adjusted models. In contrast, heavy drinkers were significantly reduced in NT1 versus controls but not compared to other hypersomniacs. The proportion of patients with excessive drug use (codeine, cocaine, and cannabis), substance dependence, or abuse was low in all subgroups, without significant differences between either hypersomnia disorder categories or compared with controls. We first described a low frequency of illicit drug use, dependence, or abuse in patients with central hypersomnia, whether Hcrt-deficient or not, and whether drug-free or medicated, in the same range as in controls. Conversely, heavy drinkers were rare in NT1 compared to controls but not to other hypersomniacs, without any change in alcohol dependence or abuse frequency. Although disruption of hypocretin signaling in rodents reduces drug-seeking behaviors, our results do not support that hypocretin deficiency constitutes a protective factor against the development of drug addiction in humans. © 2016 Associated Professional Sleep Societies, LLC.

Polygenic variation maintained by balancing selection: pleiotropy, sex-dependent allelic effects and G x E interactions.

PubMed Central

Turelli, Michael; Barton, N H

2004-01-01

We investigate three alternative selection-based scenarios proposed to maintain polygenic variation: pleiotropic balancing selection, G x E interactions (with spatial or temporal variation in allelic effects), and sex-dependent allelic effects. Each analysis assumes an additive polygenic trait with n diallelic loci under stabilizing selection. We allow loci to have different effects and consider equilibria at which the population mean departs from the stabilizing-selection optimum. Under weak selection, each model produces essentially identical, approximate allele-frequency dynamics. Variation is maintained under pleiotropic balancing selection only at loci for which the strength of balancing selection exceeds the effective strength of stabilizing selection. In addition, for all models, polymorphism requires that the population mean be close enough to the optimum that directional selection does not overwhelm balancing selection. This balance allows many simultaneously stable equilibria, and we explore their properties numerically. Both spatial and temporal G x E can maintain variation at loci for which the coefficient of variation (across environments) of the effect of a substitution exceeds a critical value greater than one. The critical value depends on the correlation between substitution effects at different loci. For large positive correlations (e.g., rho(ij)2>3/4), even extreme fluctuations in allelic effects cannot maintain variation. Surprisingly, this constraint on correlations implies that sex-dependent allelic effects cannot maintain polygenic variation. We present numerical results that support our analytical approximations and discuss our results in connection to relevant data and alternative variance-maintaining mechanisms. PMID:15020487

Consequence and Resilience Modeling for Chemical Supply Chains

NASA Technical Reports Server (NTRS)

Stamber, Kevin L.; Vugrin, Eric D.; Ehlen, Mark A.; Sun, Amy C.; Warren, Drake E.; Welk, Margaret E.

2011-01-01

The U.S. chemical sector produces more than 70,000 chemicals that are essential material inputs to critical infrastructure systems, such as the energy, public health, and food and agriculture sectors. Disruptions to the chemical sector can potentially cascade to other dependent sectors, resulting in serious national consequences. To address this concern, the U.S. Department of Homeland Security (DHS) tasked Sandia National Laboratories to develop a predictive consequence modeling and simulation capability for global chemical supply chains. This paper describes that capability , which includes a dynamic supply chain simulation platform called N_ABLE(tm). The paper also presents results from a case study that simulates the consequences of a Gulf Coast hurricane on selected segments of the U.S. chemical sector. The case study identified consequences that include impacted chemical facilities, cascading impacts to other parts of the chemical sector. and estimates of the lengths of chemical shortages and recovery . Overall. these simulation results can DHS prepare for and respond to actual disruptions.

Transposon-mediated random gene disruption with moderate halophilic bacteria and its application for halophilic bacterial siderophore analysis.

PubMed

Matsui, Toru; Nishino, Tomohiko

2016-12-01

Analytical conditions using chromo azurol S was validated for quantification of siderophore in aqueous samples, followed by the characterization of siderophore derived from newly isolated moderately halophilic bacteria. Conditions with good linearity between the absorbance and the siderophore concentration were obtained at a siderophore concentration less than 20 µM, in the wavelength range between 630 and 660 nm with developing time for at least 2 h. Of the halophilic bacteria isolated from Tunisian soil, Halomonas sp., namely strain 21a was selected as siderophore producing halophiles. The strain produced siderophore significantly in the absence of iron in minimal medium. Siderophore-deficient mutant, namely IIa10, of the strain 21a was obtained from gene disruptant library constructed using transposon complex by electroporation. Genomic sequence analysis of the mutant IIa10 revealed that the transposon-inserted gene was TonB-dependent receptor. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cruentaren A Binds F1F0 ATP Synthase To Modulate the Hsp90 Protein Folding Machinery

PubMed Central

2015-01-01

The molecular chaperone Hsp90 requires the assistance of immunophilins, co-chaperones, and partner proteins for the conformational maturation of client proteins. Hsp90 inhibition represents a promising anticancer strategy due to the dependence of numerous oncogenic signaling pathways upon Hsp90 function. Historically, small molecules have been designed to inhibit ATPase activity at the Hsp90 N-terminus; however, these molecules also induce the pro-survival heat shock response (HSR). Therefore, inhibitors that exhibit alternative mechanisms of action that do not elicit the HSR are actively sought. Small molecules that disrupt Hsp90-co-chaperone interactions can destabilize the Hsp90 complex without induction of the HSR, which leads to inhibition of cell proliferation. In this article, selective inhibition of F1F0 ATP synthase by cruentaren A was shown to disrupt the Hsp90-F1F0 ATP synthase interaction and result in client protein degradation without induction of the HSR. PMID:24450340

Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity.

PubMed

Speer, Colenso M; Sun, Chao; Liets, Lauren C; Stafford, Ben K; Chapman, Barbara; Cheng, Hwai-Jong

2014-11-07

Spontaneous retinal activity (SRA) is important during eye-specific segregation within the dorsal lateral geniculate nucleus (dLGN), but the feature(s) of activity critical for retinogeniculate refinement are controversial. Pharmacologically or genetically manipulating cholinergic signaling during SRA perturbs correlated retinal ganglion cell (RGC) spiking and disrupts eye-specific retinofugal refinement in vivo, consistent with an instructive role for SRA during visual system development. Paradoxically, ablating the starburst amacrine cells (SACs) that generate cholinergic spontaneous activity disrupts correlated RGC firing without impacting retinal activity levels or eye-specific segregation in the dLGN. Such experiments suggest that patterned SRA during retinal waves is not critical for eye-specific refinement and instead, normal activity levels are permissive for retinogeniculate development. Here we revisit the effects of ablating the cholinergic network during eye-specific segregation and show that SAC ablation disrupts, but does not eliminate, retinal waves with no concomitant impact on normal eye-specific segregation in the dLGN. We induced SAC ablation in postnatal ferret pups beginning at birth by intraocular injection of a novel immunotoxin selective for the ferret vesicular acetylcholine transporter (Ferret VAChT-Sap). Through dual-patch whole-cell and multi-electrode array recording we found that SAC ablation altered SRA patterns and led to significantly smaller retinal waves compared with controls. Despite these defects, eye-specific segregation was normal. Further, interocular competition for target territory in the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes. Our data demonstrate normal eye-specific retinogeniculate development despite significant abnormalities in patterned SRA. Comparing our current results with earlier studies suggests that defects in retinal wave size, absolute levels of SRA, correlations between RGC pairs, RGC burst frequency, high frequency RGC firing during bursts, and the number of spikes per RGC burst are each uncorrelated with abnormalities in eye-specific segregation in the dLGN. An increase in the fraction of asynchronous spikes occurring outside of bursts and waves correlates with eye-specific segregation defects in studies reported to date. These findings highlight the relative importance of different features of SRA while providing additional constraints for computational models of Hebbian plasticity mechanisms in the developing visual system.

The genetical theory of social behaviour

PubMed Central

Lehmann, Laurent; Rousset, François

2014-01-01

We survey the population genetic basis of social evolution, using a logically consistent set of arguments to cover a wide range of biological scenarios. We start by reconsidering Hamilton's (Hamilton 1964 J. Theoret. Biol. 7, 1–16 (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under the assumptions of additive gene action, weak selection and constant environment and demography. This yields a prediction for the direction of allele frequency change in terms of phenotypic costs and benefits and genealogical concepts of relatedness, which holds for any frequency of the trait in the population, and provides the foundation for further developments and extensions. We then allow for any type of gene interaction within and between individuals, strong selection and fluctuating environments and demography, which may depend on the evolving trait itself. We reach three conclusions pertaining to selection on social behaviours under broad conditions. (i) Selection can be understood by focusing on a one-generation change in mean allele frequency, a computation which underpins the utility of reproductive value weights; (ii) in large populations under the assumptions of additive gene action and weak selection, this change is of constant sign for any allele frequency and is predicted by a phenotypic selection gradient; (iii) under the assumptions of trait substitution sequences, such phenotypic selection gradients suffice to characterize long-term multi-dimensional stochastic evolution, with almost no knowledge about the genetic details underlying the coevolving traits. Having such simple results about the effect of selection regardless of population structure and type of social interactions can help to delineate the common features of distinct biological processes. Finally, we clarify some persistent divergences within social evolution theory, with respect to exactness, synergies, maximization, dynamic sufficiency and the role of genetic arguments. PMID:24686929

The genetical theory of social behaviour.

PubMed

Lehmann, Laurent; Rousset, François

2014-05-19

We survey the population genetic basis of social evolution, using a logically consistent set of arguments to cover a wide range of biological scenarios. We start by reconsidering Hamilton's (Hamilton 1964 J. Theoret. Biol. 7, 1-16 (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under the assumptions of additive gene action, weak selection and constant environment and demography. This yields a prediction for the direction of allele frequency change in terms of phenotypic costs and benefits and genealogical concepts of relatedness, which holds for any frequency of the trait in the population, and provides the foundation for further developments and extensions. We then allow for any type of gene interaction within and between individuals, strong selection and fluctuating environments and demography, which may depend on the evolving trait itself. We reach three conclusions pertaining to selection on social behaviours under broad conditions. (i) Selection can be understood by focusing on a one-generation change in mean allele frequency, a computation which underpins the utility of reproductive value weights; (ii) in large populations under the assumptions of additive gene action and weak selection, this change is of constant sign for any allele frequency and is predicted by a phenotypic selection gradient; (iii) under the assumptions of trait substitution sequences, such phenotypic selection gradients suffice to characterize long-term multi-dimensional stochastic evolution, with almost no knowledge about the genetic details underlying the coevolving traits. Having such simple results about the effect of selection regardless of population structure and type of social interactions can help to delineate the common features of distinct biological processes. Finally, we clarify some persistent divergences within social evolution theory, with respect to exactness, synergies, maximization, dynamic sufficiency and the role of genetic arguments.

Thyroid hormone suppresses hepatocarcinogenesis via DAPK2 and SQSTM1-dependent selective autophagy.

PubMed

Chi, Hsiang-Cheng; Chen, Shen-Liang; Tsai, Chung-Ying; Chuang, Wen-Yu; Huang, Ya-Hui; Tsai, Ming-Ming; Wu, Sheng-Ming; Sun, Cheng-Pu; Yeh, Chau-Ting; Lin, Kwang-Huei

2016-12-01

Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DEN-induced hepatotoxicity or carcinogenesis.

BEHAVIORAL PHARMACOLOGY OF THE ODOR SPAN TASK: EFFECTS OF FLUNITRAZEPAM, KETAMINE, METHAMPHETAMINE AND METHYLPHENIDATE

PubMed Central

Galizio, Mark; April, Brooke; Deal, Melissa; Hawkey, Andrew; Panoz-Brown, Danielle; Prichard, Ashley; Bruce, Katherine

2018-01-01

The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task. The present experiments explored the behavioral pharmacology of a modified version of the Odor Span Task by determining the effects of stimulant drugs methylphenidate and methamphetamine, NMDA antagonist ketamine, and positive GABAA modulator flunitrazepam. All four drugs produced dose-dependent impairment of performances on the Odor Span Task, but for methylphenidate and methamphetamine, these occurred only at doses that had similar effects on performance of a simple odor discrimination. Generally, these disruptions were based on omission of responding at the effective doses. The effects of ketamine and flunitrazepam were more selective in some rats. That is, some rats tested under flunitrazepam and ketamine showed decreases in accuracy on the Odor Span Task at doses that did not affect simple discrimination performance. These selective effects indicate disruption of within-session stimulus control. Overall, these findings support the potential of the Odor Span Task as a baseline for the behavioral pharmacological analysis of remembering. PMID:27747877

Enhanced Microwave Absorption Properties of Carbon Black/Silicone Rubber Coating by Frequency-Selective Surface

NASA Astrophysics Data System (ADS)

Yang, Zhaoning; Luo, Fa; Gao, Lu; Qing, Yuchang; Zhou, Wancheng; Zhu, Dongmei

2016-10-01

A square frequency-selective surface (FSS) design has been employed to improve the microwave absorption properties of carbon black/silicone rubber (CBSR) composite coating. The FSS is placed on the surface of the CBSR coating. The effects of FSS design parameters on the microwave absorption properties of the CBSR coating have been investigated, including the size and period of the FSS design, and the thickness and permittivity of the coating. Simulation results indicate that the absorption peak for the CBSR coating alone is related to its thickness and electromagnetic parameters, while the combination of the CBSR coating with a FSS can exhibit a new absorption peak in the reflection curve; the frequency of the new absorption peak is determined by the resonance of the square FSS design and tightly depends on the size of the squares, with larger squares in the FSS design leading to a lower frequency of the new absorption peak. The enhancement of the absorption performance depends on achievement of a new absorption peak using a suitable size and period of the FSS design. In addition, the FSS design has a stable frequency response for both transverse electromagnetic (TE) and transverse magnetic (TM) polarizations as the incident angle varies from 0° to 40°. The optimized results indicate that the bandwidth with reflection loss below -5 dB can encompass the whole frequency range from 8 GHz to 18 GHz for thickness of the CBSR coating of only 1.8 mm. The simulation results are confirmed by experiments.

A Novel Biocontainment Strategy Makes Bacterial Growth and Survival Dependent on Phosphite.

PubMed

Hirota, Ryuichi; Abe, Kenji; Katsuura, Zen-Ichiro; Noguchi, Reiji; Moribe, Shigeaki; Motomura, Kei; Ishida, Takenori; Alexandrov, Maxym; Funabashi, Hisakage; Ikeda, Takeshi; Kuroda, Akio

2017-03-20

There is a growing demand to develop biocontainment strategies that prevent unintended proliferation of genetically modified organisms in the open environment. We found that the hypophosphite (H 3 PO 2 , HPt) transporter HtxBCDE from Pseudomonas stutzeri WM88 was also capable of transporting phosphite (H 3 PO 3 , Pt) but not phosphate (H 3 PO 4 , Pi), suggesting the potential for engineering a Pt/HPt-dependent bacterial strain as a biocontainment strategy. We disrupted all Pi and organic Pi transporters in an Escherichia coli strain expressing HtxABCDE and a Pt dehydrogenase, leaving Pt/HPt uptake and oxidation as the only means to obtain Pi. Challenge on non-permissive growth medium revealed that no escape mutants appeared for at least 21 days with a detection limit of 1.94 × 10 -13 per colony forming unit. This represents, to the best of our knowledge, the lowest escape frequency among reported strategies. Since Pt/HPt are ecologically rare and not available in amounts sufficient for the growth of the Pt/HPt-dependent bacteria, this strategy offers a reliable and practical method for biocontainment.

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome.

PubMed

Limpitikul, Worawan B; Dick, Ivy E; Tester, David J; Boczek, Nicole J; Limphong, Pattraranee; Yang, Wanjun; Choi, Myoung Hyun; Babich, Jennifer; DiSilvestre, Deborah; Kanter, Ronald J; Tomaselli, Gordon F; Ackerman, Michael J; Yue, David T

2017-01-06

Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long-QT syndrome (LQTS) with mutations involving CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca 2+ /calmodulin (CaM)-dependent inactivation of L-type Ca 2+ channels. To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS. We generated and characterized the functional properties of induced pluripotent stem cell-derived cardiomyocytes from a patient with D130G-CALM2-mediated LQTS, thus creating a platform with which to devise and test novel therapeutic strategies. The patient-derived induced pluripotent stem cell-derived cardiomyocytes display (1) significantly prolonged action potentials, (2) disrupted Ca 2+ cycling properties, and (3) diminished Ca 2+ /CaM-dependent inactivation of L-type Ca 2+ channels. Next, taking advantage of the fact that calmodulinopathy patients harbor a mutation in only 1 of 6 redundant CaM-encoding alleles, we devised a strategy using CRISPR interference to selectively suppress the mutant gene while sparing the wild-type counterparts. Indeed, suppression of CALM2 expression produced a functional rescue in induced pluripotent stem cell-derived cardiomyocytes with D130G-CALM2, as shown by the normalization of action potential duration and Ca 2+ /CaM-dependent inactivation after treatment. Moreover, CRISPR interference can be designed to achieve selective knockdown of any of the 3 CALM genes, making it a generalizable therapeutic strategy for any calmodulinopathy. Overall, this therapeutic strategy holds great promise for calmodulinopathy patients as it represents a generalizable intervention capable of specifically altering CaM expression and potentially attenuating LQTS-triggered cardiac events, thus initiating a path toward precision medicine. © 2016 American Heart Association, Inc.

Scale-dependent measurements of meteorite strength: Implications for asteroid fragmentation

NASA Astrophysics Data System (ADS)

Cotto-Figueroa, Desireé; Asphaug, Erik; Garvie, Laurence A. J.; Rai, Ashwin; Johnston, Joel; Borkowski, Luke; Datta, Siddhant; Chattopadhyay, Aditi; Morris, Melissa A.

2016-10-01

Measuring the strengths of asteroidal materials is important for developing mitigation strategies for potential Earth impactors and for understanding properties of in situ materials on asteroids during human and robotic exploration. Studies of asteroid disruption and fragmentation have typically used the strengths determined from terrestrial analog materials, although questions have been raised regarding the suitability of these materials. The few published measurements of meteorite strength are typically significantly greater than those estimated from the stratospheric breakup of meter-sized meteoroids. Given the paucity of relevant strength data, the scale-varying strength properties of meteoritic and asteroidal materials are poorly constrained. Based on our uniaxial failure studies of centimeter-sized cubes of a carbonaceous and ordinary chondrite, we develop the first Weibull failure distribution analysis of meteorites. This Weibull distribution projected to meter scales, overlaps the strengths determined from asteroidal airbursts and can be used to predict properties of to the 100 m scale. In addition, our analysis shows that meter-scale boulders on asteroids are significantly weaker than small pieces of meteorites, while large meteorites surviving on Earth are selected by attrition. Further, the common use of terrestrial analog materials to predict scale-dependent strength properties significantly overestimates the strength of meter-sized asteroidal materials and therefore is unlikely well suited for the modeling of asteroid disruption and fragmentation. Given the strength scale-dependence determined for carbonaceous and ordinary chondrite meteorites, our results suggest that boulders of similar composition on asteroids will have compressive strengths significantly less than typical terrestrial rocks.

Controlled permeation of cell membrane by single bubble acoustic cavitation

PubMed Central

Zhou, Y.; Yang, K.; Cui, J.; Ye, J. Y.; Deng, C. X.

2011-01-01

Sonoporation is the membrane disruption generated by ultrasound and has been exploited as a non-viral strategy for drug and gene delivery. Acoustic cavitation of microbubbles has been recognized to play an important role in sonoporation. However, due to the lack of adequate techniques for precise control of cavitation activities and real-time assessment of the resulting sub-micron process of sonoporation, limited knowledge has been available regarding the detail processes and correlation of cavitation with membrane disruption at the single cell level. In the current study, we developed a combined approach including optical, acoustic, and electrophysiological techniques to enable synchronized manipulation, imaging, and measurement of cavitation of single bubbles and the resulting cell membrane disruption in real-time. Using a self-focused femtosecond laser and high frequency (7.44 MHz) pulses, a single microbubble was generated and positioned at a desired distance from the membrane of a Xenopus oocyte. Cavitation of the bubble was achieved by applying a low frequency (1.5 MHz) ultrasound pulse (duration 13.3 or 40 µs) to induce bubble collapse. Disruption of the cell membrane was assessed by the increase in the transmembrane current (TMC) of the cell under voltage clamp. Simultaneous high-speed bright field imaging of cavitation and measurements of the TMC were obtained to correlate the ultrasound-generated bubble activities with the cell membrane poration. The change in membrane permeability was directly associated with the formation of a sub-micrometer pore from a local membrane rupture generated by bubble collapse or bubble compression depending on ultrasound amplitude and duration. The impact of the bubble collapse on membrane permeation decreased rapidly with increasing distance (D) between the bubble (diameter d) and the cell membrane. The effective range of cavitation impact on membrane poration was determined to be D/d = 0.75. The maximum mean radius of the pores was estimated from the measured TMC to be 0.106 ± 0.032 µm (n = 70) for acoustic pressure of 1.5 MPa (duration 13.3 µs), and increased to 0.171 ± 0.030 µm (n = 125) for acoustic pressure of 1.7 MPa and to 0.182 ± 0.052 µm (n=112) for a pulse duration of 40 µs (1.5 MPa). These results from controlled cell membrane permeation by cavitation of single bubbles revealed insights and key factors affecting sonoporation at the single cell level. PMID:21945682

Dorsal CA1 interneurons contribute to acute stress-induced spatial memory deficits.

PubMed

Yu, Jing-Ying; Fang, Ping; Wang, Chi; Wang, Xing-Xing; Li, Kun; Gong, Qian; Luo, Ben-Yan; Wang, Xiao-Dong

2018-06-01

Exposure to severely stressful experiences disrupts the activity of neuronal circuits and impairs declarative memory. GABAergic interneurons coordinate neuronal network activity, but their involvement in stress-evoked memory loss remains to be elucidated. Here, we provide evidence that interneurons in area CA1 of the dorsal hippocampus partially modulate acute stress-induced memory deficits. In adult male mice, both acute forced swim stress and restraint stress impaired hippocampus-dependent spatial memory and increased the density of c-fos-positive interneurons in the dorsal CA1. Selective activation of dorsal CA1 interneurons by chemogenetics disrupted memory performance in the spatial object recognition task. In comparison, anxiety-related behavior, spatial working memory and novel object recognition memory remained intact when dorsal CA1 interneurons were overactivated. Moreover, chemogenetic activation of dorsal CA1 interneurons suppressed the activity of adjacent pyramidal neurons, whereas a single exposure to forced swim stress but not restraint stress increased the activity of CA1 pyramidal neurons. However, chemogenetic inhibition of dorsal CA1 interneurons led to spatial memory impairments and failed to attenuate acute stress-induced memory loss. These findings suggest that acute stress may overactivate interneurons in the dorsal CA1, which reduces the activity of pyramidal neurons and in turn disrupts long-term memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

Use of Phenylboronic Acids to Investigate Boron Function in Plants. Possible Role of Boron in Transvacuolar Cytoplasmic Strands and Cell-to-Wall Adhesion

PubMed Central

Bassil, Elias; Hu, Hening; Brown, Patrick H.

2004-01-01

The only defined physiological role of boron in plants is as a cross-linking molecule involving reversible covalent bonds with cis-diols on either side of borate. Boronic acids, which form the same reversible bonds with cis-diols but cannot cross-link two molecules, were used to selectively disrupt boron function in plants. In cultured tobacco (Nicotiana tabacum cv BY-2) cells, addition of boronic acids caused the disruption of cytoplasmic strands and cell-to-cell wall detachment. The effect of the boronic acids could be relieved by the addition of boron-complexing sugars and was proportional to the boronic acid-binding strength of the sugar. Experiments with germinating petunia (Petunia hybrida) pollen and boronate-affinity chromatography showed that boronic acids and boron compete for the same binding sites. The boronic acids appear to specifically disrupt or prevent borate-dependent cross-links important for the structural integrity of the cell, including the organization of transvacuolar cytoplasmic strands. Boron likely plays a structural role in the plant cytoskeleton. We conclude that boronic acids can be used to rapidly and reversibly induce boron deficiency-like responses and therefore are useful tools for investigating boron function in plants. PMID:15466241

Optimum Adaptive Modulation and Channel Coding Scheme for Frequency Domain Channel-Dependent Scheduling in OFDM Based Evolved UTRA Downlink

NASA Astrophysics Data System (ADS)

Miki, Nobuhiko; Kishiyama, Yoshihisa; Higuchi, Kenichi; Sawahashi, Mamoru; Nakagawa, Masao

In the Evolved UTRA (UMTS Terrestrial Radio Access) downlink, Orthogonal Frequency Division Multiplexing (OFDM) based radio access was adopted because of its inherent immunity to multipath interference and flexible accommodation of different spectrum arrangements. This paper presents the optimum adaptive modulation and channel coding (AMC) scheme when resource blocks (RBs) is simultaneously assigned to the same user when frequency and time domain channel-dependent scheduling is assumed in the downlink OFDMA radio access with single-antenna transmission. We start by presenting selection methods for the modulation and coding scheme (MCS) employing mutual information both for RB-common and RB-dependent modulation schemes. Simulation results show that, irrespective of the application of power adaptation to RB-dependent modulation, the improvement in the achievable throughput of the RB-dependent modulation scheme compared to that for the RB-common modulation scheme is slight, i.e., 4 to 5%. In addition, the number of required control signaling bits in the RB-dependent modulation scheme becomes greater than that for the RB-common modulation scheme. Therefore, we conclude that the RB-common modulation and channel coding rate scheme is preferred, when multiple RBs of the same coded stream are assigned to one user in the case of single-antenna transmission.

Delay/Disruption Tolerant Networks for Human Space Flight Video Project

NASA Technical Reports Server (NTRS)

Fink, Patrick W.; Ngo, Phong; Schlesinger, Adam

2010-01-01

The movie describes collaboration between NASA and Vint Cerf on the development of Disruption Tolerant Networks (DTN) for use in space exploration. Current evaluation efforts at Johnson Space Center are focused on the use of DTNs in space communications. Tests include the ability of rovers to store data for later display, tracking local and remote habitat inventory using radio-frequency identification tags, and merging networks.

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

PubMed

Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

2014-09-02

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Frequency-dependent Lg Q within the continental United States

USGS Publications Warehouse

Erickson, D.; McNamara, D.E.; Benz, H.M.

2004-01-01

Frequency-dependent crustal attenuation (1/Q) is determined for seven distinct physiographic/tectonic regions of the continental United States using high-quality Lg waveforms recorded on broadband stations in the frequency band 0.5 to 16 Hz. Lg attenuation is determined from time-domain amplitude measurements in one-octave frequency bands centered on the frequencies 0.75, 1.0, 3.0, 6.0, and 12.0 Hz. Modeling errors are determined using a delete-j jackknife resampling technique. The frequency-dependent quality factor is modeled in the form of Q = Q0 fη. Regions were initially selected based on tectonic provinces but were eventually limited and adjusted to maximize ray path coverage in each area. Earthquake data was recorded on several different networks and constrained to events occurring within the crust (<40 km depth) and at least mb 3.5 in size. A singular value decomposition inversion technique was applied to the data to simultaneously solve for source and receiver terms along with Q for each region at specific frequencies. The lowest crustal Q was observed in northern and southern California where Q is described by the functions Q = 152(±37)f0.72(±0.16) and Q = 105(±26)f0.67(±0.16), respectively. The Basin and Range Province, Pacific Northwest, and Rocky Mountain states also display lower Q and a strong frequency dependence characterized by the functions Q = 200(±40)f0.68(±0.12), Q = 152(±49)f0.76(±0.18), and Q = 166(±37)f0.61(±0.14), respectively. In contrast, in the central and northeast United States Q functions are Q = 640(±225)f0.344(±0.22) and Q = 650(±143)f0.36(±0.14), respectively, show a high crustal Q and a weaker frequency dependence. These results improve upon previous Lg modeling by subdividing the United States into smaller, distinct tectonic regions and using significantly more data that provide improved constraints on frequency-dependent attenuation and errors. A detailed attenuation map of the continental United States can provide significant input into hazard map mitigation. Both scattering and intrinsic attenuation mechanisms are likely to play a comparable role in the frequency range considered in the study.

Using behavioral economics to predict opioid use during prescription opioid dependence treatment.

PubMed

Worley, Matthew J; Shoptaw, Steven J; Bickel, Warren K; Ling, Walter

2015-03-01

Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, p<.001) and a greater proportion of their income on drugs (OR=1.31, p<.001) were more likely to use opioids during treatment. Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Using behavioral economics to predict opioid use during prescription opioid dependence treatment

PubMed Central

Worley, Matthew J.; Shoptaw, Steven J.; Bickel, Warren K.; Ling, Walter

2015-01-01

Background Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. Methods Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N = 353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. Results Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR = 1.30, p < .001) and a greater proportion of their income on drugs (OR = 1.31, p < .001) were more likely to use opioids during treatment. Conclusions Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population. PMID:25622776

Individual Alpha Peak Frequency Predicts 10 Hz Flicker Effects on Selective Attention.

PubMed

Gulbinaite, Rasa; van Viegen, Tara; Wieling, Martijn; Cohen, Michael X; VanRullen, Rufin

2017-10-18

Rhythmic visual stimulation ("flicker") is primarily used to "tag" processing of low-level visual and high-level cognitive phenomena. However, preliminary evidence suggests that flicker may also entrain endogenous brain oscillations, thereby modulating cognitive processes supported by those brain rhythms. Here we tested the interaction between 10 Hz flicker and endogenous alpha-band (∼10 Hz) oscillations during a selective visuospatial attention task. We recorded EEG from human participants (both genders) while they performed a modified Eriksen flanker task in which distractors and targets flickered within (10 Hz) or outside (7.5 or 15 Hz) the alpha band. By using a combination of EEG source separation, time-frequency, and single-trial linear mixed-effects modeling, we demonstrate that 10 Hz flicker interfered with stimulus processing more on incongruent than congruent trials (high vs low selective attention demands). Crucially, the effect of 10 Hz flicker on task performance was predicted by the distance between 10 Hz and individual alpha peak frequency (estimated during the task). Finally, the flicker effect on task performance was more strongly predicted by EEG flicker responses during stimulus processing than during preparation for the upcoming stimulus, suggesting that 10 Hz flicker interfered more with reactive than proactive selective attention. These findings are consistent with our hypothesis that visual flicker entrained endogenous alpha-band networks, which in turn impaired task performance. Our findings also provide novel evidence for frequency-dependent exogenous modulation of cognition that is determined by the correspondence between the exogenous flicker frequency and the endogenous brain rhythms. SIGNIFICANCE STATEMENT Here we provide novel evidence that the interaction between exogenous rhythmic visual stimulation and endogenous brain rhythms can have frequency-specific behavioral effects. We show that alpha-band (10 Hz) flicker impairs stimulus processing in a selective attention task when the stimulus flicker rate matches individual alpha peak frequency. The effect of sensory flicker on task performance was stronger when selective attention demands were high, and was stronger during stimulus processing and response selection compared with the prestimulus anticipatory period. These findings provide novel evidence that frequency-specific sensory flicker affects online attentional processing, and also demonstrate that the correspondence between exogenous and endogenous rhythms is an overlooked prerequisite when testing for frequency-specific cognitive effects of flicker. Copyright © 2017 the authors 0270-6474/17/3710173-12$15.00/0.

Exogenous attention can be counter-selective: onset cues disrupt sensitivity to color changes.

PubMed

Müller-Plath, Gisela; Klöckner, Nils

2014-03-01

In peripheral spatial cueing paradigms, exogenous attentional capture is commonly observed after salient onset cues or with cues contingent on target characteristics. We proposed that exogenously captured attention disrupts the selectivity to target features. We tested this by experimentally emulating the everyday observation that in a viewing situation in which the observer is monitoring a stationary display fort change to occur, the onset of a salient stimulus (onset cue) or a change in a stationary stimulus similar to the expected one (contingent cue) has a distracting effect. As predicted, we found that both types of cues reduced the target detection sensitivity but enhanced the bias to respond in a go-nogo-paradigm. With the onset cue, the sensitivity loss was more pronounced at the side of the cue, whereas the contingent cue affected both sides likewise. Moreover, the effects of the onset cue interacted with the task difficulty: the more selectivity a task required the more immune it was against disruption, but the more likely was a response. We concluded that onset capture disrupts selective attention by adding noise to the processing of the target location. The effects of contingent capture could be explained with cue-target confounding. Finally, we suggest a new model of attentional capture in which exogenous and endogenous components interact in a dynamic way.

Temporal binding of neural responses for focused attention in biosonar

PubMed Central

Simmons, James A.

2014-01-01

Big brown bats emit biosonar sounds and perceive their surroundings from the delays of echoes received by the ears. Broadcasts are frequency modulated (FM) and contain two prominent harmonics sweeping from 50 to 25 kHz (FM1) and from 100 to 50 kHz (FM2). Individual frequencies in each broadcast and each echo evoke single-spike auditory responses. Echo delay is encoded by the time elapsed between volleys of responses to broadcasts and volleys of responses to echoes. If echoes have the same spectrum as broadcasts, the volley of neural responses to FM1 and FM2 is internally synchronized for each sound, which leads to sharply focused delay images. Because of amplitude–latency trading, disruption of response synchrony within the volleys occurs if the echoes are lowpass filtered, leading to blurred, defocused delay images. This effect is consistent with the temporal binding hypothesis for perceptual image formation. Bats perform inexplicably well in cluttered surroundings where echoes from off-side objects ought to cause masking. Off-side echoes are lowpass filtered because of the shape of the broadcast beam, and they evoke desynchronized auditory responses. The resulting defocused images of clutter do not mask perception of focused images for targets. Neural response synchronization may select a target to be the focus of attention, while desynchronization may impose inattention on the surroundings by defocusing perception of clutter. The formation of focused biosonar images from synchronized neural responses, and the defocusing that occurs with disruption of synchrony, quantitatively demonstrates how temporal binding may control attention and bring a perceptual object into existence. PMID:25122915

Features of anti-inflammatory effects of modulated extremely high-frequency electromagnetic radiation.

PubMed

Gapeyev, Andrew B; Mikhailik, Elena N; Chemeris, Nikolay K

2009-09-01

Using a model of acute zymosan-induced paw edema in NMRI mice, we test the hypothesis that anti-inflammatory effects of extremely high-frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1-0.7 mW/cm(2) and frequencies from the range of 42.2-42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti-inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03-100 Hz did not lead to considerable changes in the effect level. On the contrary, at "ineffective" carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07-0.1 and 20-30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti-inflammatory action of low-intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed.

How can we model selectively neutral density dependence in evolutionary games.

PubMed

Argasinski, Krzysztof; Kozłowski, Jan

2008-03-01

The problem of density dependence appears in all approaches to the modelling of population dynamics. It is pertinent to classic models (i.e., Lotka-Volterra's), and also population genetics and game theoretical models related to the replicator dynamics. There is no density dependence in the classic formulation of replicator dynamics, which means that population size may grow to infinity. Therefore the question arises: How is unlimited population growth suppressed in frequency-dependent models? Two categories of solutions can be found in the literature. In the first, replicator dynamics is independent of background fitness. In the second type of solution, a multiplicative suppression coefficient is used, as in a logistic equation. Both approaches have disadvantages. The first one is incompatible with the methods of life history theory and basic probabilistic intuitions. The logistic type of suppression of per capita growth rate stops trajectories of selection when population size reaches the maximal value (carrying capacity); hence this method does not satisfy selective neutrality. To overcome these difficulties, we must explicitly consider turn-over of individuals dependent on mortality rate. This new approach leads to two interesting predictions. First, the equilibrium value of population size is lower than carrying capacity and depends on the mortality rate. Second, although the phase portrait of selection trajectories is the same as in density-independent replicator dynamics, pace of selection slows down when population size approaches equilibrium, and then remains constant and dependent on the rate of turn-over of individuals.

On the importance of balancing selection in plants

PubMed Central

Delph, Lynda F.; Kelly, John K.

2013-01-01

Summary Balancing selection refers to a variety of selective regimes that maintain advantageous genetic diversity within populations. We review the history of the ideas regarding the types of selection that maintain such polymorphism in flowering plants, notably heterozygote advantage, negative frequency-dependent selection, and spatial heterogeneity. One shared feature of these mechanisms is that whether an allele is beneficial or detrimental is conditional on its frequency in the population. We highlight examples of balancing selection on a variety of discrete traits. These include the well-referenced case of self-incompatibility and recent evidence from species with nuclear-cytoplasmic gynodioecy, both of which exhibit trans-specific polymorphism, a hallmark of balancing selection. We also discuss and give examples of how spatial heterogeneity in particular, which is often thought unlikely to allow protected polymorphism, can maintain genetic variation in plants (which are rooted in place) as a result of microhabitat selection. Lastly, we discuss limitations of the protected polymorphism concept for quantitative traits, where selection can inflate the genetic variance without maintaining specific alleles indefinitely. We conclude that while discrete-morph variation provides the most unambiguous cases of protected polymorphism, they represent only a fraction of the balancing selection at work in plants. PMID:23952298

SYBR safeTM efficiently replaces ethidium bromide in Aspergillus fumigatus gene disruption.

PubMed

Canela, H M S; Takami, L A; Ferreira, M E S

2017-02-08

Invasive aspergillosis is a disease responsible for high mortality rates, caused mainly by Aspergillus fumigatus. The available drugs are limited and this disease continues to occur at an unacceptable frequency. Gene disruption is essential in the search for new drug targets. An efficient protocol for A. fumigatus gene disruption was described but it requires ethidium bromide, a genotoxic agent, for DNA staining. Therefore, the present study tested SYBR safe TM , a non-genotoxic DNA stain, in A. fumigatus gene disruption protocol. The chosen gene was cipC, which has already been disrupted successfully in our laboratory. A deletion cassette was constructed in Saccharomyces cerevisiae and used in A. fumigatus transformation. There was no statistical difference between the tested DNA stains. The success rate of S. cerevisiae transformation was 63.3% for ethidium bromide and 70% for SYBR safe TM . For A. fumigatus gene disruption, the success rate for ethidium bromide was 100 and 97% for SYBR safe TM . In conclusion, SYBR safe TM efficiently replaced ethidium bromide, making this dye a safe and efficient alternative for DNA staining in A. fumigatus gene disruption.

NIMROD Simulations of Low-q Disruptions in the Compact Toroidal Hybrid Device (CTH)

NASA Astrophysics Data System (ADS)

Howell, E. C.; Pandya, M. D.; Hanson, J. D.; Mauer, D. A.; Ennis, D. A.; Hartwell, G. J.

2016-10-01

Nonlinear MHD simulations of low-q disruptions in the CTH are presented. CTH is a current carrying stellarator that is used to study the effects of 3D shaping. The application of 3D shaping stabilizes low-q disruptions in CTH. The amount of 3D shaping is controlled by adjusting the external rotational transform, and it is characterized by the ratio of the external rotational transform to the total transform: f =ιvac / ι . Disruptions are routinely observed during operation with weak shaping (f < 0.05). The frequency of disruptions decreases with increasing amounts of 3D shaping, and the disruptions are completely suppressed for f > 0.1 . Nonlinear simulations are performed using the NIMROD code to better understand how the shaping suppresses the disruptions. Comparisons of runs with weak (f = 0.04) and strong (f = 0.10) shaping are shown. This material is based upon work supported by Auburn University and the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Award Numbers DE-FG02-03ER54692 and DE-FG02-00ER54610.

A reliable facility location design model with site-dependent disruption in the imperfect information context

PubMed Central

Yun, Lifen; Wang, Xifu; Fan, Hongqiang; Li, Xiaopeng

2017-01-01

This paper proposes a reliable facility location design model under imperfect information with site-dependent disruptions; i.e., each facility is subject to a unique disruption probability that varies across the space. In the imperfect information contexts, customers adopt a realistic “trial-and-error” strategy to visit facilities; i.e., they visit a number of pre-assigned facilities sequentially until they arrive at the first operational facility or give up looking for the service. This proposed model aims to balance initial facility investment and expected long-term operational cost by finding the optimal facility locations. A nonlinear integer programming model is proposed to describe this problem. We apply a linearization technique to reduce the difficulty of solving the proposed model. A number of problem instances are studied to illustrate the performance of the proposed model. The results indicate that our proposed model can reveal a number of interesting insights into the facility location design with site-dependent disruptions, including the benefit of backup facilities and system robustness against variation of the loss-of-service penalty. PMID:28486564

Srs2 promotes synthesis-dependent strand annealing by disrupting DNA polymerase δ-extending D-loops

PubMed Central

Liu, Jie; Ede, Christopher; Wright, William D; Gore, Steven K; Jenkins, Shirin S; Freudenthal, Bret D; Todd Washington, M; Veaute, Xavier; Heyer, Wolf-Dietrich

2017-01-01

Synthesis-dependent strand annealing (SDSA) is the preferred mode of homologous recombination in somatic cells leading to an obligatory non-crossover outcome, thus avoiding the potential for chromosomal rearrangements and loss of heterozygosity. Genetic analysis identified the Srs2 helicase as a prime candidate to promote SDSA. Here, we demonstrate that Srs2 disrupts D-loops in an ATP-dependent fashion and with a distinct polarity. Specifically, we partly reconstitute the SDSA pathway using Rad51, Rad54, RPA, RFC, DNA Polymerase δ with different forms of PCNA. Consistent with genetic data showing the requirement for SUMO and PCNA binding for the SDSA role of Srs2, Srs2 displays a slight but significant preference to disrupt extending D-loops over unextended D-loops when SUMOylated PCNA is present, compared to unmodified PCNA or monoubiquitinated PCNA. Our data establish a biochemical mechanism for the role of Srs2 in crossover suppression by promoting SDSA through disruption of extended D-loops. DOI: http://dx.doi.org/10.7554/eLife.22195.001 PMID:28535142

The evolution of sexes: A specific test of the disruptive selection theory.

PubMed

da Silva, Jack

2018-01-01

The disruptive selection theory of the evolution of anisogamy posits that the evolution of a larger body or greater organismal complexity selects for a larger zygote, which in turn selects for larger gametes. This may provide the opportunity for one mating type to produce more numerous, small gametes, forcing the other mating type to produce fewer, large gametes. Predictions common to this and related theories have been partially upheld. Here, a prediction specific to the disruptive selection theory is derived from a previously published game-theoretic model that represents the most complete description of the theory. The prediction, that the ratio of macrogamete to microgamete size should be above three for anisogamous species, is supported for the volvocine algae. A fully population genetic implementation of the model, involving mutation, genetic drift, and selection, is used to verify the game-theoretic approach and accurately simulates the evolution of gamete sizes in anisogamous species. This model was extended to include a locus for gamete motility and shows that oogamy should evolve whenever there is costly motility. The classic twofold cost of sex may be derived from the fitness functions of these models, showing that this cost is ultimately due to genetic conflict.

Pancreatic trauma.

PubMed

Lahiri, R; Bhattacharya, S

2013-05-01

Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases, experienced HPB surgeons should be involved. Complications following pancreatic trauma are common and the majority can be managed without further surgery.

Empirical Distributions of F ST from Large-Scale Human Polymorphism Data

PubMed Central

Elhaik, Eran

2012-01-01

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright’s F ST that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-F ST may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically F ST analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global F ST distribution closely follows an exponential distribution. Third, although the overall F ST distribution is similarly shaped (inverse J), F ST distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-F ST of these groups is linear in allele frequency. These results suggest that investigating the extremes of the F ST distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection. PMID:23185452

Empirical distributions of F(ST) from large-scale human polymorphism data.

PubMed

Elhaik, Eran

2012-01-01

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright's F(ST) that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-F(ST) may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically F(ST) analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global F(ST) distribution closely follows an exponential distribution. Third, although the overall F(ST) distribution is similarly shaped (inverse J), F(ST) distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-F(ST) of these groups is linear in allele frequency. These results suggest that investigating the extremes of the F(ST) distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection.

An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields

PubMed Central

Tuszynski, Jack A.; Wenger, Cornelia; Friesen, Douglas E.; Preto, Jordane

2016-01-01

Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields’ disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels. PMID:27845746

Selective THz control of magnetic order: new opportunities from superradiant undulator sources

NASA Astrophysics Data System (ADS)

Kovalev, S.; Wang, Zhe; Deinert, J.-C.; Awari, N.; Chen, M.; Green, B.; Germanskiy, S.; de Oliveira, T. V. A. G.; Lee, J. S.; Deac, A.; Turchinovich, D.; Stojanovic, N.; Eisebitt, S.; Radu, I.; Bonetti, S.; Kampfrath, T.; Gensch, M.

2018-03-01

Recent advancements of accelerator technology enable the generation of carrier-envelope-phase stable THz pulses with high fields at adjustable high repetition rates. The appropriate choice of THz radiator allows generation of narrow-band, spectrally dense, multicycle THz transients of tunable THz frequency which are ideally suited to selectively excite low-energy excitations such as magnons or phonons. They also allow one to study the frequency dependence of nonresonant THz-field interactions with various order parameters with high dynamic range. In this paper, we discuss the future prospects of this new type of THz light source for studying the coherent control of magnetic order based on recent results.

Indolyl Azaspiroketal Mannich Bases Are Potent Antimycobacterial Agents with Selective Membrane Permeabilizing Effects and in Vivo Activity.

PubMed

Nyantakyi, Samuel Agyei; Li, Ming; Gopal, Pooja; Zimmerman, Matthew; Dartois, Véronique; Gengenbacher, Martin; Dick, Thomas; Go, Mei-Lin

2018-06-25

The inclusion of an azaspiroketal Mannich base in the membrane targeting antitubercular 6-methoxy-1- n-octyl-1 H-indole scaffold resulted in analogs with improved selectivity and submicromolar activity against Mycobacterium tuberculosis H37Rv. The potency enhancing properties of the spiro-fused ring motif was affirmed by SAR and validated in a mouse model of tuberculosis. As expected for membrane inserting agents, the indolyl azaspiroketal Mannich bases perturbed phospholipid vesicles, permeabilized bacterial cells, and induced the mycobacterial cell envelope stress reporter promoter p iniBAC. Surprisingly, their membrane disruptive effects did not appear to be associated with bacterial membrane depolarization. This profile was not uniquely associated with azaspiroketal Mannich bases but was characteristic of indolyl Mannich bases as a class. Whereas resistant mycobacteria could not be isolated for a less potent indolyl Mannich base, the more potent azaspiroketal analog displayed low spontaneous resistance mutation frequency of 10 -8 /CFU. This may indicate involvement of an additional envelope-related target in its mechanism of action.

Plant-parasite coevolution: bridging the gap between genetics and ecology.

PubMed

Brown, James K M; Tellier, Aurélien

2011-01-01

We review current ideas about coevolution of plants and parasites, particularly processes that generate genetic diversity. Frequencies of host resistance and parasite virulence alleles that interact in gene-for-gene (GFG) relationships coevolve in the familiar boom-and-bust cycle, in which resistance is selected when virulence is rare, and virulence is selected when resistance is common. The cycle can result in stable polymorphism when diverse ecological and epidemiological factors cause negative direct frequency-dependent selection (ndFDS) on host resistance, parasite virulence, or both, such that the benefit of a trait to fitness declines as its frequency increases. Polymorphism can also be stabilized by overdominance, when heterozygous hosts have greater resistance than homozygotes to diverse pathogens. Genetic diversity can also persist in the form of statistical polymorphism, sustained by random processes acting on gene frequencies and population size. Stable polymorphism allows alleles to be long-lived and genetic variation to be detectable in natural populations. In agriculture, many of the factors promoting stability in host-parasite interactions have been lost, leading to arms races of host defenses and parasite effectors. Copyright © 2011 by Annual Reviews. All rights reserved.

Humans have already increased the risk of major disruptions to Pacific rainfall

NASA Astrophysics Data System (ADS)

Power, Scott B.; Delage, François P. D.; Chung, Christine T. Y.; Ye, Hua; Murphy, Bradley F.

2017-02-01

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to ~ 1 year have major impacts on severe weather, agricultural production, ecosystems, and disease within the Pacific, and in many countries beyond. The frequency with which major disruptions to Pacific rainfall occur has been projected to increase over the 21st century, in response to global warming caused by large 21st century greenhouse gas emissions. Here we use the latest generation of climate models to show that humans may have contributed to the major disruption that occurred in the real world during the late 20th century. We demonstrate that although marked and sustained reductions in 21st century anthropogenic greenhouse gas emissions can greatly moderate the likelihood of major disruption, elevated risk of occurrence appears locked in now, and for at least the remainder of the 21st century.

Humans have already increased the risk of major disruptions to Pacific rainfall

PubMed Central

Power, Scott B.; Delage, François P. D.; Chung, Christine T. Y.; Ye, Hua; Murphy, Bradley F.

2017-01-01

Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to ∼ 1 year have major impacts on severe weather, agricultural production, ecosystems, and disease within the Pacific, and in many countries beyond. The frequency with which major disruptions to Pacific rainfall occur has been projected to increase over the 21st century, in response to global warming caused by large 21st century greenhouse gas emissions. Here we use the latest generation of climate models to show that humans may have contributed to the major disruption that occurred in the real world during the late 20th century. We demonstrate that although marked and sustained reductions in 21st century anthropogenic greenhouse gas emissions can greatly moderate the likelihood of major disruption, elevated risk of occurrence appears locked in now, and for at least the remainder of the 21st century. PMID:28176783

Disruption of chaperone-mediated autophagy-dependent degradation of MEF2A by oxidative stress-induced lysosome destabilization

PubMed Central

Zhang, Li; Sun, Yang; Fei, Mingjian; Tan, Cheng; Wu, Jing; Zheng, Jie; Tang, Jiqing; Sun, Wei; Lv, Zhaoliang; Bao, Jiandong; Xu, Qiang; Yu, Huixin

2014-01-01

Oxidative stress has been implicated in both normal aging and various neurodegenerative disorders and it may be a major cause of neuronal death. Chaperone-mediated autophagy (CMA) targets selective cytoplasmic proteins for degradation by lysosomes and protects neurons against various extracellular stimuli including oxidative stress. MEF2A (myocyte enhancer factor 2A), a key transcription factor, protects primary neurons from oxidative stress-induced cell damage. However, the precise mechanisms of how the protein stability and the transcriptional activity of MEF2A are regulated under oxidative stress remain unknown. In this study, we report that MEF2A is physiologically degraded through the CMA pathway. In pathological conditions, mild oxidative stress (200 μM H2O2) enhances the degradation of MEF2A as well as its activity, whereas excessive oxidative stress (> 400 μM H2O2) disrupts its degradation process and leads to the accumulation of nonfunctional MEF2A. Under excessive oxidative stress, an N-terminal HDAC4 (histone deacetylase 4) cleavage product (HDAC4-NT), is significantly induced by lysosomal serine proteases released from ruptured lysosomes in a PRKACA (protein kinase, cAMP-dependent, catalytic, α)-independent manner. The production of HDAC4-NT, as a MEF2 repressor, may account for the reduced DNA-binding and transcriptional activity of MEF2A. Our work provides reliable evidence for the first time that MEF2A is targeted to lysosomes for CMA degradation; oxidative stress-induced lysosome destabilization leads to the disruption of MEF2A degradation as well as the dysregulation of its function. These findings may shed light on the underlying mechanisms of pathogenic processes of neuronal damage in various neurodegenerative-related diseases. PMID:24879151

Embryonic GABA(B) receptor blockade alters cell migration, adult hypothalamic structure, and anxiety- and depression-like behaviors sex specifically in mice.

PubMed

Stratton, Matthew S; Staros, Michelle; Budefeld, Tomaz; Searcy, Brian T; Nash, Connor; Eitel, Chad; Carbone, David; Handa, Robert J; Majdic, Gregor; Tobet, Stuart A

2014-01-01

Neurons of the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic- pituitary-adrenal (HPA) axis and the autonomic nervous system. Females lacking functional GABA(B) receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABA(B) receptor to a 7-day critical period (E11-E17) during embryonic development. Experiments tested the role of GABA(B) receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABA(B) receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABA(B) receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABA(B) receptor antagonist. Embryonic exposure to GABA(B) receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABA(B) receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity.

Apex-angle-dependent resonances in triangular split-ring resonators

NASA Astrophysics Data System (ADS)

Burnett, Max A.; Fiddy, Michael A.

2016-02-01

Along with other frequency selective structures (Pendry et al. in IEEE Trans Microw Theory Tech 47(11):2075-2084, 1999) (circles and squares), triangular split-ring resonators (TSRRs) only allow frequencies near the center resonant frequency to propagate. Further, TSRRs are attractive due to their small surface area (Vidhyalakshmi et al. in Stopband characteristics of complementary triangular split ring resonator loaded microstrip line, 2011), comparatively, and large quality factors ( Q) as previously investigated by Gay-Balmaz et al. (J Appl Phys 92(5):2929-2936, 2002). In this work, we examine the effects of varying the apex angle on the resonant frequency, the Q factor, and the phase shift imparted by the TSRR element within the GHz frequency regime.

Simultaneous Planck, Swift, and Fermi Observations of X-ray and Gamma-ray Selected Blazars

NASA Technical Reports Server (NTRS)

Giommi, P.; Polenta, G.; Laehteenmaeki, A.; Thompson, D. J.; Capalbi, M.; Cutini, S.; Gasparrini, D.; Gonzalez, Nuevo, J.; Leon-Tavares, J.; Lopez-Caniego, M.;

Building of an Experimental Cline With Arabidopsis thaliana to Estimate Herbicide Fitness Cost

PubMed Central

Roux, Fabrice; Giancola, Sandra; Durand, Stéphanie; Reboud, Xavier

2006-01-01

Various management strategies aim at maintaining pesticide resistance frequency under a threshold value by taking advantage of the benefit of the fitness penalty (the cost) expressed by the resistance allele outside the treated area or during the pesticide selection “off years.” One method to estimate a fitness cost is to analyze the resistance allele frequency along transects across treated and untreated areas. On the basis of the shape of the cline, this method gives the relative contributions of both gene flow and the fitness difference between genotypes in the treated and untreated areas. Taking advantage of the properties of such migration–selection balance, an artificial cline was built up to optimize the conditions where the fitness cost of two herbicide-resistant mutants (acetolactate synthase and auxin-induced target genes) in the model species Arabidopsis thaliana could be more accurately measured. The analysis of the microevolutionary dynamics in these experimental populations indicated mean fitness costs of ∼15 and 92% for the csr1-1 and axr2-1 resistances, respectively. In addition, negative frequency dependence for the fitness cost was also detected for the axr2-1 resistance. The advantages and disadvantages of the cline approach are discussed in regard to other methods of cost estimation. This comparison highlights the powerful ability of an experimental cline to measure low fitness costs and detect sensibility to frequency-dependent variations. PMID:16582450

Sound source localization on an axial fan at different operating points

NASA Astrophysics Data System (ADS)

Zenger, Florian J.; Herold, Gert; Becker, Stefan; Sarradj, Ennes

2016-08-01

A generic fan with unskewed fan blades is investigated using a microphone array method. The relative motion of the fan with respect to the stationary microphone array is compensated by interpolating the microphone data to a virtual rotating array with the same rotational speed as the fan. Hence, beamforming algorithms with deconvolution, in this case CLEAN-SC, could be applied. Sound maps and integrated spectra of sub-components are evaluated for five operating points. At selected frequency bands, the presented method yields sound maps featuring a clear circular source pattern corresponding to the nine fan blades. Depending on the adjusted operating point, sound sources are located on the leading or trailing edges of the fan blades. Integrated spectra show that in most cases leading edge noise is dominant for the low-frequency part and trailing edge noise for the high-frequency part. The shift from leading to trailing edge noise is strongly dependent on the operating point and frequency range considered.

Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

PubMed

Okada, Takeshi; Kawakita, Fumihiro; Nishikawa, Hirofumi; Nakano, Fumi; Liu, Lei; Suzuki, Hidenori

2018-05-31

There are no direct evidences showing the linkage between Toll-like receptor 4 (TLR4) and blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). The purpose of this study was to examine if selective blockage of TLR4 prevents BBB disruption after SAH in mice and if the TLR4 signaling involves mitogen-activated protein kinases (MAPKs). One hundred and fifty-one C57BL/6 male mice underwent sham or endovascular perforation SAH operation, randomly followed by an intracerebroventricular infusion of vehicle or two dosages (117 or 585 ng) of a selective TLR4 antagonist IAXO-102 at 30 min post-operation. The effects were evaluated by survival rates, neurological scores, and brain water content at 24-72 h and immunoglobulin G immunostaining and Western blotting at 24 h post-SAH. IAXO-102 significantly prevented post-SAH neurological impairments, brain edema, and BBB disruption, resulting in improved survival rates. IAXO-102 also significantly suppressed post-SAH activation of a major isoform of MAPK p46 c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-9 as well as periostin induction and preserved tight junction protein zona occludens-1. Another selective TLR4 antagonist TAK-242, which has a different binding site from IAXO-102, also showed similar effects to IAXO-102. This study first provided the evidence that TLR4 signaling is involved in post-SAH acute BBB disruption and that the signaling is mediated at least partly by JNK activation. TLR4-targeted therapy may be promising to reduce post-SAH morbidities and mortalities.

Sleep Homeostatic and Waking Behavioral Phenotypes in Egr3-Deficient Mice Associated with Serotonin Receptor 5-HT2 Deficits.

PubMed

Grønli, Janne; Clegern, William C; Schmidt, Michelle A; Nemri, Rahmi S; Rempe, Michael J; Gallitano, Amelia L; Wisor, Jonathan P

2016-12-01

The expression of the immediate early gene early growth response 3 ( Egr3 ) is a functional marker of brain activity including responses to novelty, sustained wakefulness, and sleep. We examined the role of this gene in regulating wakefulness and sleep. Electroencephalogram/electromyogram (EEG/EMG) were recorded in Egr3 -/- and wild-type (WT) mice during 24 h baseline, 6 h sleep disruption and 6 h recovery. Serotonergic signaling was assessed with 6 h EEG/EMG recordings after injections of nonselective 5-HT2 antagonist (clozapine), selective 5-HT2 antagonists (5-HT2A; MDL100907 and 5-HT2BC; SB206553) and a cocktail of both selective antagonists, administered in a randomized order to each animal. Egr3 -/- mice did not exhibit abnormalities in the timing of wakefulness and slow wave sleep (SWS); however, EEG dynamics in SWS (suppressed 1-3 Hz power) and in quiet wakefulness (elevated 3-8 Hz and 15-35 Hz power) differed in comparison to WT-mice. Egr3 -/- mice showed an exaggerated response to sleep disruption as measured by active wakefulness, but with a blunted increase in homeostatic sleep drive (elevated 1-4 Hz power) relative to WT-mice. Egr3 -/-mice exhibit greatly reduced sedative effects of clozapine at the electroencephalographic level. In addition, clozapine induced a previously undescribed dissociated state (low amplitude, low frequency EEG and a stable, low muscle tone) lasting up to 2 h in WT-mice. Egr3 -/- mice did not exhibit this phenomenon. Selective 5-HT2A antagonist, alone or in combination with selective 5-HT2BC antagonist, caused EEG slowing coincident with behavioral quiescence in WT-mice but not in Egr3 -/- mice. Egr3 has an essential role in regulating cortical arousal, wakefulness, and sleep, presumably by its regulation of 5-HT2 receptors. © 2016 Associated Professional Sleep Societies, LLC.

Cortical drive of low-frequency oscillations in the human nucleus accumbens during action selection.

PubMed

Stenner, Max-Philipp; Litvak, Vladimir; Rutledge, Robb B; Zaehle, Tino; Schmitt, Friedhelm C; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J

2015-07-01

The nucleus accumbens is thought to contribute to action selection by integrating behaviorally relevant information from multiple regions, including prefrontal cortex. Studies in rodents suggest that information flow to the nucleus accumbens may be regulated via task-dependent oscillatory coupling between regions. During instrumental behavior, local field potentials (LFP) in the rat nucleus accumbens and prefrontal cortex are coupled at delta frequencies (Gruber AJ, Hussain RJ, O'Donnell P. PLoS One 4: e5062, 2009), possibly mediating suppression of afferent input from other areas and thereby supporting cortical control (Calhoon GG, O'Donnell P. Neuron 78: 181-190, 2013). In this report, we demonstrate low-frequency cortico-accumbens coupling in humans, both at rest and during a decision-making task. We recorded LFP from the nucleus accumbens in six epilepsy patients who underwent implantation of deep brain stimulation electrodes. All patients showed significant coherence and phase-synchronization between LFP and surface EEG at delta and low theta frequencies. Although the direction of this coupling as indexed by Granger causality varied between subjects in the resting-state data, all patients showed a cortical drive of the nucleus accumbens during action selection in a decision-making task. In three patients this was accompanied by a significant coherence increase over baseline. Our results suggest that low-frequency cortico-accumbens coupling represents a highly conserved regulatory mechanism for action selection. Copyright © 2015 the American Physiological Society.

Selective Tuning of Gilbert Damping in Spin-Valve Trilayer by Insertion of Rare-Earth Nanolayers.

PubMed

Zhang, Wen; Zhang, Dong; Wong, Ping Kwan Johnny; Yuan, Honglei; Jiang, Sheng; van der Laan, Gerrit; Zhai, Ya; Lu, Zuhong

2015-08-12

Selective tuning of the Gilbert damping constant, α, in a NiFe/Cu/FeCo spin-valve trilayer has been achieved by inserting different rare-earth nanolayers adjacent to the ferromagnetic layers. Frequency dependent analysis of the ferromagnetic resonances shows that the initially small magnitude of α in the NiFe and FeCo layers is improved by Tb and Gd insertions to various amounts. Using the element-specific technique of X-ray magnetic circular dichroism, we find that the observed increase in α can be attributed primarily to the orbital moment enhancement of Ni and Co, rather than that of Fe. The amplitude of the enhancement depends on the specific rare-earth element, as well as on the lattice and electronic band structure of the transition metals. Our results demonstrate an effective way for individual control of the magnetization dynamics in the different layers of the spin-valve sandwich structures, which will be important for practical applications in high-frequency spintronic devices.

Selective wave-transmitting electromagnetic absorber through composite metasurface

NASA Astrophysics Data System (ADS)

Sun, Zhiwei; Zhao, Junming; Zhu, Bo; Jiang, Tian; Feng, Yijun

2017-11-01

Selective wave-transmitting absorbers which have one or more narrow transmission bands inside a wide absorption band are often demanded in wireless communication and radome applications for reducing the coupling between different systems, improving anti-jamming capability, and reducing antennas' radar cross section. Here we propose a feasible method that utilizing composite of two metasurfaces with different polarization dependent characteristics, one works as electromagnetic polarization rotator and the other as a wideband polarization dependent electromagnetic wave absorber. The polarization rotator produces a cross polarization output in the wave-transmitting band, while preserves the polarization of the incidence outside the band. The metasurface absorber works for certain linear polarization with a much wider absorption band covering the wave-transmitting frequency. When combining these two metasurfaces properly, the whole structure behaves as a wideband absorber with a certain frequency transmission window. The proposal may be applied in radome designs to reduce the radar cross section of antenna or improving the electromagnetic compatibility in communication devices.

Morphological and population genomic evidence that human faces have evolved to signal individual identity.

PubMed

Sheehan, Michael J; Nachman, Michael W

2014-09-16

Facial recognition plays a key role in human interactions, and there has been great interest in understanding the evolution of human abilities for individual recognition and tracking social relationships. Individual recognition requires sufficient cognitive abilities and phenotypic diversity within a population for discrimination to be possible. Despite the importance of facial recognition in humans, the evolution of facial identity has received little attention. Here we demonstrate that faces evolved to signal individual identity under negative frequency-dependent selection. Faces show elevated phenotypic variation and lower between-trait correlations compared with other traits. Regions surrounding face-associated single nucleotide polymorphisms show elevated diversity consistent with frequency-dependent selection. Genetic variation maintained by identity signalling tends to be shared across populations and, for some loci, predates the origin of Homo sapiens. Studies of human social evolution tend to emphasize cognitive adaptations, but we show that social evolution has shaped patterns of human phenotypic and genetic diversity as well.

Noise Pollution Filters Bird Communities Based on Vocal Frequency

PubMed Central

Francis, Clinton D.; Ortega, Catherine P.; Cruz, Alexander

2011-01-01

Background Human-generated noise pollution now permeates natural habitats worldwide, presenting evolutionarily novel acoustic conditions unprecedented to most landscapes. These acoustics not only harm humans, but threaten wildlife, and especially birds, via changes to species densities, foraging behavior, reproductive success, and predator-prey interactions. Explanations for negative effects of noise on birds include disruption of acoustic communication through energetic masking, potentially forcing species that rely upon acoustic communication to abandon otherwise suitable areas. However, this hypothesis has not been adequately tested because confounding stimuli often co-vary with noise and are difficult to separate from noise exposure. Methodology/Principal Findings Using a natural experiment that controls for confounding stimuli, we evaluate whether species vocal features or urban-tolerance classifications explain their responses to noise measured through habitat use. Two data sets representing nesting and abundance responses reveal that noise filters bird communities nonrandomly. Signal duration and urban tolerance failed to explain species-specific responses, but birds with low-frequency signals that are more susceptible to masking from noise avoided noisy areas and birds with higher frequency vocalizations remained. Signal frequency was also negatively correlated with body mass, suggesting that larger birds may be more sensitive to noise due to the link between body size and vocal frequency. Conclusions/Significance Our findings suggest that acoustic masking by noise may be a strong selective force shaping the ecology of birds worldwide. Larger birds with lower frequency signals may be excluded from noisy areas, whereas smaller species persist via transmission of higher frequency signals. We discuss our findings as they relate to interspecific relationships among body size, vocal amplitude and frequency and suggest that they are immediately relevant to the global problem of increases in noise by providing critical insight as to which species traits influence tolerance of these novel acoustics. PMID:22096517

Level of Automation and Failure Frequency Effects on Simulated Lunar Lander Performance

NASA Technical Reports Server (NTRS)

Marquez, Jessica J.; Ramirez, Margarita

2014-01-01

A human-in-the-loop experiment was conducted at the NASA Ames Research Center Vertical Motion Simulator, where instrument-rated pilots completed a simulated terminal descent phase of a lunar landing. Ten pilots participated in a 2 x 2 mixed design experiment, with level of automation as the within-subjects factor and failure frequency as the between subjects factor. The two evaluated levels of automation were high (fully automated landing) and low (manual controlled landing). During test trials, participants were exposed to either a high number of failures (75% failure frequency) or low number of failures (25% failure frequency). In order to investigate the pilots' sensitivity to changes in levels of automation and failure frequency, the dependent measure selected for this experiment was accuracy of failure diagnosis, from which D Prime and Decision Criterion were derived. For each of the dependent measures, no significant difference was found for level of automation and no significant interaction was detected between level of automation and failure frequency. A significant effect was identified for failure frequency suggesting failure frequency has a significant effect on pilots' sensitivity to failure detection and diagnosis. Participants were more likely to correctly identify and diagnose failures if they experienced the higher levels of failures, regardless of level of automation

Frequency Dependent Nudging of Hydrographic Data Into a Numerical Model of the North Atlantic

NASA Astrophysics Data System (ADS)

Thompson, K. R.; Wright, D. G.

2002-12-01

Nudging is one of the simplest ways of assimilating data into ocean models and it has been used for many years in studies of large-scale ocean circulation. One of its drawbacks is the suppression of eddies when nudging an eddy-permitting ocean model strongly toward an observed seasonal climatology. We propose a straightforward extension of nudging in which the model's climatology, rather than its instantaneous state, is nudged toward the observed seasonal climatology. In effect we propose nudging in specific frequency bands that are centered on the discrete frequencies evident in the observed climatology (e.g. 0, 1/12 and 1/6 cycles per month). This extension of conventional nudging allows the difference between the observed and modeled climatologies arbitrarily to be made small while allowing variations outside the selected frequency bands to evolve freely. We show how the method can be implemented efficiently in complex models using a Kalman filter and also discuss the benefits of spatially smoothing the nudges. We conclude with a demonstration of frequency dependent nudging using a 1/3 degree model of the North Atlantic.

Ultrasound-assisted advanced oxidation processes for water decontamination.

PubMed

Ince, Nilsun H

2018-01-01

The study reflects a part of my experience in sonochemistry and ultrasound-assisted advanced oxidation processes (AOPs) acquired during the last fifteen years with my research team. The data discussed were selected from studies with azo dyes, endocrine disrupting compounds and analgesic/anti-inflammatory pharmaceuticals, which are all classified as "hazardous" or "emerging" contaminants. The research focused on their treatability by ultrasound (US) and AOPs with emphasis on the mineralization of organic carbon. Some of the highlights as pointed out in the manuscript are: i) ultrasound is capable of partially or completely oxidizing the above contaminant groups if the operating conditions are properly selected and optimized, but incapable of mineralizing them; ii) the mechanism of degradation in homogeneous solutions is OH-mediated oxidation in the bulk solution or at the bubble-liquid interface, depending on the molecular properties of the contaminant, the applied frequency and pH; iii) US-assisted AOPs such as ozonation, UV/peroxide, Fenton and UV/Fenton are substantially more effective than ultrasound alone, particularly for the mineralization process; iv) catalytic processes involving TiO 2 , alumina and zero-valent iron and assisted by ultrasound are promising options not only for the destruction of the parent compounds, but also for the mineralization of their oxidation byproducts. The degradation reactions in heterogeneous solutions take place mostly at the catalyst surface despite the high-water solubility of the compounds; v) sonolytic modification of the above catalysts to reduce their particle size (to nano-levels) or to decorate the surface with metallic nanoparticles increases the catalytic activity under sonolysis, photolysis and both, and improves the stability of the catalyst. Copyright © 2017 Elsevier B.V. All rights reserved.

Determining Selection across Heterogeneous Landscapes: A Perturbation-Based Method and Its Application to Modeling Evolution in Space.

PubMed

Wickman, Jonas; Diehl, Sebastian; Blasius, Bernd; Klausmeier, Christopher A; Ryabov, Alexey B; Brännström, Åke

2017-04-01

Spatial structure can decisively influence the way evolutionary processes unfold. To date, several methods have been used to study evolution in spatial systems, including population genetics, quantitative genetics, moment-closure approximations, and individual-based models. Here we extend the study of spatial evolutionary dynamics to eco-evolutionary models based on reaction-diffusion equations and adaptive dynamics. Specifically, we derive expressions for the strength of directional and stabilizing/disruptive selection that apply both in continuous space and to metacommunities with symmetrical dispersal between patches. For directional selection on a quantitative trait, this yields a way to integrate local directional selection across space and determine whether the trait value will increase or decrease. The robustness of this prediction is validated against quantitative genetics. For stabilizing/disruptive selection, we show that spatial heterogeneity always contributes to disruptive selection and hence always promotes evolutionary branching. The expression for directional selection is numerically very efficient and hence lends itself to simulation studies of evolutionary community assembly. We illustrate the application and utility of the expressions for this purpose with two examples of the evolution of resource utilization. Finally, we outline the domain of applicability of reaction-diffusion equations as a modeling framework and discuss their limitations.

[Biological and neural bases of partner preferences in rodents: models to understand human pair bonds].

PubMed

Coria-Avila, G A; Hernández-Aguilar, M E; Toledo-Cárdenas, R; García-Hernández, L I; Manzo, J; Pacheco, P; Miquel, M; Pfaus, J G

To analyse the biological and neural bases of partner preference formation in rodents as models to understand human pair bonding. Rodents are social individuals, capable of forming short- or long-lasting partner preferences that develop slowly by stimuli like cohabitation, or rapidly by stimuli like sex and stress. Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others. Additional areas may participate depending on the nature of the conditioned stimuli by which and individual recognizes a preferred partner. Animal models help us understand that the capacity of an individual to display long-lasting and selective preferences depends on neural bases, selected throughout evolution. The challenge in neuroscience is to use this knowledge to create new solutions for mental problems associated with the incapacity of an individual to display a social bond, keep one, or cope with the disruption of a consolidated one.

Auditory biological marker of concussion in children

PubMed Central

Kraus, Nina; Thompson, Elaine C.; Krizman, Jennifer; Cook, Katherine; White-Schwoch, Travis; LaBella, Cynthia R.

2016-01-01

Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries. PMID:28005070

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

NASA Astrophysics Data System (ADS)

Matsuda, Shinji; Kakegawa, Wataru; Budisantoso, Timotheus; Nomura, Toshihiro; Kohda, Kazuhisa; Yuzaki, Michisuke

2013-11-01

Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin’s interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors—transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes—through its sequential binding to AP-2 and AP-3A.

[Improving self-control in substance dependent persons and pathological gamblers--a pilot study].

PubMed

Nespor, K; Csémy, L

2006-01-01

Impaired self-control is an important symptom of addictive diseases. The average number of factors improving self-control among 117 men dependent on alcohol, other substances and pathological gamblers was 5.55 (SD=3.5). We classified strategies how to improve self-control into following groups (their ordering reflects the frequency of their use in our sample): 1. The help of others (professional treatment, self-help groups, and family), 2. Distraction and similar techniques, 3. The use of motivation, 4. Life-style changes including appropriate rest, 5. Physical activity, sports, physical work, 6. The use of environments, 7. Mastering of social and other relevant skills, 8. Relaxation based approaches, 9. Techniques working with improved self-awareness, 10. Pharmacotherapy, 11. Acknowledgement of an addictive disease and abstinence, 12. Disrupting risky behavioral patterns. To improve of self-control in addictive diseases simple techniques are appropriate because of temporarily impaired cognitive functions during craving. Frequent repetition are also important.

Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions

PubMed Central

Wilson, R. Bryce; Davis, Dana; Mitchell, Aaron P.

1999-01-01

Disruption of newly identified genes in the pathogen Candida albicans is a vital step in determination of gene function. Several gene disruption methods described previously employ long regions of homology flanking a selectable marker. Here, we describe disruption of C. albicans genes with PCR products that have 50 to 60 bp of homology to a genomic sequence on each end of a selectable marker. We used the method to disrupt two known genes, ARG5 and ADE2, and two sequences newly identified through the Candida genome project, HRM101 and ENX3. HRM101 and ENX3 are homologous to genes in the conserved RIM101 (previously called RIM1) and PacC pathways of Saccharomyces cerevisiae and Aspergillus nidulans. We show that three independent hrm101/hrm101 mutants and two independent enx3/enx3 mutants are defective in filamentation on Spider medium. These observations argue that HRM101 and ENX3 sequences are indeed portions of genes and that the respective gene products have related functions. PMID:10074081

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

Public goods games in populations with fluctuating size.

PubMed

McAvoy, Alex; Fraiman, Nicolas; Hauert, Christoph; Wakeley, John; Nowak, Martin A

2018-05-01

Many mathematical frameworks of evolutionary game dynamics assume that the total population size is constant and that selection affects only the relative frequency of strategies. Here, we consider evolutionary game dynamics in an extended Wright-Fisher process with variable population size. In such a scenario, it is possible that the entire population becomes extinct. Survival of the population may depend on which strategy prevails in the game dynamics. Studying cooperative dilemmas, it is a natural feature of such a model that cooperators enable survival, while defectors drive extinction. Although defectors are favored for any mixed population, random drift could lead to their elimination and the resulting pure-cooperator population could survive. On the other hand, if the defectors remain, then the population will quickly go extinct because the frequency of cooperators steadily declines and defectors alone cannot survive. In a mutation-selection model, we find that (i) a steady supply of cooperators can enable long-term population survival, provided selection is sufficiently strong, and (ii) selection can increase the abundance of cooperators but reduce their relative frequency. Thus, evolutionary game dynamics in populations with variable size generate a multifaceted notion of what constitutes a trait's long-term success. Copyright © 2018 Elsevier Inc. All rights reserved.

A scattering analysis of echoes due to biosonar signals emitted by foraging beaked whales

NASA Astrophysics Data System (ADS)

Jones, Benjamin A.; Stanton, Timothy K.; Lavery, Andone C.; Johnson, Mark P.; Madsen, Peter T.; Tyack, Peter L.

2005-09-01

Blainville's beaked whales (Mesoplodon densirostris) hunt their prey by echolocation at depths of more than 500 meters. These whales use a FM upswept, ultrasonic click, of greater than an octave bandwidth to search for, localize, and close on individual prey which generally consist of mesopelagic fishes and squid. It is well known that acoustic scattering from organisms of varying morphology (e.g., swimbladder-bearing or fluidlike) is strongly frequency dependent. However, it is unknown if the broadband nature of the whales' outgoing signal, and the frequency dependence of the echoes, is a key component in the classification and selection of their prey. Non-invasive, acoustic ``Dtags,'' which sample stereo acoustic data at a rate which satisfies the high-frequency Nyquist criterion for the animal's transmit signal, were affixed to beaked whales. The Dtags successfully recorded transmitted signals and associated echoes. Structure was observed in the frequency content of echoes from isolated targets in the water column which may be used for classification by the whales. An analysis of the echoes identified as possibly due to prey has demonstrated that multiple classes of frequency responses are present. These results will be compared with the frequency responses of possible prey types.

Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice

PubMed Central

Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara

2017-01-01

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and serves a critical role in learning and memory. PMID:28674172

Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice.

PubMed

Tang, Sheng; Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara; Pance, Katarina; Lee, Jun Y; Cui, Yue; Coulter, Douglas A; Zhou, Zhaolan

2017-08-02

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and serves a critical role in learning and memory. Copyright © 2017 the authors 0270-6474/17/377420-18$15.00/0.

On Strong Positive Frequency Dependencies of Quality Factors in Local-Earthquake Seismic Studies

NASA Astrophysics Data System (ADS)

Morozov, Igor B.; Jhajhria, Atul; Deng, Wubing

2018-03-01

Many observations of seismic waves from local earthquakes are interpreted in terms of the frequency-dependent quality factor Q( f ) = Q0 f^{η } , where η is often close to or exceeds one. However, such steep positive frequency dependencies of Q require careful analysis with regard to their physical consistency. In particular, the case of η = 1 corresponds to frequency-independent (elastic) amplitude decays with time and consequently requires no Q-type attenuation mechanisms. For η > 1, several problems with physical meanings of such Q-factors occur. First, contrary to the key premise of seismic attenuation, high-frequency parts of the wavefield are enhanced with increasing propagation times relative to the low-frequency ones. Second, such attenuation cannot be implemented by mechanical models of wave-propagating media. Third, with η > 1, the velocity dispersion associated with such Q(f) occurs over unrealistically short frequency range and has an unexpected oscillatory shape. Cases η = 1 and η > 1 are usually attributed to scattering; however, this scattering must exhibit fortuitous tuning into the observation frequency band, which appears unlikely. The reason for the above problems is that the inferred Q values are affected by the conventional single-station measurement procedure. Both parameters Q 0 and are apparent, i.e., dependent on the selected parameterization and inversion method, and they should not be directly attributed to the subsurface. For η ≈ 1, parameter Q 0 actually describes the frequency-independent amplitude decay in access of some assumed geometric spreading t -α , where α is usually taken equal one. The case η > 1 is not allowed physically and could serve as an indicator of problematic interpretations. Although the case 0 < η < 1 is possible, its parameters Q 0 and may also be biased by the measurement procedure. To avoid such difficulties of Q-based approaches, we recommend measuring and interpreting the amplitude-decay rates (such as parameter α) directly.

Contemporary evolution of resistance at the major insecticide target site gene Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae

PubMed Central

Weetman, David; Mitchell, Sara N; Wilding, Craig S; Birks, Daniel P; Yawson, Alexander E; Essandoh, John; Mawejje, Henry D; Djogbenou, Luc S; Steen, Keith; Rippon, Emily J; Clarkson, Christopher S; Field, Stuart G; Rigden, Daniel J; Donnelly, Martin J

2015-01-01

Functionally constrained genes are ideal insecticide targets because disruption is often fatal, and resistance mutations are typically costly. Synaptic acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by insecticides used increasingly in malaria control. In Anopheles and Culex mosquitoes, a glycine–serine substitution at codon 119 of the Ace-1 gene confers both resistance and fitness costs, especially for 119S/S homozygotes. G119S in Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and, despite expectations of cost, resistant 119S alleles are increasing significantly in frequency. Sequencing of Accra females detected only a single Ace-1 119S haplotype, whereas 119G diversity was high overall but very low at non-synonymous sites, evidence of strong purifying selection driven by functional constraint. Flanking microsatellites showed reduced diversity, elevated linkage disequilibrium and high differentiation of 119S, relative to 119G homozygotes across up to two megabases of the genome. Yet these signals of selection were inconsistent and sometimes weak tens of kilobases from Ace-1. This unexpected finding is attributable to apparently ubiquitous amplification of 119S alleles as part of a large copy number variant (CNV) far exceeding the size of the Ace-1 gene, whereas 119G alleles were unduplicated. Ace-1 CNV was detectable in archived samples collected when the 119S allele was rare in Ghana. Multicopy amplification of resistant alleles has not been observed previously and is likely to underpin the recent increase in 119S frequency. The large CNV compromised localization of the strong selective sweep around Ace-1, emphasizing the need to integrate CNV analysis into genome scans for selection. PMID:25865270

Impaired pulsation absorber mechanism in idiopathic normal pressure hydrocephalus: laboratory investigation.

PubMed

Park, Eun-Hyoung; Eide, Per Kristian; Zurakowski, David; Madsen, Joseph R

2012-12-01

The pathophysiology of normal pressure hydrocephalus (NPH), and the related problem of patient selection for treatment of this condition, have been of great interest since the description of this seemingly paradoxical condition nearly 50 years ago. Recently, Eide has reported that measurements of the amplitude of the intracranial pressure (ICP) can both positively and negatively predict response to CSF shunting. Specifically, the fraction of time spent in a "high amplitude" (> 4 mm Hg) state predicted response to shunting, which may represent a marker for hydrocephalic pathophysiology. Increased ICP amplitude might suggest decreased brain compliance, meaning a static measure of a pressure-volume ratio. Recent studies of canine data have shown that the brain compliance can be described as a frequency-dependent function. The normal canine brain seems to show enhanced ability to absorb the pulsations around the heart rate, quantified as a cardiac pulsation absorbance (CPA), with properties like a notch filter in engineering. This frequency dependence of the function is diminished with development of hydrocephalus in dogs. In this pilot study, the authors sought to determine whether frequency dependence could be observed in humans, and whether the frequency dependence would be any different in epochs with high ICP amplitude compared with epochs of low ICP amplitude. Systems analysis was applied to arterial blood pressure (ABP) and ICP waveforms recorded from 10 patients undergoing evaluations of idiopathic NPH to calculate a time-varying transfer function that reveals frequency dependence and CPA, the measure of frequency-dependent compliance previously used in animal experiments. The ICP amplitude was also calculated in the same samples, so that epochs with high (> 4 mm Hg) versus low (≤ 4 mm Hg) amplitude could be compared in CPA and transfer functions. Transfer function analysis for the more "normal" epochs with low amplitude exhibits a dip or notch in the physiological frequency range of the heart rate, confirming in humans the pulsation absorber phenomenon previously observed in canine studies. Under high amplitude, however, the dip in the transfer function is absent. An inverse relationship between CPA index and ICP amplitude is evident and statistically significant. Thus, elevated ICP amplitude indicates decreased performance of the human pulsation absorber. The results suggest that the human intracranial system shows frequency dependence as seen in animal experiments. There is an inverse relationship between CPA index and ICP amplitude, indicating that higher amplitudes may occur with a reduced performance of the pulsation absorber. Our findings show that frequency dependence can be observed in humans and imply that reduced frequency-dependent compliance may be responsible for elevated ICP amplitude observed in patients who respond to CSF shunting.

Soil permittivity response to bulk electrical conductivity for selected soil water sensors

USDA-ARS?s Scientific Manuscript database

Bulk electrical conductivity can dominate the low frequency dielectric loss spectrum in soils, masking changes in the real permittivity and causing errors in estimated water content. We examined the dependence of measured apparent permittivity (Ka) on bulk electrical conductivity in contrasting soil...

Antagonistic versus non-antagonistic models of balancing selection: Characterizing the relative timescales and hitchhiking effects of partial selective sweeps

PubMed Central

Connallon, Tim; Clark, Andrew G.

2012-01-01

Antagonistically selected alleles -- those with opposing fitness effects between sexes, environments, or fitness components -- represent an important component of additive genetic variance in fitness-related traits, with stably balanced polymorphisms often hypothesized to contribute to observed quantitative genetic variation. Balancing selection hypotheses imply that intermediate-frequency alleles disproportionately contribute to genetic variance of life history traits and fitness. Such alleles may also associate with population genetic footprints of recent selection, including reduced genetic diversity and inflated linkage disequilibrium at linked, neutral sites. Here, we compare the evolutionary dynamics of different balancing selection models, and characterize the evolutionary timescale and hitchhiking effects of partial selective sweeps generated under antagonistic versus non-antagonistic (e.g., overdominant and frequency-dependent selection) processes. We show that that the evolutionary timescales of partial sweeps tend to be much longer, and hitchhiking effects are drastically weaker, under scenarios of antagonistic selection. These results predict an interesting mismatch between molecular population genetic and quantitative genetic patterns of variation. Balanced, antagonistically selected alleles are expected to contribute more to additive genetic variance for fitness than alleles maintained by classic, non-antagonistic mechanisms. Nevertheless, classical mechanisms of balancing selection are much more likely to generate strong population genetic signatures of recent balancing selection. PMID:23461340

Evaluation of pesticide toxicities with differing mechanisms using Caenorhabditis elegans.

PubMed

Ruan, Qin-Li; Ju, Jing-Juan; Li, Yun-Hui; Liu, Ran; Pu, Yue-Pu; Yin, Li-Hong; Wang, Da-Yong

2009-01-01

The aim of this study was to (1) determine whether model organism Caenorhabditis elegans was sensitive to pesticides at the maximum concentration limits regulated by national agency standards, and (2) examine the multi-biological toxicities occurring as a result of exposure to pesticides. Five pesticides, namely, chlorpyrifos, imibacloprid, buprofezin, cyhalothrin, and glyphosate, with four different mechanisms of action were selected for the investigation. In accordance with national agency requirements, 4 exposed groups were used for each tested pesticide with the concentration scales ranging from 1.0 x 10(-3) to 1 mg/L. L4 larvae were exposed for 24 and 72 h, respectively. Endpoints of locomotion, propagation, and development were selected for the assay as parameters of toxicity. After exposure for 24 h, both the body bend frequency and head thrash frequency of nematodes exposed to chlorpyrifos, imibacloprid, and cyhalothrin decreased in a concentration-dependent manner, and there were significant differences between exposed groups at maximum concentration level (MCL) compared to control. The generation time of nematodes exposed to buprofezin 24 h significantly increased in a concentration-dependent manner in the highest exposed group. When exposed for 72 h, the body bend frequency and head thrash frequency of nematodes exposed to cyhalothrin markedly decreased at MCL. The generation time and brood size of nematodes exposed to buprofezin were reduced in a concentration-dependent manner. The behavior of nematodes was sensitive to pesticides with neurotoxic properties, while pesticides affecting insect growth modified the reproductive system. The effects of pesticides on nematodes exposed for 24 h appeared more sensitive than with exposure for 72 h. Caenorhabditis elegans may thus be used for assessing the adverse effects of pesticide residues in aquatic environment.

Position-dependent hearing in three species of bushcrickets (Tettigoniidae, Orthoptera)

PubMed Central

Lakes-Harlan, Reinhard; Scherberich, Jan

2015-01-01

A primary task of auditory systems is the localization of sound sources in space. Sound source localization in azimuth is usually based on temporal or intensity differences of sounds between the bilaterally arranged ears. In mammals, localization in elevation is possible by transfer functions at the ear, especially the pinnae. Although insects are able to locate sound sources, little attention is given to the mechanisms of acoustic orientation to elevated positions. Here we comparatively analyse the peripheral hearing thresholds of three species of bushcrickets in respect to sound source positions in space. The hearing thresholds across frequencies depend on the location of a sound source in the three-dimensional hearing space in front of the animal. Thresholds differ for different azimuthal positions and for different positions in elevation. This position-dependent frequency tuning is species specific. Largest differences in thresholds between positions are found in Ancylecha fenestrata. Correspondingly, A. fenestrata has a rather complex ear morphology including cuticular folds covering the anterior tympanal membrane. The position-dependent tuning might contribute to sound source localization in the habitats. Acoustic orientation might be a selective factor for the evolution of morphological structures at the bushcricket ear and, speculatively, even for frequency fractioning in the ear. PMID:26543574

Position-dependent hearing in three species of bushcrickets (Tettigoniidae, Orthoptera).

PubMed

Lakes-Harlan, Reinhard; Scherberich, Jan

2015-06-01

A primary task of auditory systems is the localization of sound sources in space. Sound source localization in azimuth is usually based on temporal or intensity differences of sounds between the bilaterally arranged ears. In mammals, localization in elevation is possible by transfer functions at the ear, especially the pinnae. Although insects are able to locate sound sources, little attention is given to the mechanisms of acoustic orientation to elevated positions. Here we comparatively analyse the peripheral hearing thresholds of three species of bushcrickets in respect to sound source positions in space. The hearing thresholds across frequencies depend on the location of a sound source in the three-dimensional hearing space in front of the animal. Thresholds differ for different azimuthal positions and for different positions in elevation. This position-dependent frequency tuning is species specific. Largest differences in thresholds between positions are found in Ancylecha fenestrata. Correspondingly, A. fenestrata has a rather complex ear morphology including cuticular folds covering the anterior tympanal membrane. The position-dependent tuning might contribute to sound source localization in the habitats. Acoustic orientation might be a selective factor for the evolution of morphological structures at the bushcricket ear and, speculatively, even for frequency fractioning in the ear.

A model of anuran auditory periphery reveals frequency-dependent adaptation to be a contributing mechanism for two-tone suppression and amplitude modulation coding.

PubMed

Wotton, J M; Ferragamo, M J

2011-10-01

Anuran auditory nerve fibers (ANF) tuned to low frequencies display unusual frequency-dependent adaptation which results in a more phasic response to signals above best frequency (BF) and a more tonic response to signals below. A network model of the first two layers of the anuran auditory system was used to test the contribution of this dynamic peripheral adaptation on two-tone suppression and amplitude modulation (AM) tuning. The model included a peripheral sandwich component, leaky-integrate-and-fire cells and adaptation was implemented by means of a non-linear increase in threshold weighted by the signal frequency. The results of simulations showed that frequency-dependent adaptation was both necessary and sufficient to produce high-frequency-side two-tone suppression for the ANF and cells of the dorsal medullary nucleus (DMN). It seems likely that both suppression and this dynamic adaptation share a common mechanism. The response of ANFs to AM signals was influenced by adaptation and carrier frequency. Vector strength synchronization to an AM signal improved with increased adaptation. The spike rate response to a carrier at BF was the expected flat function with AM rate. However, for non-BF carrier frequencies the response showed a weak band-pass pattern due to the influence of signal sidebands and adaptation. The DMN received inputs from three ANFs and when the frequency tuning of inputs was near the carrier, then the rate response was a low-pass or all-pass shape. When most of the inputs were biased above or below the carrier, then band-pass responses were observed. Frequency-dependent adaptation enhanced the band-pass tuning for AM rate, particularly when the response of the inputs was predominantly phasic for a given carrier. Different combinations of inputs can therefore bias a DMN cell to be especially well suited to detect specific ranges of AM rates for a particular carrier frequency. Such selection of inputs would clearly be advantageous to the frog in recognizing distinct spectral and temporal parameters in communication calls. Copyright © 2011 Elsevier B.V. All rights reserved.

Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit.

PubMed

Banks, William A; Gray, Alicia M; Erickson, Michelle A; Salameh, Therese S; Damodarasamy, Mamatha; Sheibani, Nader; Meabon, James S; Wing, Emily E; Morofuji, Yoichi; Cook, David G; Reed, May J

2015-11-25

Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, but many mechanistic questions remain. We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using (14)C-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co- or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to (14)C-sucrose and radioactive albumin. In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with (14)C-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and (14)C-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes. The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is to be dependent on COX but not on oxidative stress. Based on in vivo and in vitro measures of neuroinflammation, it appears that astrocytes, microglia/macrophages, and pericytes play little role in the LPS-mediated disruption of the BBB.

Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex.

PubMed

Mejias, Jorge F; Murray, John D; Kennedy, Henry; Wang, Xiao-Jing

2016-11-01

Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions.

Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex

PubMed Central

Mejias, Jorge F.; Murray, John D.; Kennedy, Henry; Wang, Xiao-Jing

2016-01-01

Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions. PMID:28138530

Marital disruption and health insurance.

PubMed

Peters, H Elizabeth; Simon, Kosali; Taber, Jamie Rubenstein

2014-08-01

Despite the high levels of marital disruption in the United States and the fact that a significant portion of health insurance coverage for those less than age 65 is based on family membership, surprisingly little research is available on the consequences of marital disruption for the health insurance coverage of men, women, and children. We address this shortfall by examining patterns of coverage surrounding marital disruption for men, women, and children, further subset by educational level. Using the 1996, 2001, and 2004 panels of the Survey of Income and Program Participation (SIPP), we find large differences in health insurance coverage across marital status groups in the cross-section. In longitudinal analyses that focus on within-person change, we find small overall coverage changes but large changes in type of coverage following marital disruption. Both men and women show increases in private coverage in their own names, but offsetting decreases in dependent coverage tend to be larger. One surprising result is that dependent coverage for children also declines after marital dissolution, even though children are still likely to be eligible for that coverage. Children and (to a lesser extent) women show increases in public coverage around the time of divorce or separation. We also find that these patterns differ by education. The most vulnerable group appears to be lower-educated women with children because the increases in private, own-name, and public insurance are not large enough to offset the large decrease in dependent coverage. As the United States implements federal health reform, it is critical that we understand the ways in which life course events-specifically, marital disruption-shape the dynamic patterns of coverage.

Can We Disrupt the Sensing of Honey Bees by the Bee Parasite Varroa destructor?

PubMed Central

Eliash, Nurit; Singh, Nitin Kumar; Kamer, Yosef; Pinnelli, Govardhana Reddy; Plettner, Erika; Soroker, Victoria

2014-01-01

Background The ectoparasitic mite, Varroa destructor, is considered to be one of the most significant threats to apiculture around the world. Chemical cues are known to play a significant role in the host-finding behavior of Varroa. The mites distinguish between bees from different task groups, and prefer nurses over foragers. We examined the possibility of disrupting the Varroa – honey bee interaction by targeting the mite's olfactory system. In particular, we examined the effect of volatile compounds, ethers of cis 5-(2′-hydroxyethyl) cyclopent-2-en-1-ol or of dihydroquinone, resorcinol or catechol. We tested the effect of these compounds on the Varroa chemosensory organ by electrophysiology and on behavior in a choice bioassay. The electrophysiological studies were conducted on the isolated foreleg. In the behavioral bioassay, the mite's preference between a nurse and a forager bee was evaluated. Principal findings We found that in the presence of some compounds, the response of the Varroa chemosensory organ to honey bee headspace volatiles significantly decreased. This effect was dose dependent and, for some of the compounds, long lasting (>1 min). Furthermore, disruption of the Varroa volatile detection was accompanied by a reversal of the mite's preference from a nurse to a forager bee. Long-term inhibition of the electrophysiological responses of mites to the tested compounds was a good predictor for an alteration in the mite's host preference. Conclusions These data indicate the potential of the selected compounds to disrupt the Varroa - honey bee associations, thus opening new avenues for Varroa control. PMID:25226388

Selective loss of orientation column maps in visual cortex during brief elevation of intraocular pressure.

PubMed

Chen, Xin; Sun, Chao; Huang, Luoxiu; Shou, Tiande

2003-01-01

To compare the orientation column maps elicited by different spatial frequency gratings in cortical area 17 of cats before and during brief elevation of intraocular pressure (IOP). IOP was elevated by injecting saline into the anterior chamber of a cat's eye through a syringe needle. The IOP was elevated enough to cause a retinal perfusion pressure (arterial pressure minus IOP) of approximately 30 mm Hg during a brief elevation of IOP. The visual stimulus gratings were varied in spatial frequency, whereas other parameters were kept constant. The orientation column maps of the cortical area 17 were monocularly elicited by drifting gratings of different spatial frequencies and revealed by a brain intrinsic signal optical imaging system. These maps were compared before and during short-term elevation of IOP. The response amplitude of the orientation maps in area 17 decreased during a brief elevation of IOP. This decrease was dependent on the retinal perfusion pressure but not on the absolute IOP. The location of the most visible maps was spatial-frequency dependent. The blurring or loss of the pattern of the orientation maps was most severe when high-spatial-frequency gratings were used and appeared most significantly on the posterior part of the exposed cortex while IOP was elevated. However, the basic patterns of the maps remained unchanged. Changes in cortical signal were not due to changes in the optics of the eye with elevation of IOP. A stable normal IOP is essential for maintaining normal visual cortical functions. During a brief and high elevation of IOP, the cortical processing of high-spatial-frequency visual information was diminished because of a selectively functional decline of the retinogeniculocortical X pathway by a mechanism of retinal circulation origin.

Cannabinoid receptors mediate methamphetamine induction of high frequency gamma oscillations in the nucleus accumbens.

PubMed

Morra, Joshua T; Glick, Stanley D; Cheer, Joseph F

2012-09-01

Patients suffering from amphetamine-induced psychosis display repetitive behaviors, partially alleviated by antipsychotics, which are reminiscent of rodent stereotypies. Due to recent evidence implicating endocannabinoid involvement in brain disorders, including psychosis, we studied the effects of endocannabinoid signaling on neuronal oscillations of rats exhibiting methamphetamine stereotypy. Neuronal network oscillations were recorded with multiple single electrode arrays aimed at the nucleus accumbens of freely-moving rats. During the experiments, animals were dosed intravenously with the CB1 receptor antagonist rimonabant (0.3 mg/kg) or vehicle followed by an ascending dose regimen of methamphetamine (0.01, 0.1, 1, and 3 mg/kg; cumulative dosing). The effects of drug administration on stereotypy and local gamma oscillations were evaluated. Methamphetamine treatment significantly increased high frequency gamma oscillations (∼80 Hz). Entrainment of a subpopulation of nucleus accumbens neurons to high frequency gamma was associated with stereotypy encoding in putative fast-spiking interneurons, but not in putative medium spiny neurons. The observed ability of methamphetamine to induce both stereotypy and high frequency gamma power was potently disrupted following CB1 receptor blockade. The present data suggest that CB1 receptor-dependent mechanisms are recruited by methamphetamine to modify striatal interneuron oscillations that accompany changes in psychomotor state, further supporting the link between endocannabinoids and schizophrenia spectrum disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anterior temporal lobes mediate semantic representation: Mimicking semantic dementia by using rTMS in normal participants

PubMed Central

Pobric, Gorana; Jefferies, Elizabeth; Ralph, Matthew A. Lambon

2007-01-01

Studies of semantic dementia and PET neuroimaging investigations suggest that the anterior temporal lobes (ATL) are a critical substrate for semantic representation. In stark contrast, classical neurological models of comprehension do not include ATL, and likewise functional MRI studies often fail to show activations in the ATL, reinforcing the classical view. Using a novel application of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the ATL, we demonstrate that the behavioral pattern of semantic dementia can be mirrored in neurologically intact participants: Specifically, we show that temporary disruption to neural processing in the ATL produces a selective semantic impairment leading to significant slowing in both picture naming and word comprehension but not to other equally demanding, nonsemantic cognitive tasks. PMID:18056637

Dielectric Barrier Discharge (DBD) Plasma Actuators Thrust-Measurement Methodology Incorporating New Anti-Thrust Hypothesis

NASA Technical Reports Server (NTRS)

Ashpis, David E.; Laun, Matthew C.

2014-01-01

We discuss thrust measurements of Dielectric Barrier Discharge (DBD) plasma actuators devices used for aerodynamic active flow control. After a review of our experience with conventional thrust measurement and significant non-repeatability of the results, we devised a suspended actuator test setup, and now present a methodology of thrust measurements with decreased uncertainty. The methodology consists of frequency scans at constant voltages. The procedure consists of increasing the frequency in a step-wise fashion from several Hz to the maximum frequency of several kHz, followed by frequency decrease back down to the start frequency of several Hz. This sequence is performed first at the highest voltage of interest, then repeated at lower voltages. The data in the descending frequency direction is more consistent and selected for reporting. Sample results show strong dependence of thrust on humidity which also affects the consistency and fluctuations of the measurements. We also observed negative values of thrust or "anti-thrust", at low frequencies between 4 Hz and up to 64 Hz. The anti-thrust is proportional to the mean-squared voltage and is frequency independent. Departures from the parabolic anti-thrust curve are correlated with appearance of visible plasma discharges. We propose the anti-thrust hypothesis. It states that the measured thrust is a sum of plasma thrust and anti-thrust, and assumes that the anti-thrust exists at all frequencies and voltages. The anti-thrust depends on actuator geometry and materials and on the test installation. It enables the separation of the plasma thrust from the measured total thrust. This approach enables more meaningful comparisons between actuators at different installations and laboratories. The dependence on test installation was validated by surrounding the actuator with a large diameter, grounded, metal sleeve.

Mutation-selection equilibrium in games with multiple strategies.

PubMed

Antal, Tibor; Traulsen, Arne; Ohtsuki, Hisashi; Tarnita, Corina E; Nowak, Martin A

2009-06-21

In evolutionary games the fitness of individuals is not constant but depends on the relative abundance of the various strategies in the population. Here we study general games among n strategies in populations of large but finite size. We explore stochastic evolutionary dynamics under weak selection, but for any mutation rate. We analyze the frequency dependent Moran process in well-mixed populations, but almost identical results are found for the Wright-Fisher and Pairwise Comparison processes. Surprisingly simple conditions specify whether a strategy is more abundant on average than 1/n, or than another strategy, in the mutation-selection equilibrium. We find one condition that holds for low mutation rate and another condition that holds for high mutation rate. A linear combination of these two conditions holds for any mutation rate. Our results allow a complete characterization of nxn games in the limit of weak selection.

Disruptive selection as a driver of evolutionary branching and caste evolution in social insects.

PubMed

Planqué, R; Powell, S; Franks, N R; van den Berg, J B

2016-11-01

Theory suggests that evolutionary branching via disruptive selection may be a relatively common and powerful force driving phenotypic divergence. Here, we extend this theory to social insects, which have novel social axes of phenotypic diversification. Our model, built around turtle ant (Cephalotes) biology, is used to explore whether disruptive selection can drive the evolutionary branching of divergent colony phenotypes that include a novel soldier caste. Soldier evolution is a recurrent theme in social insect diversification that is exemplified in the turtle ants. We show that phenotypic mutants can gain competitive advantages that induce disruptive selection and subsequent branching. A soldier caste does not generally appear before branching, but can evolve from subsequent competition. The soldier caste then evolves in association with specialized resource preferences that maximize defensive performance. Overall, our model indicates that resource specialization may occur in the absence of morphological specialization, but that when morphological specialization evolves, it is always in association with resource specialization. This evolutionary coupling of ecological and morphological specialization is consistent with recent empirical evidence, but contrary to predictions of classical caste theory. Our model provides a new theoretical understanding of the ecology of caste evolution that explicitly considers the process of adaptive phenotypic divergence and diversification. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Sexual Well-Being Among Partnered Women With Breast Cancer Recurrence

PubMed Central

Andersen, Barbara L.; Carpenter, Kristen M.; Yang, Hae-Chung; Shapiro, Charles L.

2007-01-01

Purpose A woman’s risk for sexual disruption after breast cancer recurrence has received little clinical or research attention. Patients and Methods Breast cancer patients recently diagnosed with recurrence (n = 60) were initially assessed at baseline and completed follow-ups at 4, 8, and 12 months. They were compared by age, stage, and duration and frequency of follow-up with matched patients who remained disease free (n = 120). Using linear mixed modeling, the groups were compared in their trajectories of change on measures of sexuality, relationship satisfaction, cancer-specific stress, and physical functioning. Recurrence subgroups, those with locoregional versus distant disease and those younger versus older than 52 years, were also compared. Results At baseline, the recurrence group had significantly lower intercourse frequency and physical functioning compared with the disease-free group and these differences were maintained. There were no significant differences in the frequencies of kissing or sexual and relationship satisfactions. For the recurrence group patients, the heightened stress of the diagnostic/early recurrence treatment period declined to the lower disease-free levels by 12 months. This effect was largely due to improvement of the patients with distant disease. Finally, sexual changes were most notable for younger patients. Conclusion To our knowledge, this is the first longitudinal, controlled study of sexuality—sexuality in the context of other quality of life domains—for women coping with recurrence. Despite disruption, patients maintained their sexual lives. Younger and distant recurrence patients, however, may have greatest risk of sexual disruption. The factors contributing to sexual disruption remain unknown, and studies investigating strategies to help patients maintain this aspect of quality of life are needed. PMID:17634495

An Efficient Method Using Gluconacetobacter europaeus To Reduce an Unfavorable Flavor Compound, Acetoin, in Rice Vinegar Production

PubMed Central

Akasaka, Naoki; Sakoda, Hisao; Hidese, Ryota; Ishii, Yuri

2013-01-01

Gluconacetobacter europaeus, one of the microorganisms most commonly used for vinegar production, produces the unfavorable flavor compound acetoin. Since acetoin reduction is important for rice vinegar production, a genetic approach was attempted to reduce acetoin produced by G. europaeus KGMA0119 using specific gene knockout without introducing exogenous antibiotic resistance genes. A uracil-auxotrophic mutant with deletion of the orotate phosphoribosyltransferase gene (pyrE) was first isolated by positive selection using 5-fluoroorotic acid. The pyrE disruptant designated KGMA0704 (ΔpyrE) showed 5-fluoroorotic acid resistance. KGMA0704 and the pyrE gene were used for further gene disruption experiments as a host cell and a selectable marker, respectively. Targeted disruption of aldC or als, which encodes α-acetolactate decarboxylase or α-acetolactate synthase, was attempted in KGMA0704. The disruption of these genes was expected to result in a decrease in acetoin levels. A disruption vector harboring the pyrE marker within the targeted gene was constructed for double-crossover recombination. The cells of KGMA0704 were transformed with the exogenous DNA using electroporation, and genotypic analyses of the transformants revealed the unique occurrence of targeted aldC or als gene disruption. The aldC disruptant KGMA4004 and the als disruptant KGMA5315 were cultivated, and the amount of acetoin was monitored. The acetoin level in KGMA4004 culture was significantly reduced to 0.009% (wt/vol) compared with KGMA0119 (0.042% [wt/vol]), whereas that of KGMA5315 was not affected (0.037% [wt/vol]). This indicates that aldC disruption is critical for acetoin reduction. G. europaeus KGMA4004 has clear application potential in the production of rice vinegar with less unfavorable flavor. PMID:24056455

Uptake of Clostridium botulinum C3 Exoenzyme into Intact HT22 and J774A.1 Cells

PubMed Central

Rohrbeck, Astrid; von Elsner, Leonie; Hagemann, Sandra; Just, Ingo

2015-01-01

The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high concentration of the C3 enzyme. However, recent work indicates that C3 is selectively endocytosed, suggesting a specific endocytotic pathway, which is not yet understood. In this study, we show that the C3 exoenzyme binds to cell surfaces and is internalized in a time-dependent manner. We show that the intermediate filament, vimentin, is involved in C3 uptake, as indicated by the inhibition of C3 internalization by acrylamide, a known vimentin disruption agent. Inhibition of C3 internalization was not observed by chemical inhibitors, like bafilomycin A, methyl-β-cyclodextrin, nocodazole or latrunculin B. Furthermore, the internalization of C3 exoenzyme was markedly inhibited in dynasore-treated HT22 cells. Our results indicate that C3 internalization depends on vimentin and does not depend strictly on both clathrin and caveolae. PMID:25648844

The mechanisms of neurotoxicity and the selective vulnerability of nervous system sites.

PubMed

Maurer, Laura L; Philbert, Martin A

2015-01-01

The spatial heterogeneity of the structure, function, and cellular composition of the nervous system confers extraordinary complexity and a multiplicity of mechanisms of chemical neurotoxicity. Because of its relatively high metabolic demands and functional dependence on postmitotic neurons, the nervous system is vulnerable to a variety of xenobiotics that affect essential homeostatic mechanisms that support function. Despite protection from the neuroglia and blood-brain barrier, the central nervous system is prone to attack from lipophilic toxicants and those that hijack endogenous transport, receptor, metabolic, and other biochemical systems. The inherent predilection of chemicals for highly conserved biochemical systems confers selective vulnerability of the nervous system to neurotoxicants. This chapter discusses selective vulnerability of the nervous system in the context of neuron-specific decrements (axonopathy, myelinopathy, disruption of neurotransmission), and the degree to which neuronal damage is facilitated or ameliorated by surrounding nonneural cells in both the central and peripheral nervous systems. © 2015 Elsevier B.V. All rights reserved.

Sum frequency generation (SFG) vibrational spectroscopy of planar phosphatidylethanolamine hybrid bilayer membranes under water.

PubMed

Kett, Peter J N; Casford, Michael T L; Davies, Paul B

2010-06-15

Sum frequency generation (SFG) spectroscopy has been used to study the structure of phosphatidylethanolamine hybrid bilayer membranes (HBMs) under water at ambient temperatures. The HBMs were formed using a modified Langmuir-Schaefer technique and consisted of a layer of dipalmitoyl phosphatidylethanolamine (DPPE) physisorbed onto an octadecanethiol (ODT) self-assembled monolayer (SAM) at a series of surface pressures from 1 to 40 mN m(-1). The DPPE and ODT were selectively deuterated so that the contributions to the SFG spectra from the two layers could be determined separately. SFG spectra in both the C-H and C-D stretching regions confirmed that a monolayer of DPPE had been adsorbed to the ODT SAM and that there were gauche defects within the alkyl chains of the phospholipid. On adsorption of a layer of DPPE, methylene modes from the ODT SAM were detected, indicating that the phospholipid had partially disordered the alkanethiol monolayer. SFG spectra recorded in air indicated that removal of water from the surface of the HBM resulted in disruption of the DPPE layer and the formation of phospholipid bilayers.

Non-invasive transcranial stimulation of rat abducens nerve by focused ultrasound

PubMed Central

Kim, Hyungmin; Taghados, Seyed Javid; Fischer, Krisztina; Maeng, Lee-So; Park, Shinsuk; Yoo, Seung-Schik

2012-01-01

Non-pharmacological and non-surgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36 msec tone burst duration (TBD), 1.5 kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histological and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB) as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential in diagnostic and therapeutic applications in diseases of the peripheral nervous system. PMID:22763009

Preparation of fullerene/glass composites

DOEpatents

Mattes, Benjamin R.; McBranch, Duncan W.; Robinson, Jeanne M.; Koskelo, Aaron C.; Love, Steven P.

1995-01-01

Synthesis of fullerene/glass composites. A direct method for preparing solid solutions of C.sub.60 in silicon dioxide (SiO.sub.2) glass matrices by means of sol-gel chemistry is described. In order to produce highly concentrated fullerene-sol-gel-composites it is necessary to increase the solubility of these "guests" in a delivery solvent which is compatible with the starter sol (receiving solvent). Sonication results in aggregate disruption by treatment with high frequency sound waves, thereby accelerating the rate of hydrolysis of the alkoxide precursor, and the solution process for the C.sub.60. Depending upon the preparative procedure, C.sub.60 dispersed within the glass matrix as microcrystalline domains, or dispersed as true molecular solutions of C.sub.60 in a solid glass matrix, is generated by the present method.

Preparation of fullerene/glass composites

DOEpatents

Mattes, B.R.; McBranch, D.W.; Robinson, J.M.; Koskelo, A.C.; Love, S.P.

1995-05-30

Synthesis of fullerene/glass composites is described. A direct method for preparing solid solutions of C{sub 60} in silicon dioxide (SiO{sub 2}) glass matrices by means of sol-gel chemistry is described. In order to produce highly concentrated fullerene-sol-gel-composites it is necessary to increase the solubility of these ``guests`` in a delivery solvent which is compatible with the starter sol (receiving solvent). Sonication results in aggregate disruption by treatment with high frequency sound waves, thereby accelerating the rate of hydrolysis of the alkoxide precursor, and the solution process for the C{sub 60}. Depending upon the preparative procedure, C{sub 60} dispersed within the glass matrix as microcrystalline domains, or dispersed as true molecular solutions of C{sub 60} in a solid glass matrix, is generated by the present method.

Modulatory effects of perforin gene dosage on pathogen-associated blood-brain barrier (BBB) disruption.

PubMed

Willenbring, Robin C; Jin, Fang; Hinton, David J; Hansen, Mike; Choi, Doo-Sup; Pavelko, Kevin D; Johnson, Aaron J

2016-08-31

CD8 T cell-mediated blood-brain barrier (BBB) disruption is dependent on the effector molecule perforin. Human perforin has extensive single nucleotide variants (SNVs), the significance of which is not fully understood. These SNVs can result in reduced, but not ablated, perforin activity or expression. However, complete loss of perforin expression or activity results in the lethal disease familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). In this study, we address the hypothesis that a single perforin allele can alter the severity of BBB disruption in vivo using a well-established model of CNS vascular permeability in C57Bl/6 mice. The results of this study provide insight into the significance of perforin SNVs in the human population. We isolated the effect a single perforin allele has on CNS vascular permeability through the use of perforin-heterozygous (perforin+/-) C57BL/6 mice in the peptide-induced fatal syndrome (PIFS) model of immune-mediated BBB disruption. Seven days following Theiler's murine encephalomyelitis virus (TMEV) CNS infection, neuroinflammation and TMEV viral control were assessed through flow cytometric analysis and quantitative real-time PCR of the viral genome, respectively. Following immune-mediated BBB disruption, gadolinium-enhanced T1-weighted MRI, with 3D volumetric analysis, and confocal microscopy were used to define CNS vascular permeability. Finally, the open field behavior test was used to assess locomotor activity of mice following immune-mediated BBB disruption. Perforin-null mice had negligible CNS vascular permeability. Perforin-WT mice have extensive CNS vascular permeability. Interestingly, perforin-heterozygous mice had an intermediate level of CNS vascular permeability as measured by both gadolinium-enhanced T1-weighted MRI and fibrinogen leakage in the brain parenchyma. Differences in BBB disruption were not a result of increased CNS immune infiltrate. Additionally, TMEV was controlled in a perforin dose-dependent manner. Furthermore, a single perforin allele is sufficient to induce locomotor deficit during immune-mediated BBB disruption. Perforin modulates BBB disruption in a dose-dependent manner. This study demonstrates a potentially advantageous role for decreased perforin expression in reducing BBB disruption. This study also provides insight into the effect SNVs in a single perforin allele could have on functional deficit in neurological disease.

Characterizing active cytoskeletal dynamics with magnetic microposts

NASA Astrophysics Data System (ADS)

Shi, Yu; Henry, Steven; Crocker, John; Reich, Daniel

Characterization of an active matter system such as the cellular cytoskeleton requires knowledge of three frequency dependent quantities: the dynamic shear modulus, G*(ω) describing its viscoelasticity, the Fourier power spectrum of forces in the material due to internal force generators f (ω) , and the spectrum of the material's active strain fluctuations x(ω) . Via use of PDMS micropost arrays with magnetic nanowires embedded in selected posts, we measure the local complex modulus of cells through mechanical actuation of the magnetic microposts. The micrometer scale microposts are also used as passive probes to measure simultaneously the frequency dependent strain fluctuations. We present data on 3T3 fibroblasts, where we find power law behavior for both the frequency dependence of cells' modulus | G (ω) | ω 0 . 27 and the power spectrum of strain fluctuations |x(ω) | ω-2 . Results for the power spectrum of active cytoskeletal stresses determined from these two measurements, and implications of this mesoscale characterization of cytoskeletal dynamics for cellular biophysics will also be discussed. Supported in part by NIH Grant 1R01HL127087.

Optimal Selection of Time Series Coefficients for Wrist Myoelectric Control Based on Intramuscular Recordings

DTIC Science & Technology

2001-10-25

considered static or invariant because the spectral behavior of EMG data is dependent on the specific muscle , contraction level, and limb function. However...produced at the onset of the muscle contraction . Because the units with lower conduction velocity (lower frequency components) are recruited first, the

Frequency-dependent population dynamics: effect of sex ratio and mating system on the elasticity of population growth rate.

PubMed

Haridas, C V; Eager, Eric Alan; Rebarber, Richard; Tenhumberg, Brigitte

2014-11-01

When vital rates depend on population structure (e.g., relative frequencies of males or females), an important question is how the long-term population growth rate λ responds to changes in rates. For instance, availability of mates may depend on the sex ratio of the population and hence reproductive rates could be frequency-dependent. In such cases change in any vital rate alters the structure, which in turn, affect frequency-dependent rates. We show that the elasticity of λ to a rate is the sum of (i) the effect of the linear change in the rate and (ii) the effect of nonlinear changes in frequency-dependent rates. The first component is always positive and is the classical elasticity in density-independent models obtained directly from the population projection matrix. The second component can be positive or negative and is absent in density-independent models. We explicitly express each component of the elasticity as a function of vital rates, eigenvalues and eigenvectors of the population projection matrix. We apply this result to a two-sex model, where male and female fertilities depend on adult sex ratio α (ratio of females to males) and the mating system (e.g., polygyny) through a harmonic mating function. We show that the nonlinear component of elasticity to a survival rate is negligible only when the average number of mates (per male) is close to α. In a strictly monogamous species, elasticity to female survival is larger than elasticity to male survival when α<1 (less females). In a polygynous species, elasticity to female survival can be larger than that of male survival even when sex ratio is female biased. Our results show how demography and mating system together determine the response to selection on sex-specific vital rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Surface density mapping of natural tissue by a scanning haptic microscope (SHM).

PubMed

Moriwaki, Takeshi; Oie, Tomonori; Takamizawa, Keiichi; Murayama, Yoshinobu; Fukuda, Toru; Omata, Sadao; Nakayama, Yasuhide

2013-02-01

To expand the performance capacity of the scanning haptic microscope (SHM) beyond surface mapping microscopy of elastic modulus or topography, surface density mapping of a natural tissue was performed by applying a measurement theory of SHM, in which a frequency change occurs upon contact of the sample surface with the SHM sensor - a microtactile sensor (MTS) that vibrates at a pre-determined constant oscillation frequency. This change was mainly stiffness-dependent at a low oscillation frequency and density-dependent at a high oscillation frequency. Two paragon examples with extremely different densities but similar macroscopic elastic moduli in the range of natural soft tissues were selected: one was agar hydrogels and the other silicon organogels with extremely low (less than 25 mg/cm(3)) and high densities (ca. 1300 mg/cm(3)), respectively. Measurements were performed in saline solution near the second-order resonance frequency, which led to the elastic modulus, and near the third-order resonance frequency. There was little difference in the frequency changes between the two resonance frequencies in agar gels. In contrast, in silicone gels, a large frequency change by MTS contact was observed near the third-order resonance frequency, indicating that the frequency change near the third-order resonance frequency reflected changes in both density and elastic modulus. Therefore, a density image of the canine aortic wall was subsequently obtained by subtracting the image observed near the second-order resonance frequency from that near the third-order resonance frequency. The elastin-rich region had a higher density than the collagen-rich region.

Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

PubMed Central

Yang, Cheng; Chen, Yan; Tang, Lei

2011-01-01

Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

The relative contribution of drift and selection to phenotypic divergence: A test case using the horseshoe bats Rhinolophus simulator and Rhinolophus swinnyi.

PubMed

Mutumi, Gregory L; Jacobs, David S; Winker, Henning

2017-06-01

Natural selection and drift can act on populations individually, simultaneously or in tandem and our understanding of phenotypic divergence depends on our ability to recognize the contribution of each. According to the quantitative theory of evolution, if an organism has diversified through neutral evolutionary processes (mutation and drift), variation of phenotypic characteristics between different geographic localities ( B ) should be directly proportional to the variation within localities ( W ), that is, B  ∝  W . Significant deviations from this null model imply that non-neutral forces such as natural selection are acting on a phenotype. We investigated the relative contributions of drift and selection to intraspecific diversity using southern African horseshoe bats as a test case. We characterized phenotypic diversity across the distributional range of Rhinolophus simulator ( n =  101) and Rhinolophus swinnyi ( n =  125) using several traits associated with flight and echolocation. Our results suggest that geographic variation in both species was predominantly caused by disruptive natural selection ( B was not directly proportional to W ). Evidence for correlated selection (co-selection) among traits further confirmed that our results were not compatible with drift. Selection rather than drift is likely the predominant evolutionary process shaping intraspecific variation in traits that strongly impact fitness.

Fire-mediated disruptive selection can explain the reseeder-resprouter dichotomy in Mediterranean-type vegetation.

PubMed

Altwegg, Res; De Klerk, Helen M; Midgley, Guy F

2015-02-01

Crown fire is a key selective pressure in Mediterranean-type plant communities. Adaptive responses to fire regimes involve trade-offs between investment for persistence (fire survival and resprouting) and reproduction (fire mortality, fast growth to reproductive maturity, and reseeding) as investments that enhance adult survival lower growth and reproductive rates. Southern hemisphere Mediterranean-type ecosystems are dominated by species with either endogenous regeneration from adult resprouting or fire-triggered seedling recruitment. Specifically, on nutrient-poor soils, these are either resprouting or reseeding life histories, with few intermediate forms, despite the fact that the transition between strategies is evolutionarily labile. How did this strong dichotomy evolve? We address this question by developing a stochastic demographic model to assess determinants of relative fitness of reseeders, resprouters and hypothetical intermediate forms. The model was parameterised using published demographic data from South African protea species and run over various relevant fire regime parameters facets. At intermediate fire return intervals, trade-offs between investment in growth versus fire resilience can cause fitness to peak at either of the extremes of the reseeder-resprouter continuum, especially when assuming realistic non-linear shapes for these trade-offs. Under these circumstances, the fitness landscape exhibits a saddle which could lead to disruptive selection. The fitness gradient between the peaks was shallow, which may explain why this life-history trait is phylogenetically labile. Resprouters had maximum fitness at shorter fire-return intervals than reseeders. The model suggests that a strong dichotomy in fire survival strategy depends on a non-linear trade-off between growth and fire persistence traits.

Information theoretic measures of network coordination in high-frequency scalp EEG reveal dynamic patterns associated with seizure termination.

PubMed

Stamoulis, Catherine; Schomer, Donald L; Chang, Bernard S

2013-08-01

How a seizure terminates is still under-studied and, despite its clinical importance, remains an obscure phase of seizure evolution. Recent studies of seizure-related scalp EEGs at frequencies >100 Hz suggest that neural activity, in the form of oscillations and/or neuronal network interactions, may play an important role in preictal/ictal seizure evolution (Andrade-Valenca et al., 2011; Stamoulis et al., 2012). However, the role of high-frequency activity in seizure termination, is unknown, if it exists at all. Using information theoretic measures of network coordination, this study investigated ictal and immediate postictal neurodynamic interactions encoded in scalp EEGs from a relatively small sample of 8 patients with focal epilepsy and multiple seizures originating in temporal and/or frontal brain regions, at frequencies ≤ 100 Hz and >100 Hz, respectively. Despite some heterogeneity in the dynamics of these interactions, consistent patterns were also estimated. Specifically, in several seizures, linear or non-linear increase in high-frequency neuronal coordination during ictal intervals, coincided with a corresponding decrease in coordination at frequencies <100 Hz, suggesting a potential interference role of high-frequency activity, to disrupt abnormal ictal synchrony at lower frequencies. These changes in network synchrony started at least 20-30s prior to seizure offset, depending on the seizure duration. Opposite patterns were estimated at frequencies ≤ 100 Hz in several seizures. These results raise the possibility that high-frequency interference may occur in the form of progressive network coordination during the ictal interval, which continues during the postictal interval. This may be one of several possible mechanisms that facilitate seizure termination. In fact, inhibition of pairwise interactions between EEGs by other signals in their spatial neighborhood, quantified by negative interaction information, was estimated at frequencies ≤ 100 Hz, at least in some seizures. Copyright © 2013 Elsevier B.V. All rights reserved.

High spatial resolution upgrade of the electron cyclotron emission radiometer for the DIII-D tokamak.

PubMed

Truong, D D; Austin, M E

2014-11-01

The 40-channel DIII-D electron cyclotron emission (ECE) radiometer provides measurements of Te(r,t) at the tokamak midplane from optically thick, second harmonic X-mode emission over a frequency range of 83-130 GHz. The frequency spacing of the radiometer's channels results in a spatial resolution of ∼1-3 cm, depending on local magnetic field and electron temperature. A new high resolution subsystem has been added to the DIII-D ECE radiometer to make sub-centimeter (0.6-0.8 cm) resolution Te measurements. The high resolution subsystem branches off from the regular channels' IF bands and consists of a microwave switch to toggle between IF bands, a switched filter bank for frequency selectivity, an adjustable local oscillator and mixer for further frequency down-conversion, and a set of eight microwave filters in the 2-4 GHz range. Higher spatial resolution is achieved through the use of a narrower (200 MHz) filter bandwidth and closer spacing between the filters' center frequencies (250 MHz). This configuration allows for full coverage of the 83-130 GHz frequency range in 2 GHz bands. Depending on the local magnetic field, this translates into a "zoomed-in" analysis of a ∼2-4 cm radial region. Expected uses of these channels include mapping the spatial dependence of Alfven eigenmodes, geodesic acoustic modes, and externally applied magnetic perturbations. Initial Te measurements, which demonstrate that the desired resolution is achieved, are presented.

Within-host competitive interactions as a mechanism for the maintenance of parasite diversity

PubMed Central

Bashey, Farrah

2015-01-01

Variation among parasite strains can affect the progression of disease or the effectiveness of treatment. What maintains parasite diversity? Here I argue that competition among parasites within the host is a major cause of variation among parasites. The competitive environment within the host can vary depending on the parasite genotypes present. For example, parasite strategies that target specific competitors, such as bacteriocins, are dependent on the presence and susceptibility of those competitors for success. Accordingly, which parasite traits are favoured by within-host selection can vary from host to host. Given the fluctuating fitness landscape across hosts, genotype by genotype (G×G) interactions among parasites should be prevalent. Moreover, selection should vary in a frequency-dependent manner, as attacking genotypes select for resistance and genotypes producing public goods select for cheaters. I review competitive coexistence theory with regard to parasites and highlight a few key examples where within-host competition promotes diversity. Finally, I discuss how within-host competition affects host health and our ability to successfully treat infectious diseases. PMID:26150667

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disrupting effects of antibiotic sulfathiazole on developmental process during sensitive life-cycle stage of Chironomus riparius.

PubMed

Park, Kiyun; Kwak, Ihn-Sil

2018-01-01

Antibiotics in the environment are a concern due to their potential to harm humans and interrupt ecosystems. Sulfathiazole (STZ), a sulfonamide antibiotic, is commonly used in aquaculture and is typically found in aquatic ecosystems. We evaluated the ecological risk of STZ by examining biological, molecular and biochemical response in Chironomus riparius. Samples were exposed to STZ for 12, 24 and 96 h, and effects of STZ were evaluated at the molecular level by analyzing changes in gene expression related to the endocrine system, cellular stress response and enzyme activity of genes on antioxidant and detoxification pathways. STZ exposure induced significant effects on survival, growth and sex ratio of emergent adults and mouthpart deformity in C. riparius. STZ caused concentration and time-dependent toxicity in most of the selected biomarkers. STZ exposure leads to significant heat-shock response of protein genes (HSP70, HSP40, HSP90 and HSP27) and to disruption by up-regulating selected genes, including the ecdysone receptor gene, estrogen-related receptors, ultraspiracle and E74 early ecdysone-responsive gene. Furthermore, STZ induced alteration of enzyme activities on antioxidant and detoxification responses (catalase, superoxide dismutase, glutathione peroxidase and peroxidase) in C. riparius. By inducing oxidative stress, antibiotic STZ disturbs the endocrine system and produces adverse effects in growth processes of invertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Columnar processing in primate pFC: evidence for executive control microcircuits.

PubMed

Opris, Ioan; Hampson, Robert E; Gerhardt, Greg A; Berger, Theodore W; Deadwyler, Sam A

2012-12-01

A common denominator for many cognitive disorders of human brain is the disruption of neural activity within pFC, whose structural basis is primarily interlaminar (columnar) microcircuits or "minicolumns." The importance of this brain region for executive decision-making has been well documented; however, because of technological constraints, the minicolumnar basis is not well understood. Here, via implementation of a unique conformal multielectrode recording array, the role of interlaminar pFC minicolumns in the executive control of task-related target selection is demonstrated in nonhuman primates performing a visuomotor DMS task. The results reveal target-specific, interlaminar correlated firing during the decision phase of the trial between multielectrode recording array-isolated minicolumnar pairs of neurons located in parallel in layers 2/3 and layer 5 of pFC. The functional significance of individual pFC minicolumns (separated by 40 μm) was shown by reduced correlated firing between cell pairs within single minicolumns on error trials with inappropriate target selection. To further demonstrate dependence on performance, a task-disrupting drug (cocaine) was administered in the middle of the session, which also reduced interlaminar firing in minicolumns that fired appropriately in the early (nondrug) portion of the session. The results provide a direct demonstration of task-specific, real-time columnar processing in pFC indicating the role of this type of microcircuit in executive control of decision-making in primate brain.

Spectral assignment and orientational analysis in a vibrational sum frequency generation study of DPPC monolayers at the air/water interface

NASA Astrophysics Data System (ADS)

Feng, Rong-Juan; Li, Xia; Zhang, Zhen; Lu, Zhou; Guo, Yuan

2016-12-01

The interfacial behavior of the benchmark zwitterionic phospholipid molecule dipalmitoylphosphatidylcholine (DPPC) has been extensively investigated by surface-selective vibrational sum frequency generation spectroscopy (VSFG). However, there is still a lack of agreement between various orientational measurements of phospholipid monolayers at the air/water interface, mainly because of the difficulty in assigning congested VSFG features. In this study, polarization-dependent VSFG measurements reveal a frequency shift between the in-plane and out-of-plane antisymmetric stretching modes of the terminal methyl groups in the DPPC alkyl tails, favoring the model of Cs local symmetry rather than the previously assumed C3v symmetry. Further VSFG experiments of isotopically labeled DPPC successfully capture the vibrational signatures of the glycerol backbone. With the newly derived VSFG polarization selection rules for Cs symmetry and the refreshed spectral assignments, the average tilt angles of the alkyl tail groups, choline headgroup, and glycerol backbone of DPPC molecules can all be determined, showing the powerful capability of VSFG spectroscopy in revealing the structural details at interfaces. The VSFG polarization dependence rules and the orientational analysis procedures developed for Cs symmetry in this work are applicable to other bulky molecules in which the methyl group cannot freely rotate, and they therefore have general applications in future VSFG studies.

Synonymous ABCA3 Variants Do Not Increase Risk for Neonatal Respiratory Distress Syndrome

PubMed Central

Wambach, Jennifer A.; Wegner, Daniel J.; Heins, Hillary B.; Druley, Todd E.; Mitra, Robi D.; Hamvas, Aaron; Cole, F. Sessions

2014-01-01

Objective To determine whether synonymous variants in the adenosine triphosphate-binding cassette A3 transporter (ABCA3) gene increase the risk for neonatal respiratory distress syndrome (RDS) in term and late preterm infants of European and African descent. Study design Using next-generation pooled sequencing of race-stratified DNA samples from infants of European and African descent at $34 weeks gestation with and without RDS (n = 503), we scanned all exons of ABCA3, validated each synonymous variant with an independent genotyping platform, and evaluated race-stratified disease risk associated with common synonymous variants and collapsed frequencies of rare synonymous variants. Results The synonymous ABCA3 variant frequency spectrum differs between infants of European descent and those of African descent. Using in silico prediction programs and statistical strategies, we found no potentially disruptive synonymous ABCA3 variants or evidence of selection pressure. Individual common synonymous variants and collapsed frequencies of rare synonymous variants did not increase disease risk in term and late-preterm infants of European or African descent. Conclusion In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent. PMID:24657120

Gamma rhythms link prefrontal interneuron dysfunction with cognitive inflexibility in Dlx5/6+/− mice

PubMed Central

Cho, Kathleen K.A.; Hoch, Renee; Lee, Anthony T.; Patel, Tosha; Rubenstein, John L.R.; Sohal, Vikaas S.

2015-01-01

SUMMARY Abnormalities in GABAergic interneurons, particularly fast-spiking interneurons (FSINs) that generate gamma (γ; ~30-120 Hz) oscillations, are hypothesized to disrupt prefrontal cortex (PFC)-dependent cognition in schizophrenia. Although γ rhythms are abnormal in schizophrenia, it remains unclear whether they directly influence cognition. Mechanisms underlying schizophrenia's typical post-adolescent onset also remain elusive. We addressed these issues using mice heterozygous for Dlx5/6, which regulate GABAergic interneuron development. In Dlx5/6+/− mice, FSINs become abnormal following adolescence, coinciding with the onset of cognitive inflexibility and deficient task-evoked γ oscillations. Inhibiting PFC interneurons in control mice reproduced these deficits, whereas stimulating them at γ-frequencies restored cognitive flexibility in adult Dlx5/6+/− mice. These pro-cognitive effects were frequency-specific and persistent. These findings elucidate a mechanism whereby abnormal FSIN development may contribute to the post-adolescent onset of schizophrenia endophenotypes. Furthermore, they demonstrate a causal, potentially therapeutic, role for PFC interneuron-driven gamma oscillations in cognitive domains at the core of schizophrenia. PMID:25754826

A Simple and Robust Method for Culturing Human-Induced Pluripotent Stem Cells in an Undifferentiated State Using Botulinum Hemagglutinin.

PubMed

Kim, Mee-Hae; Matsubara, Yoshifumi; Fujinaga, Yukako; Kino-Oka, Masahiro

2018-02-01

Clinical and industrial applications of human-induced pluripotent stem cells (hiPSCs) is hindered by the lack of robust culture strategies capable of sustaining a culture in an undifferentiated state. Here, a simple and robust hiPSC-culture-propagation strategy incorporating botulinum hemagglutinin (HA)-mediated selective removal of cells deviating from an undifferentiated state is developed. After HA treatment, cell-cell adhesion is disrupted, and deviated cells detached from the central region of the colony to subsequently form tight monolayer colonies following prolonged incubation. The authors find that the temporal and dose-dependent activity of HA regulated deviated-cell removal and recoverability after disruption of cell-cell adhesion in hiPSC colonies. The effects of HA are confirmed under all culture conditions examined, regardless of hiPSC line and feeder-dependent or -free culture conditions. After routine application of our HA-treatment paradigm for serial passages, hiPSCs maintains expression of pluripotent markers and readily forms embryoid bodies expressing markers for all three germ-cell layers. This method enables highly efficient culturing of hiPSCs and use of entire undifferentiated portions without having to pick deviated cells manually. This simple and readily reproducible culture strategy is a potentially useful tool for improving the robust and scalable maintenance of undifferentiated hiPSC cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Why is auditory frequency weighting so important in regulation of underwater noise?

PubMed

Tougaard, Jakob; Dähne, Michael

2017-10-01

A key question related to regulating noise from pile driving, air guns, and sonars is how to take into account the hearing abilities of different animals by means of auditory frequency weighting. Recordings of pile driving sounds, both in the presence and absence of a bubble curtain, were evaluated against recent thresholds for temporary threshold shift (TTS) for harbor porpoises by means of four different weighting functions. The assessed effectivity, expressed as time until TTS, depended strongly on choice of weighting function: 2 orders of magnitude larger for an audiogram-weighted TTS criterion relative to an unweighted criterion, highlighting the importance of selecting the right frequency weighting.

An empirical analysis of the distribution of overshoots in a stationary Gaussian stochastic process

NASA Technical Reports Server (NTRS)

Carter, M. C.; Madison, M. W.

1973-01-01

The frequency distribution of overshoots in a stationary Gaussian stochastic process is analyzed. The primary processes involved in this analysis are computer simulation and statistical estimation. Computer simulation is used to simulate stationary Gaussian stochastic processes that have selected autocorrelation functions. An analysis of the simulation results reveals a frequency distribution for overshoots with a functional dependence on the mean and variance of the process. Statistical estimation is then used to estimate the mean and variance of a process. It is shown that for an autocorrelation function, the mean and the variance for the number of overshoots, a frequency distribution for overshoots can be estimated.

The May 1967 great storm and radio disruption event: Extreme space weather and extraordinary responses

NASA Astrophysics Data System (ADS)

Knipp, D. J.; Ramsay, A. C.; Beard, E. D.; Boright, A. L.; Cade, W. B.; Hewins, I. M.; McFadden, R. H.; Denig, W. F.; Kilcommons, L. M.; Shea, M. A.; Smart, D. F.

2016-09-01

Although listed as one of the most significant events of the last 80 years, the space weather storm of late May 1967 has been of mostly fading academic interest. The storm made its initial mark with a colossal solar radio burst causing radio interference at frequencies between 0.01 and 9.0 GHz and near-simultaneous disruptions of dayside radio communication by intense fluxes of ionizing solar X-rays. Aspects of military control and communication were immediately challenged. Within hours a solar energetic particle event disrupted high-frequency communication in the polar cap. Subsequently, record-setting geomagnetic and ionospheric storms compounded the disruptions. We explain how the May 1967 storm was nearly one with ultimate societal impact, were it not for the nascent efforts of the United States Air Force in expanding its terrestrial weather monitoring-analysis-warning-prediction efforts into the realm of space weather forecasting. An important and long-lasting outcome of this storm was more formal Department of Defense-support for current-day space weather forecasting. This story develops during the rapid rise of solar cycle 20 and the intense Cold War in the latter half of the twentieth century. We detail the events of late May 1967 in the intersecting categories of solar-terrestrial interactions and the political-military backdrop of the Cold War. This was one of the "Great Storms" of the twentieth century, despite the apparent lack of large geomagnetically induced currents. Radio disruptions like those discussed here warrant the attention of today's radio-reliant, cellular-phone and satellite-navigation enabled world.

The May 1967 Great Storm and Radio Disruption Event: The Impacts We Didn't Know About

NASA Astrophysics Data System (ADS)

Knipp, D.

2016-12-01

Although listed as one of the most significant events of the last 80 years, the space weather storm of late May 1967 has been of mostly fading academic interest. The storm made its initial mark with a colossal solar radio burst causing radio interference at frequencies between 0.01-9.0 GHz and near-simultaneous disruptions of dayside radio communication by intense fluxes of ionizing solar X-rays. Aspects of military control and communication were immediately challenged. Within hours a solar energetic particle event disrupted high frequency communication in the polar cap. Subsequently record-setting geomagnetic and ionospheric storms compounded the disruptions. We explain how the May 1967 storm was nearly one with ultimate societal impact, were it not for the nascent efforts of the United States Air Force in expanding its terrestrial weather monitoring-analysis-warning-prediction efforts into the realm of space weather forecasting. This event is also one with severe impacts on thermospheric temperature and satellite drag. This story develops during the rapid rise of solar cycle 20 and the intense Cold War in the latter half of the 20th Century. We detail the events of late May 1967 in the intersecting categories of solar-terrestrial interactions and the political-military backdrop of the Cold War. This was one of the "Great Storms" of the 20th century, despite the lack of large geomagnetically-induced currents. Radio disruptions like those discussed here warrant the attention of today's radio-reliant, cellular-phone and satellite-navigation enabled world.