Functional connectivity change as shared signal dynamics

Science.gov (United States)

Cole, Michael W.; Yang, Genevieve J.; Murray, John D.; Repovš, Grega; Anticevic, Alan

2015-01-01

Background An increasing number of neuroscientific studies gain insights by focusing on differences in functional connectivity – between groups, individuals, temporal windows, or task conditions. We found using simulations that additional insights into such differences can be gained by forgoing variance normalization, a procedure used by most functional connectivity measures. Simulations indicated that these functional connectivity measures are sensitive to increases in independent fluctuations (unshared signal) in time series, consistently reducing functional connectivity estimates (e.g., correlations) even though such changes are unrelated to corresponding fluctuations (shared signal) between those time series. This is inconsistent with the common notion of functional connectivity as the amount of inter-region interaction. New Method Simulations revealed that a version of correlation without variance normalization – covariance – was able to isolate differences in shared signal, increasing interpretability of observed functional connectivity change. Simulations also revealed cases problematic for non-normalized methods, leading to a “covariance conjunction” method combining the benefits of both normalized and non-normalized approaches. Results We found that covariance and covariance conjunction methods can detect functional connectivity changes across a variety of tasks and rest in both clinical and non-clinical functional MRI datasets. Comparison with Existing Method(s) We verified using a variety of tasks and rest in both clinical and non-clinical functional MRI datasets that it matters in practice whether correlation, covariance, or covariance conjunction methods are used. Conclusions These results demonstrate the practical and theoretical utility of isolating changes in shared signal, improving the ability to interpret observed functional connectivity change. PMID:26642966

Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling.

Science.gov (United States)

Noctor, Graham; Foyer, Christine H

2016-07-01

Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. © 2016 American Society of Plant Biologists. All Rights Reserved.

Sensibility to Changes of Vibrational Modes of Excited Electron: Sum Frequency Signals Versus Difference Frequency Signals

International Nuclear Information System (INIS)

Gu Anna; Liang Xianting

2011-01-01

In this paper, we investigate a two electronic level system with vibrational modes coupled to a Brownian oscillator bath. The difference frequency generation (DFG) signals and sum frequency generation (SFG) signals are calculated. It is shown that, for the same model, the SFG signals are more sensitive than the DFG signals to the changes of the vibrational modes of the electronic two-level system. Because the SFG conversion efficiency can be improved by using the time-delay method, the findings in this paper predict that the SFG spectrum may probe the changes of the microstructure more effectively. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack.

Science.gov (United States)

De Vos, Martin; Van Oosten, Vivian R; Van Poecke, Remco M P; Van Pelt, Johan A; Pozo, Maria J; Mueller, Martin J; Buchala, Antony J; Métraux, Jean-Pierre; Van Loon, L C; Dicke, Marcel; Pieterse, Corné M J

2005-09-01

Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and E occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.

10Be and relative paleointensity signals across the last geomagnetic reversal

Science.gov (United States)

Savranskaia, T.; Valet, J. P.; Bassinot, F. C.; Meynadier, L.; Simon, Q.; Bourles, D. L.; Thouveny, N.; Thevarasan, A.; Villedieu, A.; Choy, S.; Gacem, L.

2017-12-01

Two techniques can be used to determine the evolution of the geomagnetic field intensity in the past. The first one relies on records of relative paleointensity (RPI) in sediments. Although they remain relatively sparse detailed records of 10Be production (expressed in terms of 10Be/9Be) provide an alternative approach. However integration of 10Be within the sediment is not better understood than the magnetization process, and therefore paleofield studies should greatly benefit from the integration of both datasets. In order to achieve this goal, it is crucial to compare and analyze the signals over a common time period. We selected five sedimentary cores from the Indian, Pacific and Atlantic Oceans and focused on the last reversal which is characterized by the largest intensity changes. Since 10Be is homogenized in the atmosphere, the same amount of 10Be should be recorded everywhere. We found different amounts of 10Be at each site during the last reversal which appear roughly correlated with accumulation rate. In contrast the 10Be amplitude is similar at all locations while higher amplitude signals are expected for low deposition rates. Taking advantage of the distribution of tektites layers, the beryllium signals have been deconvolved, but this procedure did not strikingly change the results. Despite atmospheric mixing we wonder whether 10Be production was slightly different at each location in presence of a multipolar transitional field. The comparison between the 10Be and RPI signals reveals large similarities but also puzzling differences. In particular, the relationship between the two signals is not the same during periods of stable polarity as during the transitional interval. A precursor with low intensity is present in several RPI records but not clearly marked on the beryllium records. We also addressed the question of a possible offset between the two signals that would be indicative of a delayed magnetization acquisition. After correlating and

Real-time measurement of relative sensor position changes using ultrasonic signal evaluation

Energy Technology Data Exchange (ETDEWEB)

Yastrebova, O.; Bulavinov, A.; Kroening, M. [Fraunhofer Institute Nondestructive Testing IZFP, Saarbruecken (Germany)

2008-07-01

Ultrasonic testing is considered to be one of the most commonly applied nondestructive testing techniques for flaw detection and material characterization. Traditional Nondestructive Testing (NDT) provides detection of material discontinuities that may cause failure within the designed lifetime of a part or component. In addition, Quantitative Nondestructive Testing (QNDT) provides means to obtain required information about type, size and location of deficiencies to the integrity of the inspected structure and further use under specific, given load conditions. The ''Acoustic Mouse'' technique has been developed as a tool for manual ultrasonic inspection to provide test results that can be evaluated quantitatively. The ultrasonic data are processed by real-time variation methods to extract position information from backscattered acoustic noise and geometric scatter signals in the inspection volume. The position and positional changes of the ''Acoustic Mouse'' sensor (transducer) are determined by the sequential analysis of ultrasonic data (highresolution sector-scans), which are acquired and reconstructed using the Sampling Phased Array technique. The results of first experiments conducted with linear scanning and intentional lift-offs demonstrate sufficient accuracy in position measurements. (orig.)

Kernicterus with abnormal high-signal changes bilaterally in the globus pallidus: A case report.

LENUS (Irish Health Repository)

Culleton, S

2018-04-01

Kernicterus is a relatively rare consequence of hyperbilirubinemia. There is an important role for MRI imaging for this entity in the appropriate clinical context as there are distinct signal changes in the globus pallidus. A case report and image findings are presented

Selection for Social Signalling Drives the Evolution of Chameleon Colour Change

Science.gov (United States)

Stuart-Fox, Devi; Moussalli, Adnan

2008-01-01

Rapid colour change is a remarkable natural phenomenon that has evolved in several vertebrate and invertebrate lineages. The two principal explanations for the evolution of this adaptive strategy are (1) natural selection for crypsis (camouflage) against a range of different backgrounds and (2) selection for conspicuous social signals that maximise detectability to conspecifics, yet minimise exposure to predators because they are only briefly displayed. Here we show that evolutionary shifts in capacity for colour change in southern African dwarf chameleons (Bradypodion spp.) are associated with increasingly conspicuous signals used in male contests and courtship. To the chameleon visual system, species showing the most dramatic colour change display social signals that contrast most against the environmental background and amongst adjacent body regions. We found no evidence for the crypsis hypothesis, a finding reinforced by visual models of how both chameleons and their avian predators perceive chameleon colour variation. Instead, our results suggest that selection for conspicuous social signals drives the evolution of colour change in this system, supporting the view that transitory display traits should be under strong selection for signal detectability. PMID:18232740

Outside-In Signal Transmission by Conformational Changes in Integrin Mac-11

Science.gov (United States)

Lefort, Craig T.; Hyun, Young-Min; Schultz, Joanne B.; Law, Foon-Yee; Waugh, Richard E.; Knauf, Philip A.; Kim, Minsoo

2010-01-01

Intracellular signals associated with or triggered by integrin ligation can control cell survival, differentiation, proliferation, and migration. Despite accumulating evidence that conformational changes regulate integrin affinity to its ligands, how integrin structure regulates signal transmission from the outside to the inside of the cell remains elusive. Using fluorescence resonance energy transfer, we addressed whether conformational changes in integrin Mac-1 are sufficient to transmit outside-in signals in human neutrophils. Mac-1 conformational activation induced by ligand occupancy or activating Ab binding, but not integrin clustering, triggered similar patterns of intracellular protein tyrosine phosphorylation, including Akt phosphorylation, and inhibited spontaneous neutrophil apoptosis, indicating that global conformational changes are critical for Mac-1-dependent outside-in signal transduction. In neutrophils and myeloid K562 cells, ligand ICAM-1 or activating Ab binding promoted switchblade-like extension of the Mac-1 extracellular domain and separation of the αM and β2 subunit cytoplasmic tails, two structural hallmarks of integrin activation. These data suggest the primacy of global conformational changes in the generation of Mac-1 outside-in signals. PMID:19864611

Melting glaciers signal climate change in Bolivia | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

2011-05-13

May 13, 2011 ... Melting glaciers signal climate change in Bolivia ... Global warming is occurring faster at high altitudes, causing the ... and how the local environment was going to change in years to come. ... New economic opportunities and better transportation to markets in La Paz have brought migrants to the area.

Selection for social signalling drives the evolution of chameleon colour change.

Directory of Open Access Journals (Sweden)

Devi Stuart-Fox

2008-01-01

Full Text Available Rapid colour change is a remarkable natural phenomenon that has evolved in several vertebrate and invertebrate lineages. The two principal explanations for the evolution of this adaptive strategy are (1 natural selection for crypsis (camouflage against a range of different backgrounds and (2 selection for conspicuous social signals that maximise detectability to conspecifics, yet minimise exposure to predators because they are only briefly displayed. Here we show that evolutionary shifts in capacity for colour change in southern African dwarf chameleons (Bradypodion spp. are associated with increasingly conspicuous signals used in male contests and courtship. To the chameleon visual system, species showing the most dramatic colour change display social signals that contrast most against the environmental background and amongst adjacent body regions. We found no evidence for the crypsis hypothesis, a finding reinforced by visual models of how both chameleons and their avian predators perceive chameleon colour variation. Instead, our results suggest that selection for conspicuous social signals drives the evolution of colour change in this system, supporting the view that transitory display traits should be under strong selection for signal detectability.

Vigilance task-related change in brain functional connectivity as revealed by wavelet phase coherence analysis of near-infrared spectroscopy signals

Directory of Open Access Journals (Sweden)

Wang Wei

2016-08-01

Full Text Available This study aims to assess the vigilance task-related change in connectivity in healthy adults using wavelet phase coherence (WPCO analysis of near-infrared spectroscopy signals (NIRS. NIRS is a non-invasive neuroimaging technique for assessing brain activity. Continuous recordings of the NIRS signals were obtained from the prefrontal cortex (PFC and sensorimotor cortical areas of 20 young healthy adults (24.9±3.3 years during a 10-min resting state and a 20-min vigilance task state. The vigilance task was used to simulate driving mental load by judging three random numbers (i.e., whether odd numbers. The task was divided into two sessions: the first 10 minutes (Task t1 and the second 10 minutes (Task t2. The WPCO of six channel pairs were calculated in five frequency intervals: 0.6–2 Hz (I, 0.145–0.6 Hz (II, 0.052–0.145 Hz (III, 0.021–0.052 Hz (IV, and 0.0095–0.021 Hz (V. The significant WPCO formed global connectivity (GC maps in intervals I and II and functional connectivity (FC maps in intervals III to V. Results show that the GC levels in interval I and FC levels in interval III were significantly lower in the Task t2 than in the resting state (p < 0.05, particularly between the left PFC and bilateral sensorimotor regions. Also, the reaction time shows an increase in Task t2 compared with that in Task t1. However, no significant difference in WPCO was found between Task t1 and resting state. The results showed that the change in FC at the range of 0.6-2 Hz was not attributed to the vigilance task pe se, but the interaction effect of vigilance task and time factors. The findings suggest that the decreased attention level might be partly attributed to the reduced GC levels between the left prefrontal region and sensorimotor area. The present results provide a new insight into the vigilance task-related brain activity.

Dynamic change of ERPs related to selective attention to signals from left and right visual field during head-down tilt

Science.gov (United States)

Wei, Jinhe; Zhao, Lun; Van, Gongdong; Chen, Wenjuan; Ren, Wei; Duan, Ran

To study further the effect of head-down tilt(HDT) on slow positive potential in the event-related potentials(ERPs), the temporal and spatial features of visual ERPs changes during 2 hour HDT(-10 °) were compared with that during HUT(+20°) in 15 normal subjects. The stimuli were consisted of two color LED flashes appeared randomly in left or right visual field(LVF or RVF) with same probability. The subjects were asked to make switch response to target signals(T) differentially: switching to left for T in LVF and to right for T in RVF, ignoring non-target signals(N). Five sets of tests were made during HUT and HDT. ERPs were obtained from 9 locations on scalp. The mean value of the ERPs in the period from 0.32-0.55 s was taken as the amplitude of slow positive potential(P400). The main results were as follows. 1)The mean amplitude of P400 decreased during HDT which was more significant at the 2nd, 3rd and 5th set of tests; 2)spatially, the reduction of mean P400 amplitude during HDT was more significant for signals from RVF and was more significant at posterior and central brain regions than that on frontal locations. As that the positive potential probably reflects the active inhibition activity in the brain during attention process, these data provide further evidence showing that the higher brain function was affected by the simulated weightlessness and that this effect was not only transient but also with interesting spatial characteristics.

Chronic Intake of Commercial Sweeteners Induces Changes in Feeding Behavior and Signaling Pathways Related to the Control of Appetite in BALB/c Mice.

Science.gov (United States)

Barrios-Correa, Alberto A; Estrada, José A; Martel, Caroline; Olivier, Martin; López-Santiago, Rubén; Contreras, Irazú

2018-01-01

Nonnutritive sweetener use is a common practice worldwide. Although considered safe for human consumption, accumulating evidence suggests these compounds may affect metabolic homeostasis; however, there is no consensus on the role of frequent sweetener intake in appetite and weight loss. We sought to determine whether frequent intake of commercial sweeteners induces changes in the JAK2/STAT3 signaling pathway in the brain of mice, as it is involved in the regulation of appetite and body composition. We supplemented adult BALB/c mice with sucrose, steviol glycosides (SG), or sucralose, daily, for 6 weeks. After supplementation, we evaluated body composition and expression of total and phosphorylated JAK2, STAT3, and Akt, as well as SOCS3 and ObRb, in brain tissue. Our results show that frequent intake of commercial SG decreases energy intake, adiposity, and weight gain in male animals, while increasing the expression of pJAK2 and pSTAT3 in the brain, whereas sucralose increases weight gain and pJAK2 expression in females. Our results suggest that chronic intake of commercial sweeteners elicits changes in signaling pathways that have been related to the control of appetite and energy balance in vivo , which may have relevant consequences for the nutritional state and long term health of the organism.

MR imaging of proximal femur: age-related changes

International Nuclear Information System (INIS)

Kim, Ju Heon; Jeon, Woo Jin; Sohn, Cheol Ho; Park, Mi Ok; Lee, Seong Mun; Joo, Yang Gu; Suh, Soo Jhi; Pyun, Young Sik

1995-01-01

The purpose of this study is to illustrate MR patterns of signal intensity of proximal femur in normal subjects according to the age distribution. T1-weighted MR images of the proximal femur in 125 subjects, aged 13 days to 25 years, were retrospectively analyzed. Age distribution was classified to 4 groups; below 4 months, 5 months to 4 years, 5 years to 14 years, and 15 years to 25 years. By the age of 4 months, the non-ossified femoral epiphysis was seen as intermediate-signal-intensity cartilage. At 5 months-4 years, the ossified femoral capital epiphysis was seen within intermediate-signal-intensity cartilage and appeared as decreased or increased signal-intensity red or yellow marrow surrounded by a rim of low-signal-intensity cortical bone. At 5-14 years, the ossified femoral capital and greater trochanteric epiphysis were seen within the intermediate-signal-intensity cartilage and appeared as decreased or increased signal-intensity red or yellow marrow. At 15-25 years, the proximal metaphyseal marrow showed increased signal intensity. Four patterns of the metaphyseal marrow were recognized by Ricci et al. The frequency of pattern 1 a progressively decreased with age. Pattern 2 and 3 were visible in the 15-25 years age group. An understanding of the spectrum of normal age-related change of the proximal femoral cartilage and marrow patterns serves as the foundation for interpretation of proximal femur pathologies

Within-Subject Testing of the Signaled-Reinforcement Effect on Operant Responding as Measured by Response Rate and Resistance to Change

Science.gov (United States)

Reed, Phil; Doughty, Adam H.

2005-01-01

Response rates under random-interval schedules are lower when a brief (500 ms) signal accompanies reinforcement than when there is no signal. The present study examined this signaled-reinforcement effect and its relation to resistance to change. In Experiment 1, rats responded on a multiple random-interval 60-s random-interval 60-s schedule, with…

Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells

Directory of Open Access Journals (Sweden)

Li CongJun

2006-09-01

Full Text Available Abstract Background Global gene expression profiles of bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The bovine microarray with 86,191 distinct 60mer oligonucleotides, each with 4 replicates, was designed and produced with Maskless Array Synthesizer technology. These oligonucleotides represent approximately 45,383 unique cattle sequences. Results 450 genes significantly regulated by butyrate with a median False Discovery Rate (FDR = 0 % were identified. The majority of these genes were repressed by butyrate and associated with cell cycle control. The expression levels of 30 selected genes identified by the microarray were confirmed using real-time PCR. The results from real-time PCR positively correlated (R = 0.867 with the results from the microarray. Conclusion This study presented the genes related to multiple signal pathways such as cell cycle control and apoptosis. The profound changes in gene expression elucidate the molecular basis for the pleiotropic effects of butyrate on biological processes. These findings enable better recognition of the full range of beneficial roles butyrate may play during cattle energy metabolism, cell growth and proliferation, and possibly in fighting gastrointestinal pathogens.

Relation between stability and resilience determines the performance of early warning signals under different environmental drivers.

Science.gov (United States)

Dai, Lei; Korolev, Kirill S; Gore, Jeff

2015-08-11

Shifting patterns of temporal fluctuations have been found to signal critical transitions in a variety of systems, from ecological communities to human physiology. However, failure of these early warning signals in some systems calls for a better understanding of their limitations. In particular, little is known about the generality of early warning signals in different deteriorating environments. In this study, we characterized how multiple environmental drivers influence the dynamics of laboratory yeast populations, which was previously shown to display alternative stable states [Dai et al., Science, 2012]. We observed that both the coefficient of variation and autocorrelation increased before population collapse in two slowly deteriorating environments, one with a rising death rate and the other one with decreasing nutrient availability. We compared the performance of early warning signals across multiple environments as "indicators for loss of resilience." We find that the varying performance is determined by how a system responds to changes in a specific driver, which can be captured by a relation between stability (recovery rate) and resilience (size of the basin of attraction). Furthermore, we demonstrate that the positive correlation between stability and resilience, as the essential assumption of indicators based on critical slowing down, can break down in this system when multiple environmental drivers are changed simultaneously. Our results suggest that the stability-resilience relation needs to be better understood for the application of early warning signals in different scenarios.

Early detection of structual changes in random signal

International Nuclear Information System (INIS)

Kuroda, Yoshiteru; Yokota, Katsuhiro

1981-01-01

Early detection of structual changes in observed random signal is very important from the point of system diagnosis. In this paper, the following procedures are applied to this problem and the results are compared. (1) auto-regressive model to random signal to calculate the prediction error, i.e., the defference between observed and predicted values. (2) auto-regressive method to caluculate the sum of the prediction error. (3) a method is based on AIC (Akaike Information Criterion). Simulation is made of these procedures, indicating their merits and demerits as a diagostic tools. (author)

The role of learning-related dopamine signals in addiction vulnerability.

Science.gov (United States)

Huys, Quentin J M; Tobler, Philippe N; Hasler, Gregor; Flagel, Shelly B

2014-01-01

Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction. © 2014 Elsevier B.V. All rights reserved.

Climate Signals: An On-Line Digital Platform for Mapping Climate Change Impacts in Real Time

Science.gov (United States)

Cutting, H.

2016-12-01

Climate Signals is an on-line digital platform for cataloging and mapping the impacts of climate change. The CS platform specifies and details the chains of connections between greenhouse gas emissions and individual climate events. Currently in open-beta release, the platform is designed to to engage and serve the general public, news media, and policy-makers, particularly in real-time during extreme climate events. Climate Signals consists of a curated relational database of events and their links to climate change, a mapping engine, and a gallery of climate change monitors offering real-time data. For each event in the database, an infographic engine provides a custom attribution "tree" that illustrates the connections to climate change. In addition, links to key contextual resources are aggregated and curated for each event. All event records are fully annotated with detailed source citations and corresponding hyper links. The system of attribution used to link events to climate change in real-time is detailed here. This open-beta release is offered for public user testing and engagement. Launched in May 2016, the operation of this platform offers lessons for public engagement in climate change impacts.

The relative importance of impacts from climate change vs. emissions change on air pollution levels in the 21st century

Directory of Open Access Journals (Sweden)

G. B. Hedegaard

2013-04-01

Full Text Available So far several studies have analysed the impacts of climate change on future air pollution levels. Significant changes due to impacts of climate change have been made clear. Nevertheless, these changes are not yet included in national, regional or global air pollution reduction strategies. The changes in future air pollution levels are caused by both impacts from climate change and anthropogenic emission changes, the importance of which needs to be quantified and compared. In this study we use the Danish Eulerian Hemispheric Model (DEHM driven by meteorological input data from the coupled Atmosphere-Ocean General Circulation Model ECHAM5/MPI-OM and forced with the newly developed RCP4.5 emissions. The relative importance of the climate signal and the signal from changes in anthropogenic emissions on the future ozone, black carbon (BC, total particulate matter with a diameter below 2.5 μm (total PM2.5 including BC, primary organic carbon (OC, mineral dust and secondary inorganic aerosols (SIA and total nitrogen (including NHx + NOy has been determined. For ozone, the impacts of anthropogenic emissions dominate, though a climate penalty is found in the Arctic region and northwestern Europe, where the signal from climate change dampens the effect from the projected emission reductions of anthropogenic ozone precursors. The investigated particles are even more dominated by the impacts from emission changes. For black carbon the emission signal dominates slightly at high latitudes, with an increase up to an order of magnitude larger, close to the emission sources in temperate and subtropical areas. Including all particulate matter with a diameter below 2.5 μm (total PM2.5 enhances the dominance from emissions change. In contrast, total nitrogen (NHx + NOy in parts of the Arctic and at low latitudes is dominated by impacts of climate change.

Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

DEFF Research Database (Denmark)

Schäfer, Katharina; Blankenburg, Felix; Kupers, Ron

2012-01-01

that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI......) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT......-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition....

Inferring the functional effect of gene expression changes in signaling pathways

Science.gov (United States)

Sebastián-León, Patricia; Carbonell, José; Salavert, Francisco; Sanchez, Rubén; Medina, Ignacio; Dopazo, Joaquín

2013-01-01

Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case–control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/. PMID:23748960

Quantifying signal changes in nano-wire based biosensors

DEFF Research Database (Denmark)

De Vico, Luca; Sørensen, Martin Hedegård; Iversen, Lars

2011-01-01

In this work, we present a computational methodology for predicting the change in signal (conductance sensitivity) of a nano-BioFET sensor (a sensor based on a biomolecule binding another biomolecule attached to a nano-wire field effect transistor) upon binding its target molecule. The methodolog...

Radioresistance-related signaling pathways in nasopharyngeal carcinoma cells

International Nuclear Information System (INIS)

Guo Ya; Zhu Xiaodong; Qu Song; Su Fang; Wang Qi; Zhang Wei

2011-01-01

Objective: To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2, and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma. Methods: The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2. CNE-2R and CNE-2 cells were cultured and administered with 60 Co γ-ray irradiation at the dose of 400 cGy for 15 times. Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes. Bioinformatic analysis was used to identify the pathways related to radioresistance. Results: The number of the differentially expressed genes that were found in these 2 experiments was 374. The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN, MYD88, CCL5, CXCL10, STAT1, LY96, FOS, CCL3, IL-6, IL-8, IL-1α, IL-1β, and IRAK2 (t=13.47-66.57, P<0.05). Conclusions: Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance. (authors)

Monitoring Local Regional Hemodynamic Signal Changes during Motor Execution and Motor Imagery Using Near-Infrared Spectroscopy

Directory of Open Access Journals (Sweden)

Naoki eIso

2016-01-01

Full Text Available The aim of this study was to clarify the topographical localization of motor-related regional hemodynamic signal changes during motor execution (ME and motor imagery (MI by using near-infrared spectroscopy (NIRS, as this technique is more clinically expedient than established methods (e.g. fMRI. Twenty right-handed healthy subjects participated in this study. The experimental protocol was a blocked design consisting of 3 cycles of 20 s of task performance and 30 s of rest. The tapping sequence task was performed with their fingers under 4 conditions: ME and MI with the right or left hand. Hemodynamic brain activity was measured with NIRS to monitor changes in oxygenated hemoglobin (oxy-Hb concentration. Oxy-Hb in the somatosensory motor cortex (SMC increased significantly only during contralateral ME and showed a significant interaction between task and hand. There was a main effect of hand in the left SMC. Although there were no significant main effects or interactions in the supplemental motor area (SMA and premotor area (PMA, oxy-Hb increased substantially under all conditions. These results clarified the topographical localization by motor-related regional hemodynamic signal changes during ME and MI by using NIRS.

Drusen regression is associated with local changes in fundus autofluorescence in intermediate age-related macular degeneration.

Science.gov (United States)

Toy, Brian C; Krishnadev, Nupura; Indaram, Maanasa; Cunningham, Denise; Cukras, Catherine A; Chew, Emily Y; Wong, Wai T

2013-09-01

To investigate the association of spontaneous drusen regression in intermediate age-related macular degeneration (AMD) with changes on fundus photography and fundus autofluorescence (FAF) imaging. Prospective observational case series. Fundus images from 58 eyes (in 58 patients) with intermediate AMD and large drusen were assessed over 2 years for areas of drusen regression that exceeded the area of circle C1 (diameter 125 μm; Age-Related Eye Disease Study grading protocol). Manual segmentation and computer-based image analysis were used to detect and delineate areas of drusen regression. Delineated regions were graded as to their appearance on fundus photographs and FAF images, and changes in FAF signal were graded manually and quantitated using automated image analysis. Drusen regression was detected in approximately half of study eyes using manual (48%) and computer-assisted (50%) techniques. At year-2, the clinical appearance of areas of drusen regression on fundus photography was mostly unremarkable, with a majority of eyes (71%) demonstrating no detectable clinical abnormalities, and the remainder (29%) showing minor pigmentary changes. However, drusen regression areas were associated with local changes in FAF that were significantly more prominent than changes on fundus photography. A majority of eyes (64%-66%) demonstrated a predominant decrease in overall FAF signal, while 14%-21% of eyes demonstrated a predominant increase in overall FAF signal. FAF imaging demonstrated that drusen regression in intermediate AMD was often accompanied by changes in local autofluorescence signal. Drusen regression may be associated with concurrent structural and physiologic changes in the outer retina. Published by Elsevier Inc.

High-signal T2 changes of the bone marrow of the foot and ankle in children: red marrow or traumatic changes?

International Nuclear Information System (INIS)

Shabshin, Nogah; Schweitzer, Mark E.; Morrison, William B.; Carrino, John A.; Keller, Marc S.; Grissom, Leslie E.

2006-01-01

High-signal T2-weighted bone marrow changes can be found in both bone marrow edema and hematopoietic marrow and are often seen on pediatric MR images of the feet and ankle. To evaluate whether high-signal T2 changes of the bone marrow seen on pediatric MRI of feet and ankles represent residual hematopoietic marrow. A total of 402 bones in 41 pediatric MRI studies of feet and ankles (34 children, 1-18 years) were reviewed by two observers who were blinded to the patients' ages. The studies were reviewed for the presence of high-signal changes of the bone marrow on sagittal fluid-sensitive images. The frequency and location of these foci were correlated with the patients' ages. High-signal T2 changes of the bone marrow were seen in 45/402 bones (11%) and in 24/41 patients younger than 16 years (59%). The changes were most commonly located in the calcaneus (54%), followed by the talus (35%) and navicular bone (35%), invariably at the endosteal surface. In 16 ankles, such foci were seen in the feet but not in the distal tibia/fibula. Symmetric presence (two ankles) or absence (four ankles) of high-signal marrow were seen in six of seven patients with bilateral ankles. High-signal T2 changes of the bone marrow in pediatric feet and ankle MRIs have a symmetric, fairly consistent pattern and disappear after the age of 15 years. We believe that these high-signal areas are normal and represent residual hematopoietic marrow. (orig.)

Effect of Electrode Belt and Body Positions on Regional Pulmonary Ventilation- and Perfusion-Related Impedance Changes Measured by Electric Impedance Tomography.

Directory of Open Access Journals (Sweden)

Elin Ericsson

Full Text Available Ventilator-induced or ventilator-associated lung injury (VILI/VALI is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation-related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion.

Close relationship between fMRI signals and transient heart rate changes accompanying K-complex. Simultaneous EEG/fMRI study

International Nuclear Information System (INIS)

Kan, Shigeyuki; Koike, Takahiko; Miyauchi, Satoru; Misaki, Masaya

2009-01-01

Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) allows the investigation of spontaneous activities in the human brain. Recently, by using this technique, increases in fMRI signal accompanying transient EEG activities such as sleep spindles and slow waves were reported. Although these fMRI signal increases appear to arise as a result of the neural activities being reflected in the EEG, when the influence of physiological activities upon fMRI signals are taken into consideration, it is highly controversial that fMRI signal increases accompanying transient EEG activities reflect actual neural activities. In the present study, we conducted simultaneous fMRI and polysomnograph recording of 18 normal adults, to study the effect of transient heart rate changes after a K-complex on fMRI signals. Significant fMRI signal increase was observed in the cerebellum, the ventral thalamus, the dorsal part of the brainstem, the periventricular white matter and the ventricle (quadrigeminal cistern). On the other hand, significant fMRI signal decrease was observed only in the right insula. Moreover, intensities of fMRI signal increase that was accompanied by a K-complex correlated positively with the magnitude of heart rate changes after a K-complex. Previous studies have reported that K-complex is closely related with sympathetic nervous activity and that the attributes of perfusion regulation in the brain differ during wakefulness and sleep. By taking these findings into consideration, our present results indicate that a close relationship exists between a K-complex and the changes in cardio- and neurovascular regulations that are mediated by the autonomic nervous system during sleep; further, these results indicate that transient heart rate changes after a K-complex can affect the fMRI signal generated in certain brain regions. (author)

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

Science.gov (United States)

Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition.

Science.gov (United States)

Meyers, Emily A; Gobeske, Kevin T; Bond, Allison M; Jarrett, Jennifer C; Peng, Chian-Yu; Kessler, John A

2016-02-01

Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

MR imaging of degenerative lumbar disc disease emphasizing on signal intensity changes in vertebral body

International Nuclear Information System (INIS)

Toyoda, Keiko; Ida, Masahiro; Murakami, Yoshitaka; Harada, Junta; Tada, Shimpei

1992-01-01

Magnetic resonance imaging was performed in 400 patients with degenerative disc disease. Signal changes and their sites in the vertebral body were classified and referred to narrowing of the intervertebral disc space. MR findings were compared with those of plain roentgenograms of the lumbar spine. Signal changes in the vertebral body were noted in 83 cases (102 vertebral bodies). Low-intensity abnormality on both T1- and T2-weighted images (WI) was the most common finding, and was most frequently seen at the end plate and/or the angle. These changes were correlated with narrowing of the disc space and osteosclerosis on the plain roentgenogram of the lumbar spine. Signal changes occasionally occurred in the inner region of the vertebral body, and these lesions tended to show a high-intensity abnormality on T1-WI. We conclude that signal changes in degenerative disc disease are not specific, but are sometimes difficult to distinguish from the signal changes in other conditions such as spinal tumor or bone marrow disorder. (author)

Analysis of MRI signal changes in the adjacent pedicle of adolescent patients with fresh lumbar spondylolysis.

Science.gov (United States)

Goda, Yuichiro; Sakai, Toshinori; Sakamaki, Tadanori; Takata, Yoichiro; Higashino, Kosaku; Sairyo, Koichi

2014-09-01

The purpose of this study is to investigate a discrepancy between MRI and computed tomography (CT) findings in the spinal level distribution of spondylolysis. Recent advances in MRI have led to the early diagnosis of spondylolysis. Therefore, bony healing can be expected before the condition has a chance to worsen. In this study, we used MRI to examine the changes in spinal level signals in the pedicles adjacent to the pars interarticularis in adolescents with fresh lumbar spondylolysis. We then compared spinal level distribution of spondylolysis with that of previous results obtained by multidetector CT. The study included 98 adolescent patients (31 women and 67 men; mean age, 13.6 years; age range, 9-18 years) with fresh lumbar spondylolysis who showed MRI signal changes in the adjacent pedicle. An MRI signal change was defined as a high signal change on fat-suppressed imaging. MRI signal changes were detected in 150 adjacent pedicles of 101 vertebrae. Of these vertebrae, MRI signal changes in only 67 (66.3%) corresponded to L5, while changes in 34 (33.7%) corresponded to L3 or L4. In our follow-up study, the bone-healing rate with no vertebral defect was 100% at L3, 97.1% at L4, and 84.4% at L5. In addition, 11 of 34 (32.4%) vertebrae with signal changes at L3 or L4 occurred with L5 terminal-stage spondylolysis (no MRI signal change). MRI revealed a higher prevalence of L3 or L4 spondylolysis than observed with CT.

MR imaging of lumbar spondylolysis: signal intensity change in the pars interarticularis and adjacent structures

Energy Technology Data Exchange (ETDEWEB)

Jang, Suk Whan; Lee, Ghi Jai; Shim, Jae Chan; Kim, Ho Kyun [Inje Univ. College of Medicine, Kimhae (Korea, Republic of)

2001-05-01

To assess changes in MR signal intensity in the pars interarticularis and adjacent structures in patients with lumbar spondylolysis. The MR images of 36 patients with lumbar spondylolysis, confirmed by plain radiographs, were retrospectively analyzed. Using a 1.0T unit, we evaluated the signal intensity of a total of 216 parts interarticulares and adjacent structures from L3 to L5, as seen on sagittal images, and differences between areas with and without spondylolysis. The signal intensity of T1-and T2-weighted images was graded 0(more hypointense than spinal body), 1(as isointense as spinal body), 2(more hyperintense than spinal body and more hypointense than epidural fat), or 3(as isointense as epidural fat). Signal intensity change in endplates and degree of spondylolisthesis were analyzed, and the relationship between these factors was determined. Spondylolysis was noted at L5 in 61 cases, at L4 in 22, and of L3 in no case. In three cases spondylolysis was unilateral, and in the remainder it was bilateral. The degree of signal intensity was the same on T1-and T2-weighted images, and no case was grade 0. Eighty-six of 133 areas without spondylolysis were grade 1, 43 were grade 2, and four were grade 3. In 42 of 47 cases, signal intensity change was localized at pedicles. Among 83 areas with spondylolysis,on the other hand, nine were grade 1, 48 were grade 2, and 26 were grade 3. Signal intensity change was most commonly observed at the pars interarticularis, pedicle, and lamina(50/74)({rho}<0.001). Signal intensity change at the pars interarticularis and adjacent structures was accompanied in most cases by degenerative endplate change(10/11) and spondylolisthesis(11/13)({rho}<0.001). In patients with spondylolysis, signal intensity was frequently higher at the pars interarticularis and adjacent structures, and is thought to have a close relationship with degenerative endplate change and spondylolisthesis. Increases in signal intensity at the pars

MR imaging of lumbar spondylolysis: signal intensity change in the pars interarticularis and adjacent structures

International Nuclear Information System (INIS)

Jang, Suk Whan; Lee, Ghi Jai; Shim, Jae Chan; Kim, Ho Kyun

2001-01-01

To assess changes in MR signal intensity in the pars interarticularis and adjacent structures in patients with lumbar spondylolysis. The MR images of 36 patients with lumbar spondylolysis, confirmed by plain radiographs, were retrospectively analyzed. Using a 1.0T unit, we evaluated the signal intensity of a total of 216 parts interarticulares and adjacent structures from L3 to L5, as seen on sagittal images, and differences between areas with and without spondylolysis. The signal intensity of T1-and T2-weighted images was graded 0(more hypointense than spinal body), 1(as isointense as spinal body), 2(more hyperintense than spinal body and more hypointense than epidural fat), or 3(as isointense as epidural fat). Signal intensity change in endplates and degree of spondylolisthesis were analyzed, and the relationship between these factors was determined. Spondylolysis was noted at L5 in 61 cases, at L4 in 22, and of L3 in no case. In three cases spondylolysis was unilateral, and in the remainder it was bilateral. The degree of signal intensity was the same on T1-and T2-weighted images, and no case was grade 0. Eighty-six of 133 areas without spondylolysis were grade 1, 43 were grade 2, and four were grade 3. In 42 of 47 cases, signal intensity change was localized at pedicles. Among 83 areas with spondylolysis,on the other hand, nine were grade 1, 48 were grade 2, and 26 were grade 3. Signal intensity change was most commonly observed at the pars interarticularis, pedicle, and lamina(50/74)(ρ<0.001). Signal intensity change at the pars interarticularis and adjacent structures was accompanied in most cases by degenerative endplate change(10/11) and spondylolisthesis(11/13)(ρ<0.001). In patients with spondylolysis, signal intensity was frequently higher at the pars interarticularis and adjacent structures, and is thought to have a close relationship with degenerative endplate change and spondylolisthesis. Increases in signal intensity at the pars interarticularis and

Hemodynamic and electrophysiological signals of conflict processing in the Chinese-character Stroop task: a simultaneous near-infrared spectroscopy and event-related potential study.

Science.gov (United States)

Zhai, Jiahuan; Li, Ting; Zhang, Zhongxing; Gong, Hui

2009-01-01

A dual-modality method combining continuous-wave near-infrared spectroscopy (NIRS) and event-related potentials (ERPs) was developed for the Chinese-character color-word Stroop task, which included congruent, incongruent, and neutral stimuli. Sixteen native Chinese speakers participated in this study. Hemodynamic and electrophysiological signals in the prefrontal cortex (PFC) were monitored simultaneously by NIRS and ERP. The hemodynamic signals were represented by relative changes in oxy-, deoxy-, and total hemoglobin concentration, whereas the electrophysiological signals were characterized by the parameters P450, N500, and P600. Both types of signals measured at four regions of the PFC were analyzed and compared spatially and temporally among the three different stimuli. We found that P600 signals correlated significantly with the hemodynamic parameters, suggesting that the PFC executes conflict-solving function. Additionally, we observed that the change in deoxy-Hb concentration showed higher sensitivity in response to the Stroop task than other hemodynamic signals. Correlation between NIRS and ERP signals revealed that the vascular response reflects the cumulative effect of neural activities. Taken together, our findings demonstrate that this new dual-modality method is a useful approach to obtaining more information during cognitive and physiological studies.

Metabolic Changes Underlying Bold Signal Variations after Administration of Zolpidem

International Nuclear Information System (INIS)

Rodriguez-Rojas, Rafael; Machado, Calixto; Alvarez, Lazaro; Carballo, Maylen; Perez-Nellar, Jesus; Estevez, Mario; Pavon, Nancy; Chinchilla, Mauricio

2010-12-01

Zolpidem is a non-benzodiazepine drug belonging to the imidazopiridine class, which has selectivity for stimulating the effect of gamma aminobutyric acid [GABA] and is used for the therapy of insomnia. Nonetheless, several reports have been published over recent years about a paradoxical arousing effect of Zolpidem in patients with severe brain damage. We studied a PVS case using 1 H-MRS and BOLD signal, before and after Zolpidem administration. Significantly increased BOLD signal was localized in left frontal superior cortex, bilateral cingulated areas, left thalamus and right head of the caudate nucleus. A transient activation was observed in frontal cortex, comprising portions of anterior cingulate, medial, and orbito-frontal cortices. Additionally, significant pharmacological activation in sensory-motor cortex is observed 1 hour after Zolpidem intake. Significant linear correlations of BOLD signal changes were found with primary concentrations of NAA, Glx and Lac in the right frontal cortex. We discussed that when Zolpidem attaches to the modified GABA receptors of the neurodormant cells, dormancy is switched off, inducing brain activation. This might explain the significant correlations of BOLD signal changes and 1 H-MRS metabolites in our patient. We concluded that 1 H-MRS and BOLD signal assessment might contribute to study neurovascular coupling in PVS cases after Zolpidem administration. Although this is a report of a single case, considering our results we recommend to apply this methodology in series of PVS and MCS patients. (author)

Ventilation and cardiac related impedance changes in children undergoing corrective open heart surgery

International Nuclear Information System (INIS)

Schibler, Andreas; Pham, Trang M T; Moray, Amol A; Stocker, Christian

2013-01-01

Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary children's hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance. (paper)

Ventilation and cardiac related impedance changes in children undergoing corrective open heart surgery.

Science.gov (United States)

Schibler, Andreas; Pham, Trang M T; Moray, Amol A; Stocker, Christian

2013-10-01

Electrical impedance tomography (EIT) can determine ventilation and perfusion relationship. Most of the data obtained so far originates from experimental settings and in healthy subjects. The aim of this study was to demonstrate that EIT measures the perioperative changes in pulmonary blood flow after repair of a ventricular septum defect in children with haemodynamic relevant septal defects undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary children's hospital ventilation and cardiac related impedance changes were measured using EIT before and after surgery in 18 spontaneously breathing patients. The EIT signals were either filtered for ventilation (ΔZV) or for cardiac (ΔZQ) related impedance changes. Impedance signals were then normalized (normΔZV, normΔZQ) for calculation of the global and regional impedance related ventilation perfusion relationship (normΔZV/normΔZQ). We observed a trend towards increased normΔZV in all lung regions, a significantly decreased normΔZQ in the global and anterior, but not the posterior lung region. The normΔZV/normΔZQ was significantly increased in the global and anterior lung region. Our study qualitatively validates our previously published modified EIT filtration technique in the clinical setting of young children with significant left-to-right shunt undergoing corrective open heart surgery, where perioperative assessment of the ventilation perfusion relation is of high clinical relevance.

Experimental study of MRI signal changes of calcification

International Nuclear Information System (INIS)

Gong Xiangyang; Li Senhua; Li Rongfen; Hong Xiang; Gong Xiaoya; Xu Fengfeng

1999-01-01

Objective: To evaluate MRI signal changes according to different calcium compound, concentration and proportion, and try to give an reasonable explanation. Methods: Sixty samples composed of different calcium powders, various concentration and proportion of calcium were examined with CT and MRI. Five different calcium particles were evaluated with scanning electron microscopy. Results: (1) CT value of calcium gradually increased as the concentration increased; (2) CaSO 4 ·H 2 O was similar to CaCO 3 in terms of MRI T 1 WI signal intensity (P > 0.05); (3) Ca 3 (PO 4 ) 2 and Ca(OH) 2 showed hyperintensity in T 1 WI and was higher than other calcium salts (P 1 WI signal intensity of Ca 3 (PO 4 ) 2 / and Ca(OH) 2 showed biphasic curves with their peaks at 0.3 g/ml; (5) T 2 WI signal intensity of all series of calcium decreased as the concentration increased; (6) Signal intensity of mixed Ca 3 (PO 4 ) 2 /CaCO 3 was higher than CaHPO 4 ·2H 2 O/CaCO 3 on T 1 WI and lower on T 2 WI (P 3 , CaHPO 4 ·2H 2 O and CaSO 4 ·2H 2 O showed regular crystal shapes and smooth surface under scanning electron microscopy, but Ca 3 (PO 4 ) 2 and Ca(OH) 2 displayed their irregular figures and rough surface. Conclusions: Calcifications show variable MR signal due to difference of calcium compounds, various concentration and proportion of calcium. Understanding of these finding will help interpretation of MR images more precisely

Time signal filtering by relative neighborhood graph localized linear approximation

DEFF Research Database (Denmark)

Sørensen, John Aasted

1994-01-01

A time signal filtering algorithm based on the relative neighborhood graph (RNG) used for localization of linear filters is proposed. The filter is constructed from a training signal during two stages. During the first stage an RNG is constructed. During the second stage, localized linear filters...

miRNA-mediated functional changes through co-regulating function related genes.

Directory of Open Access Journals (Sweden)

Jie He

Full Text Available BACKGROUND: MicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation. RESULTS: To explore the internal mechanism of miRNA-mediated regulation, we re-analyzed the data collected from genome-wide miRNA microarray with bioinformatics assay, and found that the transfection of miR-181b and miR-34a in Hela and HCT-116 tumor cells regulated large numbers of genes, among which, the genes related to cell growth and cell death demonstrated high Enrichment scores, suggesting that these miRNAs may be important in cell growth and cell death. MiR-181b induced changes in protein expression of most genes that were seemingly related to enhancing cell growth and decreasing cell death, while miR-34a mediated contrary changes of gene expression. Cell growth assays further confirmed this finding. In further study on miR-20b-mediated osteogenesis in hMSCs, miR-20b was found to enhance osteogenesis by activating BMPs/Runx2 signaling pathway in several stages by co-repressing of PPARγ, Bambi and Crim1. CONCLUSIONS: With its multi-target characteristics, miR-181b, miR-34a and miR-20b provoked detectable functional changes by co-regulating functionally-related gene groups or several genes in the same signaling pathway, and thus mild regulation from individual miRNA targeting genes could have contributed to an additive effect. This might also be one of the modes of miRNA-mediated gene regulation.

Early Transcriptional Changes Induced by Wnt/β-Catenin Signaling in Hippocampal Neurons

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Eduardo Pérez-Palma

2016-01-01

Full Text Available Wnt/β-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring in neurodegenerative and neurodevelopmental disorders. Since one of the main effects of Wnt/β-catenin signaling is the modulation of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed genes, including known Wnt/β-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a, Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364, p-adjusted = 2.5 × 10−7, forebrain development (GO:0030900, p-adjusted = 7.3 × 10−7, and stem cell differentiation (GO:0048863 p-adjusted = 7.3 × 10−7. Likewise, following activation of the signaling cascade, the expression of a significant number of genes with transcription factor activity (GO:0043565, p-adjusted = 4.1 × 10−6 was induced. We also studied molecular networks enriched upon Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486, p-adjusted = 4.5 × 10−19, learning or memory (GO:0007611, p-adjusted = 4.0 × 10−5, and neurotransmitter secretion (GO:0007269, p-adjusted = 5.3 × 10−12. Our results indicate that Wnt/β-catenin mediated transcription controls multiple biological processes related to neuronal structure and activity that are affected in synaptic dysfunction disorders.

MRI of the alar and transverse ligaments in whiplash-associated disorders (WAD) grades 1-2: high-signal changes by age, gender, event and time since trauma

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Vetti, Nils; Kraakenes, Jostein; Roervik, Jarle; Espeland, Ansgar [Haukeland University Hospital, Department of Radiology, Bergen (Norway); University of Bergen, Section for Radiology, Department of Surgical Sciences, Bergen (Norway); Eide, Geir Egil [Haukeland University Hospital, Centre for Clinical Research, Bergen (Norway); University of Bergen, Department of Public Health and Primary Health Care, Bergen (Norway); Gilhus, Nils Erik [Haukeland University Hospital, Department of Neurology, Bergen (Norway); University of Bergen, Section for Neurology, Department of Clinical Medicine, Bergen (Norway)

2009-04-15

This study describes the prevalence of high-signal changes at magnetic resonance imaging (MRI) of the alar and transverse ligaments in whiplash-associated disorders (WAD) grades 1-2 in relation to age, gender, spinal degeneration, type of trauma event and time since trauma. In 1,266 consecutive WAD1-2 patients (779 women, 487 men; mean age 42 years) referred from clinicians, high-signal changes in the alar and transverse ligaments at high-resolution proton-weighted MRI were prospectively graded 0-3 based on a previously reported, reliable grading system. Type of event according to The International Statistical Classification of Diseases and Related Health Problems and time of trauma were obtained from referral letters. MRI showed grades 2-3 alar ligament changes in 449 (35.5%; 95% confidence interval (CI), 32.8 to 38.1%) and grades 2-3 transverse ligament changes in 311 (24.6%; 95% CI, 22.2% to 26.9%) of the 1,266 patients. Grades 2-3 changes were more common in men than women, odds ratio 1.9 (95% CI, 1.5 to 2.5) for alar and 1.5 (95% CI, 1.1 to 2.0) for transverse ligament changes. High-signal changes were not related to age, spinal degeneration, type of trauma event or time since trauma (median 5 years). Unilateral changes were more often left- than right-sided. High-signal changes of the alar and transverse ligaments are common in WAD1-2 and unlikely to represent age-dependent degeneration. Their male and left-side preponderance cannot be explained by variation in ligament stretching or image artefacts. Further studies are needed to clarify whether such changes are caused by trauma. (orig.)

MRI of the alar and transverse ligaments in whiplash-associated disorders (WAD) grades 1-2: high-signal changes by age, gender, event and time since trauma

International Nuclear Information System (INIS)

Vetti, Nils; Kraakenes, Jostein; Roervik, Jarle; Espeland, Ansgar; Eide, Geir Egil; Gilhus, Nils Erik

2009-01-01

This study describes the prevalence of high-signal changes at magnetic resonance imaging (MRI) of the alar and transverse ligaments in whiplash-associated disorders (WAD) grades 1-2 in relation to age, gender, spinal degeneration, type of trauma event and time since trauma. In 1,266 consecutive WAD1-2 patients (779 women, 487 men; mean age 42 years) referred from clinicians, high-signal changes in the alar and transverse ligaments at high-resolution proton-weighted MRI were prospectively graded 0-3 based on a previously reported, reliable grading system. Type of event according to The International Statistical Classification of Diseases and Related Health Problems and time of trauma were obtained from referral letters. MRI showed grades 2-3 alar ligament changes in 449 (35.5%; 95% confidence interval (CI), 32.8 to 38.1%) and grades 2-3 transverse ligament changes in 311 (24.6%; 95% CI, 22.2% to 26.9%) of the 1,266 patients. Grades 2-3 changes were more common in men than women, odds ratio 1.9 (95% CI, 1.5 to 2.5) for alar and 1.5 (95% CI, 1.1 to 2.0) for transverse ligament changes. High-signal changes were not related to age, spinal degeneration, type of trauma event or time since trauma (median 5 years). Unilateral changes were more often left- than right-sided. High-signal changes of the alar and transverse ligaments are common in WAD1-2 and unlikely to represent age-dependent degeneration. Their male and left-side preponderance cannot be explained by variation in ligament stretching or image artefacts. Further studies are needed to clarify whether such changes are caused by trauma. (orig.)

Oncogenic Ras-Induced Morphologic Change Is through MEK/ERK Signaling Pathway to Downregulate Stat3 at a Posttranslational Level in NIH3T3 Cells

Directory of Open Access Journals (Sweden)

Hsuan-Heng Yeh

2008-01-01

Full Text Available Ras is a key regulator of the MAP kinase-signaling cascade and may cause morphologic change of Ras-transformed cells. Signal transducer and activator of transcription 3 (Stat3 can be activated by cytokine stimulation. In this study, we unravel that Ha-rasV12 overexpression can downregulate the expression of Stat3 protein at a posttranslational level in NIH3T3 cells. Furthermore, we demonstrate that Stat3 expression downregulated by Ha-rasV12 overexpression is through proteosome degradation and not through a mTOR/p70S6K-related signaling pathway. The suppression of Stat3 accompanied by the morphologic change induced by Ha-rasV12 was through mitogen extracellular kinase (MEK/extracellular-regulated kinase (ERK signaling pathway. Microtubule disruption is involved in Ha-rasV12-induced morphologic change, which could be reversed by overexpression of Stat3. Taken together, we are the first to demonstrate that Stat3 protein plays a critical role in Ha-rasV12-induced morphologic change. Oncogenic Ras-triggered morphologic change is through the activation of MEK/ERK to posttranslationally downregulate Stat3 expression. Our finding may shed light on developing novel therapeutic strategies against Ras-related tumorigenesis.

Signal analysis for failure detection

International Nuclear Information System (INIS)

Parpaglione, M.C.; Perez, L.V.; Rubio, D.A.; Czibener, D.; D'Attellis, C.E.; Brudny, P.I.; Ruzzante, J.E.

1994-01-01

Several methods for analysis of acoustic emission signals are presented. They are mainly oriented to detection of changes in noisy signals and characterization of higher amplitude discrete pulses or bursts. The aim was to relate changes and events with failure, crack or wear in materials, being the final goal to obtain automatic means of detecting such changes and/or events. Performance evaluation was made using both simulated and laboratory test signals. The methods being presented are the following: 1. Application of the Hopfield Neural Network (NN) model for classifying faults in pipes and detecting wear of a bearing. 2. Application of the Kohonnen and Back Propagation Neural Network model for the same problem. 3. Application of Kalman filtering to determine time occurrence of bursts. 4. Application of a bank of Kalman filters (KF) for failure detection in pipes. 5. Study of amplitude distribution of signals for detecting changes in their shape. 6. Application of the entropy distance to measure differences between signals. (author). 10 refs, 11 figs

Ridding fMRI data of motion-related influences: Removal of signals with distinct spatial and physical bases in multiecho data.

Science.gov (United States)

Power, Jonathan D; Plitt, Mark; Gotts, Stephen J; Kundu, Prantik; Voon, Valerie; Bandettini, Peter A; Martin, Alex

2018-02-27

"Functional connectivity" techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO 2 ) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.

Age-related changes in brain hemodynamics; A calibrated MRI study

DEFF Research Database (Denmark)

De Vis, J B; Hendrikse, J; Bhogal, A

2015-01-01

INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood....... A dual-echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO2 were...... calculated. RESULTS: Whole brain CBF was 49 ± 14 and 40 ± 9 ml/100 g/min in young and older subjects respectively (P brain, in the frontal...

MR imaging of the lacrimal gland. Age-related and gender-dependent changes in size and structure

International Nuclear Information System (INIS)

Ueno, H.; Ariji, E.; Izumi, M.; Uetani, M.; Hayashi, K.; Nakamura, T.

1996-01-01

Purpose: The subject of this study was to define age-related and gender-dependent changes in MR features of the lacrimal gland. Material and Methods: MR images were retrospectively analyzed in 104 normal subjects aged 2-79 years to measure thickness and area of the lacrimal gland, its MR signal intensity ratio, and SD of the MR signal intensity profile. Results: Thickness and area of the lacrimal gland decreased with age in women (p<0.001), but not in men. Furthermore, MR signal intensity ratio of the lacrimal gland showed an age-related increase in women (p<0.001), but not in men. On the other hand, SD of the MR signal intensity increased with age in both women and men (p<0.001). Conclusion: These findings demonstrate that gender has a significant influence on lacrimal gland structure during development and aging. (orig.)

Mis-segmentation in voxel-based morphometry due to a signal intensity change in the putamen.

Science.gov (United States)

Goto, Masami; Abe, Osamu; Miyati, Tosiaki; Aoki, Shigeki; Gomi, Tsutomu; Takeda, Tohoru

2017-12-01

The aims of this study were to demonstrate an association between changes in the signal intensity of the putamen on three-dimensional T1-weighted magnetic resonance images (3D-T1WI) and mis-segmentation, using the voxel-based morphometry (VBM) 8 toolbox. The sagittal 3D-T1WIs of 22 healthy volunteers were obtained for VBM analysis using the 1.5-T MR scanner. We prepared five levels of 3D-T1WI signal intensity (baseline, same level, background level, low level, and high level) in regions of interest containing the putamen. Groups of smoothed, spatially normalized tissue images were compared to the baseline group using a paired t test. The baseline was compared to the other four levels. In all comparisons, significant volume changes were observed around and outside the area that included the signal intensity change. The present study demonstrated an association between a change in the signal intensity of the putamen on 3D-T1WI and changed volume in segmented tissue images.

Age-related changes in normal adult pancreas: MR imaging evaluation

International Nuclear Information System (INIS)

Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Sone, Teruki; Noda, Yasufumi; Higaki, Atsushi; Kanki, Akihiko; Tanimoto, Daigo; Higashi, Hiroki

2012-01-01

Objective: To investigate age-related changes in normal adult pancreas as identified by magnetic resonance imaging (MRI). Materials and methods: We examined 115 patients without pancreatic diseases (21–90 years) who underwent upper abdominal MRI to evaluate the normal pancreatic MRI findings related to aging. The parameters examined were the pancreatic anteroposterior (AP) diameter, pancreatic lobulation, pancreatic signal intensity (SI), depiction of the main pancreatic duct (MPD), grade of the visual SI decrease on the opposed-phase T1-weighted images compared with in-phase images, and enhancement effect of the pancreas in the arterial phase of dynamic imaging. Results: The pancreatic AP diameter significantly reduced (head, p = 0.0172; body, p = 0.0007; tail, p < 0.0001), and lobulation (p < 0.0001) and parenchymal fatty change (p < 0.0001) became more evident with aging. No significant correlation was observed between aging and pancreatic SI, however the SI on the in-phase T1-weighted images tended to decrease with aging. No significant correlation was observed between aging and the depiction of the MPD as well as aging and contrast enhancement. Conclusion: MRI findings of pancreatic atrophy, lobulation, and fatty degeneration are characteristic changes related to aging, and it is necessary to recognize these changes in the interpretation of abdominal MRI in patients with and without pancreatic disease

Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

Directory of Open Access Journals (Sweden)

Wei Chi

Full Text Available The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus. How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male from the rice field eel to investigate changes in transcriptional level during the sex reversal process.Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes. These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary.This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes.

Science.gov (United States)

Wang, Xiaomei; Malawista, Anna; Qian, Feng; Ramsey, Christine; Allore, Heather G; Montgomery, Ruth R

2018-02-09

The multifactorial immune deterioration in aging--termed "inflamm-aging"--is comprised of a state of low-grade, chronic inflammation and complex dysregulation of responses to immune stimulation. The TAM family (Tyro 3, Axl, and Mer) of receptor tyrosine kinases are negative regulators of Toll like receptor-mediated immune responses that broadly inhibit cytokine receptor cascades to inhibit inflammation. Here we demonstrate elevated expression of TAM receptors in monocytes of older adults, and an age-dependent difference in signaling mediator AKT resulting in dysregulated responses to signaling though Mer. Our results may be especially significant in tissue, where levels of Mer are highest, and may present avenues for modulation of chronic tissue inflammation noted in aging.

Early warning signals of abrupt temperature change in different regions of China over the past 50 years

International Nuclear Information System (INIS)

Tong Ji-Long; Wu Hao; Hou Wei; He Wen-Ping; Zhou Jie

2014-01-01

In this paper, the early warning signals of abrupt temperature change in different regions of China are investigated. Seven regions are divided on the basis of different climate temperature patterns, obtained through the rotated empirical orthogonal function, and the signal-to-noise temperature ratios for each region are then calculated. Based on the concept of critical slowing down, the temperature data that contain noise in the different regions of China are preprocessed to study the early warning signals of abrupt climate change. First, the Mann–Kendall method is used to identify the instant of abrupt climate change in the temperature data. Second, autocorrelation coefficients that can identify critical slowing down are calculated. The results show that the critical slowing down phenomenon appeared in temperature data about 5–10 years before abrupt climate change occurred, which indicates that the critical slowing down phenomenon is a possible early warning signal for abrupt climate change, and that noise has less influence on the detection results of the early warning signals. Accordingly, this demonstrates that the model is reliable in identifying the early warning signals of abrupt climate change based on detecting the critical slowing down phenomenon, which provides an experimental basis for the actual application of the method. (geophysics, astronomy, and astrophysics)

Optimization of Quantum-state-preserving Frequency Conversion by Changing the Input Signal

DEFF Research Database (Denmark)

Andersen, Lasse Mejling; Reddy, D. V.; McKinstrie, C. J.

We optimize frequency conversion based on four-wave mixing by using the input modes of the system. We find a 10-25 % higher conversion efficiency relative to a pump-shaped input signal.......We optimize frequency conversion based on four-wave mixing by using the input modes of the system. We find a 10-25 % higher conversion efficiency relative to a pump-shaped input signal....

ROS-related redox regulation and signaling in plants.

Science.gov (United States)

Noctor, Graham; Reichheld, Jean-Philippe; Foyer, Christine H

2017-07-18

As sessile oxygenic organisms with a plastic developmental programme, plants are uniquely positioned to exploit reactive oxygen species (ROS) as powerful signals. Plants harbor numerous ROS-generating pathways, and these oxidants and related redox-active compounds have become tightly embedded into plant function and development during the course of evolution. One dominant view of ROS-removing systems sees them as beneficial antioxidants battling to keep damaging ROS below dangerous levels. However, it is now established that ROS are a necessary part of subcellular and intercellular communication in plants and that some of their signaling functions require ROS-metabolizing systems. For these reasons, it is suggested that "ROS processing systems" would be a more accurate term than "antioxidative systems" to describe cellular components that are most likely to interact with ROS and, in doing so, transmit oxidative signals. Within this framework, our update provides an overview of the complexity and compartmentation of ROS production and removal. We place particular emphasis on the importance of ROS-interacting systems such as the complex cellular thiol network in the redox regulation of phytohormone signaling pathways that are crucial for plant development and defense against external threats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combinations of SNPs Related to Signal Transduction in Bipolar Disorder

DEFF Research Database (Denmark)

Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente

2011-01-01

of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission...... and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC...... in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder....

Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques

Energy Technology Data Exchange (ETDEWEB)

Tang, T.Y.; Sadat, U. [Cambridge University Hospitals NHS Foundation Trust, University Department of Radiology, Cambridge (United Kingdom); Cambridge University Hospitals NHS Foundation Trust, Cambridge Vascular Unit, Cambridge (United Kingdom); Patterson, A.J.; Graves, M.J.; Howarth, S.P.S.; U-King-Im, J.M.; Li, Z.Y.; Young, V.E.; Gillard, J.H. [Cambridge University Hospitals NHS Foundation Trust, University Department of Radiology, Cambridge (United Kingdom); Miller, S.R. [GlaxoSmithKline, Biostatistics and Data Sciences, Harlow (United Kingdom); Walsh, S.R.; Boyle, J.R.; Gaunt, M.E. [Cambridge University Hospitals NHS Foundation Trust, Cambridge Vascular Unit, Cambridge (United Kingdom)

2009-07-15

Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T{sub 1}-weighted (T{sub 1}w), T{sub 2}*-weighted (T{sub 2}*w) and quantitative T{sub 2}* (qT{sub 2}*) imaging. Six patients with an asymptomatic carotid stenosis underwent high resolution T{sub 1}w, T{sub 2}*w and qT{sub 2}* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem trademark, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T{sub 1}w, T{sub 2}*w and qT{sub 2}* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T{sub 1}w, T{sub 2}*w and qT{sub 2}*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. This study showed that a suitable imaging window for T{sub 1}w, T{sub 2}*w and qT{sub 2}* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients. (orig.)

Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques

International Nuclear Information System (INIS)

Tang, T.Y.; Sadat, U.; Patterson, A.J.; Graves, M.J.; Howarth, S.P.S.; U-King-Im, J.M.; Li, Z.Y.; Young, V.E.; Gillard, J.H.; Miller, S.R.; Walsh, S.R.; Boyle, J.R.; Gaunt, M.E.

2009-01-01

Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T 1 -weighted (T 1 w), T 2 *-weighted (T 2 *w) and quantitative T 2 * (qT 2 *) imaging. Six patients with an asymptomatic carotid stenosis underwent high resolution T 1 w, T 2 *w and qT 2 * MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem trademark, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T 1 w, T 2 *w and qT 2 * sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T 1 w, T 2 *w and qT 2 *, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. This study showed that a suitable imaging window for T 1 w, T 2 *w and qT 2 * signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients. (orig.)

The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways.

Science.gov (United States)

Sun, Yahui; Ma, Chenkai; Halgamuge, Saman

2017-12-28

Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases.

Predictors of new vertebral endplate signal (Modic) changes in the general population

DEFF Research Database (Denmark)

Jensen, Tue Secher; Kjaer, Per; Korsholm, Lars

2010-01-01

predictors of new VESC were female gender, disc-related MRI findings (disc degeneration, disc bulges, disc herniation, and other endplate changes) and lifestyle factors [high physical work or leisure activity, high body mass index (BMI), and heavy smoking]. Bivariate and multivariate logistic regressions...... with disc degeneration, bulges or herniations at 40 were the only predictors of new VESC at age 44. Therefore, the development of new VESC at the age of 44 appears to be based on the status and dynamics of the disc, rather than being the result of gender or lifestyle factors such as smoking and physical...... were used to identify predictors of new VESC. New VESC at the age of 44 appeared in 67 of the 344. The majority (84%) of these new signal changes were type 1 VESC and almost half (45%) were only in the endplate and did not extend into the vertebral body. In the multivariate analysis, lumbar disc levels...

Interdependence of free zinc changes and protein complex assembly - insights into zinc signal regulation.

Science.gov (United States)

Kocyła, Anna; Adamczyk, Justyna; Krężel, Artur

2018-01-24

Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood. In this study, we aimed to examine how zinc protein domains with various Zn(ii)-binding architectures are formed under free Zn(ii) concentration changes and how formation of the Zn(ii)-dependent assemblies is related to the protein concentration and reactivity. To accomplish these goals we chose four zinc domains with different Zn(ii)-to-protein binding stoichiometries: classical zinc finger (ZnP), LIM domain (Zn 2 P), zinc hook (ZnP 2 ) and zinc clasp (ZnP 1 P 2 ) folds. Our research demonstrated a lack of changes in the saturation level of intraprotein zinc binding sites, despite various peptide concentrations, while homo- and heterodimers indicated a concentration-dependent tendency. In other words, at a certain free Zn(ii) concentration, the fraction of a formed dimeric complex increases or decreases with subunit concentration changes. Secondly, even small or local changes in free Zn(ii) may significantly affect protein saturation depending on its architecture, function and subcellular concentration. In our paper, we indicate the importance of interdependence of free Zn(ii) availability and protein subunit concentrations for cellular zinc signal regulation.

Joint Maximum Likelihood Time Delay Estimation of Unknown Event-Related Potential Signals for EEG Sensor Signal Quality Enhancement

Science.gov (United States)

Kim, Kyungsoo; Lim, Sung-Ho; Lee, Jaeseok; Kang, Won-Seok; Moon, Cheil; Choi, Ji-Woong

2016-01-01

Electroencephalograms (EEGs) measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI) studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR) is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP) signal that represents a brain’s response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE) schemes based on a joint maximum likelihood (ML) criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°. PMID:27322267

Joint Maximum Likelihood Time Delay Estimation of Unknown Event-Related Potential Signals for EEG Sensor Signal Quality Enhancement

Directory of Open Access Journals (Sweden)

Kyungsoo Kim

2016-06-01

Full Text Available Electroencephalograms (EEGs measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP signal that represents a brain’s response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE schemes based on a joint maximum likelihood (ML criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°.

Methamphetamine exposure triggers apoptosis and autophagy in neuronal cells by activating the C/EBPβ-related signaling pathway.

Science.gov (United States)

Xu, Xiang; Huang, Enping; Luo, Baoying; Cai, Dunpeng; Zhao, Xu; Luo, Qin; Jin, Yili; Chen, Ling; Wang, Qi; Liu, Chao; Lin, Zhoumeng; Xie, Wei-Bing; Wang, Huijun

2018-06-25

Methamphetamine (Meth) is a widely abused psychoactive drug that primarily damages the nervous system, notably causing dopaminergic neuronal apoptosis. CCAAT-enhancer binding protein (C/EBPβ) is a transcription factor and an important regulator of cell apoptosis and autophagy. Insulin-like growth factor binding protein (IGFBP5) is a proapoptotic factor that mediates Meth-induced neuronal apoptosis, and Trib3 (tribbles pseudokinase 3) is an endoplasmic reticulum (ER) stress-inducible gene involved in autophagic cell death through the mammalian target of rapamycin (mTOR) signaling pathway. To test the hypothesis that C/EBPβ is involved in Meth-induced IGFBP5-mediated neuronal apoptosis and Trib3-mediated neuronal autophagy, we measured the protein expression of C/EBPβ after Meth exposure and evaluated the effects of silencing C/EBPβ, IGFBP5, or Trib3 on Meth-induced apoptosis and autophagy in neuronal cells and in the rat striatum after intrastriatal Meth injection. We found that, at relatively high doses, Meth exposure increased C/EBPβ protein expression, which was accompanied by increased neuronal apoptosis and autophagy; triggered the IGFBP5-mediated, p53-up-regulated modulator of apoptosis (PUMA)-related mitochondrial apoptotic signaling pathway; and stimulated the Trib3-mediated ER stress signaling pathway through the Akt-mTOR signaling axis. We also found that autophagy is an early response to Meth-induced stress upstream of apoptosis and plays a detrimental role in Meth-induced neuronal cell death. These results suggest that Meth exposure induces C/EBPβ expression, which plays an essential role in the neuronal apoptosis and autophagy induced by relatively high doses of Meth; however, relatively low concentrations of Meth did not change the expression of C/EBPβ in vitro. Further studies are needed to elucidate the role of C/EBPβ in low-dose Meth-induced neurotoxicity.-Xu, X., Huang, E., Luo, B., Cai, D., Zhao, X., Luo, Q., Jin, Y., Chen, L., Wang, Q

Performance Improvement of Power Analysis Attacks on AES with Encryption-Related Signals

Science.gov (United States)

Lee, You-Seok; Lee, Young-Jun; Han, Dong-Guk; Kim, Ho-Won; Kim, Hyoung-Nam

A power analysis attack is a well-known side-channel attack but the efficiency of the attack is frequently degraded by the existence of power components, irrelative to the encryption included in signals used for the attack. To enhance the performance of the power analysis attack, we propose a preprocessing method based on extracting encryption-related parts from the measured power signals. Experimental results show that the attacks with the preprocessed signals detect correct keys with much fewer signals, compared to the conventional power analysis attacks.

Dopamine signaling in reward-related behaviors.

Science.gov (United States)

Baik, Ja-Hyun

2013-01-01

Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

Dopamine Signaling in reward-related behaviors

Directory of Open Access Journals (Sweden)

Ja-Hyun eBaik

2013-10-01

Full Text Available Dopamine (DA regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DAmesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural rewards such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

Building interpersonal trust within organizations: A relational signaling approach

NARCIS (Netherlands)

Six, F.E.

2007-01-01

This article develops the foundations for a theory of interpersonal trust-building based on relational signalling theory (RST). RST is based on the assumptions that rationality is bounded through framing, that preferences are partially determined by altruism (through a distinction between foreground

Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials

Science.gov (United States)

Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe

2004-09-01

We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity.

In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change.

Science.gov (United States)

Figley, Chase R; Leitch, Jordan K; Stroman, Patrick W

2010-10-01

Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. Copyright © 2010 Elsevier Inc. All rights reserved.

Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

Energy Technology Data Exchange (ETDEWEB)

Goyal, Manoj K; Sinha, Sanjib [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India); Ravishankar, Shivshankar; Shivshankar, Jai Jai [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

2009-03-15

Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 {+-} 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 {+-} 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

International Nuclear Information System (INIS)

Goyal, Manoj K.; Sinha, Sanjib; Ravishankar, Shivshankar; Shivshankar, Jai Jai

2009-01-01

Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 ± 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 ± 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

Age-Related Alterations in Signaling Pathways in Articular Chondrocytes: Implications for the Pathogenesis and Progression of Osteoarthritis - A Mini-Review.

Science.gov (United States)

van der Kraan, Peter; Matta, Csaba; Mobasheri, Ali

2017-01-01

Musculoskeletal conditions are a major burden on individuals, healthcare systems, and social care systems throughout the world, with indirect costs having a predominant economic impact. Aging is a major contributing factor to the development and progression of arthritic and musculoskeletal diseases. Indeed, aging and inflammation (often referred to as 'inflammaging') are critical risk factors for the development of osteoarthritis (OA), which is one of the most common forms of joint disease. The term 'chondrosenescence' has recently been introduced to define the age-dependent deterioration of chondrocyte function and how it undermines cartilage function in OA. An important component of chondrosenescence is the age-related deregulation of subcellular signaling pathways in chondrocytes. This mini-review discusses the role of age-related alterations in chondrocyte signaling pathways. We focus our attention on two major areas: age-dependent alterations in transforming growth factor-β signaling and changes in protein kinase and phosphoprotein phosphatase activities in aging chondrocytes. A better understanding of the basic signaling mechanisms underlying aging in chondrocytes is likely to facilitate the development of new therapeutic and preventive strategies for OA and a range of other age-related osteoarticular disorders. © 2016 The Author(s) Published by S. Karger AG, Basel.

Attending Weak Signals: The Prevention of Work-related Illnesses

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Roy Liff

2017-06-01

Full Text Available This article examines the characteristics of communication among managers, human resource (HR experts, and occupational health care specialists, as they deal with such informal information as weak signals in the prevention of work-related illnesses, using a theoretical framework in which the prevention of work-related illness is analogous to theory on crisis management. This is a qualitative study in which individual and focus-group interviews were conducted in a Swedish context with occupational health care specialists, managers, and HR experts. The results suggest that organizational solutions have failed and continue to fail at controlling workers’ health problems, although the main difficulty is not in identifying the ‘right’ individually oriented weak signals. Rather, it is upper management’s reliance on formal information (e.g., statistics and surveys – because of the difficulty in supplementing it with informal information (e.g., rumors and gossip – that makes it difficult to improve traditional health and safety work

Interleukin 4 signals through two related pathways.

Science.gov (United States)

Pernis, A; Witthuhn, B; Keegan, A D; Nelms, K; Garfein, E; Ihle, J N; Paul, W E; Pierce, J H; Rothman, P

1995-08-15

The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors.

Comparison of GFL–GFRα complexes: further evidence relating GFL bend angle to RET signalling

International Nuclear Information System (INIS)

Parkash, Vimal; Goldman, Adrian

2009-01-01

The second crystal structure of the GDNF-GFRα1 complex provides further evidence that GFL signalling through RET is determined by the bend angle in the GFL. Glial cell line-derived neurotrophic factor (GDNF) activates the receptor tyrosine kinase RET by binding to the GDNF-family receptor α1 (GFRα1) and forming the GDNF 2 –GFRα1 2 –RET 2 heterohexamer complex. A previous crystal structure of the GDNF 2 –GFRα1 2 complex suggested that differences in signalling in GDNF-family ligand (GFL) complexes might arise from differences in the bend angle between the two monomers in the GFL homodimer. Here, a 2.35 Å resolution structure of the GDNF 2 –GFRα1 2 complex crystallized with new cell dimensions is reported. The structure was refined to a final R factor of 22.5% (R free = 28%). The structures of both biological tetrameric complexes in the asymmetric unit are very similar to 2v5e and different from the artemin–GFRα3 structure, even though there is a small change in the structure of the GDNF. By comparison of all known GDNF and artemin structures, it is concluded that GDNF is more bent and more flexible than artemin and that this may be related to RET signalling. Comparisons also suggest that the differences between artemin and GDNF arise from the increased curvature of the artemin ‘fingers’, which both increases the buried surface area in the monomer–monomer interface and changes the intermonomer bend angle. From sequence comparison, it is suggested that neuturin (the second GFL) adopts an artemin-like conformation, while persephin has a different conformation to the other three

Effects of glyceryl trinitrate and calcitonin-gene-related peptide on BOLD signal and arterial diameter –methodological studies by fMRI and MRA

DEFF Research Database (Denmark)

Asghar, Mohammed Sohail; Ashina, Messoud

2013-01-01

Over the last decades MRI has proved to be very useful in the field of drug development and discovery. Pharmacological MRI (phMRI) explores the interaction between brain physiology, neuronal activity and drugs[1]. The BOLD-signal is an indirect method to investigate brain activity by way...... of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological...... substance on the BOLD-response per see before that substance can be used in an fMRI experiment. Furthermore MR-angiography is useful in determining the vascular site-of-action of vasoactive substances....

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

International Nuclear Information System (INIS)

Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

2002-01-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

Energy Technology Data Exchange (ETDEWEB)

Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

2002-04-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways.

Directory of Open Access Journals (Sweden)

Jane Palsgaard

Full Text Available BACKGROUND: Gene expression alterations have previously been associated with type 2 diabetes, however whether these changes are primary causes or secondary effects of type 2 diabetes is not known. As healthy first degree relatives of people with type 2 diabetes have an increased risk of developing type 2 diabetes, they provide a good model in the search for primary causes of the disease. METHODS/PRINCIPAL FINDINGS: We determined gene expression profiles in skeletal muscle biopsies from Caucasian males with type 2 diabetes, healthy first degree relatives, and healthy controls. Gene expression was measured using Affymetrix Human Genome U133 Plus 2.0 Arrays covering the entire human genome. These arrays have not previously been used for this type of study. We show for the first time that genes involved in insulin signaling are significantly upregulated in first degree relatives and significantly downregulated in people with type 2 diabetes. On the individual gene level, 11 genes showed altered expression levels in first degree relatives compared to controls, among others KIF1B and GDF8 (myostatin. LDHB was found to have a decreased expression in both groups compared to controls. CONCLUSIONS/SIGNIFICANCE: We hypothesize that increased expression of insulin signaling molecules in first degree relatives of people with type 2 diabetes, work in concert with increased levels of insulin as a compensatory mechanism, counter-acting otherwise reduced insulin signaling activity, protecting these individuals from severe insulin resistance. This compensation is lost in people with type 2 diabetes where expression of insulin signaling molecules is reduced.

Intra- and interobserver reproducibility of vertebral endplate signal (modic) changes in the lumbar spine

DEFF Research Database (Denmark)

Jensen, Tue Secher; Sorensen, Joan Solgaard; Kjær, Per

2007-01-01

. PURPOSE: To assess the intra- and interobserver reliability of the "Nordic Modic classification" protocol. MATERIAL AND METHODS: MRI scans of 50 individuals representative of the general Danish population aged 40 were evaluated by two observers. Criteria for grading the changes were developed...... by the Nordic Modic Consensus Group. After consensus was established, all 50 MRI examinations were evaluated independently by each observer. Intraobserver reliability was assessed by re-evaluation of the 50 examinations by one of the observers. Kappa statistics were used to calculate agreement. RESULTS: Intra....... CONCLUSION: In this study, we found convincing reproducibility of a detailed evaluation protocol of vertebral endplate signal changes, the "Nordic Modic Classification." The authors recommend that the evaluation protocol should be used in future studies investigating vertebral endplate signal changes....

A role for CaV1 and calcineurin signaling in depolarization-induced changes in neuronal DNA methylation.

Science.gov (United States)

Hannon, Eilis; Chand, Annisa N; Evans, Mark D; Wong, Chloe C Y; Grubb, Matthew S; Mill, Jonathan

2015-07-01

Direct manipulations of neuronal activity have been shown to induce changes in DNA methylation (DNAm), although little is known about the cellular signaling pathways involved. Using reduced representation bisulfite sequencing, we identify DNAm changes associated with moderate chronic depolarization in dissociated rat hippocampal cultures. Consistent with previous findings, these changes occurred primarily in the vicinity of loci implicated in neuronal function, being enriched in intergenic regions and underrepresented in CpG-rich promoter regulatory regions. We subsequently used 2 pharmacological interventions (nifedipine and FK-506) to test whether the identified changes depended on 2 interrelated signaling pathways known to mediate multiple forms of neuronal plasticity. Both pharmacological manipulations had notable effects on the extent and magnitude of depolarization-induced DNAm changes indicating that a high proportion of activity-induced changes are likely to be mediated by calcium entry through L-type Ca V 1 channels and/or downstream signaling via the calcium-dependent phosphatase calcineurin.

A role for CaV1 and calcineurin signaling in depolarization-induced changes in neuronal DNA methylation

Directory of Open Access Journals (Sweden)

Eilis Hannon

2015-07-01

Full Text Available Direct manipulations of neuronal activity have been shown to induce changes in DNA methylation (DNAm, although little is known about the cellular signaling pathways involved. Using reduced representation bisulfite sequencing, we identify DNAm changes associated with moderate chronic depolarization in dissociated rat hippocampal cultures. Consistent with previous findings, these changes occurred primarily in the vicinity of loci implicated in neuronal function, being enriched in intergenic regions and underrepresented in CpG-rich promoter regulatory regions. We subsequently used 2 pharmacological interventions (nifedipine and FK-506 to test whether the identified changes depended on 2 interrelated signaling pathways known to mediate multiple forms of neuronal plasticity. Both pharmacological manipulations had notable effects on the extent and magnitude of depolarization-induced DNAm changes indicating that a high proportion of activity-induced changes are likely to be mediated by calcium entry through L-type CaV1 channels and/or downstream signaling via the calcium-dependent phosphatase calcineurin.

Establishing the functional connectivity of the frontotemporal network in pre-attentive change detection with Transcranial Magnetic Stimulation and event-related optical signal.

Science.gov (United States)

Tse, Chun-Yu; Long-Yin, Yip; Lui, Troby Ka-Yan; Xiao, Xue-Zhen; Wang, Yang; Chu, Winnie Chiu Wing; Parks, Nathan Allen; Chan, Sandra Sau-Man; Neggers, Sebastiaan Franciscus Wijnandus

2018-06-18

Current theories of pre-attentive deviant detection postulate that before the Superior Temporal Cortex (STC) detects a change, the Inferior Frontal Cortex (IFC) engages in stimulus analysis, which is particularly critical for ambiguous deviations (e.g., deviant preceded by a short train of standards). These theories rest on the assumption that IFC and STC are functionally connected, which has only been supported by correlational brain imaging studies. We examined this functional connectivity assumption by applying Transcranial Magnetic Stimulation (TMS) to disrupt IFC function, while measuring the later STC mismatch response with the event-related optical signal (EROS). EROS can localize brain activity in both spatial and temporal dimensions via measurement of optical property changes associated with neuronal activity, and is inert to the electromagnetic interference produced by TMS. Specifically, the STC mismatch response at 120-180 ms elicited by a deviant preceded by a short standard train when IFC TMS was applied at 80 ms was compared with the STC mismatch responses in temporal control (TMS with 200 ms delay), spatial control (sham TMS at vertex), auditory control (TMS pulse noise only), and cognitive control (deviant preceded by a long standard train) conditions. The STC mismatch response to deviants preceded by the short train was abolished by TMS of the IFC at 80 ms, while the STC responses remained intact in all other control conditions. These results confirm the involvement of the IFC in the STC mismatch response and support a functional connection between IFC and STC. Copyright © 2018. Published by Elsevier Inc.

In hypertrophic cardiomyopathy reduction of relative resting myocardial blood flow is related to late enhancement, T2-signal and LV wall thickness.

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Katja Hueper

Full Text Available To quantify resting myocardial blood flow (MBF in the left ventricular (LV wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE, T2-signal abnormalities (dark and bright signal, LV outflow tract obstruction and age.Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal, LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher's exact test.804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001, extent of LGE (p<0.001, presence of edema, defined as focal T2 bright signal (p<0.001, T2 dark signal (p<0.001 and age (p = 0.032 correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p = 0.901. Multiple linear regression analysis revealed that LGE (p<0.001, edema (p = 0.026 and T2 dark signal (p = 0.019 were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion.In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of

Measurement of choroid plexus perfusion using dynamic susceptibility MR imaging: capillary permeability and age-related changes

Energy Technology Data Exchange (ETDEWEB)

Bouzerar, Roger; Chaarani, Bader; Baledent, Olivier [University Hospital, Image Processing Department, Amiens (France); Gondry-Jouet, Catherine [University Hospital, Radiology Department, Amiens (France); Zmudka, Jadwiga [University Hospital, Geriatric Unit, Amiens (France)

2013-12-15

The cerebrospinal fluid (CSF) plays a major role in the physiology of the central nervous system. The continuous turnover of CSF is mainly attributed to the highly vascularized choroid plexus (CP) located in the cerebral ventricles which represent a complex interface between blood and CSF. We propose a method for evaluating CP functionality in vivo using perfusion MR imaging and establish the age-related changes of associated parameters. Fifteen patients with small intracranial tumors were retrospectively studied. MR Imaging was performed on a 3T MR Scanner. Gradient-echo echo planar images were acquired after bolus injection of gadolinium-based contrast agent (CA). The software developed used the combined T1- and T2-effects. The decomposition of the relaxivity signals enables the calculation of the CP capillary permeability (K{sub 2}). The relative cerebral blood volume (rCBV), mean transit time (MTT), and signal slope decrease (SSD) were also calculated. The mean permeability K{sub 2} of the extracted CP was 0.033+/-0.18 s{sup -1}. K{sub 2} and SSD significantly decreased with subject's age whereas MTT significantly increased with subject's age. No significant correlation was found for age-related changes in rCBV and rCBF. The decrease in CP permeability is in line with the age-related changes in CSF secretion observed in animals. The MTT increase indicates significant structural changes corroborated by microscopy studies in animals or humans. Overall, DSC MR-perfusion enables an in vivo evaluation of the hemodynamic state of CP. Clinical applications such as neurodegenerative diseases could be considered thanks to specific functional studies of CP. (orig.)

Incidental magnetic resonance imaging signal changes in the extensor carpi radialis brevis origin are more common with age.

Science.gov (United States)

van Leeuwen, Wouter F; Janssen, Stein J; Ring, David; Chen, Neal

2016-07-01

Patients with enthesopathy of the extensor carpi radialis brevis (ECRB) demonstrate signal changes on magnetic resonance imaging (MRI). It is likely that these MRI changes persist for many years or may be permanent, regardless of symptoms, and represent an estimation of disease prevalence. We tested the hypothesis that the prevalence of incidental signal changes in the ECRB origin increases with age. We searched MRI reports of 3374 patients who underwent an MRI scan, including the elbow, for signal changes in the ECRB origin. Medical records were reviewed for symptoms consistent with ECRB enthesopathy. Prevalences of incidental and symptomatic signal changes were calculated and stratified by age. We used multivariate logistic regression analysis to test whether age, sex, and race were independently associated with ECRB enthesopathy and calculated odds ratios. Signal changes in ECRB origin were identified on MRI scans of 369 of 3374 patients (11%) without a clinical suspicion of tennis elbow. The prevalence increased from 5.7% in patients aged between 18 and 30 years up to 16% in patients aged 71 years and older. Older age (odds ratio, 1.04; P elbow MRI scans. Increased MRI signal in the ECRB origin is common in symptomatic and in asymptomatic elbows. Our findings support the concept that ECRB enthesopathy is a highly prevalent, self-limited process that seems to affect a minimum of 1 in approximately every 7 people. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Cellular Signal Mechanisms of Reward-Related Plasticity in the Hippocampus

Directory of Open Access Journals (Sweden)

Masako Isokawa

2012-01-01

Full Text Available The hippocampus has the extraordinary capacity to process and store information. Consequently, there is an intense interest in the mechanisms that underline learning and memory. Synaptic plasticity has been hypothesized to be the neuronal substrate for learning. Ca2+ and Ca2+-activated kinases control cellular processes of most forms of hippocampal synapse plasticity. In this paper, I aim to integrate our current understanding of Ca2+-mediated synaptic plasticity and metaplasticity in motivational and reward-related learning in the hippocampus. I will introduce two representative neuromodulators that are widely studied in reward-related learning (e.g., ghrelin and endocannabinoids and show how they might contribute to hippocampal neuron activities and Ca2+-mediated signaling processes in synaptic plasticity. Additionally, I will discuss functional significance of these two systems and their signaling pathways for its relevance to maladaptive reward learning leading to addiction.

Single amino acid change in STING leads to constitutive active signaling.

Directory of Open Access Journals (Sweden)

Eric D Tang

Full Text Available The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

Single amino acid change in STING leads to constitutive active signaling.

Science.gov (United States)

Tang, Eric D; Wang, Cun-Yu

2015-01-01

The production of cytokines by the immune system in response to cytosolic DNA plays an important role in host defense, autoimmune disease, and cancer immunogenicity. Recently a cytosolic DNA signaling pathway that is dependent on the endoplasmic reticulum adaptor and cyclic dinucleotide sensor protein STING has been identified. Association of cytosolic DNA with cyclic-GMP-AMP synthase (cGAS) activates its enzymatic activity to synthesize the cyclic dinucleotide second messenger cGAMP from GTP and ATP. Direct detection of cGAMP by STING triggers the activation of IRF3 and NF-kB, and the production of type I interferons and proinflammatory cytokines. The mechanism of how STING is able to mediate downstream signaling remains incompletely understood although it has been shown that dimerization is a prerequisite. Here, we identify a single amino acid change in STING that confers constitutive active signaling. This mutation appears to both enhance ability of STING to both dimerize and associate with its downstream target TBK1.

Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

Science.gov (United States)

Samanta, Sudipta; Mukherjee, Sanchita

2017-04-01

The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

Age-related oral changes.

LENUS (Irish Health Repository)

Mckenna, Gerald

2010-10-01

Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

Climate change signal and uncertainty in CMIP5-based projections of global ocean surface wave heights

Science.gov (United States)

Wang, Xiaolan L.; Feng, Yang; Swail, Val R.

2015-05-01

This study uses the analysis of variance approaches to quantify the climate change signal and uncertainty in multimodel ensembles of statistical simulations of significant wave height (Hs), which are based on the CMIP5 historical, RCP4.5 and RCP8.5 forcing scenario simulations of sea level pressure. Here the signal of climate change refers to the temporal variations caused by the prescribed forcing. "Significant" means "significantly different from zero at 5% level." In a four-model ensemble of Hs simulations, the common signal—the signal that is simulated in all the four models—is found to strengthen over time. For the historical followed by RCP8.5 scenario, the common signal in annual mean Hs is found to be significant in 16.6% and 82.2% of the area by year 2005 and 2099, respectively. The global average of the variance proportion of the common signal increases from 0.75% in year 2005 to 12.0% by year 2099. The signal is strongest in the eastern tropical Pacific (ETP), featuring significant increases in both the annual mean and maximum of Hs in this region. The climate model uncertainty (i.e., intermodel variability) is significant nearly globally; its magnitude is comparable to or greater than that of the common signal in most areas, except in the ETP where the signal is much larger. In a 20-model ensemble of Hs simulations for the period 2006-2099, the model uncertainty is found to be significant globally; it is about 10 times as large as the variability between the RCP4.5 and RCP8.5 scenarios. The copyright line for this article was changed on 10 JUNE 2015 after original online publication.

Signals from flavor changing scalar neutral currents at μ+μ- colliders

International Nuclear Information System (INIS)

Reina, L.

1996-01-01

We illustrate the possibility of observing signals from Flavor Changing Neutral Currents, originating from the scalar sector of a Two Higgs Doublet Model. In particular, we focus on the tree level process μ + μ - → bar tc + bar ct, via scalar exchange in the s-channel, as a distinctive process for μ + μ - colliders. 12 refs., 1 fig

Extraction of fast neuronal changes from multichannel functional near-infrared spectroscopy signals using independent component analysis

Science.gov (United States)

Morren, Geert; Wolf, Martin; Lemmerling, Philippe; Wolf, Ursula; Choi, Jee H.; Gratton, Enrico; De Lathauwer, Lieven; Van Huffel, Sabine

2002-06-01

Fast changes in the range of milliseconds in the optical properties of cerebral tissue, which are associated with brain activity, can be detected using non-invasive near-infrared spectroscopy (NIRS). These changes in light scattering are due to an alteration in the refractive index at neuronal membranes. The aim of this study was to develop highly sensitive data analysis algorithms to detect this fast signal, which is small compared to other physiological signals. A frequency-domain tissue oximeter, whose laser diodes were modulated at 110MHz was used. The amplitude, mean intensity and phase of the modulated optical signal was measured at 96Hz sample rate. The probe consisting of 4 crossed source detector pairs was placed above the motor cortex, contralateral to the hand performing a tapping exercise consisting of alternating rest- and tapping periods of 20s each. The tapping frequency, which was set to 3.55Hz or 2.5 times the heart rate of the subject to avoid the influence of harmonics on the signal, could not be observed in any of the individual signals measured by the detectors. An adaptive filter was used to remove the arterial pulsatility from the optical signals. Independent Component Analysis allowed to separate signal components in which the tapping frequency was clearly visible.

Multiple logistic regression model of signalling practices of drivers on urban highways

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Puan, Othman Che; Ibrahim, Muttaka Na'iya; Zakaria, Rozana

2015-05-01

Giving signal is a way of informing other road users, especially to the conflicting drivers, the intention of a driver to change his/her movement course. Other users are exposed to hazard situation and risks of accident if the driver who changes his/her course failed to give signal as required. This paper describes the application of logistic regression model for the analysis of driver's signalling practices on multilane highways based on possible factors affecting driver's decision such as driver's gender, vehicle's type, vehicle's speed and traffic flow intensity. Data pertaining to the analysis of such factors were collected manually. More than 2000 drivers who have performed a lane changing manoeuvre while driving on two sections of multilane highways were observed. Finding from the study shows that relatively a large proportion of drivers failed to give any signals when changing lane. The result of the analysis indicates that although the proportion of the drivers who failed to provide signal prior to lane changing manoeuvre is high, the degree of compliances of the female drivers is better than the male drivers. A binary logistic model was developed to represent the probability of a driver to provide signal indication prior to lane changing manoeuvre. The model indicates that driver's gender, type of vehicle's driven, speed of vehicle and traffic volume influence the driver's decision to provide a signal indication prior to a lane changing manoeuvre on a multilane urban highway. In terms of types of vehicles driven, about 97% of motorcyclists failed to comply with the signal indication requirement. The proportion of non-compliance drivers under stable traffic flow conditions is much higher than when the flow is relatively heavy. This is consistent with the data which indicates a high degree of non-compliances when the average speed of the traffic stream is relatively high.

Auditory Warnings, Signal-Referent Relations, and Natural Indicators: Re-Thinking Theory and Application

Science.gov (United States)

Petocz, Agnes; Keller, Peter E.; Stevens, Catherine J.

2008-01-01

In auditory warning design the idea of the strength of the association between sound and referent has been pivotal. Research has proceeded via constructing classification systems of signal-referent associations and then testing predictions about ease of learning of different levels of signal-referent relation strength across and within different…

Modulation, resolution and signal processing in radar, sonar and related systems

CERN Document Server

Benjamin, R; Costrell, L

1966-01-01

Electronics and Instrumentation, Volume 35: Modulation, Resolution and Signal Processing in Radar, Sonar and Related Systems presents the practical limitations and potentialities of advanced modulation systems. This book discusses the concepts and techniques in the radar context, but they are equally essential to sonar and to a wide range of signaling and data-processing applications, including seismology, radio astronomy, and band-spread communications.Organized into 15 chapters, this volume begins with an overview of the principal developments sought in pulse radar. This text then provides a

Investigation on changes of modularity and robustness by edge-removal mutations in signaling networks.

Science.gov (United States)

Truong, Cong-Doan; Kwon, Yung-Keun

2017-12-21

Biological networks consisting of molecular components and interactions are represented by a graph model. There have been some studies based on that model to analyze a relationship between structural characteristics and dynamical behaviors in signaling network. However, little attention has been paid to changes of modularity and robustness in mutant networks. In this paper, we investigated the changes of modularity and robustness by edge-removal mutations in three signaling networks. We first observed that both the modularity and robustness increased on average in the mutant network by the edge-removal mutations. However, the modularity change was negatively correlated with the robustness change. This implies that it is unlikely that both the modularity and the robustness values simultaneously increase by the edge-removal mutations. Another interesting finding is that the modularity change was positively correlated with the degree, the number of feedback loops, and the edge betweenness of the removed edges whereas the robustness change was negatively correlated with them. We note that these results were consistently observed in randomly structure networks. Additionally, we identified two groups of genes which are incident to the highly-modularity-increasing and the highly-robustness-decreasing edges with respect to the edge-removal mutations, respectively, and observed that they are likely to be central by forming a connected component of a considerably large size. The gene-ontology enrichment of each of these gene groups was significantly different from the rest of genes. Finally, we showed that the highly-robustness-decreasing edges can be promising edgetic drug-targets, which validates the usefulness of our analysis. Taken together, the analysis of changes of robustness and modularity against edge-removal mutations can be useful to unravel novel dynamical characteristics underlying in signaling networks.

MRI of the sacroiliac joints in spondyloarthritis: the added value of intra-articular signal changes for a 'positive MRI'.

Science.gov (United States)

Laloo, Frederiek; Herregods, N; Jaremko, J L; Verstraete, K; Jans, L

2018-05-01

To determine if intra-articular signal changes at the sacroiliac joint space on MRI have added diagnostic value for spondyloarthritis, when compared to bone marrow edema (BME). A retrospective study was performed on the MRIs of sacroiliac joints of 363 patients, aged 16-45 years, clinically suspected of sacroiliitis. BME of the sacroiliac joints was correlated to intra-articular sacroiliac joint MR signal changes: high T1 signal, fluid signal, ankylosis and vacuum phenomenon (VP). These MRI findings were correlated with final clinical diagnosis. Sensitivity (SN), specificity (SP), likelihood ratios (LR), predictive values and post-test probabilities were calculated. BME had SN of 68.9%, SP of 74.0% and LR+ of 2.6 for diagnosis of spondyloarthritis. BME in absence of intra-articular signal changes had a lower SN and LR+ for spondyloarthritis (SN = 20.5%, LR+ 1.4). Concomitant BME and high T1 signal (SP = 97.2%, LR + = 10.5), BME and fluid signal (SP = 98.6%, LR + = 10.3) or BME and ankylosis (SP = 100%) had higher SP and LR+ for spondyloarthritis. Concomitant BME and VP had low LR+ for spondyloarthritis (SP = 91%, LR + =0.9). When BME was absent, intra-articular signal changes were less prevalent, but remained highly specific for spondyloarthritis. Our results suggest that both periarticular and intra-articular MR signal of the sacroiliac joint should be examined to determine whether an MRI is 'positive' or 'not positive' for sacroiliitis associated with spondyloarthritis.

Developmental changes of BOLD signal correlations with global human EEG power and synchronization during working memory.

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Lars Michels

Full Text Available In humans, theta band (5-7 Hz power typically increases when performing cognitively demanding working memory (WM tasks, and simultaneous EEG-fMRI recordings have revealed an inverse relationship between theta power and the BOLD (blood oxygen level dependent signal in the default mode network during WM. However, synchronization also plays a fundamental role in cognitive processing, and the level of theta and higher frequency band synchronization is modulated during WM. Yet, little is known about the link between BOLD, EEG power, and EEG synchronization during WM, and how these measures develop with human brain maturation or relate to behavioral changes. We examined EEG-BOLD signal correlations from 18 young adults and 15 school-aged children for age-dependent effects during a load-modulated Sternberg WM task. Frontal load (in-dependent EEG theta power was significantly enhanced in children compared to adults, while adults showed stronger fMRI load effects. Children demonstrated a stronger negative correlation between global theta power and the BOLD signal in the default mode network relative to adults. Therefore, we conclude that theta power mediates the suppression of a task-irrelevant network. We further conclude that children suppress this network even more than adults, probably from an increased level of task-preparedness to compensate for not fully mature cognitive functions, reflected in lower response accuracy and increased reaction time. In contrast to power, correlations between instantaneous theta global field synchronization and the BOLD signal were exclusively positive in both age groups but only significant in adults in the frontal-parietal and posterior cingulate cortices. Furthermore, theta synchronization was weaker in children and was--in contrast to EEG power--positively correlated with response accuracy in both age groups. In summary we conclude that theta EEG-BOLD signal correlations differ between spectral power and

Signal intensity changes of normal brain at varying high b-value diffusion-weighted images using 3.0T MR scanner

International Nuclear Information System (INIS)

Lee, Jin Hee; Sohn, Chul Ho; Choi, Jin Soo

2003-01-01

Using diffusion-weighted MR imaging (DWI), to evaluate the signal intensity characteristics of normal adult brain as diffusion gradient strength (b value) increases from 1,000 to 3,000 s/mm 2 . Twenty-one healthy volunteers with neither neurologic symptoms nor pathologic findings at axial and sagittal T2-weighted MR imaging were involved in this study. All images were obtained with a 3.0T MR scanner. Six sets of spin-echo echo-planar images were acquired in the axial plane using progressively increasing strengths of diffusion-sensitizing gradients (corresponding to b values of 0, 1,000, 1,500, 2,000, 2,500, and 3,000 s/mm 2 ). All imaging parameters other than TE remained constant. Changes in normal white-gray matter signal intensity observed at variable b-value DWI were qualitatively analysed, and the signal-to-noise ratios (SNRs) in six anatomic regions (frontal and parietal white matter, genu and splenium corporis callosi, the posterior limb of the internal capsule, and the thalamus) quantitatively, and the ratios were averaged and compared with the average SNR of 1,000 s/mm DWI. As gradient strength increased from 1,000 to 3,000 s/mm 2 , both gray-and white-matter structures diminished in signal intensity, and images obtained at a b value of 3,000 s/mm 2 appeared very noisy. White matter became progressively hyperintense to gray matter as the diffusion sensitizing gradient increased, especially at the centrum semiovale, the posterior limb of the internal capsule, and the splenium corporis callosi, but the genu corporis callosi; showed exceptional intermediate low signal intensity. At quantitative assessment, the signal-to-noise ratio decreased as the diffusion sensitizing gradient increased. Relative to the images obtained at a b value of 1,000 s/mm 2 , average SNRs were 0.71 (b=1,500 s/mm 2 ), 0.52 (b=2,000 s/mm 2 ), 0.41 (b=2,500 s/mm 2 ), 0.33 (b=3,000 s/mm 2 ). As the diffusion sensitizing gradient increased, the signal-to-noise ratio of brain structures

Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

International Nuclear Information System (INIS)

Ray, Anamika; Liu Jing; Ayoubi, Patricia; Pope, Carey

2010-01-01

Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse

Clustering of transcriptional profiles identifies changes to insulin signaling as an early event in a mouse model of Alzheimer's disease.

Science.gov (United States)

Jackson, Harriet M; Soto, Ileana; Graham, Leah C; Carter, Gregory W; Howell, Gareth R

2013-11-25

Alzheimer's disease affects more than 35 million people worldwide but there is no known cure. Age is the strongest risk factor for Alzheimer's disease but it is not clear how age-related changes impact the disease. Here, we used a mouse model of Alzheimer's disease to identify age-specific changes that occur prior to and at the onset of traditional Alzheimer-related phenotypes including amyloid plaque formation. To identify these early events we used transcriptional profiling of mouse brains combined with computational approaches including singular value decomposition and hierarchical clustering. Our study identifies three key events in early stages of Alzheimer's disease. First, the most important drivers of Alzheimer's disease onset in these mice are age-specific changes. These include perturbations of the ribosome and oxidative phosphorylation pathways. Second, the earliest detectable disease-specific changes occur to genes commonly associated with the hypothalamic-adrenal-pituitary (HPA) axis. These include the down-regulation of genes relating to metabolism, depression and appetite. Finally, insulin signaling, in particular the down-regulation of the insulin receptor substrate 4 (Irs4) gene, may be an important event in the transition from age-related changes to Alzheimer's disease specific-changes. A combination of transcriptional profiling combined with computational analyses has uncovered novel features relevant to Alzheimer's disease in a widely used mouse model and offers avenues for further exploration into early stages of AD.

Inorganic Arsenic–Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell–Conditioned Media Model

Science.gov (United States)

Shearer, Joseph J.; Wold, Eric A.; Umbaugh, Charles S.; Lichti, Cheryl F.; Nilsson, Carol L.; Figueiredo, Marxa L.

2015-01-01

Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal–epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. Objective: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched prostate tumor microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASCs). Results: ASC-conditioned media (CM) collected after 1 week of iAs exposure increased prostate cancer cell viability, whereas CM from ASCs that received no iAs exposure decreased cell viability. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the HMOX1/THBS1/TGFβ signaling pathway by iAs. These results were validated by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blotting, confirming a concentration-dependent increase in HMOX1 and a decrease in THBS1 expression in ASC following iAs exposure. Subsequently, we used a TGFβ pathway reporter construct to confirm a decrease in stromal TGFβ signaling in ASC following iAs exposure. Conclusions: Our results suggest a concentration-dependent alteration of stromal signaling: specifically, attenuation of stromal-mediated TGFβ signaling following exposure to iAs. Our results indicate iAs may enhance prostate cancer cell viability through a previously unreported stromal-based mechanism. These findings indicate that the stroma may mediate the effects of iAs in tumor progression, which may have future therapeutic implications. Citation: Shearer JJ, Wold EA, Umbaugh CS, Lichti CF, Nilsson CL

Automatic Threshold Determination for a Local Approach of Change Detection in Long-Term Signal Recordings

Directory of Open Access Journals (Sweden)

David Hewson

2007-01-01

Full Text Available CUSUM (cumulative sum is a well-known method that can be used to detect changes in a signal when the parameters of this signal are known. This paper presents an adaptation of the CUSUM-based change detection algorithms to long-term signal recordings where the various hypotheses contained in the signal are unknown. The starting point of the work was the dynamic cumulative sum (DCS algorithm, previously developed for application to long-term electromyography (EMG recordings. DCS has been improved in two ways. The first was a new procedure to estimate the distribution parameters to ensure the respect of the detectability property. The second was the definition of two separate, automatically determined thresholds. One of them (lower threshold acted to stop the estimation process, the other one (upper threshold was applied to the detection function. The automatic determination of the thresholds was based on the Kullback-Leibler distance which gives information about the distance between the detected segments (events. Tests on simulated data demonstrated the efficiency of these improvements of the DCS algorithm.

Herbivore-Induced DNA Demethylation Changes Floral Signalling and Attractiveness to Pollinators in Brassica rapa.

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Roman T Kellenberger

Full Text Available Plants have to fine-tune their signals to optimise the trade-off between herbivore deterrence and pollinator attraction. An important mechanism in mediating plant-insect interactions is the regulation of gene expression via DNA methylation. However, the effect of herbivore-induced DNA methylation changes on pollinator-relevant plant signalling has not been systematically investigated. Here, we assessed the impact of foliar herbivory on DNA methylation and floral traits in the model crop plant Brassica rapa. Methylation-sensitive amplified fragment length polymorphism (MSAP analysis showed that leaf damage by the caterpillar Pieris brassicae was associated with genome-wide methylation changes in both leaves and flowers of B. rapa as well as a downturn in flower number, morphology and scent. A comparison to plants with jasmonic acid-induced defence showed similar demethylation patterns in leaves, but both the floral methylome and phenotype differed significantly from P. brassicae infested plants. Standardised genome-wide demethylation with 5-azacytidine in five different B. rapa full-sib groups further resulted in a genotype-specific downturn of floral morphology and scent, which significantly reduced the attractiveness of the plants to the pollinator bee Bombus terrestris. These results suggest that DNA methylation plays an important role in adjusting plant signalling in response to changing insect communities.

The IBO germination quantitative trait locus encodes a phosphatase 2C-related variant with a nonsynonymous amino acid change that interferes with abscisic acid signaling.

Science.gov (United States)

Amiguet-Vercher, Amélia; Santuari, Luca; Gonzalez-Guzman, Miguel; Depuydt, Stephen; Rodriguez, Pedro L; Hardtke, Christian S

2015-02-01

Natural genetic variation is crucial for adaptability of plants to different environments. Seed dormancy prevents precocious germination in unsuitable conditions and is an adaptation to a major macro-environmental parameter, the seasonal variation in temperature and day length. Here we report the isolation of IBO, a quantitative trait locus (QTL) that governs c. 30% of germination rate variance in an Arabidopsis recombinant inbred line (RIL) population derived from the parental accessions Eilenburg-0 (Eil-0) and Loch Ness-0 (Lc-0). IBO encodes an uncharacterized phosphatase 2C-related protein, but neither the Eil-0 nor the Lc-0 variant, which differ in a single amino acid, have any appreciable phosphatase activity in in vitro assays. However, we found that the amino acid change in the Lc-0 variant of the IBO protein confers reduced germination rate. Moreover, unlike the Eil-0 variant of the protein, the Lc-0 variant can interfere with the activity of the phosphatase 2C ABSCISIC ACID INSENSITIVE 1 in vitro. This suggests that the Lc-0 variant possibly interferes with abscisic acid signaling, a notion that is supported by physiological assays. Thus, we isolated an example of a QTL allele with a nonsynonymous amino acid change that might mediate local adaptation of seed germination timing. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease.

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Alkadhi, Karim A; Tran, Trinh T

2015-08-01

An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Aβ1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals.

Impaired Wnt Signaling in the Prefrontal Cortex of Alzheimer's Disease

DEFF Research Database (Denmark)

Folke, Jonas; Pakkenberg, Bente; Brudek, Tomasz

2018-01-01

Wnt pathway is involved in synaptic plasticity and neuronal survival, and alterations in Wnt signaling have previously been reported both in aging and neurodegenerative diseases, including Alzheimer's disease (AD). This study sought to evaluate Wnt signaling pathway interplay integrity across......, in addition to downstream effects associated with disease progression and cognitive decline. This study is the first that comprehensively evaluates Wnt signaling pathway in the prefrontal cortical lobe structures of AD brains, in relation to age-related coordinated Wnt signaling changes. Our findings further...

MRI signal changes of the bone marrow in HIV-infected patients with lipodystrophy: correlation with clinical parameters

International Nuclear Information System (INIS)

Garcia, Ana I.; Tomas, Xavier; Pomes, Jaume; Amo, Montserrat del; Milinkovic, Ana; Perez, Inaki; Mallolas, Josep; Rios, Jose; Vidal-Sicart, Sergi

2011-01-01

To assess the prevalence, imaging appearance, and clinical significance, of bone marrow MR signal changes in a group of human immunodeficiency virus (HIV)-infected patients with lipodystrophy syndrome. Twenty-eight HIV-infected patients with lipodystrophy syndrome treated with highly active antiretroviral therapy, and 12 HIV-negative controls underwent MRI of the legs. Whole-body MRI, SPECT/CT, and a complete radiographic skeletal survey were obtained in subjects with signal changes in bone marrow. MRI and clinical evaluations were reviewed 6 months after baseline to determine changes after switching from thymidine analogs (TA) to tenofovir-DF (TDF). MRI results correlated with clinical parameters. We observed foci of a serous-like pattern (low signal and no enhancement on T1-weighted, high signal on T2-weighted images) in 4 out of 28 patients (14.3%) and an intermediate signal on T1-weighted images in 4 out of 28 patients (14.3%). Serous-like lesions were located in the lower limbs and scattered in the talus, calcaneus, femurs, and humeral bones; they showed slight uptake on SPECT bone scans and were normal on CT and radiographs. Patients with serous-like lesions had significantly lower peripheral and total fat at baseline than other groups (P < 0.05). No changes at 6 months were observed on MRI, and the serous-like lesion group showed good peripheral fat recovery after changing drug treatment. A serous-like MRI pattern is observed in the peripheral skeletons of HIV-infected patients with lipodystrophy, which correlates with peripheral lipoatrophy, and should not be misdiagnosed as malignant or infectious diseases. Although the MR lesions did not improve after switching the treatment, there was evidence of lipoatrophy recovery. (orig.)

Hypoxia signaling pathways: modulators of oxygen-related organelles

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Schönenberger, Miriam J.; Kovacs, Werner J.

2015-01-01

Oxygen (O2) is an essential substrate in cellular metabolism, bioenergetics, and signaling and as such linked to the survival and normal function of all metazoans. Low O2 tension (hypoxia) is a fundamental feature of physiological processes as well as pathophysiological conditions such as cancer and ischemic diseases. Central to the molecular mechanisms underlying O2 homeostasis are the hypoxia-inducible factors-1 and -2 alpha (HIF-1α and EPAS1/HIF-2α) that function as master regulators of the adaptive response to hypoxia. HIF-induced genes promote characteristic tumor behaviors, including angiogenesis and metabolic reprogramming. The aim of this review is to critically explore current knowledge of how HIF-α signaling regulates the abundance and function of major O2-consuming organelles. Abundant evidence suggests key roles for HIF-1α in the regulation of mitochondrial homeostasis. An essential adaptation to sustained hypoxia is repression of mitochondrial respiration and induction of glycolysis. HIF-1α activates several genes that trigger mitophagy and represses regulators of mitochondrial biogenesis. Several lines of evidence point to a strong relationship between hypoxia, the accumulation of misfolded proteins in the endoplasmic reticulum, and activation of the unfolded protein response. Surprisingly, although peroxisomes depend highly on molecular O2 for their function, there has been no evidence linking HIF signaling to peroxisomes. We discuss our recent findings that establish HIF-2α as a negative regulator of peroxisome abundance and suggest a mechanism by which cells attune peroxisomal function with O2 availability. HIF-2α activation augments peroxisome turnover by pexophagy and thereby changes lipid composition reminiscent of peroxisomal disorders. We discuss potential mechanisms by which HIF-2α might trigger pexophagy and place special emphasis on the potential pathological implications of HIF-2α-mediated pexophagy for human health. PMID:26258123

Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks

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Christina eSchmidt

2012-07-01

Full Text Available Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus and the brainstem locus coeruleus (LC. However, how age- related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications to aging in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarise and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviours.

Life in a changing world: TCH gene regulation of expression and responses to environmental signals

Science.gov (United States)

Braam, J.; Sistrunk, M. L.; Polisensky, D. H.; Xu, W.; Purugganan, M. M.; Antosiewicz, D. M.; Campbell, P.; Johnson, K. A.

1996-01-01

The Arabidopsis TCH genes were discovered as a consequence of their marked upregulation of expression in response to seemingly innocuous stimuli such as touch. Further analyses have indicated that these genes are upregulated by a variety of diverse stimuli. Understanding the mechanism(s) and factors that control TCH gene regulation will shed light on the signaling pathways that enable plants to respond to changing environmental conditions. The TCH proteins include calmodulin, calmodulin-related proteins and a xyloglucan endotransglycosylase. Expression analyses and localization of protein accumulation indicate that the potential sites of TCH protein function include expanding cells and tissues under mechanical strain. We hypothesize that the TCH proteins may collaborate in cell wall biogenesis.

A model for food and stimulus changes that signal time-based contingency changes.

Science.gov (United States)

Cowie, Sarah; Davison, Michael; Elliffe, Douglas

2014-11-01

When the availability of reinforcers depends on time since an event, time functions as a discriminative stimulus. Behavioral control by elapsed time is generally weak, but may be enhanced by added stimuli that act as additional time markers. The present paper assessed the effect of brief and continuous added stimuli on control by time-based changes in the reinforcer differential, using a procedure in which the local reinforcer ratio reversed at a fixed time after the most recent reinforcer delivery. Local choice was enhanced by the presentation of the brief stimuli, even when the stimulus change signalled only elapsed time, but not the local reinforcer ratio. The effect of the brief stimulus presentations on choice decreased as a function of time since the most recent stimulus change. We compared the ability of several versions of a model of local choice to describe these data. The data were best described by a model which assumed that error in discriminating the local reinforcer ratio arose from imprecise discrimination of reinforcers in both time and space, suggesting that timing behavior is controlled not only by discrimination elapsed time, but by discrimination of the reinforcer differential in time. © Society for the Experimental Analysis of Behavior.

Numerical modelling of the pump-to-signal relative intensity noise ...

Indian Academy of Sciences (India)

An accurate numerical model to investigate the pump-to-signal relative intensity noise (RIN) transfer in two-pump fibre optical parametric amplifiers (2-P FOPAs) for low modulation frequencies is presented. Compared to other models in the field, this model takes into account the fibre loss, pump depletion as well as the gain ...

Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

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Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

2017-03-01

Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.

Estrogen signalling in the pathogenesis of age-related macular degeneration.

Science.gov (United States)

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Perceptual consequences of different signal changes due to binaural noise reduction: do hearing loss and working memory capacity play a role?

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Neher, Tobias; Grimm, Giso; Hohmann, Volker

2014-01-01

In a previous study, ) investigated whether pure-tone average (PTA) hearing loss and working memory capacity (WMC) modulate benefit from different binaural noise reduction (NR) settings. Results showed that listeners with smaller WMC preferred strong over moderate NR even at the expense of poorer speech recognition due to greater speech distortion (SD), whereas listeners with larger WMC did not. To enable a better understanding of these findings, the main aims of the present study were (1) to explore the perceptual consequences of changes to the signal mixture, target speech, and background noise caused by binaural NR, and (2) to determine whether response to these changes varies with WMC and PTA. As in the previous study, four age-matched groups of elderly listeners (with N = 10 per group) characterized by either mild or moderate PTAs and either better or worse performance on a visual measure of WMC participated. Five processing conditions were tested, which were based on the previously used (binaural coherence-based) NR scheme designed to attenuate diffuse signal components at mid to high frequencies. The five conditions differed in terms of the type of processing that was applied (no NR, strong NR, or strong NR with restoration of the long-term stimulus spectrum) and in terms of whether the target speech and background noise were processed in the same manner or whether one signal was left unprocessed while the other signal was processed with the gains computed for the signal mixture. Comparison across these conditions allowed assessing the effects of changes in high-frequency audibility (HFA), SD, and noise attenuation and distortion (NAD). Outcome measures included a dual-task paradigm combining speech recognition with a visual reaction time (VRT) task as well as ratings of perceived effort and overall preference. All measurements were carried out using headphone simulations of a frontal target speaker in a busy cafeteria. Relative to no NR, strong NR was found

Lumber intervertebral disk; Correlation with the signal intensity of magnetic resonance imaging and the histological changes

Energy Technology Data Exchange (ETDEWEB)

Uchida, Ryusei; Takahashi, Sadao; Ando, Tadashi; Kumano, Kiyoshi; Hiranuma, Kenji; Kanazawa, Yousuke; Konishi, Seiji; Eguchi, Masanobu; Tanioka, Hisaya (KantoRosai Hospital, Kawasaki, Kanagawa (Japan))

1989-11-01

We studied to provide precise correlations between the intensity of MRI signals and the degenerative changes of the nucleus pulposes of the L4/5 intervertebral disk herniations. 23 cases with the L4/5 intervertebral disk herniations having surgical treatment were examined using Magnetom H 15 (1.5 tesla) with surface coil. The images were obtained with T2 images (long TR (1000{approx}1600 msec), TE (60{approx}90 msec)). The intensity was measured using FUJI densitometer FD 101 at the lumber vertebral body and the intervertebral disk. We calculated the L4/5 intervertebral disk degeneration ratio (determined by comparing the modified L4/5 MR signal intensity with the modified L2/3 MR signal itensity). Histological changes were examined in the cellular components of the nucleus pulposus (such as the number of the nucleus cells, nucleus cell nesting and HE stainability of the nucleus cell) and the matrics substance (such as fibrillation, hyaline degeneration and granular degeneration). Histochemical studies were performed using Scott's Method (AB-0.4 M MgCl{sub 2} Alcinophilia, AB-09 M, MgCl{sub 2} Alcinophilia) to investigate glycosaminoglycans of the nucleus pulposus. We compared the histological and histochemical changes with the MR L4/5 intervetebral disk degeneration ratio. The decreasing MRI signal intensity of the nucleous pulposus was (1) corresponded to the pathological changes such as the increasing number of the cell nesting, fibrillation and hyaline degeneration of the nucleus polposus. (2) corresponded to the decrease in the total glycosaminoglycans of the nucleus pulposus. (3) corresponded to the early stage of degeneration of the nucleus polposus, but in aging when all levels of intervertebral disk degeneration appeared, we could not know the degree of the disk degeneration from the signal intensity of MRI. (J.P.N.).

You changed your mind! Infants interpret a change in word as signaling a change in an agent's goals.

Science.gov (United States)

Jin, Kyong-Sun; Song, Hyun-Joo

2017-10-01

Language provides information about our psychological states. For instance, adults can use language to convey information about their goals or preferences. The current research examined whether 14- and 12-month-old infants could interpret a change in an agent's word as signaling a change in her goals. In two experiments, 14-month-olds (Experiment 1) and 12-month-olds (Experiment 2) were first familiarized to an event in which an agent uttered a novel word and then reached for one of two novel objects. During the test trials, the agent uttered a different novel word (different-word condition) or the same word (same-word condition) and then reached for the same object or the other object. Both 14- and 12-month-olds in the different-word condition expected the agent to change her goal and reach for the other object. In contrast, the infants in the same-word condition expected the agent to maintain her goal. In Experiment 3, 12-month-olds who heard two distinct sounds instead of the agent's novel words expected the agent to maintain her goal regardless of the change in the nonlinguistic sounds. Together, these results indicate that by 12months of age infants can use an agent's verbal information to detect a change in her goals. Copyright © 2017 Elsevier Inc. All rights reserved.

N,N-dimethyl hexadecylamine and related amines regulate root morphogenesis via jasmonic acid signaling in Arabidopsis thaliana.

Science.gov (United States)

Raya-González, Javier; Velázquez-Becerra, Crisanto; Barrera-Ortiz, Salvador; López-Bucio, José; Valencia-Cantero, Eduardo

2017-05-01

Plant growth-promoting rhizobacteria are natural inhabitants of roots, colonize diverse monocot and dicot species, and affect several functional traits such as root architecture, adaptation to adverse environments, and protect plants from pathogens. N,N-dimethyl-hexadecylamine (C16-DMA) is a rhizobacterial amino lipid that modulates the postembryonic development of several plants, likely as part of volatile blends. In this work, we evaluated the bioactivity of C16-DMA and other related N,N-dimethyl-amines with varied length and found that inhibition of primary root growth was related to the length of the acyl chain. C16-DMA inhibited primary root growth affecting cell division and elongation, while promoting lateral root formation and root hair growth and density in Arabidopsis thaliana (Arabidopsis) wild-type (WT) seedlings. Interestingly, C16-DMA induced the expression of the jasmonic acid (JA)-responsive gene marker pLOX2:uidA, while JA-related mutants jar1, coi1-1, and myc2 affected on JA biosynthesis and perception, respectively, are compromised in C16-DMA responses. Comparison of auxin-regulated gene expression, root architectural changes in WT, and auxin-related mutants aux1-7, tir1/afb2/afb3, and arf7-1/arf19-1 to C16-DMA shows that the C16-DMA effects occur independently of auxin signaling. Together, these results reveal a novel class of aminolipids modulating root organogenesis via crosstalk with the JA signaling pathway.

Modeling pedestrian crossing speed profiles considering speed change behavior for the safety assessment of signalized intersections.

Science.gov (United States)

Iryo-Asano, Miho; Alhajyaseen, Wael K M

2017-11-01

Pedestrian safety is one of the most challenging issues in road networks. Understanding how pedestrians maneuver across an intersection is the key to applying countermeasures against traffic crashes. It is known that the behaviors of pedestrians at signalized crosswalks are significantly different from those in ordinary walking spaces, and they are highly influenced by signal indication, potential conflicts with vehicles, and intersection geometries. One of the most important characteristics of pedestrian behavior at crosswalks is the possible sudden speed change while crossing. Such sudden behavioral change may not be expected by conflicting vehicles, which may lead to hazardous situations. This study aims to quantitatively model the sudden speed changes of pedestrians as they cross signalized crosswalks under uncongested conditions. Pedestrian speed profiles are collected from empirical data and speed change events are extracted assuming that the speed profiles are stepwise functions. The occurrence of speed change events is described by a discrete choice model as a function of the necessary walking speed to complete crossing before the red interval ends, current speed, and the presence of turning vehicles in the conflict area. The amount of speed change before and after the event is modeled using regression analysis. A Monte Carlo simulation is applied for the entire speed profile of the pedestrians. The results show that the model can represent the pedestrian travel time distribution more accurately than the constant speed model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age-related Multiscale Changes in Brain Signal Variability in Pre-task versus Post-task Resting-state EEG.

Science.gov (United States)

Wang, Hongye; McIntosh, Anthony R; Kovacevic, Natasa; Karachalios, Maria; Protzner, Andrea B

2016-07-01

Recent empirical work suggests that, during healthy aging, the variability of network dynamics changes during task performance. Such variability appears to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into resting-state dynamics. We recorded EEG in young, middle-aged, and older adults during a "rest-task-rest" design and investigated if aging modifies the interaction between resting-state activity and external stimulus-induced activity. Using multiscale entropy as our measure of variability, we found that, with increasing age, resting-state dynamics shifts from distributed to more local neural processing, especially at posterior sources. In the young group, resting-state dynamics also changed from pre- to post-task, where fine-scale entropy increased in task-positive regions and coarse-scale entropy increased in the posterior cingulate, a key region associated with the default mode network. Lastly, pre- and post-task resting-state dynamics were linked to performance on the intervening task for all age groups, but this relationship became weaker with increasing age. Our results suggest that age-related changes in resting-state dynamics occur across different spatial and temporal scales and have consequences for information processing capacity.

Decadal changes of surface elevation over permafrost area estimated using reflected GPS signals

Science.gov (United States)

Liu, Lin; Larson, Kristine M.

2018-02-01

Conventional benchmark-based survey and Global Positioning System (GPS) have been used to measure surface elevation changes over permafrost areas, usually once or a few times a year. Here we use reflected GPS signals to measure temporal changes of ground surface elevation due to dynamics of the active layer and near-surface permafrost. Applying the GPS interferometric reflectometry technique to the multipath signal-to-noise ratio data collected by a continuously operating GPS receiver mounted deep in permafrost in Barrow, Alaska, we can retrieve the vertical distance between the antenna and reflecting surface. Using this unique kind of observables, we obtain daily changes of surface elevation during July and August from 2004 to 2015. Our results show distinct temporal variations at three timescales: regular thaw settlement within each summer, strong interannual variability that is characterized by a sub-decadal subsidence trend followed by a brief uplift trend, and a secular subsidence trend of 0.26 ± 0.02 cm year-1 during 2004 and 2015. This method provides a new way to fully utilize data from continuously operating GPS sites in cold regions for studying dynamics of the frozen ground consistently and sustainably over a long time.

Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration.

Directory of Open Access Journals (Sweden)

John Paul SanGiovanni

Full Text Available We conducted a nested candidate gene study and pathway-based enrichment analysis on data from a multi-national 77,000-person project on the molecular genetics of age-related macular degeneration (AMD to identify AMD-associated DNA-sequence variants in genes encoding constituents of a netrin-1 (NTN1-based signaling pathway that converges on DNA-binding transcription complexes through a 3'-5'-cyclic adenosine monophosphate-calcineurin (cAMP-CN-dependent axis. AMD-associated single nucleotide polymorphisms (SNPs existed in 9 linkage disequilibrium-independent genomic regions; these included loci overlapping NTN1 (rs9899630, P ≤ 9.48 x 10(-5, DCC (Deleted in Colorectal Cancer--the gene encoding a primary NTN1 receptor (rs8097127, P ≤ 3.03 x 10(-5, and 6 other netrin-related genes. Analysis of the NTN1-DCC pathway with exact methods demonstrated robust enrichment with AMD-associated SNPs (corrected P-value = 0.038, supporting the idea that processes driven by NTN1-DCC signaling systems operate in advanced AMD. The NTN1-DCC pathway contains targets of FDA-approved drugs and may offer promise for guiding applied clinical research on preventive and therapeutic interventions for AMD.

Modelling and forecasting long-term dynamics of Western Baltic macrobenthic fauna in relation to climate signals and environmental change

Science.gov (United States)

Gröger, Joachim; Rumohr, Heye

2006-05-01

Long-term macrobenthos data from Kiel Bight in the Western Baltic collected between 1968 and 2000 have been correlated with the winter NAO index (North Atlantic Oscillation Index) and other environmental data such as temperature, salinity and oxygen content in the bottom water in order to detect systematic patterns related to so far unexplained abiotic signals in the dynamics of zoobenthic species assemblages. The benthos data come from a cluster of five stations (Süderfahrt/ Millionenviertel) in Kiel Bay. Our investigations concentrated on the macrobenthic dynamics with a focus on the number of species m - 2 (species richness). Using logarithms and the time series analysis approach of Box/Jenkins (ARIMA modelling, transfer function modelling) it was shown that species richness was strongly influenced by the winter NAO (adjusted for a linear time trend within the 1968-2000 period) and salinity (with a shift/lag of four years). Bootstrapping experiments (i.e. sampling from the error process) and analysis of prediction power (by means of the one- or more-years leaving-out method) showed that the parameter estimates behaved in a stable way, leading to a relatively robust model.

On semi-classical questions related to signal analysis

KAUST Repository

Helffer, Bernard

2011-12-01

This study explores the reconstruction of a signal using spectral quantities associated with some self-adjoint realization of an h-dependent Schrödinger operator -h2(d2/dx2)-y(x), h>0, when the parameter h tends to 0. Theoretical results in semi-classical analysis are proved. Some numerical results are also presented. We first consider as a toy model the sech2 function. Then we study a real signal given by arterial blood pressure measurements. This approach seems to be very promising in signal analysis. Indeed it provides new spectral quantities that can give relevant information on some signals as it is the case for arterial blood pressure signal. © 2011 - IOS Press and the authors. All rights reserved.

Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

KAUST Repository

Zeis, T.

2015-04-01

Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

Rapid stress-induced transcriptomic changes in the brain depend on beta-adrenergic signaling.

Science.gov (United States)

Roszkowski, Martin; Manuella, Francesca; von Ziegler, Lukas; Durán-Pacheco, Gonzalo; Moreau, Jean-Luc; Mansuy, Isabelle M; Bohacek, Johannes

2016-08-01

Acute exposure to stressful experiences can rapidly increase anxiety and cause neuropsychiatric disorders. The effects of stress result in part from the release of neurotransmitters and hormones, which regulate gene expression in different brain regions. The fast neuroendocrine response to stress is largely mediated by norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a slower and more sustained release of corticosterone. While corticosterone is an important regulator of gene expression, it is not clear which stress-signals contribute to the rapid regulation of gene expression observed immediately after stress exposure. Here, we demonstrate in mice that 45 min after an acute swim stress challenge, large changes in gene expression occur across the transcriptome in the hippocampus, a region sensitive to the effects of stress. We identify multiple candidate genes that are rapidly and transiently altered in both males and females. Using a pharmacological approach, we show that most of these rapidly induced genes are regulated by NE through β-adrenergic receptor signaling. We find that CRH and corticosterone can also contribute to rapid changes in gene expression, although these effects appear to be restricted to fewer genes. These results newly reveal a widespread impact of NE on the transcriptome and identify novel genes associated with stress and adrenergic signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation

Science.gov (United States)

Collins, Anne L.; Greenfield, Venuz Y.; Bye, Jeffrey K.; Linker, Kay E.; Wang, Alice S.; Wassum, Kate M.

2016-01-01

Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well-trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID:26869075

Changes in actin dynamics are involved in salicylic acid signaling pathway.

Science.gov (United States)

Matoušková, Jindřiška; Janda, Martin; Fišer, Radovan; Sašek, Vladimír; Kocourková, Daniela; Burketová, Lenka; Dušková, Jiřina; Martinec, Jan; Valentová, Olga

2014-06-01

Changes in actin cytoskeleton dynamics are one of the crucial players in many physiological as well as non-physiological processes in plant cells. Positioning of actin filament arrays is necessary for successful establishment of primary lines of defense toward pathogen attack, depolymerization leads very often to the enhanced susceptibility to the invading pathogen. On the other hand it was also shown that the disruption of actin cytoskeleton leads to the induction of defense response leading to the expression of PATHOGENESIS RELATED proteins (PR). In this study we show that pharmacological actin depolymerization leads to the specific induction of genes in salicylic acid pathway but not that involved in jasmonic acid signaling. Life imaging of leafs of Arabidopsis thaliana with GFP-tagged fimbrin (GFP-fABD2) treated with 1 mM salicylic acid revealed rapid disruption of actin filaments resembling the pattern viewed after treatment with 200 nM latrunculin B. The effect of salicylic acid on actin filament fragmentation was prevented by exogenous addition of phosphatidic acid, which binds to the capping protein and thus promotes actin polymerization. The quantitative evaluation of actin filament dynamics is also presented. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Modic changes, possible causes and relation to low back pain

DEFF Research Database (Denmark)

Albert, Hanne Birgit; Kjær, Per; Jensen, Tue Secher

2007-01-01

In patients with low back pain (LBP) it is only possible to diagnose a small proportion, (approximately 20%), on a patho-anatomical basis. Therefore, the identification of relevant LBP subgroups, preferably on a patho-anatomical basis, is strongly needed. Signal changes on MRI in the vertebral body......, and type 3 is sclerotic bone. The temporal evolution of MC is uncertain, but the time span is years. Subchondral bone marrow signal changes associated with pain can be observed in different specific infectious, degenerative and immunological diseases such as osseous infections, osteoarthritis, ankylosing...... cannot thrive in the highly aerobic environment of the MC type 1. Perspectives: One or both of the described mechanisms can - if proven - be of significant importance for this specific subgroup of patients with LBP. Hence, it would be possible to give a more precise and relevant diagnosis to 20...

Subsurface event detection and classification using Wireless Signal Networks.

Science.gov (United States)

Yoon, Suk-Un; Ghazanfari, Ehsan; Cheng, Liang; Pamukcu, Sibel; Suleiman, Muhannad T

2012-11-05

Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs). The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events.

Invariance algorithms for processing NDE signals

Science.gov (United States)

Mandayam, Shreekanth; Udpa, Lalita; Udpa, Satish S.; Lord, William

1996-11-01

Signals that are obtained in a variety of nondestructive evaluation (NDE) processes capture information not only about the characteristics of the flaw, but also reflect variations in the specimen's material properties. Such signal changes may be viewed as anomalies that could obscure defect related information. An example of this situation occurs during in-line inspection of gas transmission pipelines. The magnetic flux leakage (MFL) method is used to conduct noninvasive measurements of the integrity of the pipe-wall. The MFL signals contain information both about the permeability of the pipe-wall and the dimensions of the flaw. Similar operational effects can be found in other NDE processes. This paper presents algorithms to render NDE signals invariant to selected test parameters, while retaining defect related information. Wavelet transform based neural network techniques are employed to develop the invariance algorithms. The invariance transformation is shown to be a necessary pre-processing step for subsequent defect characterization and visualization schemes. Results demonstrating the successful application of the method are presented.

Initiatives related to climate change in Ghana. Towards change in Ghana

International Nuclear Information System (INIS)

Wuertenberger, L.; Bunzeck, I.G.; Van Tilburg, X.

2011-04-01

To support the development of a National Climate Change Policy Framework (NCCPF) and a further harmonization of climate change related activities in Ghana, the Ministry of Finance and Economic Planning (MoFEP) and the Ministry of Environment, Science and Technology (MEST) expressed demand for a mapping of the most important past and current climate change related initiatives in the country, and of international climate change related funding opportunities, that Ghana might be able to access. The initiatives mapping demonstrates Ghana's longstanding engagement with climate change, dating back to more than 15 years ago. The report shows a multitude of activities including a number of large (5 mln. USD to > 100 mln. USD), GEF or World Bank financed projects, and a range of smaller projects (in the order of 100 000 - 500 000 USD). The majority of current initiatives are related to forestry and REDD. This report concludes with a discussion on observed trends, such as a broadening involvement of MDAs in adaptation initiatives and a focus on low carbon growth, and of points for attention, such as a need for coordination, for private sector involvement and supporting systems (such as institutional capacity, governance and monitoring systems)

Concurrency and climate change signal in Scottish flooding

Science.gov (United States)

Harding, A. E.; Butler, A.; Goody, N.; Bertram, D.; Baggaley, N.; Tett, S. F.

2013-12-01

The Scottish Environment Protection Agency maintains a database of river gauging stations and intensity rain-gauges with a 3-hourly resolution that covers the majority of Scotland. Both SEPA and a number of other Scottish agencies are invested in climate change attribution in this data set. SEPA's main interest lies in trend detection and changes in river level (';stage') data throughout Scotland. Emergency response teams are more concerned with the concurrency of multiple flood events that might stretch their ability to respond effectively. Unfortunately, much of the rainfall signal within SEPA's river-gauge data is altered by land use changes, modified by artificial interventions such as reservoirs, compromised by tidal flow, or obscured by measurement issues. Data reduction techniques, indices of extreme rainfall, and hydrology-driven discrimination have been employed to produce a reduced set of flood-relevant information for 24-hour ';flashy' events. Links between this set and North Atlantic circulation have been explored, as have patterns of mutual occurrence across Scotland and location- and seasonally- dependent trends through time. Both frontal systems and summer convective storms have been characterised in terms of subsequent flood-inducing flow regime, their changing behaviour over the last fifty years, and their spatial extent. This is the first stage of an ongoing project that will intelligently expand to take less robust river and rain-gauge stations into account through statistical analysis and hydrological modelling. It is also the first study of its type to analyse a nation-scale dataset of both rainfall and river flow from multiple catchments for flood event concurrency. As rainfall events are expected to intensify across much of Europe, this kind of research is likely to have an increasing degree of relevance for policy-makers. This project demonstrates that productive, policy-relevant and mutually-rewarding partnerships are already underway.

Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex.

Science.gov (United States)

Takahashi, Yuji K; Roesch, Matthew R; Wilson, Robert C; Toreson, Kathy; O'Donnell, Patricio; Niv, Yael; Schoenbaum, Geoffrey

2011-10-30

The orbitofrontal cortex has been hypothesized to carry information regarding the value of expected rewards. Such information is essential for associative learning, which relies on comparisons between expected and obtained reward for generating instructive error signals. These error signals are thought to be conveyed by dopamine neurons. To test whether orbitofrontal cortex contributes to these error signals, we recorded from dopamine neurons in orbitofrontal-lesioned rats performing a reward learning task. Lesions caused marked changes in dopaminergic error signaling. However, the effect of lesions was not consistent with a simple loss of information regarding expected value. Instead, without orbitofrontal input, dopaminergic error signals failed to reflect internal information about the impending response that distinguished externally similar states leading to differently valued future rewards. These results are consistent with current conceptualizations of orbitofrontal cortex as supporting model-based behavior and suggest an unexpected role for this information in dopaminergic error signaling.

Ocean acidification affects marine chemical communication by changing structure and function of peptide signalling molecules.

Science.gov (United States)

Roggatz, Christina C; Lorch, Mark; Hardege, Jörg D; Benoit, David M

2016-12-01

Ocean acidification is a global challenge that faces marine organisms in the near future with a predicted rapid drop in pH of up to 0.4 units by the end of this century. Effects of the change in ocean carbon chemistry and pH on the development, growth and fitness of marine animals are well documented. Recent evidence also suggests that a range of chemically mediated behaviours and interactions in marine fish and invertebrates will be affected. Marine animals use chemical cues, for example, to detect predators, for settlement, homing and reproduction. But, while effects of high CO 2 conditions on these behaviours are described across many species, little is known about the underlying mechanisms, particularly in invertebrates. Here, we investigate the direct influence of future oceanic pH conditions on the structure and function of three peptide signalling molecules with an interdisciplinary combination of methods. NMR spectroscopy and quantum chemical calculations were used to assess the direct molecular influence of pH on the peptide cues, and we tested the functionality of the cues in different pH conditions using behavioural bioassays with shore crabs (Carcinus maenas) as a model system. We found that peptide signalling cues are susceptible to protonation in future pH conditions, which will alter their overall charge. We also show that structure and electrostatic properties important for receptor binding differ significantly between the peptide forms present today and the protonated signalling peptides likely to be dominating in future oceans. The bioassays suggest an impaired functionality of the signalling peptides at low pH. Physiological changes due to high CO 2 conditions were found to play a less significant role in influencing the investigated behaviour. From our results, we conclude that the change of charge, structure and consequently function of signalling molecules presents one possible mechanism to explain altered behaviour under future oceanic p

Quantifying uncertainties of climate signals related to the 11-year solar cycle

Science.gov (United States)

Kruschke, T.; Kunze, M.; Matthes, K. B.; Langematz, U.; Wahl, S.

2017-12-01

Although state-of-the-art reconstructions based on proxies and (semi-)empirical models converge in terms of total solar irradiance, they still significantly differ in terms of spectral solar irradiance (SSI) with respect to the mean spectral distribution of energy input and temporal variability. This study aims at quantifying uncertainties for the Earth's climate related to the 11-year solar cycle by forcing two chemistry-climate models (CCMs) - CESM1(WACCM) and EMAC - with five different SSI reconstructions (NRLSSI1, NRLSSI2, SATIRE-T, SATIRE-S, CMIP6-SSI) and the reference spectrum RSSV1-ATLAS3, derived from observations. We conduct a unique set of timeslice experiments. External forcings and boundary conditions are fixed and identical for all experiments, except for the solar forcing. The set of analyzed simulations consists of one solar minimum simulation, employing RSSV1-ATLAS3 and five solar maximum experiments. The latter are a result of adding the amplitude of solar cycle 22 according to the five reconstructions to RSSV1-ATLAS3. Our results show that the climate response to the 11y solar cycle is generally robust across CCMs and SSI forcings. However, analyzing the variance of the solar maximum ensemble by means of ANOVA-statistics reveals additional information on the uncertainties of the mean climate signals. The annual mean response agrees very well between the two CCMs for most parts of the lower and middle atmosphere. Only the upper mesosphere is subject to significant differences related to the choice of the model. However, the different SSI forcings lead to significant differences in ozone concentrations, shortwave heating rates, and temperature throughout large parts of the mesosphere and upper stratosphere. Regarding the seasonal evolution of the climate signals, our findings for short wave heating rates, and temperature are similar to the annual means with respect to the relative importance of the choice of the model or the SSI forcing for the

Snore related signals processing in a private cloud computing system.

Science.gov (United States)

Qian, Kun; Guo, Jian; Xu, Huijie; Zhu, Zhaomeng; Zhang, Gongxuan

2014-09-01

Snore related signals (SRS) have been demonstrated to carry important information about the obstruction site and degree in the upper airway of Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) patients in recent years. To make this acoustic signal analysis method more accurate and robust, big SRS data processing is inevitable. As an emerging concept and technology, cloud computing has motivated numerous researchers and engineers to exploit applications both in academic and industry field, which could have an ability to implement a huge blue print in biomedical engineering. Considering the security and transferring requirement of biomedical data, we designed a system based on private cloud computing to process SRS. Then we set the comparable experiments of processing a 5-hour audio recording of an OSAHS patient by a personal computer, a server and a private cloud computing system to demonstrate the efficiency of the infrastructure we proposed.

An algebraic approach to signaling cascades with N layers

DEFF Research Database (Denmark)

Feliu, Elisenda; Knudsen, Michael; Andersen, Lars Nørvang

2012-01-01

Posttranslational modification of proteins is key in transmission of signals in cells. Many signaling pathways contain several layers of modification cycles that mediate and change the signal through the pathway. Here, we study a simple signaling cascade consisting of n layers of modification cyc...... state for any given total amounts of substrates and enzymes.We demonstrate that many steady-state concentrations are related through rational functions that can be found recursively. For example, stimulus-response curves arise as inverse functions to explicit rational functions. We show...

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

DEFF Research Database (Denmark)

Kim, S.G.; Rostrup, Egill; Larsson, H.B.

1999-01-01

signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec......The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can...

Subsurface Event Detection and Classification Using Wireless Signal Networks

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Muhannad T. Suleiman

2012-11-01

Full Text Available Subsurface environment sensing and monitoring applications such as detection of water intrusion or a landslide, which could significantly change the physical properties of the host soil, can be accomplished using a novel concept, Wireless Signal Networks (WSiNs. The wireless signal networks take advantage of the variations of radio signal strength on the distributed underground sensor nodes of WSiNs to monitor and characterize the sensed area. To characterize subsurface environments for event detection and classification, this paper provides a detailed list and experimental data of soil properties on how radio propagation is affected by soil properties in subsurface communication environments. Experiments demonstrated that calibrated wireless signal strength variations can be used as indicators to sense changes in the subsurface environment. The concept of WSiNs for the subsurface event detection is evaluated with applications such as detection of water intrusion, relative density change, and relative motion using actual underground sensor nodes. To classify geo-events using the measured signal strength as a main indicator of geo-events, we propose a window-based minimum distance classifier based on Bayesian decision theory. The window-based classifier for wireless signal networks has two steps: event detection and event classification. With the event detection, the window-based classifier classifies geo-events on the event occurring regions that are called a classification window. The proposed window-based classification method is evaluated with a water leakage experiment in which the data has been measured in laboratory experiments. In these experiments, the proposed detection and classification method based on wireless signal network can detect and classify subsurface events.

Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus.

Science.gov (United States)

Blanco, Eduardo; Galeano, Pablo; Palomino, Ana; Pavón, Francisco J; Rivera, Patricia; Serrano, Antonia; Alen, Francisco; Rubio, Leticia; Vargas, Antonio; Castilla-Ortega, Estela; Decara, Juan; Bilbao, Ainhoa; de Fonseca, Fernando Rodríguez; Suárez, Juan

2016-03-01

In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug-associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization. Results showed that acute cocaine administration induced an overall down-regulation of glutamate-related gene expression and, specifically, a low phosphorylation level of GluA1. In contrast, locomotor sensitization to cocaine produced an up-regulation of several glutamate receptor-related genes and, specifically, an increased protein expression of the GluN1 receptor subunit. Regarding the endocannabinoid system, acute and repeated cocaine administration were associated with an increased gene/protein expression of CB1 receptors and a decreased gene/protein expression of the endocannabinoid-synthesis enzymes N-acyl phosphatidylethanolamine D (NAPE-PLD) and diacylglycerol lipase alpha (DAGLα). These changes resulted in an overall decrease in endocannabinoid synthesis/degradation ratios, especially NAPE-PLD/fatty acid amide hydrolase and DAGLα/monoacylglycerol lipase, suggesting a reduced endocannabinoid production associated with a compensatory up-regulation of CB1 receptor. Overall, these findings suggest that repeated cocaine administration resulting in locomotor sensitization induces a down-regulation of the endocannabinoid signaling that could

On semi-classical questions related to signal analysis

KAUST Repository

Helffer, Bernard; Laleg-Kirati, Taous-Meriem

2011-01-01

. Indeed it provides new spectral quantities that can give relevant information on some signals as it is the case for arterial blood pressure signal. © 2011 - IOS Press and the authors. All rights reserved.

Retroactive signaling in short signaling pathways.

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Jacques-Alexandre Sepulchre

Full Text Available In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles.

Climate change-related migration and infectious disease.

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McMichael, Celia

2015-01-01

Anthropogenic climate change will have significant impacts on both human migration and population health, including infectious disease. It will amplify and alter migration pathways, and will contribute to the changing ecology and transmission dynamics of infectious disease. However there has been limited consideration of the intersections between migration and health in the context of a changing climate. This article argues that climate-change related migration - in conjunction with other drivers of migration - will contribute to changing profiles of infectious disease. It considers infectious disease risks for different climate-related migration pathways, including: forced displacement, slow-onset migration particularly to urban-poor areas, planned resettlement, and labor migration associated with climate change adaptation initiatives. Migration can reduce vulnerability to climate change, but it is critical to better understand and respond to health impacts - including infectious diseases - for migrant populations and host communities.

[Cognitive aging mechanism of signaling effects on the memory for procedural sentences].

Science.gov (United States)

Yamamoto, Hiroki; Shimada, Hideaki

2006-08-01

The aim of this study was to clarify the cognitive aging mechanism of signaling effects on the memory for procedural sentences. Participants were 60 younger adults (college students) and 60 older adults. Both age groups were assigned into two groups; half of each group was presented with procedural sentences with signals that highlighted their top-level structure and the other half with procedural sentences without them. Both groups were requested to perform the sentence arrangement task and the reconstruction task. Each task was composed of procedural sentences with or without signals. Results indicated that signaling supported changes in strategy utilization during the successive organizational processes and that changes in strategy utilization resulting from signaling improved the memory for procedural sentences. Moreover, age-related factors interfered with these signaling effects. This study clarified the cognitive aging mechanism of signaling effects in which signaling supports changes in the strategy utilization during organizational processes at encoding and this mediation promotes memory for procedural sentences, though disuse of the strategy utilization due to aging restrains their memory for procedural sentences.

Suburban immigrants to wildlands disrupt honest signaling in ultra-violet plumage

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Angela Tringali

2015-06-01

Full Text Available Urbanization changes habitat in a multitude of ways, including altering food availability. Access to human-provided food can change the relationship between body condition and honest advertisements of fitness, which may result in changes to behavior, demography, and metapopulation dynamics. We compared plumage color, its relationship with body condition and feather growth, and use as signal of dominance between a suburban and a wildland population of Florida Scrub-Jay (Aphelocoma coerulescens. Although plumage color was not related to body condition at either site, suburban birds had plumage with a greater proportion of total reflectance in the ultra-violet (UV and peak reflectance at shorter wavelengths. Despite the use of plumage reflectance as a signal of dominance among individuals in the wildlands, we found no evidence of status signaling at the suburban site. However, birds emigrating from the suburban site to the wildland site tended to be more successful at acquiring breeder status but less successful at reproducing than were immigrants from an adjacent wildland site, suggesting that signaled and realized quality differ. These differences in signaling content among populations could have demographic effects at metapopulation scales and may represent an evolutionary trap whereby suburban immigrants are preferred as mates even though their reproductive success relative to effort is lower.

Citrulline diet supplementation improves specific age-related raft changes in wild-type rodent hippocampus.

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Marquet-de Rougé, Perrine; Clamagirand, Christine; Facchinetti, Patricia; Rose, Christiane; Sargueil, Françoise; Guihenneuc-Jouyaux, Chantal; Cynober, Luc; Moinard, Christophe; Allinquant, Bernadette

2013-10-01

The levels of molecules crucial for signal transduction processing change in the brain with aging. Lipid rafts are membrane microdomains involved in cell signaling. We describe here substantial biophysical and biochemical changes occurring within the rafts in hippocampus neurons from aging wild-type rats and mice. Using continuous sucrose density gradients, we observed light-, medium-, and heavy raft subpopulations in young adult rodent hippocampus neurons containing very low levels of amyloid precursor protein (APP) and almost no caveolin-1 (CAV-1). By contrast, old rodents had a homogeneous age-specific high-density caveolar raft subpopulation containing significantly more cholesterol (CHOL), CAV-1, and APP. C99-APP-Cter fragment detection demonstrates that the first step of amyloidogenic APP processing takes place in this caveolar structure during physiological aging of the rat brain. In this age-specific caveolar raft subpopulation, levels of the C99-APP-Cter fragment are exponentially correlated with those of APP, suggesting that high APP concentrations may be associated with a risk of large increases in beta-amyloid peptide levels. Citrulline (an intermediate amino acid of the urea cycle) supplementation in the diet of aged rats for 3 months reduced these age-related hippocampus raft changes, resulting in raft patterns tightly close to those in young animals: CHOL, CAV-1, and APP concentrations were significantly lower and the C99-APP-Cter fragment was less abundant in the heavy raft subpopulation than in controls. Thus, we report substantial changes in raft structures during the aging of rodent hippocampus and describe new and promising areas of investigation concerning the possible protective effect of citrulline on brain function during aging.

Viking relativity experiment: Verification of signal retardation by solar gravity

International Nuclear Information System (INIS)

Reasenberg, R.D.; Shapiro, I.I.; MacNeil, P.E.; Goldstein, R.B.; Breidenthal, J.C.; Brenkle, J.P.; Cain, D.L.; Kaufman, T.M.; Komarek, T.A.; Zygielbaum, A.I.

1979-01-01

Analysis of 14 months of data obtained from radio ranging to the Viking spacecraft verified, to an estimated accuracy of 0.1%, the prediction of the general theory of relativity that the round-trip times of light signals traveling between the Earth and Mars are increased by the direct effect of solar gravity. The correspondig value for the metric parameter γ is 1.000 +- 0.002, where the quoted uncertainty, twice the formal standard deviation, allows for possible systematic errors

The ratio of red light to far red light alters Arabidopsis axillary bud growth and abscisic acid signalling before stem auxin changes.

Science.gov (United States)

Holalu, Srinidhi V; Finlayson, Scott A

2017-02-01

Arabidopsis thaliana shoot branching is inhibited by a low red light to far red light ratio (R:FR, an indicator of competition), and by loss of phytochrome B function. Prior studies have shown that phytochrome B deficiency suppresses bud growth by elevating systemic auxin signalling, and that increasing the R:FR promotes the growth of buds suppressed by low R:FR by inhibiting bud abscisic acid (ABA) accumulation and signalling. Here, systemic auxin signalling and bud ABA signalling were examined in the context of rapid bud responses to an increased R:FR. Increasing the R:FR promoted the growth of buds inhibited by a low R:FR within 6 h. Relative to a low R:FR, bud ABA accumulation and signalling in plants given a high R:FR showed a sustained decline within 3 h, prior to increased growth. Main stem auxin levels and signalling showed a weak, transient response. Systemic effects and those localised to the bud were further examined by decapitating plants maintained either under a low R:FR or provided with a high R:FR. Increasing the R:FR promoted bud growth before decapitation, but decapitated plants eventually formed longer branches. The data suggest that rapid responses to an increased R:FR may be mediated by changes in bud ABA physiology, although systemic auxin signalling is necessary for sustained bud repression under a low R:FR. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Relations of Change in Condition Severity and School Self-Concept To Change in Achievement-Related Behavior in Children with Asthma or Epilepsy.

Science.gov (United States)

Huberty, Thomas J.; Austin, Joan K.; Huster, Gertrude A.; Dunn, David W.

2000-01-01

Explores relation of gender, change in condition of severity, and change in school self-concept, to change in teachers' ratings of academic-related behaviors in children with asthma or epilepsy. Tests showed that these children were near population mean in academic-related behaviors, except students with high-severity epilepsy. (Author/JDM)

Varroa destructor induces changes in the expression of immunity-related genes during the development of Apis mellifera worker and drone broods.

Science.gov (United States)

Zaobidna, Ewa A; Żółtowska, Krystyna; Łopieńska-Biernat, Elżbieta

2017-12-20

The ectoparasitic mite Varroa destructor has emerged as the major pest of honeybees. Despite extensive research efforts, the pathogenesis of varroosis has not been fully explained. Earlier studies suggested that V. destructor infestation leads to the suppression of the host's immune system. The aim of this study was to analyze the immune responses of 14 genes in the Toll signal transduction pathways, including effector genes of antimicrobial peptides (AMPs), in developing Apis mellifera workers and drones infested with V. destructor. Four developmental stages (L5 larvae, prepupae, and 2 pupal stages) and newly emerged imagines were analyzed. In workers, the most significant changes were observed in L5 larvae in the initial stages of infestation. A significant increase in the relative expression of 10 of the 14 analyzed genes, including defensin-1 and defensin-2, was observed in infested bees relative to non-infested individuals. The immune response in drones developed at a slower rate. The expression of genes regulating cytoplasmic signal transduction increased in prepupae, whereas the expression of defensin-1 and defensin-2 effector genes increased in P3 pupae with red eyes. The expression of many immunity-related genes was silenced in successive life stages and in imagines, and it was more profound in workers than in drones. The results indicate that V. destructor significantly influences immune responses regulated by the Toll signal transduction pathway in bees. In infested bees, the observed changes in Toll pathway genes varied between life stages and the sexes.

Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling.

Science.gov (United States)

Xu, Enjun; Brosché, Mikael

2014-06-04

Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling.

Magnetoencephalography signals are influenced by skull defects.

Science.gov (United States)

Lau, S; Flemming, L; Haueisen, J

2014-08-01

Magnetoencephalography (MEG) signals had previously been hypothesized to have negligible sensitivity to skull defects. The objective is to experimentally investigate the influence of conducting skull defects on MEG and EEG signals. A miniaturized electric dipole was implanted in vivo into rabbit brains. Simultaneous recording using 64-channel EEG and 16-channel MEG was conducted, first above the intact skull and then above a skull defect. Skull defects were filled with agar gels, which had been formulated to have tissue-like homogeneous conductivities. The dipole was moved beneath the skull defects, and measurements were taken at regularly spaced points. The EEG signal amplitude increased 2-10 times, whereas the MEG signal amplitude reduced by as much as 20%. The EEG signal amplitude deviated more when the source was under the edge of the defect, whereas the MEG signal amplitude deviated more when the source was central under the defect. The change in MEG field-map topography (relative difference measure, RDM(∗)=0.15) was geometrically related to the skull defect edge. MEG and EEG signals can be substantially affected by skull defects. MEG source modeling requires realistic volume conductor head models that incorporate skull defects. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Analysis of changed bio-signal to radiation exposure of nuclear medicine worker

International Nuclear Information System (INIS)

Lee, Hwun Jae; Lee, Sang Bock

2007-01-01

In this paper, we are evaluated about bio-signal between general workers and nuclear medicine workers which is more radiation exposure relatively. In order to reciprocal evaluated two group, we experimented nuclear medicine workers in Chung-Buk National University Hospital at department of nuclear medicine and worker in Chon-Nam National University Hospital at CT room, general radiographic room, medical recording room, receipt room, general office room. Used of experimental equipments as follows, for a level of radiation measurement by pocket dosimeter which made by Arrow-Tech company, for heart rate and blood pressure measurement by TONOPORT V which made by GE medical systems company, for heat flux and skin temperature and energy expenditure measurement by Armband senseware 2000 which made by Bodymedia company. Result of experiment obtains as follows : 1) Individual radiation exposure is recorded 3.05 uSv at department of nuclear medicine and order as follows CT room, general radiograpic room, medical recording room, receipt room, general office room. Department of nuclear medicine more 1.5 times than other places. 2) Radiation accumulated dose is not related to Heat flux, Skin temperature, Energy expenditure. 3) Blood pressure is recorded equal to nuclear medical workers, general officer, general people about systolic blood pressure and diastolic blood pressure. Compared to blood pressure between nuclear medical works which is more radiation exposure and other workers was not changed. Consequently, more radiation exposed workers at nuclear medicine field doesn't have hazard

Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

Directory of Open Access Journals (Sweden)

Justine H. Dewald

2016-11-01

Full Text Available Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in number of diseases such as cancer and chronic inflammation. In that context, pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases involved in the biosynthesis of carbohydrate chains. These changes in cell surface glycosylation are also known to regulate cell signaling and could contribute to disease pathogenesis. This review summarizes our current knowledge of the glycosylation changes induced by pro-inflammatory cytokines, with a particular focus on cancer and cystic fibrosis, and their consequences on cell interactions and signaling.

Variants of Insulin-Signaling Inhibitor Genes in Type 2 Diabetes and Related Metabolic Abnormalities

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Carlo de Lorenzo

2013-01-01

Full Text Available Insulin resistance has a central role in the pathogenesis of several metabolic diseases, including type 2 diabetes, obesity, glucose intolerance, metabolic syndrome, atherosclerosis, and cardiovascular diseases. Insulin resistance and related traits are likely to be caused by abnormalities in the genes encoding for proteins involved in the composite network of insulin-signaling; in this review we have focused our attention on genetic variants of insulin-signaling inhibitor molecules. These proteins interfere with different steps in insulin-signaling: ENPP1/PC-1 and the phosphatases PTP1B and PTPRF/LAR inhibit the insulin receptor activation; INPPL1/SHIP-2 hydrolyzes PI3-kinase products, hampering the phosphoinositide-mediated downstream signaling; and TRIB3 binds the serine-threonine kinase Akt, reducing its phosphorylation levels. While several variants have been described over the years for all these genes, solid evidence of an association with type 2 diabetes and related diseases seems to exist only for rs1044498 of the ENPP1 gene and for rs2295490 of the TRIB3 gene. However, overall the data recapitulated in this Review article may supply useful elements to interpret the results of novel, more technically advanced genetic studies; indeed it is becoming increasingly evident that genetic information on metabolic diseases should be interpreted taking into account the complex biological pathways underlying their pathogenesis.

Overexpression of suppressor of cytokine signaling 3 in the arcuate nucleus of juvenile Phodopus sungorus alters seasonal body weight changes.

Science.gov (United States)

Ganjam, Goutham K; Benzler, Jonas; Pinkenburg, Olaf; Boucsein, Alisa; Stöhr, Sigrid; Steger, Juliane; Culmsee, Carsten; Barrett, Perry; Tups, Alexander

2013-12-01

The profound seasonal cycle in body weight exhibited by the Djungarian hamster (Phodopus sungorus) is associated with the development of hypothalamic leptin resistance during long day photoperiod (LD, 16:8 h light dark cycle), when body weight is elevated relative to short day photoperiod (SD, 8:16 h light dark cycle). We previously have shown that this seasonal change in physiology is associated with higher levels of mRNA for the potent inhibitor of leptin signaling, suppressor of cytokine signaling-3 (SOCS3), in the arcuate nucleus (ARC) of LD hamsters relative to hamsters in SD. The alteration in SOCS3 gene expression preceded the body weight change suggesting that SOCS3 might be the molecular switch of seasonal body weight changes. To functionally characterize the role of SOCS3 in seasonal body weight regulation, we injected SOCS3 expressing recombinant adeno-associated virus type-2 (rAAV2-SOCS3) constructs into the ARC of leptin sensitive SD hamsters immediately after weaning. Hamsters that received rAAV2 expressing enhanced green fluorescent protein (rAAV2-EGFP) served as controls. ARC-directed SOCS3 overexpression led to a significant increase in body weight over a period of 12 weeks without fully restoring the LD phenotype. This increase was partially due to elevated brown and white adipose tissue mass. Gene expression of pro-opiomelanocortin was increased while thyroid hormone converting enzyme DIO3 mRNA levels were reduced in SD hamsters with SOCS3 overexpression. In conclusion, our data suggest that ARC-directed SOCS3 overexpression partially overcomes the profound seasonal body weight cycle exhibited by the hamster which is associated with altered pro-opiomelanocortin and DIO3 gene expression.

Acute swelling of the limbs: magnetic resonance pictorial review of fascial and muscle signal changes

Energy Technology Data Exchange (ETDEWEB)

Revelon, Geraldine [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Rahmouni, Alain [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Jazaerli, Nedal [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Godeau, Bertrand [Department of Internal Medicine, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Chosidow, Olivier [Department of Dermatology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Authier, Jerome [Department of Pathology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Mathieu, Didier [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Roujeau, Jean-Claude [Department of Dermatology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France); Vasile, Norbert [Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, 51 Avenue du Marechal De Lattre De Tassigny, 94000 Creteil (France)

1999-04-01

Objective: This pictorial review analyzes the magnetic resonance (MR) fascial/muscular changes in 69 patients referred as emergencies with acute swelling of the limbs (ASL) from various causes. Methods and material: A prospective MR imaging (MRI) study of 69 patients referred as emergencies for ASL was performed. Our population consisted of 45 patients with skin and soft-tissue infections (cellulitis and necrotizing fasciitis, and pyomyositis), six patients with soft-tissue inflammatory diseases (dermatomyositis, graft-versus-host disease), 11 patients with acute deep venous thrombosis, three patients with rhabdomyolysis, one patient with acute denervation and three other patients with rare diseases. Hematomas, tumorous or infectious bone involvement and soft-tissue tumors were excluded. All studies included spin echo T1-weighted images and spin echo T2-weighted images. Gadolinium-enhanced spin echo T1-weighted images were obtained when an abscess was suspected on T2-weighted images. Selective fat-saturated T1- and T2-weighted sequences were also used. MRI analysis was performed to obtain a compartmentalized anatomical approach according to the location of signal abnormalities in subcutaneous fat, superficial and deep fascia and muscle. Results: In all patients with ASL, MRI demonstrated soft-tissue abnormalities involving subcutaneous fat, superficial fascia, deep fascia, or muscle. Although MR findings were non-specific, MRI appears sensitive for detecting subtle fascial and muscle signal changes. Conclusions: In skin and soft-tissue infections, MRI can be helpful for therapeutic management by determining the depth of soft-tissue involvement, particularly within fasciae and muscles, which is partly related to the severity of cellulitis with severe systemic manifestations. MRI can also aid the surgeon in diagnosing abscesses. In inflammatory diseases, MRI can determine the best site for biopsy and also monitor therapeutic response.

Characteristics and natural course of vertebral endplate signal (Modic) changes in the Danish general population

DEFF Research Database (Denmark)

Jensen, Tue S; Bendix, Tom; Sorensen, Joan S

2009-01-01

BACKGROUND: Vertebral endplate signal changes (VESC) are more common among patients with low back pain (LBP) and/or sciatica than in people who are not seeking care for back pain. The distribution and characteristics of VESC have been described in people from clinical and non-clinical populations...

Dynamic time warping and machine learning for signal quality assessment of pulsatile signals

International Nuclear Information System (INIS)

Li, Q; Clifford, G D

2012-01-01

In this work, we describe a beat-by-beat method for assessing the clinical utility of pulsatile waveforms, primarily recorded from cardiovascular blood volume or pressure changes, concentrating on the photoplethysmogram (PPG). Physiological blood flow is nonstationary, with pulses changing in height, width and morphology due to changes in heart rate, cardiac output, sensor type and hardware or software pre-processing requirements. Moreover, considerable inter-individual and sensor-location variability exists. Simple template matching methods are therefore inappropriate, and a patient-specific adaptive initialization is therefore required. We introduce dynamic time warping to stretch each beat to match a running template and combine it with several other features related to signal quality, including correlation and the percentage of the beat that appeared to be clipped. The features were then presented to a multi-layer perceptron neural network to learn the relationships between the parameters in the presence of good- and bad-quality pulses. An expert-labeled database of 1055 segments of PPG, each 6 s long, recorded from 104 separate critical care admissions during both normal and verified arrhythmic events, was used to train and test our algorithms. An accuracy of 97.5% on the training set and 95.2% on test set was found. The algorithm could be deployed as a stand-alone signal quality assessment algorithm for vetting the clinical utility of PPG traces or any similar quasi-periodic signal. (paper)

Dynamic time warping and machine learning for signal quality assessment of pulsatile signals.

Science.gov (United States)

Li, Q; Clifford, G D

2012-09-01

In this work, we describe a beat-by-beat method for assessing the clinical utility of pulsatile waveforms, primarily recorded from cardiovascular blood volume or pressure changes, concentrating on the photoplethysmogram (PPG). Physiological blood flow is nonstationary, with pulses changing in height, width and morphology due to changes in heart rate, cardiac output, sensor type and hardware or software pre-processing requirements. Moreover, considerable inter-individual and sensor-location variability exists. Simple template matching methods are therefore inappropriate, and a patient-specific adaptive initialization is therefore required. We introduce dynamic time warping to stretch each beat to match a running template and combine it with several other features related to signal quality, including correlation and the percentage of the beat that appeared to be clipped. The features were then presented to a multi-layer perceptron neural network to learn the relationships between the parameters in the presence of good- and bad-quality pulses. An expert-labeled database of 1055 segments of PPG, each 6 s long, recorded from 104 separate critical care admissions during both normal and verified arrhythmic events, was used to train and test our algorithms. An accuracy of 97.5% on the training set and 95.2% on test set was found. The algorithm could be deployed as a stand-alone signal quality assessment algorithm for vetting the clinical utility of PPG traces or any similar quasi-periodic signal.

Relative blood volume changes underestimate total blood volume changes during hemodialysis

NARCIS (Netherlands)

Dasselaar, Judith J.; Lub-de Hooge, Marjolijn N.; Pruim, Jan; Nijnuis, Hugo; Wiersum, Anneke; de Jong, Paul E.; Huisman, Roel M.; Franssen, Casper F. M.

Background: Measurements of relative blood volume changes (ARBV) during hemodialysis (HD) are based on hemoconcentration and assume uniform mixing of erythrocytes and plasma throughout the circulation. However, whole-body hematocrit (Ht) is lower than systemic Ht. During HD, a change in the ratio

Is It Possible to Distinguish Global and Regional Climate Change from Urban Land Cover Induced Signals? A Mid-Latitude City Example

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Sarah Wiesner

2018-01-01

Full Text Available The local climate in cities differs from the one in rural areas, most prominently characterized by increased surface and air temperatures, known as the “(surface urban heat island”. As climate has changed and continues to change in all areas of the world, the question arises whether the effects that are noticeable in urban areas are “homemade”, or whether some of them originate from global and regional scale climate changes. Identifying the locally induced changes of urban meteorological parameters is especially relevant for the development of adaptation and mitigation measures. This study aims to distinguish global and regional climate change signals from those induced by urban land cover. Therefore, it provides a compilation of observed and projected climate changes, as well as urban influences on important meteorological parameters. It is concluded that evidence for climate change signals is found predominantly in air temperature. The effect of urban land cover on local climate can be detected for several meteorological parameters, which are air and surface temperature, humidity, and wind. The meteorology of urban areas is a mixture of signals in which the influencing parameters cannot be isolated, but can be assessed qualitatively. Blending interactions between local effects and regional changes are likely to occur.

Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

Science.gov (United States)

Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

2013-11-12

Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

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Sun, Hai-Ying; Hu, Yu-Juan; Zhao, Xue-Yan; Zhong, Yi; Zeng, Ling-Ling; Chen, Xu-Bo; Yuan, Jie; Wu, Jing; Sun, Yu; Kong, Wen; Kong, Wei-Jia

2015-07-01

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis. © 2015 FEBS.

Comprehensive identification of age-related lipidome changes in rat amygdala during normal aging.

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Roman Šmidák

Full Text Available Brain lipids are integral components of brain structure and function. However, only recent advancements of chromatographic techniques together with mass spectrometry allow comprehensive identification of lipid species in complex brain tissue. Lipid composition varies between the individual areas and the majority of previous reports was focusing on individual lipids rather than a lipidome. Herein, a mass spectrometry-based approach was used to evaluate age-related changes in the lipidome of the rat amygdala obtained from young (3 months and old (20 months males of the Sprague-Dawley rat strain. A total number of 70 lipid species with significantly changed levels between the two animal groups were identified spanning four main lipid classes, i.e. glycerolipids, glycerophospholipids, sphingolipids and sterol lipids. These included phospholipids with pleiotropic brain function, such as derivatives of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. The analysis also revealed significant level changes of phosphatidic acid, diacylglycerol, sphingomyelin and ceramide that directly represent lipid signaling and affect amygdala neuronal activity. The amygdala is a crucial brain region for cognitive functions and former studies on rats and humans showed that this region changes its activity during normal aging. As the information on amygdala lipidome is very limited the results obtained in the present study represent a significant novelty and may contribute to further studies on the role of lipid molecules in age-associated changes of amygdala function.

The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

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Krithika Srikanthan

2016-09-01

Full Text Available Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS, which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.

[The role of Smads and related transcription factors in the signal transduction of bone morphogenetic protein inducing bone formation].

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Xu, Xiao-liang; Dai, Ke-rong; Tang, Ting-ting

2003-09-01

To clarify the mechanisms of the signal transduction of bone morphogenetic proteins (BMPs) inducing bone formation and to provide theoretical basis for basic and applying research of BMPs. We looked up the literature of the role of Smads and related transcription factors in the signal transduction of BMPs inducing bone formation. The signal transduction processes of BMPs included: 1. BMPs combined with type II and type I receptors; 2. the type I receptor phosphorylated Smads; and 3. Smads entered the cell nucleus, interacted with transcription factors and influenced the transcription of related proteins. Smads could be divided into receptor-regulated Smads (R-Smads: Smad1, Smad2, Smad3, Smad5, Smad8 and Smad9), common-mediator Smad (co-Smad: Smad4), and inhibitory Smads (I-Smads: Smad6 and Smad7). Smad1, Smad5, Smad8, and probable Smad9 were involved in the signal transduction of BMPs. Multiple kinases, such as focal adhesion kinase (FAK), Ras-extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and Akt serine/threonine kinase were related to Smads signal transduction. Smad1 and Smad5 related with transcription factors included core binding factor A1 (CBFA1), smad-interacting protein 1 (SIP1), ornithine decarboxylase antizyme (OAZ), activating protein-1 (AP-1), xenopus ventralizing homeobox protein-2 (Xvent-2), sandostatin (Ski), antiproliferative proteins (Tob), and homeodomain-containing transcriptian factor-8 (Hoxc-8), et al. CBFA1 could interact with Smad1, Smad2, Smad3, and Smad5, so it was involved in TGF-beta and BMP-2 signal transduction, and played an important role in the bone formation. Cleidocranial dysplasia (CCD) was thought to be caused by heterozygous mutations in CBFA1. The CBFA1 knockout mice showed no osteogenesis and had maturational disturbance of chondrocytes. Smads and related transcription factors, especially Smad1, Smad5, Smad8 and CBFA1, play an important role in the signal transduction of BMPs inducing bone

Changes in insulin-like growth factor signaling alter phenotypes in Fragile X Mice.

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Wise, T L

2017-02-01

Fragile X syndrome (FXS) is an inherited form of intellectual disability that is usually caused by expansion of a polymorphic CGG repeat in the 5' untranslated region of the X-linked FMR1 gene, which leads to hypermethylation and transcriptional silencing. Two non-neurological phenotypes of FXS are enlarged testes and connective tissue dysplasia, which could be caused by alterations in a growth factor signaling pathway. FXS patients also frequently have autistic-like symptoms, suggesting that the signaling pathways affected in FXS may overlap with those affected in autism. Identifying these pathways is important for both understanding the effects of FMR1 inactivation and developing treatments for both FXS and autism. Here we show that decreasing the levels of the insulin-like growth factor (Igf) receptor 1 corrects a number of phenotypes in the mouse model of FXS, including macro-orchidism, and that increasing the levels of IGF2 exacerbates the seizure susceptibility phenotype. These results suggest that the pathways altered by the loss of the FMR1-encoded protein (FMRP) may overlap with the pathways affected by changes in Igf signaling or that one or more of the proteins that play a role in Igf signaling could interact with FMRP. They also indicate a new set of potential targets for drug treatment of FXS and autism spectrum disorders. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

A Brain–Computer Interface for Potential Nonverbal Facial Communication Based on EEG Signals Related to Specific Emotions

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Koji eKashihara

2014-08-01

Full Text Available Unlike assistive technology for verbal communication, the brain–machine or brain–computer interface (BMI/BCI has not been established as a nonverbal communication tool for amyotrophic lateral sclerosis (ALS patients. Face-to-face communication enables access to rich emotional information, but individuals suffering from neurological disorders, such as ALS and autism, may not express their emotions or communicate their negative feelings. Although emotions may be inferred by looking at facial expressions, emotional prediction for neutral faces necessitates advanced judgment. The process that underlies brain neuronal responses to neutral faces and causes emotional changes remains unknown. To address this problem, therefore, this study attempted to decode conditioned emotional reactions to neutral face stimuli. This direction was motivated by the assumption that if electroencephalogram (EEG signals can be used to detect patients’ emotional responses to specific inexpressive faces, the results could be incorporated into the design and development of BMI/BCI-based nonverbal communication tools. To these ends, this study investigated how a neutral face associated with a negative emotion modulates rapid central responses in face processing and then identified cortical activities. The conditioned neutral face-triggered event-related potentials that originated from the posterior temporal lobe statistically significantly changed during late face processing (600–700 ms after stimulus, rather than in early face processing activities, such as P1 and N170 responses. Source localization revealed that the conditioned neutral faces increased activity in the right fusiform gyrus. This study also developed an efficient method for detecting implicit negative emotional responses to specific faces by using EEG signals.

Comparison of facet joint activity on 99mTc-MDP SPECT/CT with facet joint signal change on MRI with fat suppression.

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Lehman, Vance T; Murphy, Robert C; Schenck, Louis A; Carter, Rickey E; Johnson, Geoffrey B; Kotsenas, Amy L; Morris, Jonathan M; Nathan, Mark A; Wald, John T; Maus, Timothy P

2016-01-01

We compared signal change on magnetic resonance imaging (MRI) with fat suppression and bone scan activity of lumbar facet joints to determine if these two imaging findings are correlated. We retrospectively identified all patients who underwent imaging of the lumbar spine for pain evaluation using both technetium-99m methylene disphosphonate single-photon emission computed tomography/computed tomography (99mTc-MDP SPECT/CT) and MRI with at least one fat-suppressed T2- or T1-weighted sequence with gadolinium enhancement within a 180-day interval, at our institution between 1 January 2008 and 19 February 2013. Facet joint activity on 99mTc-MDP SPECT/CT and peri-facet signal change on MRI were rated as normal or increased. Agreement between the two examination types were determined with the κ and prevalence-adjusted bias-adjusted κ (PABAK) statistics. This study included 60 patients (28 male, 47%), with a mean age of 49±19.7 years (range, 12-93 years). The κ value indicated no agreement between 99mTc-MDP SPECT/CT and MRI (κ=-0.026; 95% confidence interval: -0.051, 0.000). The PABAK values were fair to high at each spinal level, which suggests that relatively low disease prevalence lowered the κ values. Together, the κ and PABAK values indicate that there is some degree of intermodality agreement, but that it is not consistent. Overall, facet joint signal change on fat-suppressed MRI did not always correlate with increased 99mTc-MDP SPECT/CT activity. MRI and 99mTc-MDP SPECT/CT for facet joint evaluation should not be considered interchangeable examinations in clinical practice or research.

Changes in transcription of cytokinin metabolism and signalling genes in grape (Vitis vinifera L.) berries are associated with the ripening-related increase in isopentenyladenine.

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Böttcher, Christine; Burbidge, Crista A; Boss, Paul K; Davies, Christopher

2015-09-16

Cytokinins are known to play an important role in fruit set and early fruit growth, but their involvement in later stages of fruit development is less well understood. Recent reports of greatly increased cytokinin concentrations in the flesh of ripening kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang & A.R. Ferguson) and grapes (Vitis vinifera L.) have suggested that these hormones are implicated in the control of ripening-related processes. A similar pattern of isopentenyladenine (iP) accumulation was observed in the ripening fruit of several grapevine cultivars, strawberry (Fragaria ananassa Duch.) and tomato (Solanum lycopersicum Mill.), suggesting a common, ripening-related role for this cytokinin. Significant differences in maximal iP concentrations between grapevine cultivars and between fruit species might reflect varying degrees of relevance or functional adaptations of this hormone in the ripening process. Grapevine orthologues of five Arabidopsis (Arabidopsis thaliana L.) gene families involved in cytokinin metabolism and signalling were identified and analysed for their expression in developing grape berries and a range of other grapevine tissues. Members of each gene family were characterised by distinct expression profiles during berry development and in different grapevine organs, suggesting a complex regulation of cellular cytokinin activities throughout the plant. The post-veraison-specific expression of a set of biosynthesis, activation, perception and signalling genes together with a lack of expression of degradation-related genes during the ripening phase were indicative of a local control of berry iP concentrations leading to the observed accumulation of iP in ripening grapes. The transcriptional analysis of grapevine genes involved in cytokinin production, degradation and response has provided a possible explanation for the ripening-associated accumulation of iP in grapes and other fruit. The pre- and post-veraison-specific expression of

Various cellular stress components change as the rat ages: An insight into the putative overall age-related cellular stress network.

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Cueno, Marni E; Imai, Kenichi

2018-02-01

Cellular stress is mainly comprised of oxidative, nitrosative, and endoplasmic reticulum stresses and has long been correlated to the ageing process. Surprisingly, the age-related difference among the various components in each independent stress pathway and the possible significance of these components in relation to the overall cellular stress network remain to be clearly elucidated. In this study, we obtained blood from ageing rats upon reaching 20-, 40-, and 72-wk.-old. Subsequently, we measured representative cellular stress-linked biomolecules (H 2 O 2 , glutathione reductase, heme, NADPH, NADP, nitric oxide, GADD153) and cell signals [substance P (SP), free fatty acid, calcium, NF-κB] in either or both blood serum and cytosol. Subsequently, network analysis of the overall cellular stress network was performed. Our results show that there are changes affecting stress-linked biomolecules and cell signals as the rat ages. Additionally, based on our network analysis data, we postulate that NADPH, H 2 O 2 , GADD153, and SP are the key components and the interactions between these components are central to the overall age-related cellular stress network in the rat blood. Thus, we propose that the main pathway affecting the overall age-related cellular stress network in the rat blood would entail NADPH-related oxidative stress (involving H 2 O 2 ) triggering GADD153 activation leading to SP induction which in-turn affects other cell signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Visual-haptic integration with pliers and tongs: signal ‘weights’ take account of changes in haptic sensitivity caused by different tools

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Chie eTakahashi

2014-02-01

Full Text Available When we hold an object while looking at it, estimates from visual and haptic cues to size are combined in a statistically optimal fashion, whereby the ‘weight’ given to each signal reflects their relative reliabilities. This allows object properties to be estimated more precisely than would otherwise be possible. Tools such as pliers and tongs systematically perturb the mapping between object size and the hand opening. This could complicate visual-haptic integration because it may alter the reliability of the haptic signal, thereby disrupting the determination of appropriate signal weights. To investigate this we first measured the reliability of haptic size estimates made with virtual pliers-like tools (created using a stereoscopic display and force-feedback robots with different ‘gains’ between hand opening and object size. Haptic reliability in tool use was straightforwardly determined by a combination of sensitivity to changes in hand opening and the effects of tool geometry. The precise pattern of sensitivity to hand opening, which violated Weber’s law, meant that haptic reliability changed with tool gain. We then examined whether the visuo-motor system accounts for these reliability changes. We measured the weight given to visual and haptic stimuli when both were available, again with different tool gains, by measuring the perceived size of stimuli in which visual and haptic sizes were varied independently. The weight given to each sensory cue changed with tool gain in a manner that closely resembled the predictions of optimal sensory integration. The results are consistent with the idea that different tool geometries are modelled by the brain, allowing it to calculate not only the distal properties of objects felt with tools, but also the certainty with which those properties are known. These findings highlight the flexibility of human sensory integration and tool-use, and potentially provide an approach for optimising the

Insulin Signaling and Heart Failure

Science.gov (United States)

Riehle, Christian; Abel, E. Dale

2016-01-01

Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

Age-Related White Matter Changes

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Yun Yun Xiong

2011-01-01

Full Text Available Age-related white matter changes (WMC are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC.

Global change integrating factors: Tropical tropopause trends

International Nuclear Information System (INIS)

Reck, R.A.

1994-01-01

This research proposes new criteria, shifts in the height and temperature of the tropical tropopause, as measures of global climate change. The search for signs of global warming in the temperature signal near the earth's surface is extremely difficult, largely because numerous factors contribute to surface temperature forcing with only a small signal-to-noise ratio relative to long-term effects. In the long term, no part of the atmosphere can be considered individually because the evolution will be a function of all states of all portions. A large surface greenhouse signal might ultimately be expected, but the analysis of surface temperature may not be particularly useful for early detection. What is suggested here is not an analysis of trends in the surface temperature field or any of its spatial averages, but rather an integrating factor or integrator, a single measure of global change that could be considered a test of significant change for the entire global system. Preferably, this global change integrator would vary slowly and would take into account many of the causes of climate change, with a relatively large signal-to-noise ratio. Such an integrator could be monitored, and abrupt or accelerated changes could serve as an early warning signal for policy makers and the public. Earlier work has suggested that temperature has much less short-term and small-scale noise in the lower stratosphere, and thus the global warming signal at that level might be more easily deconvoluted, because the cooling rate near the 200-mb level is almost constant with latitude. A study of the temperature signal at this pressure level might show a clearer trend due to increased levels of greenhouse gases, but it would yield information about the troposphere only by inference

Evolutionary Interactions Between Visual and Chemical Signals: Chemosignals Compensate for the Loss of a Visual Signal in Male Sceloporus Lizards.

Science.gov (United States)

Pruett, Jake A; Zúñiga-Vega, J Jaime; Campos, Stephanie M; Soini, Helena A; Novotny, Milos V; Vital-García, Cuauhcihuatl; Martins, Emília P; Hews, Diana K

2016-11-01

Animals rely on multimodal signals to obtain information from conspecifics through alternative sensory systems, and the evolutionary loss of a signal in one modality may lead to compensation through increased use of signals in an alternative modality. We investigated associations between chemical signaling and evolutionary loss of abdominal color patches in males of four species (two plain-bellied and two colorful-bellied) of Sceloporus lizards. We conducted field trials to compare behavioral responses of male lizards to swabs with femoral gland (FG) secretions from conspecific males and control swabs (clean paper). We also analyzed the volatile organic compound (VOC) composition of male FG secretions by stir bar extraction and gas chromatography-mass spectrometry (GC-MS) to test the hypothesis that loss of the visual signal is associated with elaboration of the chemical signal. Males of plain-bellied, but not colorful-bellied species exhibited different rates of visual displays when exposed to swabs of conspecific FG secretions relative to control swabs. The VOC composition of male Sceloporus FG secretions was similar across all four species, and no clear association between relative abundances of VOCs and evolutionary loss of abdominal color patches was observed. The emerging pattern is that behavioral responses to conspecific chemical signals are species- and context-specific in male Sceloporus, and compensatory changes in receivers, but not signalers may be involved in mediating increased responsiveness to chemical signals in males of plain-bellied species.

Evaluation of median nerve T2 signal changes in patients with surgically treated carpal tunnel syndrome.

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Samanci, Yavuz; Karagöz, Yeşim; Yaman, Mehmet; Atçı, İbrahim Burak; Emre, Ufuk; Kılıçkesmez, Nuri Özgür; Çelik, Suat Erol

2016-11-01

To determine the accuracy of median nerve T2 evaluation and its relation with Boston Questionnaire (BQ) and nerve conduction studies (NCSs) in pre-operative and post-operative carpal tunnel syndrome (CTS) patients in comparison with healthy volunteers. Twenty-three CTS patients and 24 healthy volunteers underwent NCSs, median nerve T2 evaluation and self-administered BQ. Pre-operative and 1st year post-operative median nerve T2 values and cross-sectional areas (CSAs) were compared both within pre-operative and post-operative CTS groups, and with healthy volunteers. The relationship between MRI findings and BQ and NCSs was analyzed. The ROC curve analysis was used for determining the accuracy. The comparison of pre-operative and post-operative T2 values and CSAs revealed statistically significant improvements in the post-operative patient group (pT2 values at all levels and BQ values, and positive and negative correlations were also found regarding T2 values and NCS findings in CTS patients. The receiver operating characteristic curve analysis for defined cut-off levels of median nerve T2 values in hands with severe CTS yielded excellent accuracy at all levels. However, this accuracy could not be demonstrated in hands with mild CTS. This study is the first to analyze T2 values in both pre-operative and post-operative CTS patients. The presence of increased T2 values in CTS patients compared to controls and excellent accuracy in hands with severe CTS indicates T2 signal changes related to CTS pathophysiology and possible utilization of T2 signal evaluation in hands with severe CTS. Copyright © 2016 Elsevier B.V. All rights reserved.

Social Relations and Technology: Continuity, Context, and Change.

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Antonucci, Toni C; Ajrouch, Kristine J; Manalel, Jasmine A

2017-11-01

Social relations, although basic to human nature, health and well-being, have become increasingly complicated as a result of changing population demography and technology. In this essay, we provide a historical overview of social relations, especially as they affect older people. We briefly review the evolution of theory and measurement surrounding social relations as well as early empirical evidence. We consider how social relations have changed over time as well as continuity and change regarding basic characteristics of social relations. Of special interest is the emerging influence of technology on how people maintain contact, especially the changing ways people can use technology to increase, decrease, maintain, or avoid social relations. We consider both negative and positive aspects of these new technologies and their influence on health and well-being. Finally, we conclude that new and emerging technologies hold great promise for the future by overcoming traditional barriers to maintaining social contact, support exchange, and information acquisition. Nevertheless, we caution that these new technologies can have the dehumanizing effect of distance thus creating the potential for insensitivity and increased negativity. In sum, we are cautiously optimistic about the promise of technology to expand, but not replace, traditional forms of social contact.

Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years

Energy Technology Data Exchange (ETDEWEB)

Kromrey, Marie-Luise; Liedtke, Kim Rouven; Langner, Soenke; Kirsch, Michael; Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Ittermann, Till [University Medicine Greifswald, Institute for Community Medicine, Greifswald (Germany); Weitschies, Werner [University Greifswald, Institute of Biopharmacy and Pharmaceutical Technology, Greifswald (Germany)

2017-02-15

To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (1.5 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. (orig.)

Signal changes in gradient echo images of human brain induced by hypo- and hyperoxia

DEFF Research Database (Denmark)

Rostrup, Egill; Larsson, H B; Toft, P B

1995-01-01

The effect of hypoxia (inspired oxygen fraction, FiO2 of 10% and 16%) and hyperoxia (FiO2) of 100%) on gradient echo images of the brain using long echo times was investigated in six healthy volunteers (age 24-28 years). Different flip angles were used with an FiO2 of 10% to assess the importance...... of saturation effects. The total cerebral blood flow was measured by a phase mapping technique during normoxia as well as hypoxia (FiO2 of 10% and 16%) and hyperoxia (FiO2 of 50% and 100%). High relative signal changes were found, independently of the flip angle, with FiO2 of 10%. With a flip angle of 40...... degrees the values of delta R2* for cortical grey matter, central grey matter, white matter and the sagittal sinus were 0.79, 0.41, 0.26 and 3.00/s; with a flip angle of 10 degrees the corresponding values were 0.70, 0.37, 0.24 and 3.15/s. The total cerebral blood flow increased by 41% during inhalation...

Event-related potentials elicited by pre-attentive emotional changes in temporal context.

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Tomomi Fujimura

Full Text Available The ability to detect emotional change in the environment is essential for adaptive behavior. The current study investigated whether event-related potentials (ERPs can reflect emotional change in a visual sequence. To assess pre-attentive processing, we examined visual mismatch negativity (vMMN: the negative potentials elicited by a deviant (infrequent stimulus embedded in a sequence of standard (frequent stimuli. Participants in two experiments pre-attentively viewed visual sequences of Japanese kanji with different emotional connotations while ERPs were recorded. The visual sequence in Experiment 1 consisted of neutral standards and two types of emotional deviants with a strong and weak intensity. Although the results indicated that strongly emotional deviants elicited more occipital negativity than neutral standards, it was unclear whether these negativities were derived from emotional deviation in the sequence or from the emotional significance of the deviants themselves. In Experiment 2, the two identical emotional deviants were presented against different emotional standards. One type of deviants was emotionally incongruent with the standard and the other type of deviants was emotionally congruent with the standard. The results indicated that occipital negativities elicited by deviants resulted from perceptual changes in a visual sequence at a latency of 100-200 ms and from emotional changes at latencies of 200-260 ms. Contrary to the results of the ERP experiment, reaction times to deviants showed no effect of emotional context; negative stimuli were consistently detected more rapidly than were positive stimuli. Taken together, the results suggest that brain signals can reflect emotional change in a temporal context.

Anterior prefrontal involvement in implicit contextual change detection

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Stefan Pollmann

2009-10-01

Full Text Available Anterior prefrontal cortex is usually associated with high level executive functions. Here, we show that the frontal pole, specifically left lateral frontopolar cortex, is involved in signaling change in implicitly learned spatial contexts, in the absence of conscious change detection. In a variant of the contextual cueing paradigm, participants first learned implicitly contingencies between distractor contexts and target locations. After learning, repeated distractor contexts were paired with new target locations. Left lateral frontopolar (BA10 and superior frontal (BA9 cortices showed selective signal increase for this target location change in repeated displays in an event-related fMRI experiment, which was most pronounced in participants with high contextual facilitation before the change. The data support the view that left lateral frontopolar cortex is involved in signaling contextual change to posterior brain areas as a precondition for adaptive changes of attentional resource allocation. This signaling occurs in the absence of awareness of learned contingencies or contextual change.

Right Hemisphere Sensitivity to Novel Metaphoric Relations: Application of the Signal Detection Theory

Science.gov (United States)

Mashal, N.; Faust, M.

2008-01-01

The present study used the signal detection theory to test the hypothesis that the right hemisphere (RH) is more sensitive than the left hemisphere (LH) to the distant semantic relations in novel metaphoric expressions. In two divided visual field experiments, sensitivity (d') and criterion ([beta]) were calculated for responses to different types…

Changes in Ghrelin-Related Factors in Gastroesophageal Reflux Disease in Rats

Directory of Open Access Journals (Sweden)

Miwa Nahata

2013-01-01

Full Text Available To examine gastrointestinal hormone profiles and functional changes in gastroesophageal reflux disease (GERD, blood levels of the orexigenic hormone ghrelin were measured in rats with experimentally induced GERD. During the experiment, plasma acyl ghrelin levels in GERD rats were higher than those in sham-operated rats, although food intake was reduced in GERD rats. Although plasma levels of the appetite-suppressing hormone leptin were significantly decreased in GERD rats, no changes were observed in cholecystokinin levels. Repeated administration of rat ghrelin to GERD rats had no effect on the reduction in body weight or food intake. Therefore, these results suggest that aberrantly increased secretion of peripheral ghrelin and decreased ghrelin responsiveness may occur in GERD rats. Neuropeptide Y and agouti-related peptide mRNA expression in the hypothalamus of GERD rats was significantly increased, whereas proopiomelanocortin mRNA expression was significantly decreased compared to that in sham-operated rats. However, melanin-concentrating hormone (MCH and prepro-orexin mRNA expression in the hypothalamus of GERD rats was similar to that in sham-operated rats. These results suggest that although GERD rats have higher plasma ghrelin levels, ghrelin signaling in GERD rats may be suppressed due to reduced MCH and/or orexin synthesis in the hypothalamus.

Sleep deprivation alters valuation signals in the ventromedial prefrontal cortex

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Camilo eLibedinsky

2011-10-01

Full Text Available Even a single night of total sleep-deprivation (SD can have dramatic effects on economic decision making. Here we tested the novel hypothesis that SD influences economic decisions by altering the valuation process. Using functional magnetic resonance imaging (fMRI we identified value signals related to the anticipation and the experience of monetary and social rewards (attractive female faces. We then derived decision value signals that were predictive of each participant’s willingness to exchange money for brief views of attractive faces in an independent market task. Strikingly, SD altered decision value signals in ventromedial prefrontal cortex (VMPFC in proportion to the corresponding change in economic preferences. These changes in preference were independent of the effects of SD on attention and vigilance. Our results provide novel evidence that signals in VMPFC track the current state of the individual, and thus reflect not static but constructed preferences.

Separating climate change signals into thermodynamic, lapse-rate and circulation effects: theory and application to the European summer climate

Science.gov (United States)

Kröner, Nico; Kotlarski, Sven; Fischer, Erich; Lüthi, Daniel; Zubler, Elias; Schär, Christoph

2017-05-01

Climate models robustly project a strong overall summer warming across Europe showing a characteristic north-south gradient with enhanced warming and drying in southern Europe. However, the processes that are responsible for this pattern are not fully understood. We here employ an extended surrogate or pseudo-warming approach to disentangle the contribution of different mechanisms to this response pattern. The basic idea of the surrogate technique is to use a regional climate model and apply a large-scale warming to the lateral boundary conditions of a present-day reference simulation, while maintaining the relative humidity (and thus implicitly increasing the specific moisture content). In comparison to previous studies, our approach includes two important extensions: first, different vertical warming profiles are applied in order to separate the effects of a mean warming from lapse-rate effects. Second, a twin-design is used, in which the climate change signals are not only added to present-day conditions, but also subtracted from a scenario experiment. We demonstrate that these extensions provide an elegant way to separate the full climate change signal into contributions from large-scale thermodynamic (TD), lapse-rate (LR), and circulation and other remaining effects (CO). The latter in particular include changes in land-ocean contrast and spatial variations of the SST warming patterns. We find that the TD effect yields a large-scale warming across Europe with no distinct latitudinal gradient. The LR effect, which is quantified for the first time in our study, leads to a stronger warming and some drying in southern Europe. It explains about 50 % of the warming amplification over the Iberian Peninsula, thus demonstrating the important role of lapse-rate changes. The effect is linked to an extending Hadley circulation. The CO effect as inherited from the driving GCM is shown to further amplify the north-south temperature change gradient. In terms of mean summer

Is the number of microembolic signals related to neurologic outcome in coronary bypass surgery?

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Malheiros Suzana M. F.

2001-01-01

Full Text Available Coronary artery bypass surgery (CABG without cardiopulmonary bypass (CPB may potentially reduce the number of microembolic signals (MES associated with aortic manipulation or generated by the pump circuit, resulting in a better neurologic outcome after surgery. Our aim was to compare the frequency of MES and neurologic complications in CABG with and without CPB. Twenty patients eligible to routine CABG without CPB were randomized to surgery with CPB and without CPB and continuously monitored by transcranial Doppler. Neurologic examination was performed in all patients before and after surgery. The two groups were similar with respect to demographics, risk factors, grade of aortic atheromatous disease and number of grafts. The frequency of MES in the nonCPB group was considerably lower than in CPB patients, however, we did not observe any change in the neurologic examination during the early postoperative period. Neurologic complications after CABG may be related to the size and composition of MES rather than to their absolute numbers. A large prospective multicentric randomized trial may help to elucidate this complex issue.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide

Energy Technology Data Exchange (ETDEWEB)

Ramalho, Joana [University of North Carolina Hospital, Chapel Hill, NC (United States); Centro Hospitalar de Lisboa Central, Lisbon (Portugal); Semelka, Richard C.; Castillo, Mauricio [University of North Carolina Hospital, Chapel Hill, NC (United States); AlObaidy, Mamdoh [University of North Carolina Hospital, Chapel Hill, NC (United States); King Faisal Specialist Hospital and Research Center, Riyadh (Saudi Arabia); Ramalho, Miguel [University of North Carolina Hospital, Chapel Hill, NC (United States); Hospital Garcia de Orta, Almada (Portugal); Nunes, Renato H. [University of North Carolina Hospital, Chapel Hill, NC (United States); Santa Casa de Misericordia de Sao Paulo, Sao Paulo (Brazil)

2016-11-15

To evaluate the impact of previous administration of gadodiamide and neural tissue gadolinium deposition in patients who received gadobenate dimeglumine. Our population included 62 patients who underwent at least three administrations of gadobenate dimeglumine, plus an additional contrast-enhanced last MRI for reference, divided into two groups: group 1, patients who in addition to gadobenate dimeglumine administrations had prior exposure to multiple doses of gadodiamide; group 2, patients without previous exposure to other gadolinium-based contrast agent (GBCAs). Quantitative analysis was performed on the first and last gadobenate dimeglumine MRIs in both groups. Dentate nucleus-to-middle cerebellar peduncle signal intensity ratios (DN/MCP) and relative change (RC) in signal over time were calculated and compared between groups using generalized additive model. Group 1 showed significant increase in baseline and follow-up DN/MCP compared to group 2 (p < 0.0001). The RC DN/MCP showed a non-statistically significant trend towards an increase in patients who underwent previous gadodiamide (p = 0.0735). There is increased T1 signal change over time in patients who underwent gadobenate dimeglumine and had received prior gadodiamide compared to those without known exposure to previous gadodiamide. A potentiating effect from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur. (orig.)

Molecular signals into the insular cortex and amygdala during aversive gustatory memory formation.

Science.gov (United States)

Bermúdez-Rattoni, Federico; Ramírez-Lugo, Leticia; Gutiérrez, Ranier; Miranda, María Isabel

2004-02-01

In this paper, we will provide evidence of the putative molecular signals and biochemical events that mediate the formation of long-lasting gustatory memory trace. When an animal drinks a novel taste (the conditioned stimulus; CS) and it is later associated with malaise (unconditioned stimulus; US), the animal will reject it in the next presentation, developing a long-lasting taste aversion, i.e., the taste cue becomes an aversive signal, and this is referred to as conditioning taste aversion. Different evidence indicates that the novel stimulus (taste) induces a rapid and strong cortical acetylcholine activity that decreases when the stimulus becomes familiar after several presentations. Cholinergic activation via muscarinic receptors initiates a series of intracellular events leading to plastic changes that could be related to short- and/or long-term memory gustatory trace. Such plastic changes facilitate the incoming US signals carried out by, in part, the glutamate release induced by the US. Altogether, these events could produce the cellular changes related to the switch from safe to aversive taste memory trace. A proposed working model to explain the biochemical sequence of signals during taste memory formation will be discussed.

Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus.

Science.gov (United States)

Tyzio, Roman; Minlebaev, Marat; Rheims, Sylvain; Ivanov, Anton; Jorquera, Isabelle; Holmes, Gregory L; Zilberter, Yuri; Ben-Ari, Yehezkiel; Khazipov, Rustem

2008-05-01

During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

Endocannabinoids and the processing of value-related signals

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Miriam eMelis

2012-02-01

Full Text Available Endocannabinoids serve as retrograde signaling molecules at many synapses within the CNS, particularly GABAergic and glutamatergic synapses. Synapses onto midbrain dopamine (DA neurons in the ventral tegmental area (VTA make no exception to this rule. In fact, the effects of cannabinoids on dopamine transmission as well as DA-related behaviors are generally exerted through the modulation of inhibitory and excitatory afferents impinging onto DA neurons. Endocannabinoids, by regulating different forms of synaptic plasticity in the VTA, provide a critical modulation of the DA neuron output and, ultimately, of the systems driving and regulating motivated behaviors. Because DA cells exhibit diverse states of activity, which crucially depend on their intrinsic properties and afferent drive, the understanding of the role played by endocannabinoids in synaptic modulations is critical for their overall functions. Particularly, endocannabinoids by selectively inhibiting afferent activity may alter the functional states of DA neurons and potentiate the responsiveness of the reward system to phasic DA.

Postnatal changes in electromyographic signals during piglet growth, and in relation to muscle fibre types

DEFF Research Database (Denmark)

Andersen, Ninette Kieme; Ravn, L.S.; Guy, J.H.

2008-01-01

This study uses non-invasive evoked surface electromyography (SEMG) to investigate postnatal muscle development in pigs, and to assess any correlation between recorded signal parameters and muscle fibre types in two different skeletal muscles. Four litters (n=43) of Large White x Landrace pigs were...... used. Evoked SEMG mesurements were taken on days 2, 5, 14, 26, 60 and 151 post partum from m. Longissimus dorsi (LD) and on days 14, 26, 60 and 151 post partum from m. Biceps femoris (BF). A third of each litter was slaughtered at days 27, 61 and 153 post partum. Biopsy samples for LD and BF were taken...... to categorize day 5 post partum, whilst for BF significant increases occurred from days 14 to 26 post partum. Fibre type development in both muscles showed a significant decrease in type IIA fibre number (Ptype IIB fibre number (P

Impaired Insulin/IGF Signaling in Experimental Alcohol-Related Myopathy

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Elizabeth Silbermann

2012-08-01

Full Text Available Alcohol-related myopathy (Alc-M is highly prevalent among heavy drinkers, although its pathogenesis is not well understood. We hypothesize that Alc-M is mediated by combined effects of insulin/IGF resistance and oxidative stress, similar to the effects of ethanol on liver and brain. We tested this hypothesis using an established model in which adult rats were pair-fed for 8 weeks with isocaloric diets containing 0% (N = 8 or 35.5% (N = 13 ethanol by caloric content. Gastrocnemius muscles were examined by histology, morphometrics, qRT-PCR analysis, and ELISAs. Chronic ethanol feeding reduced myofiber size and mRNA expression of IGF-1 polypeptide, insulin, IGF-1, and IGF-2 receptors, IRS-1, and IRS-2. Multiplex ELISAs demonstrated ethanol-associated inhibition of insulin, IRS-1, Akt, and p70S6K signaling, and increased activation of GSK-3β. In addition, ethanol-exposed muscles had increased 4-hydroxy-2-nonenal immunoreactivity, reflecting lipid peroxidation, and reduced levels of mitochondrial Complex IV, Complex V, and acetylcholinesterase. These results demonstrate that experimental Alc-M is associated with inhibition of insulin/IGF/IRS and downstream signaling that mediates metabolism and cell survival, similar to findings in alcoholic liver and brain degeneration. Moreover, the increased oxidative stress, which could be mediated by mitochondrial dysfunction, may have led to inhibition of acetylcholinesterase, which itself is sufficient to cause myofiber atrophy and degeneration.

Signal estimation and change detection in tank data for nuclear safeguards

International Nuclear Information System (INIS)

Burr, Tom; Suzuki, Mitsutoshi; Howell, John; Longo, Claire E.; Hamada, Michael S.

2011-01-01

Process monitoring (PM) is increasingly important in nuclear safeguards as a complement to mass-balance based nuclear materials accounting (NMA). Typically, PM involves more frequent but lower quality measurements than NMA. While NMA estimates special nuclear material (SNM) mass balances and uncertainties, PM often tracks SNM attributes qualitatively or in the case of solution monitoring (SM) tracks bulk mass and volume. Automatic event marking is used in several nuclear safeguards PM systems. The aims are to locate the start and stop times and signal changes associated with key events. This paper describes results using both real and simulated SM data to quantify the errors associated with imperfect marking of start and stop times of tank events such as receipts and shipments. In the context of safeguards, one can look both forward and backward in modest time intervals to recognize events. Event marking methods evaluated include differencing, multi-scale principal component analysis using wavelets, and piecewise linear regression (PLR). All methods are evaluated on both raw and smoothed data, and several smoothing options are compared, including standard filters, hybrid filters, and local kernel smoothing. The main finding for real and simulated examples considered is that a two-step strategy is most effective. First, any reasonably effective initial smoother is used to provide a good initial guess at change point locations. Second, PLR is applied, looking for one change point at a time. In contrast, PLR that allows for multiple change points simultaneously has worse performance.

Effects of human fatigue on speech signals

Science.gov (United States)

Stamoulis, Catherine

2004-05-01

Cognitive performance may be significantly affected by fatigue. In the case of critical personnel, such as pilots, monitoring human fatigue is essential to ensure safety and success of a given operation. One of the modalities that may be used for this purpose is speech, which is sensitive to respiratory changes and increased muscle tension of vocal cords, induced by fatigue. Age, gender, vocal tract length, physical and emotional state may significantly alter speech intensity, duration, rhythm, and spectral characteristics. In addition to changes in speech rhythm, fatigue may also affect the quality of speech, such as articulation. In a noisy environment, detecting fatigue-related changes in speech signals, particularly subtle changes at the onset of fatigue, may be difficult. Therefore, in a performance-monitoring system, speech parameters which are significantly affected by fatigue need to be identified and extracted from input signals. For this purpose, a series of experiments was performed under slowly varying cognitive load conditions and at different times of the day. The results of the data analysis are presented here.

Ginseng Total Saponins Reverse Corticosterone-Induced Changes in Depression-Like Behavior and Hippocampal Plasticity-Related Proteins by Interfering with GSK-3β-CREB Signaling Pathway

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Lin Chen

2014-01-01

Full Text Available This study aimed to explore the antidepressant mechanisms of ginseng total saponins (GTS in the corticosterone-induced mouse depression model. In Experiment 1, GTS (50, 25, and 12.5 mg kg−1 d−1, intragastrically were given for 3 weeks. In Experiment 2, the same doses of GTS were administrated after each corticosterone (20 mg kg−1 d−1, subcutaneously injection for 22 days. In both experiments, mice underwent a forced swimming test and a tail suspension test on day 20 and day 21, respectively, and were sacrificed on day 22. Results of Experiment 1 revealed that GTS (50 and 25 mg kg−1 d−1 exhibited antidepressant activity and not statistically altered hippocampal protein levels of brain-derived neurotrophic factor (BDNF and neurofilament light chain (NF-L. Results of Experiment 2 showed that GTS (50 and 25 mg kg−1 d−1 ameliorated depression-like behavior without normalizing hypercortisolism. The GTS treatments reversed the corticosterone-induced changes in mRNA levels of BDNF and NF-L, and protein levels of BDNF NF-L, phosphor-cAMP response element-binding protein (Ser133, and phosphor-glycogen synthase kinase-3β (Ser9 in the hippocampus. These findings imply that the effect of GTS on corticosterone-induced depression-like behavior may be mediated partly through interfering with hippocampal GSK-3β-CREB signaling pathway and reversing decrease of some plasticity-related proteins.

Impact of the choice of the precipitation reference data set on climate model selection and the resulting climate change signal

Science.gov (United States)

Gampe, D.; Ludwig, R.

2017-12-01

Regional Climate Models (RCMs) that downscale General Circulation Models (GCMs) are the primary tool to project future climate and serve as input to many impact models to assess the related changes and impacts under such climate conditions. Such RCMs are made available through the Coordinated Regional climate Downscaling Experiment (CORDEX). The ensemble of models provides a range of possible future climate changes around the ensemble mean climate change signal. The model outputs however are prone to biases compared to regional observations. A bias correction of these deviations is a crucial step in the impact modelling chain to allow the reproduction of historic conditions of i.e. river discharge. However, the detection and quantification of model biases are highly dependent on the selected regional reference data set. Additionally, in practice due to computational constraints it is usually not feasible to consider the entire ensembles of climate simulations with all members as input for impact models which provide information to support decision-making. Although more and more studies focus on model selection based on the preservation of the climate model spread, a selection based on validity, i.e. the representation of the historic conditions is still a widely applied approach. In this study, several available reference data sets for precipitation are selected to detect the model bias for the reference period 1989 - 2008 over the alpine catchment of the Adige River located in Northern Italy. The reference data sets originate from various sources, such as station data or reanalysis. These data sets are remapped to the common RCM grid at 0.11° resolution and several indicators, such as dry and wet spells, extreme precipitation and general climatology, are calculate to evaluate the capability of the RCMs to produce the historical conditions. The resulting RCM spread is compared against the spread of the reference data set to determine the related uncertainties and

Modulation of Hippocampal Neural Plasticity by Glucose-Related Signaling

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Marco Mainardi

2015-01-01

Full Text Available Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression, structural plasticity (i.e., dynamics of dendritic spines, and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

Optimal Signal Quality Index for Photoplethysmogram Signals

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Mohamed Elgendi

2016-09-01

Full Text Available A photoplethysmogram (PPG is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

Optimal Signal Quality Index for Photoplethysmogram Signals.

Science.gov (United States)

Elgendi, Mohamed

2016-09-22

A photoplethysmogram (PPG) is a noninvasive circulatory signal related to the pulsatile volume of blood in tissue and is typically collected by pulse oximeters. PPG signals collected via mobile devices are prone to artifacts that negatively impact measurement accuracy, which can lead to a significant number of misleading diagnoses. Given the rapidly increased use of mobile devices to collect PPG signals, developing an optimal signal quality index (SQI) is essential to classify the signal quality from these devices. Eight SQIs were developed and tested based on: perfusion, kurtosis, skewness, relative power, non-stationarity, zero crossing, entropy, and the matching of systolic wave detectors. Two independent annotators annotated all PPG data (106 recordings, 60 s each) and a third expert conducted the adjudication of differences. The independent annotators labeled each PPG signal with one of the following labels: excellent, acceptable or unfit for diagnosis. All indices were compared using Mahalanobis distance, linear discriminant analysis, quadratic discriminant analysis, and support vector machine with leave-one-out cross-validation. The skewness index outperformed the other seven indices in differentiating between excellent PPG and acceptable, acceptable combined with unfit, and unfit recordings, with overall F 1 scores of 86.0%, 87.2%, and 79.1%, respectively.

Dopaminergic Modulation of Incentive Motivation in Adolescence: Age-Related Changes in Signaling, Individual Differences, and Implications for the Development of Self-Regulation

Science.gov (United States)

Luciana, Monica; Wahlstrom, Dustin; Porter, James N.; Collins, Paul F.

2012-01-01

Behavioral activation that is associated with incentive-reward motivation increases in adolescence relative to childhood and adulthood. This quadratic developmental pattern is generally supported by behavioral and experimental neuroscience findings. It is suggested that a focus on changes in dopamine neurotransmission is informative in…

Exercise and dietary change ameliorate high fat diet induced obesity and insulin resistance via mTOR signaling pathway.

Science.gov (United States)

Bae, Ju Yong; Shin, Ki Ok; Woo, Jinhee; Woo, Sang Heon; Jang, Ki Soeng; Lee, Yul Hyo; Kang, Sunghwun

2016-06-01

The purpose of this study was to investigate the effect of exercise and dietary change on obesity and insulin resistance and mTOR signaling protein levels in skeletal muscles of obese rats. Sixty male Sprague-Dawley rats were divided into CO (Normal diet) and HF (High Fat diet) groups in order to induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO + Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND + Training) groups (10 rats / group). The training groups underwent moderate-intensity treadmill exercise for 8 weeks, after which soleus muscles were excised and analyzed. Data was statistically analyzed by independent t-test and One-way ANOVA tests with a 0.05 significance level. Fasting blood glucose, plasma insulin, and HOMA-IR in the HF group were significantly higher, as compared with other groups (p continuous high fat intake, regular exercise and dietary change showed a positive effect on insulin resistance and mTOR signaling protein levels.

Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

Energy Technology Data Exchange (ETDEWEB)

Falzon, Miriam, E-mail: mfalzon@utmb.edu; Bhatia, Vandanajay [Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

2015-06-18

Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

Directory of Open Access Journals (Sweden)

Miriam Falzon

2015-06-01

Full Text Available Chronic pancreatitis (CP, a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

International Nuclear Information System (INIS)

Falzon, Miriam; Bhatia, Vandanajay

2015-01-01

Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation

Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

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Xin-Yu Huang

2016-01-01

Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

Sugar signalling and gene expression in relation to carbohydrate ...

Indian Academy of Sciences (India)

Sucrose is required for plant growth and development. The sugar status of plant cells is sensed by sensor proteins. The signal generated by signal transduction cascades, which could involve mitogen-activated protein kinases, protein phosphatases, Ca2+ and calmodulins, results in appropriate gene expression. A variety of ...

Qualitative analysis of intracranial CSF flow on cine-MR imaging, with special reference to signal ratio of CSF to fat tissue

International Nuclear Information System (INIS)

Kadowaki, Chikafusa; Hara, Mitsuhiro; Numoto, Mitsuo; Takeuchi, Kazuo; Saito, Isamu

1993-01-01

Cine magnetic resonance images (MR) dramatically demonstrate the pulsatile flow of cerebrospinal fluid (CSF) stimulated by the pulsatile motion of the brain following cardiac pulsation. Reduced signal intensity, frequently observed especially in the aqueduct of Sylvius, the third ventricle and the fourth ventricle, is believed to reflect the pulsatile motion of the CSF. Qualitative analysis of MR signal intensity of CSF on each cine frame is compared with CSF flow within the ventricles on real-time cine MR images. While the chronological changes in signal intensities of CSF within the ventricles show only marginal changes in signal intensity in the third ventricle related to downward flow of CSF passing through the foramen of Monro during the early stage of cardiac systole, these changes are thought to have no significant correlation with the CSF flow in the CSF pathway. The chronological changes in relative signal ratios, SR [signal intensities of CSF/signal intensities of fat] can show CSF flow and turbulence within the ventricles. Under normal conditions, within the third ventricle the SR decreases due to pulsatile CSF flow through the foramen of Monro during the early stage of cardiac systole, and decreases because of the flow of CSF from the anterior to the posterior part of the third ventricle, the downward flow of CSF through the aqueduct leads to a lower SR during cardiac diastole. These changes in the fourth ventricle are stimulated by the changes in SR in the third ventricle. The new method of analyzing chronological changes in the relative MR signal ratio of CSF to fat [SR] has the distinct advantage of providing an accurate evaluation of CSF dynamics, and it provides us with important diagnostic information leading to clarification of the pathophysiology of CSF dynamics. (author)

Specificity of herbivore-induced hormonal signaling and defensive traits in five closely related milkweeds (Asclepias spp.).

Science.gov (United States)

Agrawal, Anurag A; Hastings, Amy P; Patrick, Eamonn T; Knight, Anna C

2014-07-01

Despite the recognition that phytohormonal signaling mediates induced responses to herbivory, we still have little understanding of how such signaling varies among closely related species and may generate herbivore-specific induced responses. We studied closely related milkweeds (Asclepias) to link: 1) plant damage by two specialist chewing herbivores (milkweed leaf beetles Labidomera clivicolis and monarch caterpillars Danaus plexippus); 2) production of the phytohormones jasmonic acid (JA), salicylic acid (SA), and abscisic acid (ABA); 3) induction of defensive cardenolides and latex; and 4) impacts on Danaus caterpillars. We first show that A. syriaca exhibits induced resistance following monarch herbivory (i.e., reduced monarch growth on previously damaged plants), while the defensively dissimilar A. tuberosa does not. We next worked with a broader group of five Asclepias, including these two species, that are highly divergent in defensive traits yet from the same clade. Three of the five species showed herbivore-induced changes in cardenolides, while induced latex was found in four species. Among the phytohormones, JA and ABA showed specific responses (although they generally increased) to insect species and among the plant species. In contrast, SA responses were consistent among plant and herbivore species, showing a decline following herbivore attack. Jasmonic acid showed a positive quantitative relationship only with latex, and this was strongest in plants damaged by D. plexippus. Although phytohormones showed qualitative tradeoffs (i.e., treatments that enhanced JA reduced SA), the few significant individual plant-level correlations among hormones were positive, and these were strongest between JA and ABA in monarch damaged plants. We conclude that: 1) latex exudation is positively associated with endogenous JA levels, even among low-latex species; 2) correlations among milkweed hormones are generally positive, although herbivore damage induces a

Ocean angular momentum signals in a climate model and implications for Earth rotation

Science.gov (United States)

Ponte, R. M.; Rajamony, J.; Gregory, J. M.

2002-03-01

Estimates of ocean angular momentum (OAM) provide an integrated measure of variability in ocean circulation and mass fields and can be directly related to observed changes in Earth rotation. We use output from a climate model to calculate 240 years of 3-monthly OAM values (two equatorial terms L1 and L2, related to polar motion or wobble, and axial term L3, related to length of day variations) representing the period 1860-2100. Control and forced runs permit the study of the effects of natural and anthropogenically forced climate variability on OAM. All OAM components exhibit a clear annual cycle, with large decadal modulations in amplitude, and also longer period fluctuations, all associated with natural climate variability in the model. Anthropogenically induced signals, inferred from the differences between forced and control runs, include an upward trend in L3, related to inhomogeneous ocean warming and increases in the transport of the Antarctic Circumpolar Current, and a significantly weaker seasonal cycle in L2 in the second half of the record, related primarily to changes in seasonal bottom pressure variability in the Southern Ocean and North Pacific. Variability in mass fields is in general more important to OAM signals than changes in circulation at the seasonal and longer periods analyzed. Relation of OAM signals to changes in surface atmospheric forcing are discussed. The important role of the oceans as an excitation source for the annual, Chandler and Markowitz wobbles, is confirmed. Natural climate variability in OAM and related excitation is likely to measurably affect the Earth rotation, but anthropogenically induced effects are comparatively weak.

Health-related mobile apps and behaviour change

African Journals Online (AJOL)

Kathryn van Boom

Health-related mobile apps and behaviour change. While our knowledge about physical activity and health, physical performance and the risk of injury increases in leaps and bounds, the conversion of this information into action and changed behaviour lags behind. There seems to be a sticking point which often causes a ...

Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate

Science.gov (United States)

von Erlach, Thomas C.; Bertazzo, Sergio; Wozniak, Michele A.; Horejs, Christine-Maria; Maynard, Stephanie A.; Attwood, Simon; Robinson, Benjamin K.; Autefage, Hélène; Kallepitis, Charalambos; del Río Hernández, Armando; Chen, Christopher S.; Goldoni, Silvia; Stevens, Molly M.

2018-03-01

Cell size and shape affect cellular processes such as cell survival, growth and differentiation1-4, thus establishing cell geometry as a fundamental regulator of cell physiology. The contributions of the cytoskeleton, specifically actomyosin tension, to these effects have been described, but the exact biophysical mechanisms that translate changes in cell geometry to changes in cell behaviour remain mostly unresolved. Using a variety of innovative materials techniques, we demonstrate that the nanostructure and lipid assembly within the cell plasma membrane are regulated by cell geometry in a ligand-independent manner. These biophysical changes trigger signalling events involving the serine/threonine kinase Akt/protein kinase B (PKB) that direct cell-geometry-dependent mesenchymal stem cell differentiation. Our study defines a central regulatory role by plasma membrane ordered lipid raft microdomains in modulating stem cell differentiation with potential translational applications.

Signal anomaly detection and characterization

International Nuclear Information System (INIS)

Morgenstern, V.M.; Upadhyaya, B.R.; Gloeckler, O.

1988-08-01

As part of a comprehensive signal validation system, we have developed a signal anomaly detector, without specifically establishing the cause of the anomaly. A signal recorded from process instrumentation is said to have an anomaly, if during steady-state operation, the deviation in the level of the signal, its root-mean-square (RMS) value, or its statistical distribution changes by a preset value. This deviation could be an unacceptable increase or a decrease in the quantity being monitored. An anomaly in a signal may be characterized by wideband or single-frequency noise, bias error, pulse-type error, nonsymmetric behavior, or a change in the signal bandwidth. Various signatures can be easily computed from data samples and compared against specified threshold values. We want to point out that in real processes, pulses can appear with different time widths, and at different rates of change of the signal. Thus, in characterizing an anomaly as a pulse-type, the fastest pulse width is constrained by the signal sampling interval. For example, if a signal is sampled at 100 Hz, we will not be able to detect pulses occurring at kHz rates. Discussion with utility and Combustion Engineering personnel indicated that it is not practical to detect pulses having a narrow time width. 9 refs., 11 figs., 8 tabs

Age-Related Neurochemical Changes in the Vestibular Nuclei

Directory of Open Access Journals (Sweden)

Paul eSmith

2016-03-01

Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

Age-Related Neurochemical Changes in the Vestibular Nuclei.

Science.gov (United States)

Smith, Paul F

2016-01-01

There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

Science.gov (United States)

Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

2016-01-01

Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

Microglia and their CX3CR1 signaling are involved in hippocampal- but not olfactory bulb-related memory and neurogenesis.

Science.gov (United States)

Reshef, Ronen; Kreisel, Tirzah; Beroukhim Kay, Dorsa; Yirmiya, Raz

2014-10-01

Recent studies demonstrate that microglia play an important role in cognitive and neuroplasticity processes, at least partly via microglial CX3C receptor 1 (CX3CR1) signaling. Furthermore, microglia are responsive to environmental enrichment (EE), which modulates learning, memory and neurogenesis. In the present study we examined the role of microglial CX3CR1 signaling in hippocampal- and olfactory-bulb (OB)-related memory and neurogenesis in homozygous mice with microglia-specific transgenic expression of GFP under the CX3CR1 promoter (CX3CR1(-/-) mice), in which the CX3CR1 gene is functionally deleted, as well as heterozygous CX3CR1(+/-) and WT controls. We report that the CX3CR1-deficient mice displayed better hippocampal-dependent memory functioning and olfactory recognition, along with increased number and soma size of hippocampal microglia, suggestive of mild activation status, but no changes in OB microglia. A similar increase in hippocampal-dependent memory functioning and microglia number was also induced by pharmacological inhibition of CX3CR1 signaling, using chronic (2weeks) i.c.v. administration of CX3CR1 blocking antibody. In control mice, EE improved hippocampal-dependent memory and neurogenesis, and increased hippocampal microglia number and soma size, whereas odor enrichment (OE) improved olfactory recognition and OB neurogenesis without changing OB microglia status. In CX3CR1-deficient mice, EE and OE did not produce any further improvement in memory functioning or neurogenesis and had no effect on microglial status. These results support the notion that in the hippocampus microglia and their interactions with neurons via the CX3CR1 play an important role in memory functioning and neurogenesis, whereas in the OB microglia do not seem to be involved in these processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Climate change and related activities

International Nuclear Information System (INIS)

1992-01-01

The production and consumption of energy contributes to the concentration of greenhouse gases in the atmosphere and is the focus of other environmental concerns as well. Yet the use of energy contributes to worldwide economic growth and development. If we are to achieve environmentally sound economic growth, we must develop and deploy energy technologies that contribute to global stewardship. The Department of Energy carries out an aggressive scientific research program to address some of the key uncertainties associated with the climate change issue. Of course, research simply to study the science of global climate change is not enough. At the heart of any regime of cost-effective actions to address the possibility of global climate change will be a panoply of new technologies-technologies both to provide the services we demand and to use energy more efficiently than in the past. These, too, are important areas of responsibility for the Department. This report is a brief description of the Department's activities in scientific research, technology development, policy studies, and international cooperation that are directly related to or have some bearing on the issue of global climate change

Absolute gravimetry - for monitoring climate change and geodynamics in Greenland

DEFF Research Database (Denmark)

Nielsen, Jens Emil

Over the recent decades, there has been an increasing interest in studying climatic changes. The reason for this interest is a wish to gain an understanding of the processes behind these climatic changes, and to be able to predict the consequences of, for example, sea level change. To say something......, there is a large interest in studying the mass changes of the Greenland Ice Sheet. There are many geophysical methods which can be used to study climatic changes. However, the interpretation of these changes is complicated due to the presence of many different signals - not all of which are related to present......-day climate change. Different geophysical methods have the ability to detect different signals. In many cases, the best results are obtained through incorporating different methods. The use of different methods for identifying certain signals has been the motivation for this PhD project. The signals...

Developmental changes in the facial morphology of the Borneo orangutan (Pongo pygmaeus): possible signals in visual communication.

Science.gov (United States)

Kuze, Noko; Malim, Titol Peter; Kohshima, Shiro

2005-04-01

Orangutans display remarkable developmental changes and sexual differences in facial morphology, such as the flanges or cheek-pads that develop only on the face of dominant adult males. These changes suggest that facial morphology is an important factor in visual communication. However, developmental changes in facial morphology have not been examined in detail. We studied developmental changes in the facial morphology of the Borneo orangutan (Pongo pygmaeus) by observing 79 individuals of various ages living in the Sepilok Orangutan Rehabilitation Centre (SORC) in Malaysia and in Japanese zoos. We also analyzed photographs of one captive male that were taken over a period of more than 16 years. There were clear morphological changes that occurred with growth, and we identified previously unreported sexual and developmental differences in facial morphology. Light-colored skin around the eyes and mouth is most prominent in animals younger than 3 years, and rapidly decreases in area through the age of approximately 7 years. At the same time, the scattered, erect hairs on the head (infant hair) become thick, dense hairs lying on the head (adult hair) in both sexes. The results suggest that these features are infant signals, and that adult signals may include darkened face color, adult hair, whiskers, and a beard, which begin to develop after the age of approximately 7 years in both sexes. In females, the eyelids remain white even after 10 years, and turn black at around the age of 20; in males, the eyelids turn black before the age of 10. The whiskers and beards of adults are thicker in males than in females, and are fully developed before the age of 10 in males, while they begin to develop in females only after approximately 20 years. White eyelids and undeveloped whiskers and beards may be visual signals that are indicative of young adult females. Our results also show that the facial morphology of the unflanged male is similar to that of the adult female, although

Thoracic spine disc-related abnormalities: longitudinal MR imaging assessment

Energy Technology Data Exchange (ETDEWEB)

Girard, Charles J.; Schweitzer, Mark E.; Morrison, William B.; Parellada, Joan A. [TJUH Radiology, Philadelphia, Pennsylvania (United States); Carrino, J.A. [Department of Radiology ASB-1, Harvard Medical School, Brigham and Women' s Hospital, L1, Room 002B, 75 Francis Street, MA 02115, Boston (United States)

2004-04-01

To describe and characterize the temporal changes in disc-related disorders of the thoracic spine using MR imaging. A retrospective longitudinal cohort study was carried out of 40 patients with two sequential thoracic spine MR images at variable intervals. The images were assessed for baseline presence of, new incidence of and changes in disc herniation, degenerative disc disease, endplate marrow signal alteration and Schmorl nodes. The range of follow-up was 4-149 weeks. Baseline presence was: disc herniation, 10% (49/480); degenerative disc disease, 14% (66/480); endplate marrow signal alteration, 2.3% (11/480); Schmorl nodes 9.6% (46/480). Most pre-existing lesions tended to remain unchanged. Herniations showed the most change, tending to improve in 27%. New incidence was: disc herniation, 1.5% (7/480), degenerative disc disease, 2% (10/480); endplate marrow signal alteration, 1.6% (8/480); Schmorl nodes, 2.1% (10/480). Disc degeneration was first visible at an 11-week interval and once established almost never changed over many weeks to months. Endplate signal alterations (Modic changes) were uncommon. Schmorl nodes show no change from baseline for up to 2 1/2 years. All findings predominated in the lower intervertebral levels from T6 to T10. The most prevalent thoracic spine disc-related findings are degeneration and herniation. Disc herniations predominate in the lower segments and are a dynamic phenomenon. Disc degeneration can be rapidly evolving but tends to remain unchanged after occurrence. Endplate marrow signal changes were an uncommon manifestation of thoracic disc disease. Schmorl nodes showed the least change over time. (orig.)

Traditional forest-related knowledge and climate change

Science.gov (United States)

John A. Parrotta; Mauro Agnoletti

2012-01-01

The holders and users of traditional forest-related knowledge are on the front lines of global efforts to deal with climate change and its impacts. Because of their close connection with, and high dependence on, forest ecosystems and landscapes, indigenous and local communities are among the fi rst to witness, understand, and experience the impacts of climate change on...

Receptor density balances signal stimulation and attenuation in membrane-assembled complexes of bacterial chemotaxis signaling proteins

Science.gov (United States)

Besschetnova, Tatiana Y.; Montefusco, David J.; Asinas, Abdalin E.; Shrout, Anthony L.; Antommattei, Frances M.; Weis, Robert M.

2008-01-01

All cells possess transmembrane signaling systems that function in the environment of the lipid bilayer. In the Escherichia coli chemotaxis pathway, the binding of attractants to a two-dimensional array of receptors and signaling proteins simultaneously inhibits an associated kinase and stimulates receptor methylation—a slower process that restores kinase activity. These two opposing effects lead to robust adaptation toward stimuli through a physical mechanism that is not understood. Here, we provide evidence of a counterbalancing influence exerted by receptor density on kinase stimulation and receptor methylation. Receptor signaling complexes were reconstituted over a range of defined surface concentrations by using a template-directed assembly method, and the kinase and receptor methylation activities were measured. Kinase activity and methylation rates were both found to vary significantly with surface concentration—yet in opposite ways: samples prepared at high surface densities stimulated kinase activity more effectively than low-density samples, whereas lower surface densities produced greater methylation rates than higher densities. FRET experiments demonstrated that the cooperative change in kinase activity coincided with a change in the arrangement of the membrane-associated receptor domains. The counterbalancing influence of density on receptor methylation and kinase stimulation leads naturally to a model for signal regulation that is compatible with the known logic of the E. coli pathway. Density-dependent mechanisms are likely to be general and may operate when two or more membrane-related processes are influenced differently by the two-dimensional concentration of pathway elements. PMID:18711126

Lover and learner: Exploring relational schema change following relationship dissolution.

Science.gov (United States)

Brunson, Julie A; Øverup, Camilla S; Acitelli, Linda K

2018-03-27

Romantic relationships are known to be very influential, but less is known about how these relationships, and particularly the breakup of these relationships, may affect individuals' relational schemas, or their expectations for relationships. Undergraduate students reported on how their views of themselves, romantic partners, and relationships changed after breaking up with a past partner. Results suggest that relational schemas change following relationship dissolution and that there are both positive and negative aspects to this change. There was also some evidence that aspects of the past relationship predicted change and the valence of change, and that change and the valence of change were related to aspects of current relationship quality. These results are an important first step in understanding how past romantic relationships influence people's expectations about relationships and, by extension, their health and wellbeing.

Quantitative change of EEG and respiration signals during mindfulness meditation

Science.gov (United States)

2014-01-01

Background This study investigates measures of mindfulness meditation (MM) as a mental practice, in which a resting but alert state of mind is maintained. A population of older people with high stress level participated in this study, while electroencephalographic (EEG) and respiration signals were recorded during a MM intervention. The physiological signals during meditation and control conditions were analyzed with signal processing. Methods EEG and respiration data were collected and analyzed on 34 novice meditators after a 6-week meditation intervention. Collected data were analyzed with spectral analysis, phase analysis and classification to evaluate an objective marker for meditation. Results Different frequency bands showed differences in meditation and control conditions. Furthermore, we established a classifier using EEG and respiration signals with a higher accuracy (85%) at discriminating between meditation and control conditions than a classifier using the EEG signal only (78%). Conclusion Support vector machine (SVM) classifier with EEG and respiration feature vector is a viable objective marker for meditation ability. This classifier should be able to quantify different levels of meditation depth and meditation experience in future studies. PMID:24939519

Planck intermediate results: III. the relation between galaxy cluster mass and Sunyaev-Zeldovich signal

DEFF Research Database (Denmark)

Bartlett, J.G.; Bucher, M.; Cardoso, J.-F.

2013-01-01

We examine the relation between the galaxy cluster mass M and Sunyaev-Zeldovich (SZ) effect signal DA2 Y500 for a sample of 19 objects for which weak lensing (WL) mass measurements obtained from Subaru Telescope data are available in the literature. Hydrostatic X-ray masses are derived from XMM-N...

Evaluating clinically significant changes in health-related quality of life

DEFF Research Database (Denmark)

Norup, Anne; Kristensen, Karin Spangsberg; Poulsen, Ingrid

2017-01-01

The objective of the study was to investigate change and predictors of change in health-related quality of life (HRQoL) in relatives of patients with severe traumatic brain injury (TBI) during rehabilitation, and to analyse associations between changes in HRQoL and symptoms of anxiety...

Hsp70-Bag3 interactions regulate cancer-related signaling networks.

Science.gov (United States)

Colvin, Teresa A; Gabai, Vladimir L; Gong, Jianlin; Calderwood, Stuart K; Li, Hu; Gummuluru, Suryaram; Matchuk, Olga N; Smirnova, Svetlana G; Orlova, Nina V; Zamulaeva, Irina A; Garcia-Marcos, Mikel; Li, Xiaokai; Young, Z T; Rauch, Jennifer N; Gestwicki, Jason E; Takayama, Shinichi; Sherman, Michael Y

2014-09-01

Bag3, a nucleotide exchange factor of the heat shock protein Hsp70, has been implicated in cell signaling. Here, we report that Bag3 interacts with the SH3 domain of Src, thereby mediating the effects of Hsp70 on Src signaling. Using several complementary approaches, we established that the Hsp70-Bag3 module is a broad-acting regulator of cancer cell signaling by modulating the activity of the transcription factors NF-κB, FoxM1, Hif1α, the translation regulator HuR, and the cell-cycle regulators p21 and survivin. We also identified a small-molecule inhibitor, YM-1, that disrupts the Hsp70-Bag3 interaction. YM-1 mirrored the effects of Hsp70 depletion on these signaling pathways, and in vivo administration of this drug was sufficient to suppress tumor growth in mice. Overall, our results defined Bag3 as a critical factor in Hsp70-modulated signaling and offered a preclinical proof-of-concept that the Hsp70-Bag3 complex may offer an appealing anticancer target. ©2014 American Association for Cancer Research.

Multimodal signal variation in space and time : how important is matching a signal with its signaler?

OpenAIRE

Taylor, Ryan C.; Klein, Barrett; Stein, Joey; Ryan, Michael J.

2011-01-01

Multimodal signals (acoustic+visual) are known to be used by many anuran amphibians during courtship displays. The relative degree to which each signal component influences female mate choice, however, remains poorly understood. In this study we used a robotic frog with an inflating vocal sac and acoustic playbacks to document responses of female túngara frogs to unimodal signal components (acoustic and visual). We then tested female responses to a synchronous multimodal signal. Finally, we t...

Motor-related signals in the auditory system for listening and learning.

Science.gov (United States)

Schneider, David M; Mooney, Richard

2015-08-01

In the auditory system, corollary discharge signals are theorized to facilitate normal hearing and the learning of acoustic behaviors, including speech and music. Despite clear evidence of corollary discharge signals in the auditory cortex and their presumed importance for hearing and auditory-guided motor learning, the circuitry and function of corollary discharge signals in the auditory cortex are not well described. In this review, we focus on recent developments in the mouse and songbird that provide insights into the circuitry that transmits corollary discharge signals to the auditory system and the function of these signals in the context of hearing and vocal learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

Amphetamine modulates brain signal variability and working memory in younger and older adults.

Science.gov (United States)

Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

2015-06-16

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling.

Science.gov (United States)

Correa, Ricardo G; Krajewska, Maryla; Ware, Carl F; Gerlic, Motti; Reed, John C

2014-03-30

Prostate cancer (PCa) is among the leading causes of cancer-related death in men. Androgen receptor (AR) signaling plays a seminal role in prostate development and homeostasis, and dysregulation of this pathway is intimately linked to prostate cancer pathogenesis and progression. Here, we identify the cytosolic NLR-related protein NWD1 as a novel modulator of AR signaling. We determined that expression of NWD1 becomes elevated during prostate cancer progression, based on analysis of primary tumor specimens. Experiments with cultured cells showed that NWD1 expression is up-regulated by the sex-determining region Y (SRY) family proteins. Gene silencing procedures, in conjunction with transcriptional profiling, showed that NWD1 is required for expression of PDEF (prostate-derived Ets factor), which is known to bind and co-regulate AR. Of note, NWD1 modulates AR protein levels. Depleting NWD1 in PCa cell lines reduces AR levels and suppresses activity of androgen-driven reporter genes. NWD1 knockdown potently suppressed growth of androgen-dependent LNCaP prostate cancer cells, thus showing its functional importance in an AR-dependent tumor cell model. Proteomic analysis suggested that NWD1 associates with various molecular chaperones commonly related to AR complexes. Altogether, these data suggest a role for tumor-associated over-expression of NWD1 in dysregulation of AR signaling in PCa.

a Universal De-Noising Algorithm for Ground-Based LIDAR Signal

Science.gov (United States)

Ma, Xin; Xiang, Chengzhi; Gong, Wei

2016-06-01

Ground-based lidar, working as an effective remote sensing tool, plays an irreplaceable role in the study of atmosphere, since it has the ability to provide the atmospheric vertical profile. However, the appearance of noise in a lidar signal is unavoidable, which leads to difficulties and complexities when searching for more information. Every de-noising method has its own characteristic but with a certain limitation, since the lidar signal will vary with the atmosphere changes. In this paper, a universal de-noising algorithm is proposed to enhance the SNR of a ground-based lidar signal, which is based on signal segmentation and reconstruction. The signal segmentation serving as the keystone of the algorithm, segments the lidar signal into three different parts, which are processed by different de-noising method according to their own characteristics. The signal reconstruction is a relatively simple procedure that is to splice the signal sections end to end. Finally, a series of simulation signal tests and real dual field-of-view lidar signal shows the feasibility of the universal de-noising algorithm.

Losing the Warning Signal: Drought Compromises the Cross-Talk of Signaling Molecules in Quercus ilex Exposed to Ozone

Directory of Open Access Journals (Sweden)

Lorenzo Cotrozzi

2017-06-01

Full Text Available Understanding the interactions between drought and acute ozone (O3 stress in terms of signaling molecules and cell death would improve the predictions of plant responses to climate change. The aim was to investigate whether drought stress influences the responses of plants to acute episodes of O3 exposure. In this study, the behavior of 84 Mediterranean evergreen Quercus ilex plants was evaluated in terms of cross-talk responses among signaling molecules. Half of the sample was subjected to drought (20% of the effective daily evapotranspiration, for 15 days and was later exposed to an acute O3 exposure (200 nL L-1 for 5 h. First, our results indicate that in well-water conditions, O3 induced a signaling pathway specific to O3-sensitive behavior. Second, different trends and consequently different roles of phytohormones and signaling molecules (ethylene, ET; abscisic acid, ABA; salycilic acid, SA and jasmonic acid, JA were observed in relation to water stress and O3. A spatial and functional correlation between these signaling molecules was observed in modulating O3-induced responses in well-watered plants. In contrast, in drought-stressed plants, these compounds were not involved either in O3-induced signaling mechanisms or in leaf senescence (a response observed in water-stressed plants before the O3-exposure. Third, these differences were ascribable to the fact that in drought conditions, most defense processes induced by O3 were compromised and/or altered. Our results highlight how Q. ilex plants suffering from water deprivation respond differently to an acute O3 episode compared to well-watered plants, and suggest new effect to be considered in plant responses to environmental changes. This poses the serious question as to whether or not multiple high-magnitude O3 events (as predicted can change these cross-talk responses, thus opening it up possible further investigations.

Session 3, Measurement systems and signal validation/processing: Rapporteur's report

International Nuclear Information System (INIS)

Shepard, R.L.

1991-01-01

Eight papers scheduled for presentation dealt with in-core flux and temperature detectors and the interpretation of their signals. Our theme discussed was how core models could be used to validate in-core detector signals, and conversely, how the detector signals could validate the core models. Methods were proposed for distinguishing between detector malfunction (invalid signals) and actual changes in core conditions. It it necessary to reconcile these conflicting possibilities so that accurate and timely assessments of the present and future state of the core may be made during reactor operation, particularly during upset conditions. A second theme addressed the advantages and disadvantages of fixed vs movable in-core detectors -- their characteristics, employment, and signal interpretation. The economic and operating tradeoffs of fixed and movable detectors were addressed. A third theme was the use of signal processing to distinguish between gamma noise and neutron flux signals and how to improve the response times of in-core detectors. The discussion in this session relates to a broader discussion of the relative merits of self-powered neutron detectors and gamma thermometers for in-core flux monitoring which took place at the Cadarache meeting in 1988, and which was continued in Session 1 of this meeting

Sterilization of proteinaceous food additives by irradiation. Temperature dependent changes in intensity of ESR signals generated by electron beam irradiation

International Nuclear Information System (INIS)

Sakaue, Kazushi; Murata, Yoshiyuki; Higashimura, Yutaka; Hayashi, Toru; Todoriki, Setsuko; Tada, Mikiro

1999-01-01

Thaumatin, egg white and soybean protein were selected as samples of proteinous food additives, and changes in the intensity of signals appearing in them after they had been irradiated with electron beams were measured by ESR. It was found by such measurement that the positions of signals of thaumatin and soy proteins are nearly the same. Changes in the intensity of radicals in thaumatin calculated on the basis of the coefficients of the respective approximations obtained by using thaumatin which had been irradiated and then stored at 4degC, 25degC, 37degC and 60degC showed that there is a temperature range to determine the remaining of such radicals (inner: 19.7degC, outer: 15.23degC) and that such radicals tend to decrease straight line-wise. It was confirmed that the intensity of signals in the protein powder such thaumatin and soy protein would not be affected at the storage condition below 15degC. (author)

Sterilization of proteinaceous food additives by irradiation. Temperature dependent changes in intensity of ESR signals generated by electron beam irradiation

Energy Technology Data Exchange (ETDEWEB)

Sakaue, Kazushi; Murata, Yoshiyuki [Graduate School of Natural Science and Technology, Okayama Univ., Okayama (Japan); Higashimura, Yutaka [San-Ei Gen F.F.I., Inc., Osaka (Japan); Hayashi, Toru; Todoriki, Setsuko [National Food Research Institute, Ministry of Agriculture, Tsukuba, Ibaraki (Japan); Tada, Mikiro [Okayama Univ. (Japan). Faculty of Agriculture

1999-09-01

Thaumatin, egg white and soybean protein were selected as samples of proteinous food additives, and changes in the intensity of signals appearing in them after they had been irradiated with electron beams were measured by ESR. It was found by such measurement that the positions of signals of thaumatin and soy proteins are nearly the same. Changes in the intensity of radicals in thaumatin calculated on the basis of the coefficients of the respective approximations obtained by using thaumatin which had been irradiated and then stored at 4degC, 25degC, 37degC and 60degC showed that there is a temperature range to determine the remaining of such radicals (inner: 19.7degC, outer: 15.23degC) and that such radicals tend to decrease straight line-wise. It was confirmed that the intensity of signals in the protein powder such thaumatin and soy protein would not be affected at the storage condition below 15degC. (author)

Signaling pathways and stem cells in uterus and fallopian tubes

NARCIS (Netherlands)

Y. Wang (Yongqian)

2012-01-01

textabstractDuring her fertile years, the endometrium of fertile women undergoes regular cycles of regeneration, differentiation and shedding, driven by changing concentrations of the steroid hormones estradiol and progesterone. In the present study, the role of Wnt/β-catenin signaling in relation

Factors affecting UV-B-induced changes in Arabidopsis thaliana L. gene expression: The role of development, protective pigments and the chloroplast signal

International Nuclear Information System (INIS)

Jordan, B.R.; James, P.E.; Mackerness, S.A.H.

1998-01-01

Gene expression is known to change in response to UV-B radiation. In this paper, we have investigated three factors in Arabidopsis leaves that are likely to influence these changes: development, protective pigments and the 'chloroplast signal'. During late leaf development the major change in pigment composition, after exposure to UV-B radiation, is an increase in UV-absorbing pigments. Chl and Chl a/b ratio do not change substantially. Similarly Chl fluorescence is not altered. In contrast, RNA transcripts of photosynthetic proteins are reduced more in older leaves than in young leaves. To determine the role of flavonoids in UV-B protection, plants of Arabidopsis mutant tt-5, which have reduced flavonoids and sinapic esters, were exposed to UV-B and RNA transcript levels determined. The tt-mutants were more sensitive to UV-B radiation than wild-type. To examine the role of the chloroplast signal in regulating UV-B induced changes in gene expression, Arabidopsis gun mutants (genome uncoupled) have been used. The results show that UV-B-induced down-regulation still takes place in gun mutants and strongly suggests that the chloroplast signal is not required. Overall, this study clearly demonstrates that UV-B-induced changes in gene expression are influenced by both developmental and cellular factors but not chloroplastic factors

Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years.

Science.gov (United States)

Kromrey, Marie-Luise; Liedtke, Kim Rouven; Ittermann, Till; Langner, Sönke; Kirsch, Michael; Weitschies, Werner; Kühn, Jens-Peter

2017-02-01

To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (0.15 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. • Gadobutrol does not lead to neuronal signal alterations after 5 years. • Neuronal deposition of macrocyclic contrast agent could not be confirmed. • Macrocyclic contrast agents in a proven dosage are safe.

Study of sensitivity change of OSL signals from quartz and feldspars as a function of preheat temperature

DEFF Research Database (Denmark)

Jungner, H.; Bøtter-Jensen, L.

1994-01-01

and as a result, the equivalent dose (ED) would be underestimated. A study of sensitivity changes in feldspars and quartz was carried out with emphasis on the effect of preheat and annealing on the OSL signal. Measurement results obtained are presented, and possible elimination of errors in dating caused...

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

Directory of Open Access Journals (Sweden)

Mikhail Sintsov

2017-12-01

Full Text Available Optical Intrinsic Signal imaging (OISi is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR and metabolism, but it may also involve changes in tissue light scattering (LS caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD signal in human preterm infants.

Changing Food Related Behavior Through Design

DEFF Research Database (Denmark)

Hermanssdottir, Sunna; Fisker, Anna Marie; Poulsen, Søren Bolvig

The aim of the workshop is to explore how designers can work actively and deliberately with changing food related behavior through socially responsible design. There will be focus on the holistic aspect of behavioral food design with active involving of the users experience. The workshop is based...

Goal disturbance changes pre/post-renal transplantation are related to changes in distress.

Science.gov (United States)

de Vries, Alicia M; Schulz, Torben; Westerhuis, Ralf; Navis, Gerjan J; Niesing, Jan; Ranchor, Adelita V; Schroevers, Maya J

2017-09-01

Renal transplantation (RTx) is considered the treatment of choice for end-stage renal disease (ESRD) given its association with lower mortality, and improved overall quality of life and psychological functioning compared to dialysis. However, much less is known about which factors underlie these psychological improvements across RTx. Goal theory suggests that experienced disturbances in important goals are related to lower psychological functioning. This study aimed to (1) identify the most disturbed and most important goals for patients before RTx, (2) to examine changes in goal disturbance and goal importance pre/post-RTx, and (3) to examine whether changes in goal disturbance are associated with changes in psychological distress over time, and whether this relationship is mediated by changes in perceived control. In this longitudinal study, 220 patients completed questionnaires before and after RTx, including questionnaires to assess goals (GOALS questionnaire), psychological distress (GHQ-12), and perceived control (Mastery scale). End-stage renal disease affected both general and disease-specific goals. Approximately 30% of the patients indicated to experience high or very high disturbance before transplantation. Goal disturbance generally decreased significantly pre- to post-RTx, whereas goal importance did not change significantly pre- to post-RTx. No mediation effect of perceived control was found. Instead, both changes in goal disturbance and perceived control showed independent effects on changes in distress. Intervention strategies targeting attainable and realistic goal setting, and perceived control in RTx recipients who do not benefit optimally from RTx, might enhance psychological functioning in this population. Statement of contribution What is already known on this subject? Kidney transplantation improves patients' psychological functioning. Experienced disturbances in important life goals are related to lower psychological functioning in chronic

Nitric oxide-induced signalling in rat lacrimal acinar cells

DEFF Research Database (Denmark)

Looms, Dagnia Karen; Tritsaris, K.; Dissing, S.

2002-01-01

-adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus...... not by itself causing fast transient increases in [Ca2+]i. In addition, we suggest that endogenously produced NO activated by ß-adrenergic receptor stimulation, plays an important role in signalling to the surrounding tissue....

The Recording and Quantification of Event-Related Potentials: II. Signal Processing and Analysis

Directory of Open Access Journals (Sweden)

Paniz Tavakoli

2015-06-01

Full Text Available Event-related potentials are an informative method for measuring the extent of information processing in the brain. The voltage deflections in an ERP waveform reflect the processing of sensory information as well as higher-level processing that involves selective attention, memory, semantic comprehension, and other types of cognitive activity. ERPs provide a non-invasive method of studying, with exceptional temporal resolution, cognitive processes in the human brain. ERPs are extracted from scalp-recorded electroencephalography by a series of signal processing steps. The present tutorial will highlight several of the analysis techniques required to obtain event-related potentials. Some methodological issues that may be encountered will also be discussed.

The relationship between prevalent medial meniscal intrasubstance signal changes and incident medial meniscal tears in women over a 1-year period assessed with 3.0 T MRI

Energy Technology Data Exchange (ETDEWEB)

Crema, Michel D. [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States); Ribeirao Preto School of Medicine, University of Sao Paulo (USP), Department of Biomechanics, Medicine and Rehabilitation of the Locomotor Apparatus, and Department of Internal Medicine, Radiology Division, Ribeirao Preto (Brazil); Institute of Diagnostic Imaging (IDI), Ribeirao Preto (Brazil); Hunter, David J. [The University of Sydney, Sydney School of Medicine, Sydney (Australia); Roemer, Frank W. [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States); Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Li, Ling [New England Baptist Hospital, Division of Research, Boston, MA (United States); Marra, Monica D. [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States); Institute of Diagnostic Imaging (IDI), Ribeirao Preto (Brazil); Nogueira-Barbosa, Marcello H. [Ribeirao Preto School of Medicine, University of Sao Paulo (USP), Department of Biomechanics, Medicine and Rehabilitation of the Locomotor Apparatus, and Department of Internal Medicine, Radiology Division, Ribeirao Preto (Brazil); Hellio Le Graverand, Marie-Pierre; Wyman, Bradley T. [Pfizer Global Research and Development, New London, CT (United States); Guermazi, Ali [Boston University School of Medicine, Department of Radiology, Quantitative Imaging Center, Boston, MA (United States)

2011-08-15

Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period. A total of 161 women aged {>=}40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher's exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0). Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body. We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period. (orig.)

The relationship between prevalent medial meniscal intrasubstance signal changes and incident medial meniscal tears in women over a 1-year period assessed with 3.0 T MRI

International Nuclear Information System (INIS)

Crema, Michel D.; Hunter, David J.; Roemer, Frank W.; Li, Ling; Marra, Monica D.; Nogueira-Barbosa, Marcello H.; Hellio Le Graverand, Marie-Pierre; Wyman, Bradley T.; Guermazi, Ali

2011-01-01

Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period. A total of 161 women aged ≥40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher's exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0). Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body. We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period. (orig.)

Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected

DEFF Research Database (Denmark)

Storgaard, H; Song, X M; Jensen, C B

2001-01-01

To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects...... phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However...... resistance in skeletal muscle from relatives of patients with type 2 diabetes....

Age-related decline in functional connectivity of the vestibular cortical network.

Science.gov (United States)

Cyran, Carolin Anna Maria; Boegle, Rainer; Stephan, Thomas; Dieterich, Marianne; Glasauer, Stefan

2016-04-01

In the elderly, major complaints include dizziness and an increasing number of falls, possibly related to an altered processing of vestibular sensory input. In this study, we therefore investigate age-related changes induced by processing of vestibular sensory stimulation. While previous functional imaging studies of healthy aging have investigated brain function during task performance or at rest, we used galvanic vestibular stimulation during functional MRI in a task-free sensory stimulation paradigm to study the effect of healthy aging on central vestibular processing, which might only become apparent during stimulation processing. Since aging may affect signatures of brain function beyond the BOLD-signal amplitude-such as functional connectivity or temporal signal variability--we employed independent component analysis and partial least squares analysis of temporal signal variability. We tested for age-associated changes unrelated to vestibular processing, using a motor paradigm, voxel-based morphometry and diffusion tensor imaging. This allows us to control for general age-related modifications, possibly originating from vascular, atrophic or structural connectivity changes. Age-correlated decreases of functional connectivity and increases of BOLD--signal variability were associated with multisensory vestibular networks. In contrast, no age-related functional connectivity changes were detected in somatosensory networks or during the motor paradigm. The functional connectivity decrease was not due to structural changes but to a decrease in response amplitude. In synopsis, our data suggest that both the age-dependent functional connectivity decrease and the variability increase may be due to deteriorating reciprocal cortico-cortical inhibition with age and related to multimodal vestibular integration of sensory inputs.

Orientation-dependent changes in MR signal intensity of articular cartilage: a manifestation of the ``magic angle`` effect

Energy Technology Data Exchange (ETDEWEB)

Wacker, F.K.; Bolze, X.; Felsenberg, D.; Wolf, K.J. [Department of Radiology, Benjamin Franklin University Hospital, Free University Berlin, D-12200 Berlin (Germany)

1998-06-01

Objective: To study magnetic resonance (MR) imaging pattern of normal hyaline articular cartilage in the knee joint with regard to the contribution of the ``magic angle`` effect to the MR signal. Design. Thirty-two healthy volunteers were imaged in a standard supine position in a 1.5-T unit using spin echo and gradient echo sequences. Nine volunteers were reimaged with the knee flexed. The signal behavior of the hyaline cartilage of the femoral condyles was evaluated qualitatively and quantitatively. The extended and flexed positions of the nine volunteers were compared. Results. A superficial and a deep hyperintense layer and a hypointense middle cartilage layer were observed. Segments of increased signal intensity were visible along the condyles; a magic angle effect on signal intensity was evident in the hypointense middle layer with both gradient echo and spin echo images. Conclusion. The MR signal behavior of hyaline cartilage is influenced by the alignment of the collagen fibers within the cartilage in relation to the magnetic field. Failure to recognize this effect may lead to inaccurate diagnosis. (orig.) With 4 figs., 17 refs.

Secreted Frizzled-related protein-2 (sFRP2) augments canonical Wnt3a-induced signaling

Energy Technology Data Exchange (ETDEWEB)

Marschall, Zofia von [Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, DHHS, Bethesda, MD (United States); Fisher, Larry W., E-mail: lfisher@dir.nidcr.nih.gov [Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, DHHS, Bethesda, MD (United States)

2010-09-24

Research highlights: {yields} sFRP2 enhances the Wnt3a-induced {beta}-catenin stabilization and its nuclear translocation. {yields} sFRP2 enhances LRP6 phosphorylation and Wnt3a/{beta}-catenin transcriptional reporter activity. {yields} Dickkopf-1 (DKK1) fully antagonizes both Wnt3a/sFRP2-induced LRP6 phosphorylation and transcriptional activity. {yields} sFRP2 enhances expression of genes known to be regulated by Wnt3a signaling. -- Abstract: Secreted Frizzled-related proteins (sFRP) are involved in embryonic development as well as pathological conditions including bone and myocardial disorders and cancer. Because of their sequence homology with the Wnt-binding domain of Frizzled, they have generally been considered antagonists of canonical Wnt signaling. However, additional activities of various sFRPs including both synergism and mimicry of Wnt signaling as well as functions other than modulation of Wnt signaling have been reported. Using human embryonic kidney cells (HEK293A), we found that sFRP2 enhanced Wnt3a-dependent phosphorylation of LRP6 as well as both cytosolic {beta}-catenin levels and its nuclear translocation. While addition of recombinant sFRP2 had no activity by itself, Top/Fop luciferase reporter assays showed a dose-dependent increase of Wnt3a-mediated transcriptional activity. sFRP2 enhancement of Wnt3a signaling was abolished by treatment with the Wnt antagonist, Dickkopf-1 (DKK1). Wnt-signaling pathway qPCR arrays showed that sFRP2 enhanced the Wnt3a-mediated transcriptional up-regulation of several genes regulated by Wnt3a including its antagonists, DKK1, and Naked cuticle-1 homolog (NKD1). These results support sFRP2's role as an enhancer of Wnt/{beta}-catenin signaling, a result with biological impact for both normal development and diverse pathologies such as tumorigenesis.

Secreted Frizzled-related protein-2 (sFRP2) augments canonical Wnt3a-induced signaling

International Nuclear Information System (INIS)

Marschall, Zofia von; Fisher, Larry W.

2010-01-01

Research highlights: → sFRP2 enhances the Wnt3a-induced β-catenin stabilization and its nuclear translocation. → sFRP2 enhances LRP6 phosphorylation and Wnt3a/β-catenin transcriptional reporter activity. → Dickkopf-1 (DKK1) fully antagonizes both Wnt3a/sFRP2-induced LRP6 phosphorylation and transcriptional activity. → sFRP2 enhances expression of genes known to be regulated by Wnt3a signaling. -- Abstract: Secreted Frizzled-related proteins (sFRP) are involved in embryonic development as well as pathological conditions including bone and myocardial disorders and cancer. Because of their sequence homology with the Wnt-binding domain of Frizzled, they have generally been considered antagonists of canonical Wnt signaling. However, additional activities of various sFRPs including both synergism and mimicry of Wnt signaling as well as functions other than modulation of Wnt signaling have been reported. Using human embryonic kidney cells (HEK293A), we found that sFRP2 enhanced Wnt3a-dependent phosphorylation of LRP6 as well as both cytosolic β-catenin levels and its nuclear translocation. While addition of recombinant sFRP2 had no activity by itself, Top/Fop luciferase reporter assays showed a dose-dependent increase of Wnt3a-mediated transcriptional activity. sFRP2 enhancement of Wnt3a signaling was abolished by treatment with the Wnt antagonist, Dickkopf-1 (DKK1). Wnt-signaling pathway qPCR arrays showed that sFRP2 enhanced the Wnt3a-mediated transcriptional up-regulation of several genes regulated by Wnt3a including its antagonists, DKK1, and Naked cuticle-1 homolog (NKD1). These results support sFRP2's role as an enhancer of Wnt/β-catenin signaling, a result with biological impact for both normal development and diverse pathologies such as tumorigenesis.

Hippocampal leptin signaling reduces food intake and modulates food-related memory processing.

Science.gov (United States)

Kanoski, Scott E; Hayes, Matthew R; Greenwald, Holly S; Fortin, Samantha M; Gianessi, Carol A; Gilbert, Jennifer R; Grill, Harvey J

2011-08-01

The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 μg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 μg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

On the pilot's behavior of detecting a system parameter change

Science.gov (United States)

Morizumi, N.; Kimura, H.

1986-01-01

The reaction of a human pilot, engaged in compensatory control, to a sudden change in the controlled element's characteristics is described. Taking the case where the change manifests itself as a variance change of the monitored signal, it is shown that the detection time, defined to be the time elapsed until the pilot detects the change, is related to the monitored signal and its derivative. Then, the detection behavior is modeled by an optimal controller, an optimal estimator, and a variance-ratio test mechanism that is performed for the monitored signal and its derivative. Results of a digital simulation show that the pilot's detection behavior can be well represented by the model proposed here.

Colour change on different body regions provides thermal and signalling advantages in bearded dragon lizards

Science.gov (United States)

Cadena, Viviana; Porter, Warren P.; Kearney, Michael R.

2016-01-01

Many terrestrial ectotherms are capable of rapid colour change, yet it is unclear how these animals accommodate the multiple functions of colour, particularly camouflage, communication and thermoregulation, especially when functions require very different colours. Thermal benefits of colour change depend on an animal's absorptance of solar energy in both UV–visible (300–700 nm) and near-infrared (NIR; 700–2600 nm) wavelengths, yet colour research has focused almost exclusively on the former. Here, we show that wild-caught bearded dragon lizards (Pogona vitticeps) exhibit substantial UV–visible and NIR skin reflectance change in response to temperature for dorsal but not ventral (throat and upper chest) body regions. By contrast, lizards showed the greatest temperature-independent colour change on the beard and upper chest during social interactions and as a result of circadian colour change. Biophysical simulations of heat transfer predicted that the maximum temperature-dependent change in dorsal reflectivity could reduce the time taken to reach active body temperature by an average of 22 min per active day, saving 85 h of basking time throughout the activity season. Our results confirm that colour change may serve a thermoregulatory function, and competing thermoregulation and signalling requirements may be met by partitioning colour change to different body regions in different circumstances.

Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

Science.gov (United States)

Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

2018-02-01

Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

The Developing, Aging Neocortex: How genetics and epigenetics influence early developmental patterning and age-related change.

Directory of Open Access Journals (Sweden)

Kelly J. Huffman

2012-10-01

Full Text Available A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging

Testing for changes in spatial relative risk.

Science.gov (United States)

Hazelton, Martin L

2017-07-30

The spatial relative risk function is a useful tool for describing geographical variation in disease incidence. We consider the problem of comparing relative risk functions between two time periods, with the idea of detecting alterations in the spatial pattern of disease risk irrespective of whether there has been a change in the overall incidence rate. Using case-control datasets for each period, we use kernel smoothing methods to derive a test statistic based on the difference between the log-relative risk functions, which we term the log-relative risk ratio. For testing a null hypothesis of an unchanging spatial pattern of risk, we show how p-values can be computed using both randomization methods and an asymptotic normal approximation. The methodology is applied to data on campylobacteriosis from 2006 to 2013 in a region of New Zealand. We find clear evidence of a change in the spatial pattern of risk between those years, which can be explained in differences by response to a public health initiative between urban and rural communities. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Stochastic resonance for signal-modulated pump noise in a single-mode laser

Institute of Scientific and Technical Information of China (English)

Liangying Zhang; Li Cao; Fahui Zhu

2006-01-01

By adopting the gain-noise model of the single-mode laser in which with bias and periodical signals serve as inputs, combining with the effect of coloured pump noise, we use the linear approximation method to calculate the power spectrum and signal-to-noise ratio (SNR) of the laser intensity under the condition of pump noise and quantum noise cross-related in the form of δ function. It is found that with the change of pump noise correlation time, both SNR and the output power will occur stochastic resonance (SR). If the bias signal α is very small, changing the intensities of pump noise and quantum noise respectively does not lead to the appearance of SR in the SNR; while α increases to a certain number, SR appears.

Zinc signaling in the hippocampus and its relation to pathogenesis of depression.

Science.gov (United States)

Takeda, Atsushi

2012-06-01

of CA1 LTP after exposure to acute stress. We propose that corticosterone-mediated increase in postsynaptic Zn(2+) signal, which is induced by acute stress, changes hippocampal function and then is possibly a risk factor under chronic stress circumstances to induce depressive symptoms. Copyright © 2012 Elsevier GmbH. All rights reserved.

Revisiting historical climatic signals to better explore the future: prospects of water cycle changes in Central Sahel

Science.gov (United States)

Leauthaud, C.; Demarty, J.; Cappelaere, B.; Grippa, M.; Kergoat, L.; Velluet, C.; Guichard, F.; Mougin, E.; Chelbi, S.; Sultan, B.

2015-06-01

Rainfall and climatic conditions are the main drivers of natural and cultivated vegetation productivity in the semiarid region of Central Sahel. In a context of decreasing cultivable area per capita, understanding and predicting changes in the water cycle are crucial. Yet, it remains challenging to project future climatic conditions in West Africa since there is no consensus on the sign of future precipitation changes in simulations coming from climate models. The Sahel region has experienced severe climatic changes in the past 60 years that can provide a first basis to understand the response of the water cycle to non-stationary conditions in this part of the world. The objective of this study was to better understand the response of the water cycle to highly variable climatic regimes in Central Sahel using historical climate records and the coupling of a land surface energy and water model with a vegetation model that, when combined, simulated the Sahelian water, energy and vegetation cycles. To do so, we relied on a reconstructed long-term climate series in Niamey, Republic of Niger, in which three precipitation regimes can be distinguished with a relative deficit exceeding 25% for the driest period compared to the wettest period. Two temperature scenarios (+2 and +4 °C) consistent with future warming scenarios were superimposed to this climatic signal to generate six virtual future 20-year climate time series. Simulations by the two coupled models forced by these virtual scenarios showed a strong response of the water budget and its components to temperature and precipitation changes, including decreases in transpiration, runoff and drainage for all scenarios but those with highest precipitation. Such climatic changes also strongly impacted soil temperature and moisture. This study illustrates the potential of using the strong climatic variations recorded in the past decades to better understand potential future climate variations.

The application of Signalling Theory to health-related trust problems: The example of herbal clinics in Ghana and Tanzania.

Science.gov (United States)

Hampshire, Kate; Hamill, Heather; Mariwah, Simon; Mwanga, Joseph; Amoako-Sakyi, Daniel

2017-09-01

In contexts where healthcare regulation is weak and levels of uncertainty high, how do patients decide whom and what to trust? In this paper, we explore the potential for using Signalling Theory (ST, a form of Behavioural Game Theory) to investigate health-related trust problems under conditions of uncertainty, using the empirical example of 'herbal clinics' in Ghana and Tanzania. Qualitative, ethnographic fieldwork was conducted over an eight-month period (2015-2016) in eight herbal clinics in Ghana and ten in Tanzania, including semi-structured interviews with herbalists (N = 18) and patients (N = 68), plus detailed ethnographic observations and twenty additional key informant interviews. The data were used to explore four ST-derived predictions, relating to herbalists' strategic communication ('signalling') of their trustworthiness to patients, and patients' interpretation of those signals. Signalling Theory is shown to provide a useful analytical framework, allowing us to go beyond the primary trust problem addressed by other researchers - cataloguing observable indicators of trustworthiness - and providing tools for tackling the trickier secondary trust problem, where the trustworthiness of those indicators must be ascertained. Signalling Theory also enables a basis for comparative work between different empirical contexts that share the underlying condition of uncertainty. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Arthritis-related work transitions: a prospective analysis of reported productivity losses, work changes, and leaving the labor force.

Science.gov (United States)

Gignac, Monique A M; Cao, Xingshan; Lacaille, Diane; Anis, Aslam H; Badley, Elizabeth M

2008-12-15

To prospectively examine arthritis-related productivity losses, work changes, and leaving employment, the relationships among these work transitions, and the factors associated with them. Participants with inflammatory arthritis or osteoarthritis were interviewed at 4 time points, 18 months apart, using a structured questionnaire. At baseline (T1), all participants (n = 490; 381 women, 109 men) were employed. At T2, T3, and T4, the sample decreased to 413, 372, and 349 participants, respectively. Respondents were recruited using community advertising and from rheumatology and rehabilitation clinics. Work transitions considered were productivity losses (absenteeism, job disruptions), work changes (reduced hours, changing jobs), and leaving employment. Also measured were demographic, illness, work context, and psychological variables. Generalized estimation equations modeled predictors of work transitions over time. Although 63.1% of respondents remained employed throughout the study, work transitions were common (reported by 76.5% of participants). Productivity losses, especially job disruptions such as being unable to take on extra work, were the most frequently reported. Work transitions were related to subsequently making other work transitions, including leaving employment. Age, sex, education, activity limitations, control, depression, and arthritis-work spillover were also associated with work transitions. This study sheds light on a process of diverse employment changes that may occur in the lives of many individuals with arthritis. It emphasizes the interrelationships among work transitions, as well as other factors in predicting work transitions, and it provides insight into work changes that may signal impending difficulties with remaining employed.

Influence of the Mg-content on ESR-signals in synthetic calcium carbonate

International Nuclear Information System (INIS)

Barabas, M.; Bach, A.; Mudelsee, M.; Mangini, A.

1989-01-01

Carbonate crystals doped with various concentrations of Mg 2+ -ions have been grown by a gel-diffusion method. An increase of the Mg/Ca-ratio to more than about 1 caused a phase change in the crystal lattice from calcite to aragonite. The properties of the ESR-signals of the synthetic carbonates were studied and compared with natural marine carbonates. The following results were derived: (a) In the presence of Mg 2+ -ions the synthetic carbonates display the same ESR-signals as natural calcites of marine origin with similar properties (thermal stability, radiation sensitivity). (b) The saturation value of the signal at g=2.0006 in synthetic calcites was found to be strongly related with the Mg-content in the crystals. (c) The signal at g=2.0036 (axial symmetry) which is present in calcite was not influenced by the Mg-concentration. Its saturation value decreases when the crystal phase changed from calcite to aragonite and in complement the signal at g=2.0031 appeared. (d) The signals at g=2.0057 and g=2.0031 are most probably not of organic origin. (author)

Modulation of signal transduction by tea catechins and related phytochemicals

International Nuclear Information System (INIS)

Shimizu, Masahito; Weinstein, I. Bernard

2005-01-01

Epidemiologic studies in human populations and experimental studies in rodents provide evidence that green tea and its constituents can inhibit both the development and growth of tumors at a variety of tissue sites. In addition, EGCG, a major biologically active component of green tea, inhibits growth and induces apoptosis in a variety of cancer cell lines. The purpose of this paper is to review evidence that these effects are mediated, at least in part, through inhibition of the activity of specific receptor tyrosine kinases (RTKs) and related downstream pathways of signal transduction. We also review evidence indicating that the antitumor effects of the related polyphenolic phytochemicals resveratrol, genistein, curcumin, and capsaicin are exerted via similar mechanisms. Some of these agents (EGCG, genistein, and curcumin) appear to directly target specific RTKs, and all of these compounds cause inhibition of the activity of the transcription factors AP-1 and NF-κB, thus inhibiting cell proliferation and enhancing apoptosis. Critical areas of future investigation include: (1) identification of the direct molecular target(s) of EGCG and related polyphenolic compounds in cells; (2) the in vivo metabolism and bioavailability of these compounds; (3) the ancillary effects of these compounds on tumor-stromal interactions; (4) the development of synergistic combinations with other antitumor agents to enhance efficacy in cancer prevention and therapy, and also minimize potential toxicities

Arrestin-related proteins mediate pH signaling in fungi

OpenAIRE

Herranz, Silvia; Rodríguez, José M.; Bussink, Henk-Jan; Sánchez-Ferrero, Juan C.; Arst, Herbert N.; Peñalva, Miguel A.; Vincent, Olivier

2005-01-01

Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian β-arrestins, ubiquitinated in a signal-dependent and 7TM protein-depe...

Fruit response to water-scarcity and biochemical changes : Water relations and biochemical changes

NARCIS (Netherlands)

Rodríguez, P.; Galindo Egea, Alejandro; Collado-González, J.; Medina, S.; Corell, M.; Memmi, H.; Girón, I.F.; Centeno, A.; Martín-Palomo, M.J.; Cruz, Z.N.; Carbonell-Barrachina, A.A.; Hernandez, F.; Torrecillas, A.; Moriana, A.; Pérez-López, D.; Garcia Tejero, Ivan Francisco; Duran Zuazo, Victor Hugo

2018-01-01

The aim of this chapter is to give a general idea of the fruit response to water-scarcity conditions, paying special attention to fruit water relations modification and fruit composition changes, which are key for fruit quality. The strengths and weaknesses of fruit water relations measurement

The Age-Related Changes in Cartilage and Osteoarthritis

Directory of Open Access Journals (Sweden)

YongPing Li

2013-01-01

Full Text Available Osteoarthritis (OA is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes’ low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.

Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.

Science.gov (United States)

Strahler, Jana; Skoluda, Nadine; Rohleder, Nicolas; Nater, Urs M

2016-09-01

Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

Science.gov (United States)

Stanley, Molly; Macauley, Shannon L.

2016-01-01

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942

Overexpression of blueberry FLOWERING LOCUS T is associated with changes in the expression of phytohormone-related genes in blueberry plants.

Science.gov (United States)

Gao, Xuan; Walworth, Aaron E; Mackie, Charity; Song, Guo-Qing

2016-01-01

Flowering locus T ( FT ) is a primary integrator in the regulation of plant flowering. Overexpressing a blueberry ( Vaccinium corymbosum L.) FT gene ( VcFT ) (herein VcFT -OX) resulted in early flowering and dwarfing in 'Aurora' plants (herein 'VcFT-Aurora'). In this study, we found that VcFT -OX reduced shoot regeneration from leaf explants. To investigate the potential roles of the phytohormone pathway genes associated with VcFT -OX, differentially expressed ( DE ) genes in leaf tissues of 'VcFT-Aurora' plants were annotated and analyzed using non-transgenic 'Aurora' plants as a control. Three DE floral genes, including the blueberry SUPPRESSOR of Overexpression of constans 1 ( VcSOC1 ) (gibberellin related), Abscisic acid responsive elements-binding factor 2 ( VcABF2 ) and protein related to ABI3/VP1 ( VcABI3/VP1 ) (ethylene-related), are present under both the phytohormone-responsive and the dwarfing-related Gene Ontology terms. The gene networks of the DE genes overall showed the molecular basis of the multifunctional aspects of VcFT overexpression beyond flowering promotion and suggested that phytohormone changes could be signaling molecules with important roles in the phenotypic changes driven by VcFT -OX.

The effect on organizational change on relational coordination – a multi case study

DEFF Research Database (Denmark)

Edwards, Kasper; Lundstrøm, Sanne Lykke

2014-01-01

This study presents results from an original empirical study of 11 organizational change projects in different wards at two Danish hospitals. The purpose of the study was to study was to study changes in relation coordination as a consequence of organizational change. We measured relational...... coordination before and after the organizational change using the 7 question relational coordination questionnaire. A group of employees were interviewed after the change project to uncover the nature and extent of the changes. We find that organizations’ relational coordination score change very little – even...... for organizational change that introduces new work relations and new processes....

Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes.

Science.gov (United States)

Daskalakis, Nikolaos P; Cohen, Hagit; Cai, Guiqing; Buxbaum, Joseph D; Yehuda, Rachel

2014-09-16

Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., "PTSD-like") and resilient (i.e., minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (4-21%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factors were first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associated with individual differences when using the most stringent statistical threshold. Corticosterone treatment 1 h after PSS-exposure prevented anxiety and hyperarousal 7 d later in both sexes, confirming the GR involvement in the PSS behavioral response. In conclusion, genes and pathways associated with extreme differences in the traumatic stress behavioral response can be distinguished from those associated with trauma exposure. Blood-based biomarkers can predict aspects of brain signaling. GR signaling is a convergent signaling pathway, associated with trauma-related individual differences in both sexes.

Regulation of wheat seed dormancy by after-ripening is mediated by specific transcriptional switches that induce changes in seed hormone metabolism and signaling.

Directory of Open Access Journals (Sweden)

Aihua Liu

Full Text Available Treatments that promote dormancy release are often correlated with changes in seed hormone content and/or sensitivity. To understand the molecular mechanisms underlying the role of after-ripening (seed dry storage in triggering hormone related changes and dormancy decay in wheat (Triticum aestivum, temporal expression patterns of genes related to abscisic acid (ABA, gibberellin (GA, jasmonate and indole acetic acid (IAA metabolism and signaling, and levels of the respective hormones were examined in dormant and after-ripened seeds in both dry and imbibed states. After-ripening mediated developmental switch from dormancy to germination appears to be associated with declines in seed sensitivity to ABA and IAA, which are mediated by transcriptional repressions of PROTEIN PHOSPHATASE 2C, SNF1-RELATED PROTEIN KINASE2, ABA INSENSITIVE5 and LIPID PHOSPHATE PHOSPHTASE2, and AUXIN RESPONSE FACTOR and RELATED TO UBIQUITIN1 genes. Transcriptomic analysis of wheat seed responsiveness to ABA suggests that ABA inhibits the germination of wheat seeds partly by repressing the transcription of genes related to chromatin assembly and cell wall modification, and activating that of GA catabolic genes. After-ripening induced seed dormancy decay in wheat is also associated with the modulation of seed IAA and jasmonate contents. Transcriptional control of members of the ALLENE OXIDE SYNTHASE, 3-KETOACYL COENZYME A THIOLASE, LIPOXYGENASE and 12-OXOPHYTODIENOATE REDUCTASE gene families appears to regulate seed jasmonate levels. Changes in the expression of GA biosynthesis genes, GA 20-OXIDASE and GA 3-OXIDASE, in response to after-ripening implicate this hormone in enhancing dormancy release and germination. These findings have important implications in the dissection of molecular mechanisms underlying regulation of seed dormancy in cereals.

Experiment and practice on signal processing

International Nuclear Information System (INIS)

2002-11-01

The contents of this book contains basic practice of CEM Tool, discrete time signal and experiment and practice of system, experiment and practice of discrete time signal sampling, practice of frequency analysis, experiment of digital filter design, application of digital signal processing, project related voice, basic principle of signal processing, the technique of basic image signal processing, biology astronomy and Robot soccer with apply of image signal processing technique, control video signal and project related image. It also has an introduction of CEM Linker I. O in the end.

Experiment and practice on signal processing

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-11-15

The contents of this book contains basic practice of CEM Tool, discrete time signal and experiment and practice of system, experiment and practice of discrete time signal sampling, practice of frequency analysis, experiment of digital filter design, application of digital signal processing, project related voice, basic principle of signal processing, the technique of basic image signal processing, biology astronomy and Robot soccer with apply of image signal processing technique, control video signal and project related image. It also has an introduction of CEM Linker I. O in the end.

Exposure to carbon ions triggers pro-inflammatory signals, changes in homeostasis and epidermal tissue organization to a similar extent as photons

Directory of Open Access Journals (Sweden)

Palma eSimoniello

2016-01-01

Full Text Available The increasing application of charged particles in radiotherapy requires a deeper understanding of early and late side effects occurring in skin, which is exposed in all radiation treatments. We measured cellular and molecular changes related to the early inflammatory response of human skin irradiated with carbon ions, in particular cell death induction and changes in differentiation and proliferation of epidermal cells during the first days after exposure.Model systems for human skin from healthy donors of different complexity, i.e. keratinocytes, co-culture of skin cells, 3D skin equivalent and skin explants, were used to investigate the alterations induced by carbon ions (spread-out Bragg-peak, dose averaged LET 100 keV/µm in comparison to X-ray and UV-B exposure. After exposure to ionizing radiation, in none of the model systems apoptosis/necrosis was observed. Carbon ions triggered inflammatory signalling and accelerated differentiation of keratinocytes to a similar extent as X-rays at the same doses. High doses of carbon ions were more effective than X-rays in reducing proliferation and inducing abnormal differentiation. In contrast, changes identified following low dose exposure (≤ 0.5 Gy were induced more effectively after X-ray exposure, i.e. enhanced proliferation and change in the polarity of basal cells.

Fast optical signal not detected in awake behaving monkeys.

Science.gov (United States)

Radhakrishnan, Harsha; Vanduffel, Wim; Deng, Hong Ping; Ekstrom, Leeland; Boas, David A; Franceschini, Maria Angela

2009-04-01

While the ability of near-infrared spectroscopy (NIRS) to measure cerebral hemodynamic evoked responses (slow optical signal) is well established, its ability to measure non-invasively the 'fast optical signal' is still controversial. Here, we aim to determine the feasibility of performing NIRS measurements of the 'fast optical signal' or Event-Related Optical Signals (EROS) under optimal experimental conditions in awake behaving macaque monkeys. These monkeys were implanted with a 'recording well' to expose the dura above the primary visual cortex (V1). A custom-made optical probe was inserted and fixed into the well. The close proximity of the probe to the brain maximized the sensitivity to changes in optical properties in the cortex. Motion artifacts were minimized by physical restraint of the head. Full-field contrast-reversing checkerboard stimuli were presented to monkeys trained to perform a visual fixation task. In separate sessions, two NIRS systems (CW4 and ISS FD oximeter), which previously showed the ability to measure the fast signal in human, were used. In some sessions EEG was acquired simultaneously with the optical signal. The increased sensitivity to cortical optical changes with our experimental setup was quantified with 3D Monte Carlo simulations on a segmented MRI monkey head. Averages of thousands of stimuli in the same animal, or grand averages across the two animals and across repeated sessions, did not lead to detection of the fast optical signal using either amplitude or phase of the optical signal. Hemodynamic responses and visual evoked potentials were instead always detected with single trials or averages of a few stimuli. Based on these negative results, despite the optimal experimental conditions, we doubt the usefulness of non-invasive fast optical signal measurements with NIRS.

75 FR 6289 - Commission Guidance Regarding Disclosure Related to Climate Change

Science.gov (United States)

2010-02-08

... Regarding Disclosure Related to Climate Change; Final Rule #0;#0;Federal Register / Vol. 75 , No. 25... Disclosure Related to Climate Change AGENCY: Securities and Exchange Commission. ACTION: Interpretation... requirements as they apply to climate change matters. DATES: Effective Date: February 8, 2010. FOR FURTHER...

Decoding signalling networks by mass spectrometry-based proteomics

DEFF Research Database (Denmark)

Choudhary, Chuna Ram; Mann, Matthias

2010-01-01

Signalling networks regulate essentially all of the biology of cells and organisms in normal and disease states. Signalling is often studied using antibody-based techniques such as western blots. Large-scale 'precision proteomics' based on mass spectrometry now enables the system......-wide characterization of signalling events at the levels of post-translational modifications, protein-protein interactions and changes in protein expression. This technology delivers accurate and unbiased information about the quantitative changes of thousands of proteins and their modifications in response to any...... perturbation. Current studies focus on phosphorylation, but acetylation, methylation, glycosylation and ubiquitylation are also becoming amenable to investigation. Large-scale proteomics-based signalling research will fundamentally change our understanding of signalling networks....

Cantharidin Induced Oral Squamous Cell Carcinoma Cell Apoptosis via the JNK-Regulated Mitochondria and Endoplasmic Reticulum Stress-Related Signaling Pathways.

Directory of Open Access Journals (Sweden)

Chin-Chuan Su

Full Text Available Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC. OSCC is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP and induced cytochrome c and apoptosis inducing factor (AIF release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways.

Productivity Change, Technical Progress, and Relative Efficiency Change in the Public Accounting Industry

OpenAIRE

Rajiv D. Banker; Hsihui Chang; Ram Natarajan

2005-01-01

We present evidence on components of productivity change in the public accounting industry toward the end of the 20th century. Using revenue and human resource data from 64 of the 100 largest public accounting firms in the United States for the 1995--1999 period, we analyze productivity change, technical progress, and relative efficiency change over time. The average public accounting firm experienced a productivity growth of 9.5% between 1995 and 1999. We find support for the hypothesis that...

Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination

Directory of Open Access Journals (Sweden)

Richard Kennedy

2016-11-01

Full Text Available The goal of annual influenza vaccination is to reduce mortality and morbidity associated with this disease through the generation of protective immune responses. The objective of the current study was to examine markers of immunosenescence and identify immunosenescence-related differences in gene expression, gene regulation, cytokine secretion, and immunologic changes in an older study population receiving seasonal influenza A/H1N1 vaccination. Surprisingly, prior studies in this cohort revealed weak correlations between immunosenescence markers and humoral immune response to vaccination. In this report we further examined the relationship of each immunosenescence marker (age, T cell receptor excision circle frequency, telomerase expression, percentage of CD28- CD4+ T cells, percentage of CD28- CD8+ T cells, and the CD4/CD8 T cell ratio with additional markers of immune response (serum cytokine and chemokine expression and measures of gene expression and/or regulation. Many of the immunosenescence markers indeed correlated with distinct sets of individual DNA methylation sites, miRNA expression levels, mRNA expression levels, serum cytokines, and leukocyte subsets. However, when the individual immunosenescence markers were grouped by pathways or functional terms, several shared biological functions were identified: antigen processing and presentation pathways, MAPK, mTOR, TCR, BCR, and calcium signaling pathways, as well as key cellular metabolic, proliferation and survival activities. Furthermore, the percent of CD4+ and/or CD8+ T cells lacking CD28 expression also correlated with miRNAs regulating clusters of genes known to be involved in viral infection. Integrated (DNA methylation, mRNA, miRNA, and protein levels network biology analysis of immunosenescence-related pathways and genesets identified both known pathways (e.g., chemokine signaling, CTL and NK cell activity, as well as a gene expression module not previously annotated with a

Pachymic acid promotes induction of autophagy related to IGF-1 signaling pathway in WI-38 cells.

Science.gov (United States)

Lee, Su-Gyeong; Kim, Moon-Moo

2017-12-01

The insulin-like growth factor 1 (IGF-1) signaling pathway has spotlighted as a mechanism to elucidate aging associated with autophagy in recent years. Therefore, we have tried to screen an effective compound capable of inducing autophagy to delay aging process. The aim of this study is to investigate whether pachymic acid, a main compound in Poria cocos, induces autophagy in the aged cells. The aging of young cells was induced by treatment with IGF-1 at 50 ng/ml three times every two days. The effect of pachymic acid on cell viability was evaluated in human lung fibroblasts, WI-38 cells, using MTT assay. The induction of autophagy was detected using autophagy detection kit. The expression of proteins related to autophagy and IGF-1 signaling pathway was examined by western blot analysis and immunofluorescence assay. In this study, pachymic acid showed cytotoxic effect in a dose dependent manner and remarkably induced autophagy at the same time. Moreover, pachymic acid increased the expression of proteins related to autophagy such as LC3-II and Beclin1 and decreased the levels of mTor phosphorylation and p70S6K in the aged cells. In particular, pachymic acid increased the expression of p-PI3K, p-FoxO and Catalase. In addition, pachymic acid remarkably increased the expression of IGFBP-3. Above results suggest that pachymic acid could induce autophagy related to IGF-1 signaling pathway in the aged cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

Equine grass sickness in Scotland: a case-control study of signalment- and meteorology-related risk factors.

Science.gov (United States)

Wylie, C E; Shaw, D J; Fordyce, F M; Lilly, A; McGorum, B C

2014-01-01

Equine grass sickness (EGS) remains a frequently fatal disease of equids in Britain. Since previous investigations of signalment- and meteorology-related risk factors for EGS have yielded some conflicting data, further investigation is warranted. To identify signalment- and meteorology-related risk factors for EGS in Scotland. Retrospective time-matched case-control study. This study was undertaken using data for 455 EGS cases and 910 time-matched controls that were referred to the Royal (Dick) School of Veterinary Studies, and average UK Meteorological Office weather station meteorological values from the month of admission of the animal, from the 3, 6 and 12 months prior to admission, and for the entire 1990-2006 period. Signalment-related risk factors associated with an increased risk of EGS were native Scottish pure breeds compared with crossbreeds (odds ratio [OR] = 3.56, 95% confidence interval [CI] 2.43-5.43) and animals living on premises located further north within the study region (OR = 1.08, 95% CI 1.06-1.10). There was a decreased risk of EGS in animals aged 11-20 years compared with animals 2-10 years (OR = 0.32, 95% CI 0.22-0.45), non-native Scottish pure breeds compared with crossbreeds (OR = 0.71, 95% CI 0.54-0.94), and stallions compared with mares (OR = 0.43, 95% CI 0.22-0.86). Meteorology-related risk factors associated with an increased risk of EGS were (if Ordnance Survey northing is excluded) more sun hours (OR>1.43) and more frost days (OR>1.13), while there was a decreased risk of EGS with higher average maximum temperature (ORmeteorological risk factors may assist studies on the aetiology of EGS. © 2013 EVJ Ltd.

Evaluating signal-to-noise ratios, loudness, and related measures as indicators of airborne sound insulation.

Science.gov (United States)

Park, H K; Bradley, J S

2009-09-01

Subjective ratings of the audibility, annoyance, and loudness of music and speech sounds transmitted through 20 different simulated walls were used to identify better single number ratings of airborne sound insulation. The first part of this research considered standard measures such as the sound transmission class the weighted sound reduction index (R(w)) and variations of these measures [H. K. Park and J. S. Bradley, J. Acoust. Soc. Am. 126, 208-219 (2009)]. This paper considers a number of other measures including signal-to-noise ratios related to the intelligibility of speech and measures related to the loudness of sounds. An exploration of the importance of the included frequencies showed that the optimum ranges of included frequencies were different for speech and music sounds. Measures related to speech intelligibility were useful indicators of responses to speech sounds but were not as successful for music sounds. A-weighted level differences, signal-to-noise ratios and an A-weighted sound transmission loss measure were good predictors of responses when the included frequencies were optimized for each type of sound. The addition of new spectrum adaptation terms to R(w) values were found to be the most practical approach for achieving more accurate predictions of subjective ratings of transmitted speech and music sounds.

Wireless data signal transmission system

DEFF Research Database (Denmark)

2014-01-01

The present invention relates to a method for providing a radio frequency signal for transmission, a system for providing a radio frequency signal for transmission and a method for wireless data transmission between a transmitter and a receiver.......The present invention relates to a method for providing a radio frequency signal for transmission, a system for providing a radio frequency signal for transmission and a method for wireless data transmission between a transmitter and a receiver....

Quantifying morphological changes of cape-related shoals

Science.gov (United States)

Paniagua-Arroyave, J. F.; Adams, P. N.; Parra, S. M.; Valle-Levinson, A.

2017-12-01

The rising demand for marine resources has motivated the study of inner shelf transport processes, especially in locations with highly-developed coastlines, endangered-species habitats, and valuable economic resources. These characteristics are found at Cape Canaveral shoals, on the Florida Atlantic coast, where transport dynamics and morphological evolution are not well understood. To study morphological changes at these shoals, two sets of paired upward- and downward-pointing acoustic Doppler current profilers (ADCPs) were deployed in winter 2015-2016. One set was deployed at the inner swale of Shoal E, 20 km southeast of the cape tip in 13 m depth, while the other set was located at the edge of Southeast shoal in 5 m deep. Upward-pointing velocity profiles and suspended particle concentrations were implemented in the Exner equation to quantify instantaneous rates of change in bed elevation. This computation includes changes in sediment concentration and the advection of suspended particles, but does not account for spatial gradients in bed-load fluxes and water velocities. The results of the computation were then compared to bed change rates measured directly by the downward-pointing ADCPs. At the easternmost ridge, quantified bed elevation change rates ranged from -7×10-7 to 4×10-7 m/s, and those at the inner swale ranged from -4×10-7 to 8×10-7 m/s. These values were two orders of magnitude smaller than rates measured by downward-pointing ADCPs. Moreover, the cumulative changes were two orders of magnitude larger at the ridge (-0.33 m, downward, and -0.13, m upward) than at the inner swale (cf. -6×10-3 m, downward, and 3×10-3 m, upward). These values suggest that bedform migration may be occurring at the ridge, that suspended sediments account for up to 30% of total bed changes, and that gradients in bed-load fluxes exert control on morphological change over the shoals. Despite uncertainties related to the ADCP-derived sediment concentrations, these

Improvements in or relating to inclinometers

International Nuclear Information System (INIS)

Killinglley, R.V.; Holden, C.R.

1976-01-01

Reference is made to instruments responsive to small changes in the inclination of a body relative to a fixed datum and capable of providing remote indication of such changes. The instrument described is stated to be suitable for checking fuel channels in a nuclear reactor for any deviations from the vertical, and for this purpose is mounted in a unit designed to be traversed along the fuel channel. It comprises essentially a pivoted pendulum weight, a pair of transducer devices, and output signal-producing and recording means. A computer may be associated with the output signals. Full constructional details are given. (U.K.)

Automatic speech signal segmentation based on the innovation adaptive filter

Directory of Open Access Journals (Sweden)

Makowski Ryszard

2014-06-01

Full Text Available Speech segmentation is an essential stage in designing automatic speech recognition systems and one can find several algorithms proposed in the literature. It is a difficult problem, as speech is immensely variable. The aim of the authors’ studies was to design an algorithm that could be employed at the stage of automatic speech recognition. This would make it possible to avoid some problems related to speech signal parametrization. Posing the problem in such a way requires the algorithm to be capable of working in real time. The only such algorithm was proposed by Tyagi et al., (2006, and it is a modified version of Brandt’s algorithm. The article presents a new algorithm for unsupervised automatic speech signal segmentation. It performs segmentation without access to information about the phonetic content of the utterances, relying exclusively on second-order statistics of a speech signal. The starting point for the proposed method is time-varying Schur coefficients of an innovation adaptive filter. The Schur algorithm is known to be fast, precise, stable and capable of rapidly tracking changes in second order signal statistics. A transfer from one phoneme to another in the speech signal always indicates a change in signal statistics caused by vocal track changes. In order to allow for the properties of human hearing, detection of inter-phoneme boundaries is performed based on statistics defined on the mel spectrum determined from the reflection coefficients. The paper presents the structure of the algorithm, defines its properties, lists parameter values, describes detection efficiency results, and compares them with those for another algorithm. The obtained segmentation results, are satisfactory.

Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes.

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Richard A Anderson

Full Text Available Insulin resistance leads to memory impairment. Cinnamon (CN improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.

Towards a Unified Understanding of Event-Related Changes in the EEG: The Firefly Model of Synchronization through Cross-Frequency Phase Modulation

Science.gov (United States)

Burgess, Adrian P.

2012-01-01

Although event-related potentials (ERPs) are widely used to study sensory, perceptual and cognitive processes, it remains unknown whether they are phase-locked signals superimposed upon the ongoing electroencephalogram (EEG) or result from phase-alignment of the EEG. Previous attempts to discriminate between these hypotheses have been unsuccessful but here a new test is presented based on the prediction that ERPs generated by phase-alignment will be associated with event-related changes in frequency whereas evoked-ERPs will not. Using empirical mode decomposition (EMD), which allows measurement of narrow-band changes in the EEG without predefining frequency bands, evidence was found for transient frequency slowing in recognition memory ERPs but not in simulated data derived from the evoked model. Furthermore, the timing of phase-alignment was frequency dependent with the earliest alignment occurring at high frequencies. Based on these findings, the Firefly model was developed, which proposes that both evoked and induced power changes derive from frequency-dependent phase-alignment of the ongoing EEG. Simulated data derived from the Firefly model provided a close match with empirical data and the model was able to account for i) the shape and timing of ERPs at different scalp sites, ii) the event-related desynchronization in alpha and synchronization in theta, and iii) changes in the power density spectrum from the pre-stimulus baseline to the post-stimulus period. The Firefly Model, therefore, provides not only a unifying account of event-related changes in the EEG but also a possible mechanism for cross-frequency information processing. PMID:23049827

Pronounced Phenotypic Changes in Transgenic Tobacco Plants Overexpressing Sucrose Synthase May Reveal a Novel Sugar Signaling Pathway

Science.gov (United States)

Nguyen, Quynh Anh; Luan, Sheng; Wi, Seung G.; Bae, Hanhong; Lee, Dae-Seok; Bae, Hyeun-Jong

2016-01-01

Soluble sugars not only serve as nutrients, but also act as signals for plant growth and development, but how sugar signals are perceived and translated into physiological responses in plants remains unclear. We manipulated sugar levels in transgenic plants by overexpressing sucrose synthase (SuSy), which is a key enzyme believed to have reversible sucrose synthesis and sucrose degradation functions. The ectopically expressed SuSy protein exhibited sucrose-degrading activity, which may change the flux of sucrose demand from photosynthetic to non-photosynthetic cells, and trigger an unknown sucrose signaling pathway that lead to increased sucrose content in the transgenic plants. An experiment on the transition from heterotrophic to autotrophic growth demonstrated the existence of a novel sucrose signaling pathway, which stimulated photosynthesis, and enhanced photosynthetic synthesis of sucrose, which was the direct cause or the sucrose increase. In addition, a light/dark time treatment experiment, using different day length ranges for photosynthesis/respiration showed the carbohydrate pattern within a 24-h day and consolidated the role of sucrose signaling pathway as a way to maintain sucrose demand, and indicated the relationships between increased sucrose and upregulation of genes controlling development of the shoot apical meristem (SAM). As a result, transgenic plants featured a higher biomass and a shorter time required to switch to reproduction compared to those of control plants, indicating altered phylotaxis and more rapid advancement of developmental stages in the transgenic plants. PMID:26793204

Task effects on BOLD signal correlates of implicit syntactic processing

Science.gov (United States)

Caplan, David

2010-01-01

BOLD signal was measured in sixteen participants who made timed font change detection judgments in visually presented sentences that varied in syntactic structure and the order of animate and inanimate nouns. Behavioral data indicated that sentences were processed to the level of syntactic structure. BOLD signal increased in visual association areas bilaterally and left supramarginal gyrus in the contrast of sentences with object- and subject-extracted relative clauses without font changes in which the animacy order of the nouns biased against the syntactically determined meaning of the sentence. This result differs from the findings in a non-word detection task (Caplan et al, 2008a), in which the same contrast led to increased BOLD signal in the left inferior frontal gyrus. The difference in areas of activation indicates that the sentences were processed differently in the two tasks. These differences were further explored in an eye tracking study using the materials in the two tasks. Issues pertaining to how parsing and interpretive operations are affected by a task that is being performed, and how this might affect BOLD signal correlates of syntactic contrasts, are discussed. PMID:20671983

Educating dental students about diet-related behavior change: does experiential learning work?

Science.gov (United States)

Taylor, George W; Stumpos, Madelyn L; Kerschbaum, Wendy; Inglehart, Marita Rohr

2014-01-01

The objective of this study was to explore whether an experiential exercise in a nutrition class would a) increase dental students' motivation to change their own diet-related behavior, b) improve their understanding of theoretical concepts related to behavior change, and c) improve their attitudes towards educating their patients about diet-related behavior. Data were collected from 218 senior dental students in one dental school (2010: 106; 2011: 112) during their nutrition class. The students agreed at the beginning that it was important to change their own diet-related behavior. After one week, the majority agreed that they had changed how they felt and thought about the targeted behavior and what they actually did. After three weeks and at the end of the term, they rated the exercise as helpful for gaining a better understanding of health education theories. The majority indicated that the exercise had helped them understand the difficulty of diet-related behavior change and that it had increased their interest in helping patients change their diet-related behavior. In conclusion, this study suggests that experiential learning about diet-related behavior change is likely to affect students' own behavior positively and to result in increased understanding of behavior change theories and positive behavioral intentions concerning future health education efforts with patients.

Thylakoid redox signals are integrated into organellar-gene-expression-dependent retrograde signalling in the prors1-1 mutant

Directory of Open Access Journals (Sweden)

Luca eTadini

2012-12-01

Full Text Available Perturbations in organellar gene expression (OGE and the thylakoid redox state (TRS activate retrograde signalling pathways that adaptively modify nuclear gene expression (NGE, according to developmental and metabolic needs. The prors1-1 mutation in Arabidopsis down-regulates the expression of the nuclear gene Prolyl-tRNA Synthetase1 (PRORS1 which acts in both plastids and mitochondria, thereby impairing protein synthesis in both organelles and triggering OGE-dependent retrograde signalling. Because the mutation also affects thylakoid electron transport, TRS-dependent signals may likewise have an impact on the changes in NGE observed in this genotype. In this study, we have investigated whether signals related to TRS are actually integrated into the OGE-dependent retrograde signalling pathway. To this end, the chaos mutation (for chlorophyll a/b binding protein harvesting-organelle specific, which shows a partial loss of PSII antennae proteins and thus a reduction in PSII light absorption capability, was introduced into the prors1-1 mutant background. The resulting double mutant displayed a prors1-1-like reduction in plastid translation rate and a chaos-like decrease in PSII antenna size, whereas the hyper-reduction of the thylakoid electron transport chain, caused by the prors1-1 mutation, was alleviated, as determined by monitoring chlorophyll (Chl fluorescence and thylakoid phosphorylation. Interestingly, a substantial fraction of the nucleus-encoded photosynthesis genes down-regulated in the prors1-1 mutant are expressed at nearly wild-type rates in prors1-1 chaos leaves, and this recovery is reflected in the steady-state levels of their protein products in the chloroplast. We therefore conclude that signals related to photosynthetic electron transport and TRS, and indirectly to carbohydrate metabolism and energy balance, are indeed fed into the OGE-dependent retrograde pathway to modulate NGE and adjust the abundance of chloroplast proteins.

Waterpipe smoking induces epigenetic changes in the small airway epithelium.

Directory of Open Access Journals (Sweden)

Matthew S Walters

Full Text Available Waterpipe (also called hookah, shisha, or narghile smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use waterpipe smoking on DNA methylation of the small airway epithelium (SAE and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 ± 1.7 sessions/wk waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05 representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05 change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling. Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.

Signal processing methods for in-situ creep specimen monitoring

Science.gov (United States)

Guers, Manton J.; Tittmann, Bernhard R.

2018-04-01

Previous work investigated using guided waves for monitoring creep deformation during accelerated life testing. The basic objective was to relate observed changes in the time-of-flight to changes in the environmental temperature and specimen gage length. The work presented in this paper investigated several signal processing strategies for possible application in the in-situ monitoring system. Signal processing methods for both group velocity (wave-packet envelope) and phase velocity (peak tracking) time-of-flight were considered. Although the Analytic Envelope found via the Hilbert transform is commonly applied for group velocity measurements, erratic behavior in the indicated time-of-flight was observed when this technique was applied to the in-situ data. The peak tracking strategies tested had generally linear trends, and tracking local minima in the raw waveform ultimately showed the most consistent results.

Interdecadal changes of summer aerosol pollution in the Yangtze River Basin of China, the relative influence of meteorological conditions and the relation to climate change.

Science.gov (United States)

Wang, Jizhi; Zhang, Xiaoye; Li, Duo; Yang, Yuanqin; Zhong, Junting; Wang, Yaqiang; Che, Haochi; Che, Huizheng; Zhang, Yangmei

2018-07-15

Winter is a season of much concern for aerosol pollution in China, but less concern for pollution in the summertime. There are even less concern and larger uncertainty about interdecadal changes in summer aerosol pollution, relative influence of meteorological conditions, and their links to climate change. Here we try to reveal the relation among interdecadal changes in summer's most important circulation system affecting China (East Asian Summer Monsoon-EASM), an index of meteorological conditions (called PLAM, Parameter Linking Air Quality and Meteorological Elements, which is almost linearly related with aerosol pollution), and aerosol optical depth (AOD) in the middle and lower reaches of the Yangtze River (M-LYR) in central eastern China during summertime since the 1960's. During the weak monsoon years, the aerosol pollution load was heavier in the M-LYR and opposite in the strong monsoon years mainly influenced by EASM and associated maintenance position of the anti-Hadley cell around 115°E. The interdecadal changes in meteorological conditions and their associated aerosol pollution in the context of such climate change have experienced four periods since the 1960's, which were a relatively large decreased period from 1961 to 1980, a large rise between 1980 and 1999, a period of slow rise or maintenance from 1999 to 2006, and a relatively rapid rise between 2006 and 2014. Among later three pollution increased periods, about 51%, 25% and 60% of the aerosol pollution change respectively come from the contribution of worsening weather conditions, which are found to be greatly affected by changes in EASM. Copyright © 2018 Elsevier B.V. All rights reserved.

Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes.

Science.gov (United States)

Rex, Maria; Hilton, Emma; Old, Robert

2002-03-01

We have investigated the induction of the six Xenopus nodal-related genes, Xnr1-Xnr6, by maternal determinants. The beta-catenin pathway was modelled by stimulation using Xwnt8, activin-like signalling was modelled by activin, and VegT action was studied by overexpression in animal cap explants. Combinations of factors were examined, and previously unrecognised interactions were revealed in animal caps and whole embryos. For the induction of Xnr5 and Xnr6 in whole embryos, using a beta-catenin antisense morpholino oligonucleotide or a dominant negative XTcf3, we have demonstrated an absolute permissive requirement for the beta-catenin/Tcf pathway, in addition to the requirement for VegT action. In animal caps Xnr5 and Xnr6 are induced in response to VegT overexpression, and this induction is dependent upon the concomitant activation of the beta-catenin pathway that VegT initiates in animal caps. For the induction of Xnr3, VegT interacts negatively so as to inhibit the induction otherwise observed with wnt-signalling alone. The negative effect of VegT is not the result of a general inhibition of wnt-signalling, and does not result from an inhibition of wnt-induced siamois expression. A 294 bp proximal promoter fragment of the Xnr3 gene is sufficient to mediate the negative effect of VegT. Further experiments, employing cycloheximide to examine the dependence of Xnr gene expression upon proteins translated after the mid-blastula stage, demonstrated that Xnrs 4, 5 and 6 are 'primary' Xnr genes whose expression in the late blastula is solely dependent upon factors present before the mid-blastula stage.

Long-distance signaling within Coleus x hybridus leaves; mediated by changes in intra-leaf CO2?

Science.gov (United States)

Stahlberg, R.; Van Volkenburgh, E.; Cleland, R. E.

2001-01-01

Rapid long-distance signaling in plants can occur via several mechanisms, including symplastic electric coupling and pressure waves. We show here in variegated Coleus leaves a rapid propagation of electrical signals that appears to be caused by changes in intra-leaf CO2 concentrations. Green leaf cells, when illuminated, undergo a rapid depolarization of their membrane potential (Vm) and an increase in their apoplastic pH (pHa) by a process that requires photosynthesis. This is followed by a slower hyperpolarization of Vm and apoplastic acidification, which do not require photosynthesis. White (chlorophyll-lacking) leaf cells, when in isolated white leaf segments, show only the slow response, but when in mixed (i.e. green and white) segments, the rapid Vm depolarization and increase in pHa propagate over more than 10 mm from the green to the white cells. Similarly, these responses propagate 12-20 mm from illuminated to unilluminated green cells. The fact that the propagation of these responses is eliminated when the leaf air spaces are infiltrated with solution indicates that the signal moves in the apoplast rather than the symplast. A depolarization of the mesophyll cells is induced in the dark by a decrease in apoplastic CO2 but not by an increase in pHa. These results support the hypothesis that the propagating signal for the depolarization of the white mesophyll cells is a photosynthetically induced decrease in the CO2 level of the air spaces throughout the leaf.

Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

Energy Technology Data Exchange (ETDEWEB)

Khin, Sann Sanda [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Pathology Research Unit, Department of Medical Research (Central Myanmar), Naypyitaw, Union of (Myanmar); Kitazawa, Riko [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Haraguchi, Ryuma [Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Mori, Kiyoshi [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Kitazawa, Sohei, E-mail: kitazawa@m.ehime-u.ac.jp [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan)

2011-03-03

Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

International Nuclear Information System (INIS)

Khin, Sann Sanda; Kitazawa, Riko; Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo; Haraguchi, Ryuma; Mori, Kiyoshi; Kitazawa, Sohei

2011-01-01

Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression

Addressing trend-related changes within cumulative effects studies in water resources planning

International Nuclear Information System (INIS)

Canter, L.W.; Chawla, M.K.; Swor, C.T.

2014-01-01

Summarized herein are 28 case studies wherein trend-related causative physical, social, or institutional changes were connected to consequential changes in runoff, water quality, and riparian and aquatic ecological features. The reviewed cases were systematically evaluated relative to their identified environmental effects; usage of analytical frameworks, and appropriate models, methods, and technologies; and the attention given to mitigation and/or management of the resultant causative and consequential changes. These changes also represent important considerations in project design and operation, and in cumulative effects studies associated therewith. The cases were grouped into five categories: institutional changes associated with legislation and policies (seven cases); physical changes from land use changes in urbanizing watersheds (eight cases); physical changes from land use changes and development projects in watersheds (four cases); physical, institutional, and social changes from land use and related policy changes in river basins (three cases); and multiple changes within a comprehensive study of land use and policy changes in the Willamette River Basin in Oregon (six cases). A tabulation of 110 models, methods and technologies used in the studies is also presented. General observations from this review were that the features were unique for each case; the consequential changes were logically based on the causative changes; the analytical frameworks provided relevant structures for the studies, and the identified methods and technologies were pertinent for addressing both the causative and consequential changes. One key lesson was that the cases provide useful, “real-world” illustrations of the importance of addressing trend-related changes in cumulative effects studies within water resources planning. Accordingly, they could be used as an “initial tool kit” for addressing trend-related changes

Addressing trend-related changes within cumulative effects studies in water resources planning

Energy Technology Data Exchange (ETDEWEB)

Canter, L.W., E-mail: envimptr@aol.com [University of Oklahoma, Norman, Oklahoma and President, Canter Associates, Inc., Horseshoe Bay, TX (United States); Chawla, M.K. [ERDC-CERL, U.S. Army Corps of Engineers, Champaign, IL (United States); Swor, C.T. [Canter Associates, Inc., Frankewing, TN (United States)

2014-01-15

Summarized herein are 28 case studies wherein trend-related causative physical, social, or institutional changes were connected to consequential changes in runoff, water quality, and riparian and aquatic ecological features. The reviewed cases were systematically evaluated relative to their identified environmental effects; usage of analytical frameworks, and appropriate models, methods, and technologies; and the attention given to mitigation and/or management of the resultant causative and consequential changes. These changes also represent important considerations in project design and operation, and in cumulative effects studies associated therewith. The cases were grouped into five categories: institutional changes associated with legislation and policies (seven cases); physical changes from land use changes in urbanizing watersheds (eight cases); physical changes from land use changes and development projects in watersheds (four cases); physical, institutional, and social changes from land use and related policy changes in river basins (three cases); and multiple changes within a comprehensive study of land use and policy changes in the Willamette River Basin in Oregon (six cases). A tabulation of 110 models, methods and technologies used in the studies is also presented. General observations from this review were that the features were unique for each case; the consequential changes were logically based on the causative changes; the analytical frameworks provided relevant structures for the studies, and the identified methods and technologies were pertinent for addressing both the causative and consequential changes. One key lesson was that the cases provide useful, “real-world” illustrations of the importance of addressing trend-related changes in cumulative effects studies within water resources planning. Accordingly, they could be used as an “initial tool kit” for addressing trend-related changes.

Changing doping-related attitudes in soccer players: how can we get stable and persistent changes?

Science.gov (United States)

Horcajo, Javier; de la Vega, Ricardo

2014-01-01

The aim of this experiment was to analyse the consequences of changing attitudes related to doping through thoughtful versus non-thoughtful processes. Participants were young soccer players. They received a persuasive message either against or in favour of the legalisation of several doping behaviours in soccer (e.g., the use of anabolic androgenic steroid - AAS), and participants' level of elaboration (i.e., deliberative thinking) was manipulated in two different experimental (high vs. low) conditions. Attitudes towards the legalisation proposal were assessed immediately following the message and one week later. Results showed attitude change was a function of message direction and was relatively equivalent for both high and low elaboration participants immediately after reading the message. That is, those who received the message against legalisation showed significantly more unfavourable attitudes towards the proposal than did those who received the message in favour of legalisation regardless of the extent of elaboration. However, attitude change was found to be persistent only for high elaboration participants one week after message exposure. In the present paper, we discuss implications of changing attitudes related to doping depending on whether the change occurred through psychological processes that require either extensive or small amounts of deliberative thinking and elaboration.

Technical Note: Intrafractional changes in time lag relationship between anterior–posterior external and superior–inferior internal motion signals in abdominal tumor sites

Science.gov (United States)

Regmi, Rajesh; Lovelock, D. Michael; Zhang, Pengpeng; Pham, Hai; Xiong, Jianping; Yorke, Ellen D.; Goodman, Karyn A.; Wu, Abraham J.; Mageras, Gig S.

2015-01-01

Purpose: To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Methods: Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior–inferior (SI) internal and anterior–posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Results: Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01–0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01–0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%–10.8%) of gate width (range 1.6–3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Conclusions: Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients. PMID:26127033

Technical Note: Intrafractional changes in time lag relationship between anterior-posterior external and superior-inferior internal motion signals in abdominal tumor sites.

Science.gov (United States)

Regmi, Rajesh; Lovelock, D Michael; Zhang, Pengpeng; Pham, Hai; Xiong, Jianping; Yorke, Ellen D; Goodman, Karyn A; Wu, Abraham J; Mageras, Gig S

2015-06-01

To investigate constancy, within a treatment session, of the time lag relationship between implanted markers in abdominal tumors and an external motion surrogate. Six gastroesophageal junction and three pancreatic cancer patients (IRB-approved protocol) received two cone-beam CTs (CBCT), one before and one after treatment. Time between scans was less than 30 min. Each patient had at least one implanted fiducial marker near the tumor. In all scans, abdominal displacement (Varian RPM) was recorded as the external motion signal. Purpose-built software tracked fiducials, representing internal signal, in CBCT projection images. Time lag between superior-inferior (SI) internal and anterior-posterior external signals was found by maximizing the correlation coefficient in each breathing cycle and averaging over all cycles. Time-lag-induced discrepancy between internal SI position and that predicted from the external signal (external prediction error) was also calculated. Mean ± standard deviation time lag, over all scans and patients, was 0.10 ± 0.07 s (range 0.01-0.36 s). External signal lagged the internal in 17/18 scans. Change in time lag between pre- and post-treatment CBCT was 0.06 ± 0.07 s (range 0.01-0.22 s), corresponding to 3.1% ± 3.7% (range 0.6%-10.8%) of gate width (range 1.6-3.1 s). In only one patient, change in time lag exceeded 10% of the gate width. External prediction error over all scans of all patients varied from 0.1 ± 0.1 to 1.6 ± 0.4 mm. Time lag between internal motion along SI and external signals is small compared to the treatment gate width of abdominal patients examined in this study. Change in time lag within a treatment session, inferred from pre- to post-treatment measurements is also small, suggesting that a single measurement of time lag at the session start is adequate. These findings require confirmation in a larger number of patients.

Climate-related global changes in the southern Caribbean. Trinidad and Tobago

Energy Technology Data Exchange (ETDEWEB)

Singh, Bhawan [Department of Geography, University of Montreal, Montreal, QU (Canada)

1997-10-30

A climate change deriving from the atmospheric build up of greenhouse gases (GHG) is supposed to become evident by the middle of the next century. This GHG-induced climate change would supposedly lead to a global warming of about 2 to 4C and a rise in mean sea level of about 60 cm towards the end of the next century. This study focuses on the field measurements and interpretations of a number of, supposedly, climate-driven regional changes, including shifts in climate and hydrology, coastal erosion and sedimentation, salinisation of coastal aquifers and estuaries, and also coral bleaching, in Trinidad and Tobago, in the southern Caribbean. The results show significant changes and shifts in temperature and rainfall, severe coastal erosion, approaching 2 to 4m per year for certain beaches, appreciable salinisation of a number of coastal aquifers and an estuary along the Caroni swamp, in Trinidad, and what appears to be partial coral bleaching, at the Culloden Reef in Tobago. These field-observed regional changes may conceivably be interpreted as early signals of a GHG-induced climate change. However, in view of the uncertainty surrounding GHG-induced climate change and sea level rise and the limitations of our data, especially the length of record, caution must be exercised in the interpretation of these results

Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats

Science.gov (United States)

Vázquez, Mariam; Sánchez, Laura; Rivera, Patricia; Gavito, Ana; Mela, Virginia; Alén, Francisco; Decara, Juan; Suárez, Juan; Giné, Elena; López-Moreno, José Antonio; Chowen, Julie; Rodríguez-de-Fonseca, Fernando; Serrano, Antonia; Viveros, María Paz

2016-01-01

Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats

Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats.

Directory of Open Access Journals (Sweden)

Francisco Javier Pavón

Full Text Available Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS, which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in

cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

Science.gov (United States)

Stewart, Randi

2012-01-01

Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets. PMID:22354781

Bystander effects: intercellular transmission of radiation damage signals

Energy Technology Data Exchange (ETDEWEB)

Little, J.B.; Azzam, E.I.; Toledo, S.M. de; Nagasawa, H

2002-07-01

Biological effects were examined in confluent cultures of fibroblasts and epithelial cells exposed to very low mean doses of alpha radiation, doses by which only 1-2% of the cells were actually traversed by an alpha particle. Enhanced frequencies of sister chromatid exchanges and HPRT mutations occurred in the non-irradiation, 'bystander' cells associated with a similar increase in the frequency of micronuclei, indicating the induction of DNA damage in these cells. In order to gain information concerning molecular pathways, changes in gene expression were examined in bystander cells by western analysis and in situ immunofluorescence staining. The expression levels of p53, p21 and MDM2 were significantly modulated in bystander cells: the damage signals leading to these changes were transmitted from irradiated to bystander cells by gap junction mediated intracellular communication. The bystander response was suppressed by incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase, suggesting the effect may be mediated by oxidative stress. To examine other signalling pathways responsive to oxidative stress, the activation of stress-related kinases and their downstream transcription factors were analysed in bystander cells by western blotting and electrophoretic mobility shift assays: a 2-4 fold increase in the phosphorylation levels of JNK, EPK1/2, p90RSK, Elk-1 and ATF2 was observed. These changes were detected by 15 min after irradiation and persisted for at least 1 h. These findings indicate the activation of multiple signal transduction pathways in bystander cells, involving signals arising from the plasma membrane as well as from DNA damage. (author)

Alteration of cancer pain-related signals by radiation: Proteomic analysis in an animal model with cancer bone invasion

International Nuclear Information System (INIS)

Park, Hee Chul; Seong, Jinsil; An, Jung Hee; Kim, Jiyoung; Kim, Un Jung; Lee, Bae Whan

2005-01-01

Purpose: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. Methods and Materials: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. Results: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca 2+ /Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca 2+ -signaling cascade, ATP-mediated fast synaptic transmission, or control of vesicular

Alteration of cancer pain-related signals by radiation: Proteomic analysis in an animal model with cancer bone invasion

Energy Technology Data Exchange (ETDEWEB)

Park, Hee Chul [Department of Radiation Oncology, Hallym University, Chuncheon (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); An, Jung Hee [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Jiyoung [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Un Jung [Yonsei Medical Research Center, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Bae Whan [Yonsei Medical Research Center, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of)

2005-04-01

Purpose: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. Methods and Materials: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. Results: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca{sup 2+}/Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca{sup 2+}-signaling cascade, ATP-mediated fast synaptic transmission, or control of

Stiffness-dependent cellular internalization of matrix-bound BMP-2 and its relation to Smad and non-Smad signaling.

Science.gov (United States)

Gilde, Flora; Fourel, Laure; Guillot, Raphael; Pignot-Paintrand, Isabelle; Okada, Takaharu; Fitzpatrick, Vincent; Boudou, Thomas; Albiges-Rizo, Corinne; Picart, Catherine

2016-12-01

Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition. However, whether and how matrix-bound BMP-2 can be internalized by cells and its relation to canonical (SMAD) and non-canonical signaling (ALP) remain open questions. In this study, we investigated the uptake and processing of BMP-2 by C2C12 myoblasts. This BMP-2 was presented either embedded in polyelectrolyte multilayer films (matrix-bound presentation) or as soluble form. Using fluorescently labeled BMP-2, we showed that the amount of matrix-bound BMP-2 internalized is dependent on the level of crosslinking of the polyelectrolyte films. Cav-1-mediated internalization is related to both SMAD and ALP signaling, while clathrin-mediated is only related to ALP signaling. BMP-2 internalization was independent of the presentation mode (sBMP-2 versus bBMP-2) for low crosslinked films (soft, EDC10) in striking contrast with high crosslinked (stiff, EDC70) films where internalization was much lower and slower for bBMP-2. As anticipated, internalization of sBMP-2 barely depended on the underlying matrix. Taken together, these results indicate that BMP-2 internalization can be tuned by the underlying matrix and activates downstream BMP-2 signaling, which is key for the effective formation of bone tissue. The presentation of growth factors from material surfaces currently presents significant challenges in academic research, clinics and industry. Being able to deliver efficiently these growth

Responding to vaccine safety signals during pandemic influenza: a modeling study.

Directory of Open Access Journals (Sweden)

Judith C Maro

Full Text Available Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system.We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1 expected vaccination benefit from averted influenza; 2 expected vaccination risk from vaccine-associated febrile seizures; 3 expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4 expected change in vaccine-seeking behavior in future influenza seasons.Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3:1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior.The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.

Earthquake Signal Visible in GRACE Data

Science.gov (United States)

2005-01-01

[figure removed for brevity, see original site] Figure1 This figure shows the effect of the December 2004 great Sumatra earthquake on the Earth's gravity field as observed by GRACE. The signal is expressed in terms of the relative acceleration of the two GRACE satellites, in this case a few nanometers per second squared, or about 1 billionth of the acceleration we experience everyday at the Earth's surface.GRACE observations show comparable signals in the region of the earthquake. Other natural variations are also apparent in the expected places, whereas no other significant change would be expected in the region of the earthquake GRACE, twin satellites launched in March 2002, are making detailed measurements of Earth's gravity field which will lead to discoveries about gravity and Earth's natural systems. These discoveries could have far-reaching benefits to society and the world's population.

Conditions for Change Related to Groupware in a Distributed Organization

DEFF Research Database (Denmark)

Simonsen, Jesper; Pors, Jens Kaaber

2003-01-01

general types of settings where the groupware has been used: Newly established organizational units, special interest groups, short term projects, and teams handling recurrent tasks. We characterize these settings and present the overall conditions that have proven to be critical to the deployment...... of groupware in the case. Challenges and expectations are discussed and ideas concerning strategies for change are suggested. It is concluded that change related to groupware faces conditions that challenge ambitious goals in three of the settings, while conditions in general favour successful change related...

Overexpression of blueberry FLOWERING LOCUS T is associated with changes in the expression of phytohormone-related genes in blueberry plants

Science.gov (United States)

Gao, Xuan; Walworth, Aaron E; Mackie, Charity; Song, Guo-qing

2016-01-01

Flowering locus T (FT) is a primary integrator in the regulation of plant flowering. Overexpressing a blueberry (Vaccinium corymbosum L.) FT gene (VcFT) (herein VcFT-OX) resulted in early flowering and dwarfing in ‘Aurora’ plants (herein ‘VcFT-Aurora’). In this study, we found that VcFT-OX reduced shoot regeneration from leaf explants. To investigate the potential roles of the phytohormone pathway genes associated with VcFT-OX, differentially expressed (DE) genes in leaf tissues of ‘VcFT-Aurora’ plants were annotated and analyzed using non-transgenic ‘Aurora’ plants as a control. Three DE floral genes, including the blueberry SUPPRESSOR of Overexpression of constans 1 (VcSOC1) (gibberellin related), Abscisic acid responsive elements-binding factor 2 (VcABF2) and protein related to ABI3/VP1 (VcABI3/VP1) (ethylene-related), are present under both the phytohormone-responsive and the dwarfing-related Gene Ontology terms. The gene networks of the DE genes overall showed the molecular basis of the multifunctional aspects of VcFT overexpression beyond flowering promotion and suggested that phytohormone changes could be signaling molecules with important roles in the phenotypic changes driven by VcFT-OX. PMID:27818778

Safety surrogate histograms (SSH): A novel real-time safety assessment of dilemma zone related conflicts at signalized intersections.

Science.gov (United States)

Ghanipoor Machiani, Sahar; Abbas, Montasir

2016-11-01

Drivers' indecisiveness in dilemma zones (DZ) could result in crash-prone situations at signalized intersections. DZ is to the area ahead of an intersection in which drivers encounter a dilemma regarding whether to stop or proceed through the intersection when the signal turns yellow. An improper decision to stop by the leading driver, combined with the following driver deciding to go, can result in a rear-end collision, unless the following driver recognizes a collision is imminent and adjusts his or her behavior at or shortly after the onset of yellow. Considering the significance of DZ-related crashes, a comprehensive safety measure is needed to characterize the level of safety at signalized intersections. In this study, a novel safety surrogate measure was developed utilizing real-time radar field data. This new measure, called safety surrogate histogram (SSH), captures the degree and frequency of DZ-related conflicts at each intersection approach. SSH includes detailed information regarding the possibility of crashes, because it is calculated based on the vehicles conflicts. An example illustrating the application of the new methodology at two study sites in Virginia is presented and discussed, and a comparison is provided between SSH and other DZ-related safety surrogate measures mentioned in the literature. The results of the study reveal the efficacy of the SSH as complementary to existing surrogate measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling.

Science.gov (United States)

Lee, Min Chul; Okamoto, Masahiro; Liu, Yu Fan; Inoue, Koshiro; Matsui, Takashi; Nogami, Haruo; Soya, Hideaki

2012-10-15

Although voluntary running has beneficial effects on hippocampal cognitive functions if done abundantly, it is still uncertain whether resistance running would be the same. For this purpose, voluntary resistance wheel running (RWR) with a load is a suitable model, since it allows increased work levels and resultant muscular adaptation in fast-twitch muscle. Here, we examined whether RWR would have potential effects on hippocampal cognitive functions with enhanced hippocampal brain-derived neurotrophic factor (BDNF), as does wheel running without a load (WR). Ten-week-old male Wistar rats were assigned randomly to sedentary (Sed), WR, and RWR (to a maximum load of 30% of body weight) groups for 4 wk. We found that in RWR, work levels increased with load, but running distance decreased by about half, which elicited muscular adaptation for fast-twitch plantaris muscle without causing any negative stress effects. Both RWR and WR led to improved spatial learning and memory as well as gene expressions of hippocampal BDNF signaling-related molecules. RWR increased hippocampal BDNF, tyrosine-related kinase B (TrkB), and cAMP response element-binding (CREB) protein levels, whereas WR increased only BDNF. With both exercise groups, there were correlations between spatial memory and BDNF protein (r = 0.41), p-CREB protein (r = 0.44), and work levels (r = 0.77). These results suggest that RWR plays a beneficial role in hippocampus-related cognitive functions associated with hippocampal BDNF signaling, even with short distances, and that work levels rather than running distance are more determinant of exercise-induced beneficial effects in wheel running with and without a load.

Analysis of signal acquisition in GPS receiver software

Directory of Open Access Journals (Sweden)

Vlada S. Sokolović

2011-01-01

. the whole receiver is software implemented in a MATLAB software package. One of the processes during the signal processing is the initial synchronization (acquisition, where a signal is detected and the carrier frequency is determined as well as the phase sequence code and the carrier Doppler frequency. The acquisition aim is to determine, in the shortest time possible, the parameters of the detected signals and forward them to the next block in synchronization. Depending on the speed and accuracy of the signal parameter determination, different methods of acquisition are applied in practice. The paper presents the methods of serial, parallel and cyclic convolution. For comparison purposes, the architectures of signal processing of particular methods for implementation in receiver software are shown. All measurements were performed on the same signal under the same conditions. On the basis of the tests performed, a detailed analysis of the collected data was carried out and the most acceptable acquisition method for implementation in software GPS receiver was proposed. Because of a relatively high level of noise at the receiver entrance and the received signal interference, the comparison of the results has been done on the basis of the analytical results and the mean time of signal synchronization. The measurement results are shown in tables for easy comparison. The results of measurements using the proposed method are presented as well. The technology of receiver software allows the user to access easily to the architecture of the receiver and therefore allows a simple change of parameters. The influence of the parameters on the process of signal acquisition is also shown in the paper. The graphic presentation shows how and to what extent some of the parameters affect the process of the receiver signal processing. All listed acquisition methods are used in practice. The proposed method is the most suitable for application in software receivers. Based on the analysis

The effect of signal leakage and glacial isostatic rebound on GRACE-derived ice mass changes in Iceland

DEFF Research Database (Denmark)

Sørensen, Louise Sandberg; Jarosch, Alexander H.; Adalgeirsdottir, Gudfinna

2017-01-01

Monthly gravity field models from the GRACE satellite mission are widely used to determine ice mass changes of large ice sheets as well as smaller glaciers and ice caps. Here, we investigate in detail the ice mass changes of the Icelandic ice caps as derived from GRACE data. The small size...... of the Icelandic ice caps, their location close to other rapidly changing ice covered areas and the low viscosity of the mantle below Iceland make this especially challenging. The mass balance of the ice caps is well constrained by field mass balance measurements, making this area ideal for such investigations. We...... the Little Ice Age (∼ 1890 AD). To minimize the signal that leaks towards Iceland from Greenland, we employ an independent mass change estimate of the Greenland Ice Sheet derived from satellite laser altimetry. We also estimate the effect of post Little Ice Age glacial isostatic adjustment, from knowledge...

Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles.

Science.gov (United States)

Nesteruk, Monika; Hennig, Ewa E; Mikula, Michal; Karczmarski, Jakub; Dzwonek, Artur; Goryca, Krzysztof; Rubel, Tymon; Paziewska, Agnieszka; Woszczynski, Marek; Ledwon, Joanna; Dabrowska, Michalina; Dadlez, Michal; Ostrowski, Jerzy

2014-03-01

Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values ≤ 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles.

Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat nigrostriatal pathway.

Directory of Open Access Journals (Sweden)

Tertia D Purves-Tyson

Full Text Available Adolescent males have an increased risk of developing schizophrenia, implicating testosterone in the precipitation of dopamine-related psychopathology. Evidence from adult rodent brain indicates that testosterone can modulate nigrostriatal dopamine. However, studies are required to understand the role testosterone plays in maturation of dopamine pathways during adolescence and to elucidate the molecular mechanism(s by which testosterone exerts its effects. We hypothesized that molecular indices of dopamine neurotransmission [synthesis (tyrosine hydroxylase, breakdown (catechol-O-methyl transferase; monoamine oxygenase, transport [vesicular monoamine transporter (VMAT, dopamine transporter (DAT] and receptors (DRD1-D5] would be changed by testosterone or its metabolites, dihydrotestosterone and 17β-estradiol, in the nigrostriatal pathway of adolescent male rats. We found that testosterone and dihydrotestosterone increased DAT and VMAT mRNAs in the substantia nigra and that testosterone increased DAT protein at the region of the cell bodies, but not in target regions in the striatum. Dopamine receptor D2 mRNA was increased and D3 mRNA was decreased in substantia nigra and/or striatum by androgens. These data suggest that increased testosterone at adolescence may change dopamine responsivity of the nigrostriatal pathway by modulating, at a molecular level, the capacity of neurons to transport and respond to dopamine. Further, dopamine turnover was increased in the dorsal striatum following gonadectomy and this was prevented by testosterone replacement. Gene expression changes in the dopaminergic cell body region may serve to modulate both dendritic dopamine feedback inhibition and reuptake in the dopaminergic somatodendritic field as well as dopamine release and re-uptake dynamics at the presynaptic terminals in the striatum. These testosterone-induced changes of molecular indices of dopamine neurotransmission in males are primarily androgen

Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

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Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

2010-03-01

Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior.

Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

Directory of Open Access Journals (Sweden)

Ana ePalomino

2014-03-01

Full Text Available Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression (CB1 receptors and enzymes that produce (DAGLα/β and NAPE-PLD and degrade (MAGL and FAAH eCB were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system (glutamate synthesizing enzymes LGA and KGA, mGluR3/5 metabotropic receptors, and NR1/2A/2B/2C-NMDA and GluR1/2/3/4-AMPA ionotropic receptor subunits and the gene expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-AG production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that

THE CHANGING DIMENSIONS OF PUBLIC RELATIONS: THE RELATIONSHIP BETWEEN BRAND MANAGEMENT AND PUBLIC RELATIONS

OpenAIRE

KÖKER, E. PELİN BAYTEKİN MİNE YENİÇERİ ALEMDAR

2008-01-01

The changes in the dimensions of public relations, due to the globalization effect on the business enterprises, are remarkable. In this manner, the relationship of public relations with re-engineering, total quality management, six sigma approach, event management, crisis management, reputation management, knowledge management and customer relationship management is evaluated in this study. Moreover, after establishing these interactions, the relationship between public relations and brand ma...

Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β Signaling in Cancer

Directory of Open Access Journals (Sweden)

Kiyoshi Mori

2011-03-01

Full Text Available Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β, induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

Does signaling of estrogen-related receptors affect structure and function of bank vole Leydig cells?

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Pawlicki, P; Milon, A; Zarzycka, M; Galas, J; Tworzydlo, W; Kaminska, A; Pardyak, L; Lesniak, K; Pacwa, A; Bilinska, B; Gorowska-Wojtowicz, E; Kotula-Balak, M

2017-06-01

To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day). Markedly more, XCT 790 (P endogenous estrogen level in treated males. Notably, immunolocalization of ERRs and above proteins, exclusively in Leydig cells, indicated their involvement in Leydig cell function control based on interactions with endogenous estrogen level and/or estrogen signaling via ERRs. Treatment with XCT 790 or DY131 significantly decreased (P endogenous estrogen status in the testis. Further understanding of mechanism(s) by which individual types of ERRs can control Leydig cell function is relevant for predicting and preventing steroidogenic and spermatogenic disorders.

Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis.

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Chen, Yanmei; Hoehenwarter, Wolfgang

2015-12-01

Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K(+) and Na(+) transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. © 2015 American Society of Plant Biologists. All Rights Reserved.

Lost without trace: oximetry signal dropout in preterm infants.

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Lim, Kathleen; Wheeler, Kevin I; Jackson, Hamish D; Sadeghi Fathabadi, Omid; Gale, Timothy J; Dargaville, Peter A

2015-09-01

Oxygen saturation (SpO2) signal dropout leaves caregivers without a reliable measure to guide oxygen therapy. We studied SpO2 dropout in preterm infants on continuous positive airway pressure, noting the SpO2 values at signal loss and recovery and thus the resultant change in SpO2, and the factors influencing this parameter. In 32 infants of median gestation 26 weeks, a total of 3932 SpO2 dropout episodes were identified (1.1 episodes/h). In the episodes overall, SpO2 decreased by 1.1%, with the SpO2 change influenced by starting SpO2 (negative correlation), but not dropout duration. For episodes starting in hypoxia (SpO2 dropout, with a downward trajectory in a quarter of cases. We conclude that after signal dropout SpO2 generally recovers in a relative normoxic range. Blind FiO2 adjustments are thus unlikely to be of benefit during most SpO2 dropout episodes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes*

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Collins, John A.; Wood, Scott T.; Nelson, Kimberly J.; Rowe, Meredith A.; Carlson, Cathy S.; Chubinskaya, Susan; Poole, Leslie B.; Furdui, Cristina M.; Loeser, Richard F.

2016-01-01

Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1–3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. PMID:26797130

Noisy signaling: theory and experiment

NARCIS (Netherlands)

de Haan, T.; Offerman, T.; Sloof, R.

2011-01-01

We introduce noise in the signaling technology of an otherwise standard wasteful signaling model (Spence, 1973). We theoretically derive the properties of the equilibria under different levels of noise and we experimentally test how behavior changes with noise. We obtain three main insights. First,

Model-based synthesis of locally contingent responses to global market signals

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Magliocca, N. R.

2015-12-01

Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI.

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Kundu, Prantik; Inati, Souheil J; Evans, Jennifer W; Luh, Wen-Ming; Bandettini, Peter A

2012-04-15

A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the

Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected

DEFF Research Database (Denmark)

Storgaard, H; Song, X M; Jensen, C B

2001-01-01

before and during a euglycemic-hyperinsulinemic clamp. IGT relatives were insulin-resistant in oxidative and nonoxidative pathways for glucose metabolism. In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide......To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects...... 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P

Signal existence verification (SEV) for GPS low received power signal detection using the time-frequency approach.

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Jan, Shau-Shiun; Sun, Chih-Cheng

2010-01-01

The detection of low received power of global positioning system (GPS) signals in the signal acquisition process is an important issue for GPS applications. Improving the miss-detection problem of low received power signal is crucial, especially for urban or indoor environments. This paper proposes a signal existence verification (SEV) process to detect and subsequently verify low received power GPS signals. The SEV process is based on the time-frequency representation of GPS signal, and it can capture the characteristic of GPS signal in the time-frequency plane to enhance the GPS signal acquisition performance. Several simulations and experiments are conducted to show the effectiveness of the proposed method for low received power signal detection. The contribution of this work is that the SEV process is an additional scheme to assist the GPS signal acquisition process in low received power signal detection, without changing the original signal acquisition or tracking algorithms.

Phylogenetic signals in the climatic niches of the world's amphibians

DEFF Research Database (Denmark)

Hof, Christian; Rahbek, Carsten; Araújo, Miguel B.

2010-01-01

amphibian orders and across biogeographical regions. To our knowledge, this is the first study providing a comprehensive analysis of the phylogenetic signal in species climatic niches for an entire clade across the world. Even though our results do not provide a strong test of the niche conservatism......The question of whether closely related species share similar ecological requirements has attracted increasing attention, because of its importance for understanding global diversity gradients and the impacts of climate change on species distributions. In fact, the assumption that related species...... are also ecologically similar has often been made, although the prevalence of such a phylogenetic signal in ecological niches remains heavily debated. Here, we provide a global analysis of phylogenetic niche relatedness for the world's amphibians. In particular, we assess which proportion of the variance...

Intracerebroventricular tempol administration in older rats reduces oxidative stress in the hypothalamus but does not change STAT3 signalling or SIRT1/AMPK pathway.

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Toklu, Hale Z; Scarpace, Philip J; Sakarya, Yasemin; Kirichenko, Nataliya; Matheny, Michael; Bruce, Erin B; Carter, Christy S; Morgan, Drake; Tümer, Nihal

2017-01-01

Hypothalamic inflammation and increased oxidative stress are believed to be mechanisms that contribute to obesity. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol), a free radical scavenger, has been shown to reduce inflammation and oxidative stress. We hypothesized that brain infusion of tempol would reduce oxidative stress, and thus would reduce food intake and body weight and improve body composition in rats with age-related obesity and known elevated oxidative stress. Furthermore, we predicted an associated increase in markers of leptin signalling, including the silent mating type information regulator 2 homolog 1 (SIRT1)/5'AMP-activated protein kinase (AMPK) pathway and the signal transducer and activator of transcription 3 (STAT3) pathway. For this purpose, osmotic minipumps were placed in the intracerebroventricular region of young (3 months) and aged (23 months) male Fischer 344 x Brown Norway rats for the continuous infusion of tempol or vehicle for 2 weeks. Tempol significantly decreased (p < 0.01) nicotinamide adenine dinucleotide phosphate oxidase activity in the hypothalamus but failed to reduce food intake or weight gain and did not alter body composition. SIRT1 activity and Acetyl p53 were decreased and phosphorylation of AMPK was increased with age, but they were unchanged with tempol. Basal phosphorylation of STAT3 was unchanged with age or tempol. These results indicate that tempol decreases oxidative stress but fails to alter feeding behaviour, body weight, or body composition. Moreover, tempol does not modulate the SIRT1/AMPK/p53 pathway and does not change leptin signalling. Thus, a reduction in hypothalamic oxidative stress is not sufficient to reverse age-related obesity.

A brain-computer interface for potential non-verbal facial communication based on EEG signals related to specific emotions.

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Kashihara, Koji

2014-01-01

Unlike assistive technology for verbal communication, the brain-machine or brain-computer interface (BMI/BCI) has not been established as a non-verbal communication tool for amyotrophic lateral sclerosis (ALS) patients. Face-to-face communication enables access to rich emotional information, but individuals suffering from neurological disorders, such as ALS and autism, may not express their emotions or communicate their negative feelings. Although emotions may be inferred by looking at facial expressions, emotional prediction for neutral faces necessitates advanced judgment. The process that underlies brain neuronal responses to neutral faces and causes emotional changes remains unknown. To address this problem, therefore, this study attempted to decode conditioned emotional reactions to neutral face stimuli. This direction was motivated by the assumption that if electroencephalogram (EEG) signals can be used to detect patients' emotional responses to specific inexpressive faces, the results could be incorporated into the design and development of BMI/BCI-based non-verbal communication tools. To these ends, this study investigated how a neutral face associated with a negative emotion modulates rapid central responses in face processing and then identified cortical activities. The conditioned neutral face-triggered event-related potentials that originated from the posterior temporal lobe statistically significantly changed during late face processing (600-700 ms) after stimulus, rather than in early face processing activities, such as P1 and N170 responses. Source localization revealed that the conditioned neutral faces increased activity in the right fusiform gyrus (FG). This study also developed an efficient method for detecting implicit negative emotional responses to specific faces by using EEG signals. A classification method based on a support vector machine enables the easy classification of neutral faces that trigger specific individual emotions. In

Wavelet analysis for nonstationary signals

International Nuclear Information System (INIS)

Penha, Rosani Maria Libardi da

1999-01-01

Mechanical vibration signals play an important role in anomalies identification resulting of equipment malfunctioning. Traditionally, Fourier spectral analysis is used where the signals are assumed to be stationary. However, occasional transient impulses and start-up process are examples of nonstationary signals that can be found in mechanical vibrations. These signals can provide important information about the equipment condition, as early fault detection. The Fourier analysis can not adequately be applied to nonstationary signals because the results provide data about the frequency composition averaged over the duration of the signal. In this work, two methods for nonstationary signal analysis are used: Short Time Fourier Transform (STFT) and wavelet transform. The STFT is a method of adapting Fourier spectral analysis for nonstationary application to time-frequency domain. To have a unique resolution throughout the entire time-frequency domain is its main limitation. The wavelet transform is a new analysis technique suitable to nonstationary signals, which handles the STFT drawbacks, providing multi-resolution frequency analysis and time localization in a unique time-scale graphic. The multiple frequency resolutions are obtained by scaling (dilatation/compression) the wavelet function. A comparison of the conventional Fourier transform, STFT and wavelet transform is made applying these techniques to: simulated signals, arrangement rotor rig vibration signal and rotate machine vibration signal Hanning window was used to STFT analysis. Daubechies and harmonic wavelets were used to continuos, discrete and multi-resolution wavelet analysis. The results show the Fourier analysis was not able to detect changes in the signal frequencies or discontinuities. The STFT analysis detected the changes in the signal frequencies, but with time-frequency resolution problems. The wavelet continuos and discrete transform demonstrated to be a high efficient tool to detect

Climate Change and Food-Related Risks

Directory of Open Access Journals (Sweden)

Isidro Juan Mirón Pérez

2017-06-01

Full Text Available There are two principal concepts to take into account relating food and climate change: food security and food safety. Most papers linking climate change to food risks deal with the first one: the security of the food supply.The increase of the concentration of carbon dioxide in the atmosphere, together with the rise of the temperatures on a global level would theorically lead to greater yields of crops grown for human and animal consumption. Howevwe, most of these studies have shown that, in general, crop yields are decreasing as this global change also brings about an increase in the frequency of extreme weather events. In adition, these weather anomalies would be unevenly spread and affect developing countries, which are less capable of tackling this change, more severely. All these factors would result in greater uncertainty in the supply of food, which consequently would be less predictable and leave it more exposed to market speculation.A rise in average temperatures would be expected to increase the risk of proliferation of foodborne disease-causing microorganisms such as Salmonella or Campylobacter. Nevertheless, a trend of this sort has not been detected yet in developed countries, where information systems allow the temporal evolution of the occurrence of those diseases to be tracked, since means for food preservation and food controls are wide spread.

On-line signal trend identification

International Nuclear Information System (INIS)

Tambouratzis, T.; Antonopoulos-Domis, M.

2004-01-01

An artificial neural network, based on the self-organizing map, is proposed for on-line signal trend identification. Trends are categorized at each incoming signal as steady-state, increasing and decreasing, while they are further classified according to characteristics such signal shape and rate of change. Tests with model-generated signals illustrate the ability of the self-organizing map to accurately and reliably perform on-line trend identification in terms of both detection and classification. The proposed methodology has been found robust to the presence of white noise

Comparing apples and oranges: fold-change detection of multiple simultaneous inputs.

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Yuval Hart

Full Text Available Sensory systems often detect multiple types of inputs. For example, a receptor in a cell-signaling system often binds multiple kinds of ligands, and sensory neurons can respond to different types of stimuli. How do sensory systems compare these different kinds of signals? Here, we consider this question in a class of sensory systems - including bacterial chemotaxis- which have a property known as fold-change detection: their output dynamics, including amplitude and response time, depends only on the relative changes in signal, rather than absolute changes, over a range of several decades of signal. We analyze how fold-change detection systems respond to multiple signals, using mathematical models. Suppose that a step of fold F1 is made in input 1, together with a step of F2 in input 2. What total response does the system provide? We show that when both input signals impact the same receptor with equal number of binding sites, the integrated response is multiplicative: the response dynamics depend only on the product of the two fold changes, F1F2. When the inputs bind the same receptor with different number of sites n1 and n2, the dynamics depend on a product of power laws, [Formula: see text]. Thus, two input signals which vary over time in an inverse way can lead to no response. When the two inputs affect two different receptors, other types of integration may be found and generally the system is not constrained to respond according to the product of the fold-change of each signal. These predictions can be readily tested experimentally, by providing cells with two simultaneously varying input signals. The present study suggests how cells can compare apples and oranges, namely by comparing each to its own background level, and then multiplying these two fold-changes.

A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation regulates WNT and BMP trans-synaptic signaling.

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Neil Dani

Full Text Available A Drosophila transgenic RNAi screen targeting the glycan genome, including all N/O/GAG-glycan biosynthesis/modification enzymes and glycan-binding lectins, was conducted to discover novel glycan functions in synaptogenesis. As proof-of-product, we characterized functionally paired heparan sulfate (HS 6-O-sulfotransferase (hs6st and sulfatase (sulf1, which bidirectionally control HS proteoglycan (HSPG sulfation. RNAi knockdown of hs6st and sulf1 causes opposite effects on functional synapse development, with decreased (hs6st and increased (sulf1 neurotransmission strength confirmed in null mutants. HSPG co-receptors for WNT and BMP intercellular signaling, Dally-like Protein and Syndecan, are differentially misregulated in the synaptomatrix of these mutants. Consistently, hs6st and sulf1 nulls differentially elevate both WNT (Wingless; Wg and BMP (Glass Bottom Boat; Gbb ligand abundance in the synaptomatrix. Anterograde Wg signaling via Wg receptor dFrizzled2 C-terminus nuclear import and retrograde Gbb signaling via synaptic MAD phosphorylation and nuclear import are differentially activated in hs6st and sulf1 mutants. Consequently, transcriptional control of presynaptic glutamate release machinery and postsynaptic glutamate receptors is bidirectionally altered in hs6st and sulf1 mutants, explaining the bidirectional change in synaptic functional strength. Genetic correction of the altered WNT/BMP signaling restores normal synaptic development in both mutant conditions, proving that altered trans-synaptic signaling causes functional differentiation defects.

Cancer-related marketing centrality motifs acting as pivot units in the human signaling network and mediating cross-talk between biological pathways.

Science.gov (United States)

Li, Wan; Chen, Lina; Li, Xia; Jia, Xu; Feng, Chenchen; Zhang, Liangcai; He, Weiming; Lv, Junjie; He, Yuehan; Li, Weiguo; Qu, Xiaoli; Zhou, Yanyan; Shi, Yuchen

2013-12-01

Network motifs in central positions are considered to not only have more in-coming and out-going connections but are also localized in an area where more paths reach the networks. These central motifs have been extensively investigated to determine their consistent functions or associations with specific function categories. However, their functional potentials in the maintenance of cross-talk between different functional communities are unclear. In this paper, we constructed an integrated human signaling network from the Pathway Interaction Database. We identified 39 essential cancer-related motifs in central roles, which we called cancer-related marketing centrality motifs, using combined centrality indices on the system level. Our results demonstrated that these cancer-related marketing centrality motifs were pivotal units in the signaling network, and could mediate cross-talk between 61 biological pathways (25 could be mediated by one motif on average), most of which were cancer-related pathways. Further analysis showed that molecules of most marketing centrality motifs were in the same or adjacent subcellular localizations, such as the motif containing PI3K, PDK1 and AKT1 in the plasma membrane, to mediate signal transduction between 32 cancer-related pathways. Finally, we analyzed the pivotal roles of cancer genes in these marketing centrality motifs in the pathogenesis of cancers, and found that non-cancer genes were potential cancer-related genes.

MRI of the normal brain from early childhood to middle age. Pt. 2. Age dependence of signal intensity changes on T2-weighted images

International Nuclear Information System (INIS)

Autti, T.; Raininko, R.; Vanhanen, S.L.; Kallio, M.; Santavuori, P.

1994-01-01

We examined 66 healthy volunteers aged 4 to 50 years by magnetic resonance imaging (MRI) and the signal intensity was measured on T2-weighted images in numerous sites and correlated with age and sex. Using distilled water and cerebrospinal fluid (CSF) as references on each slice, we calculated the signal intensities of the brain structures. Calculated ratios between structures did not change with age, except for those of the globus pallidus and thalamus, in which the signal intensities decreased more rapidly. The signal intensities of other brain structures changed equally but this could not be discerned visually and quantitative measurements were required. The signal intensities in the white and deep grey matter decreased rapidly in the first decade and then gradually to reach a plateau after the age of 18 years. Maturation of the brain thus seems to continue until near the end of the second decade of life. No sex differences were found. Quantitative analysis requires intensity references. The CSF in the tips of the frontal horns seems to be as reliable as an external fluid reference for intensity, and can be used in routine examinations provided the frontal horns are large enough to avoid partial volume effect. (orig.)

Functional morphology of the bovid astragalus in relation to habitat: controlling phylogenetic signal in ecomorphology.

Science.gov (United States)

Barr, W Andrew

2014-11-01

Bovid astragali are one of the most commonly preserved bones in the fossil record. Accordingly, astragali are an important target for studies seeking to predict the habitat preferences of fossil bovids based on bony anatomy. However, previous work has not tested functional hypotheses linking astragalar morphology with habitat while controlling for body size and phylogenetic signal. This article presents a functional framework relating the morphology of the bovid astragalus to habitat-specific locomotor ecology and tests four hypotheses emanating from this framework. Highly cursorial bovids living in structurally open habitats are hypothesized to differ from their less cursorial closed-habitat dwelling relatives in having (1) relatively short astragali to maintain rotational speed throughout the camming motion of the rotating astragalus, (2) a greater range of angular excursion at the hock, (3) relatively larger joint surface areas, and (4) a more pronounced "spline-and-groove" morphology promoting lateral joint stability. A diverse sample of 181 astragali from 50 extant species was scanned using a Next Engine laser scanner. Species were assigned to one of four habitat categories based on the published ecological literature. A series of 11 linear measurements and three joint surface areas were measured on each astragalus. A geometric mean body size proxy was used to size-correct the measurement data. Phylogenetic generalized least squares (PGLS) was used to test for differences between habitat categories while controlling for body size differences and phylogenetic signal. Statistically significant PGLS results support Hypotheses 1 and 2 (which are not mutually exclusive) as well as Hypothesis 3. No support was found for Hypothesis 4. These findings confirm that the morphology of the bovid astragalus is related to habitat-specific locomotor ecology, and that this relationship is statistically significant after controlling for body size and phylogeny. Thus, this study

Recent sea level change analysed with kernel EOF

DEFF Research Database (Denmark)

Nielsen, Allan Aasbjerg; Andersen, Ole Baltazar; Knudsen, Per

2009-01-01

-2008. Preliminary analysis shows some interesting features related to climate change and particularly the pulsing of the El Niño/Southern Oscillation. Large scale ocean events associated with the El Niño/Southern Oscillation related signals are conveniently concentrated in the first SSH kernel EOF modes....

ESR signal changes recorded in γ-irradiated bovine livers

International Nuclear Information System (INIS)

Kikuchi, Masahiro; Kobayashi, Yasuhiko

2015-01-01

After fresh raw livers of bovine were exposed to γ-rays on ice, radiation-induced radicals in the livers were measured in liquid nitrogen using electron spin resonance spectroscopy. In the magnetic field of 320.5 to 335.5 mT, the signals responsible to absorbed doses were found. The signal intensity from a main peak was increased up to 5 kGy. The side peaks existing both low and high magnetic field of the main peak showed linear responses as increasing absorbed doses. Radiation-induced radicals were found in a tissue without bones from animals. Without complicated sample preparations, the raw bovine livers can be easily measured on ESR at liquid nitrogen temperature. The ESR method may be applicable to distinguish irradiated fresh raw livers within a few days after irradiation. (author)

Projecting Future Heat-Related Mortality under Climate Change Scenarios: A Systematic Review

Science.gov (United States)

Barnett, Adrian Gerard; Wang, Xiaoming; Vaneckova, Pavla; FitzGerald, Gerard; Tong, Shilu

2011-01-01

Background: Heat-related mortality is a matter of great public health concern, especially in the light of climate change. Although many studies have found associations between high temperatures and mortality, more research is needed to project the future impacts of climate change on heat-related mortality. Objectives: We conducted a systematic review of research and methods for projecting future heat-related mortality under climate change scenarios. Data sources and extraction: A literature search was conducted in August 2010, using the electronic databases PubMed, Scopus, ScienceDirect, ProQuest, and Web of Science. The search was limited to peer-reviewed journal articles published in English from January 1980 through July 2010. Data synthesis: Fourteen studies fulfilled the inclusion criteria. Most projections showed that climate change would result in a substantial increase in heat-related mortality. Projecting heat-related mortality requires understanding historical temperature–mortality relationships and considering the future changes in climate, population, and acclimatization. Further research is needed to provide a stronger theoretical framework for projections, including a better understanding of socioeconomic development, adaptation strategies, land-use patterns, air pollution, and mortality displacement. Conclusions: Scenario-based projection research will meaningfully contribute to assessing and managing the potential impacts of climate change on heat-related mortality. PMID:21816703

Determinants of intention to change health-related behavior and actual change in patients with TIA or minor ischemic stroke.

Science.gov (United States)

Brouwer-Goossensen, Dorien; Genugten, Lenneke van; Lingsma, Hester; Dippel, Diederik; Koudstaal, Peter; Hertog, Heleen den

2016-04-01

To assess determinants of intention to change health-related behavior and actual change in patients with TIA or ischemic stroke. In this prospective cohort study, 100 patients with TIA or minor ischemic stroke completed questionnaires on behavioral intention and sociocognitive factors including perception of severity, susceptibility, fear, response-efficacy and self-efficacy at baseline. Questionnaires on physical activity, diet and smoking were completed at baseline and at 3 months. Associations between sociocognitive factors and behavioral intention and actual change were studied with multivariable linear and logistic regression. Self-efficacy, response efficacy, and fear were independently associated with behavioral intention, with self-efficacy as the strongest determinant of intention to increase physical activity (aBeta 0.40; 95% CI 0.12-0.71), adapt a healthy diet (aBeta 0.49; 95% CI 0.23-0.75), and quit smoking (aBeta 0.51; 95% CI 0.13-0.88). Intention to change tended to be associated with actual health-related behavior change. Self-efficacy, fear, and response-efficacy were determinants of intention to change health-related behavior after TIA or ischemic stroke. These determinants of intention to change health-related behavior after TIA or ischemic stroke should be taken into account in the development of future interventions promoting health-related behavior change in these group of patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

SU-F-J-137: Intrafractional Change of the Relationship Between Internal Fiducials and External Breathing Signal in Pancreatic Cancer Stereotactic Body Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Pettersson, N; Murphy, J; Simpson, D; Cervino, L [University of California, San Diego, La Jolla, CA (United States)

2016-06-15

Purpose: The use of respiratory gating for management of breathing motion during stereotactic body radiation therapy (SBRT) relies on a consistent relationship between the breathing signal and the actual position of the internal target. This relationship was investigated in patients treated for pancreatic cancer. Methods: Four patients with pancreatic cancer undergoing SBRT that had implanted fiducials in the tumor were included in this study. Treatment plans were generated based on the exhale phases (30–70%) from the pre-treatment 4DCT. The margin between the internal target volume (ITV) and the planning target volume was three mm. After patient setup using cone-beam CT, simultaneous fluoroscopic imaging and breathing motion monitoring were used during at least three breathing cycles to verify the fiducial position and to optimize the gating window. After treatment, fluoroscopic images were acquired for verification purposes and exported for retrospective analyses. Fiducial positions were determined using a template-matching algorithm. For each dataset, we established a linear relationship between the fiducial position and the anterior-posterior (AP) breathing signal. The relationships before and after treatment were compared and the dose distribution impact evaluated. Results: Seven pre- and post-treatment fluoroscopic pairs were available for fiducial position analyses in the superior-inferior (SI) and left-right (LR) directions, and five in the AP direction. Time between image acquisitions was typically six to eight minutes. An average absolute change of 1.2±0.7 mm (range: 0.1–1.7) of the SI fiducial position relative to the external signal was found. Corresponding numbers for the LR and AP fiducial positions were 0.9±1.0 mm (range: 0.2–3.0) and 0.5±0.4 mm (range: 0.2–1.2), respectively. The dose distribution impact was small in both the ITV and organs-at-risk. Conclusion: The relationship change between fiducial position and external breathing

SU-F-J-137: Intrafractional Change of the Relationship Between Internal Fiducials and External Breathing Signal in Pancreatic Cancer Stereotactic Body Radiation Therapy

International Nuclear Information System (INIS)

Pettersson, N; Murphy, J; Simpson, D; Cervino, L

2016-01-01

Purpose: The use of respiratory gating for management of breathing motion during stereotactic body radiation therapy (SBRT) relies on a consistent relationship between the breathing signal and the actual position of the internal target. This relationship was investigated in patients treated for pancreatic cancer. Methods: Four patients with pancreatic cancer undergoing SBRT that had implanted fiducials in the tumor were included in this study. Treatment plans were generated based on the exhale phases (30–70%) from the pre-treatment 4DCT. The margin between the internal target volume (ITV) and the planning target volume was three mm. After patient setup using cone-beam CT, simultaneous fluoroscopic imaging and breathing motion monitoring were used during at least three breathing cycles to verify the fiducial position and to optimize the gating window. After treatment, fluoroscopic images were acquired for verification purposes and exported for retrospective analyses. Fiducial positions were determined using a template-matching algorithm. For each dataset, we established a linear relationship between the fiducial position and the anterior-posterior (AP) breathing signal. The relationships before and after treatment were compared and the dose distribution impact evaluated. Results: Seven pre- and post-treatment fluoroscopic pairs were available for fiducial position analyses in the superior-inferior (SI) and left-right (LR) directions, and five in the AP direction. Time between image acquisitions was typically six to eight minutes. An average absolute change of 1.2±0.7 mm (range: 0.1–1.7) of the SI fiducial position relative to the external signal was found. Corresponding numbers for the LR and AP fiducial positions were 0.9±1.0 mm (range: 0.2–3.0) and 0.5±0.4 mm (range: 0.2–1.2), respectively. The dose distribution impact was small in both the ITV and organs-at-risk. Conclusion: The relationship change between fiducial position and external breathing

Current Nomenclature of Pseudohypoparathyroidism: Inactivating Parathyroid Hormone/Parathyroid Hormone-Related Protein Signaling Disorder.

Science.gov (United States)

Turan, Serap

2017-12-30

Disorders related to parathyroid hormone (PTH) resistance and PTH signaling pathway impairment are historically classified under the term of pseudohypoparathyroidism (PHP). The disease was first described and named by Fuller Albright and colleagues in 1942. Albright hereditary osteodystrophy (AHO) is described as an associated clinical entity with PHP, characterized by brachydactyly, subcutaneous ossifications, round face, short stature and a stocky build. The classification of PHP is further divided into PHP-Ia, pseudo-PHP (pPHP), PHP-Ib, PHP-Ic and PHP-II according to the presence or absence of AHO, together with an in vivo response to exogenous PTH and the measurement of Gsα protein activity in peripheral erythrocyte membranes in vitro. However, PHP classification fails to differentiate all patients with different clinical and molecular findings for PHP subtypes and classification become more complicated with more recent molecular characterization and new forms having been identified. So far, new classifications have been established by the EuroPHP network to cover all disorders of the PTH receptor and its signaling pathway. Inactivating PTH/PTH-related protein signaling disorder (iPPSD) is the new name proposed for a group of these disorders and which can be further divided into subtypes - iPPSD1 to iPPSD6. These are termed, starting from PTH receptor inactivation mutation (Eiken and Blomstrand dysplasia) as iPPSD1, inactivating Gsα mutations (PHP-Ia, PHP-Ic and pPHP) as iPPSD2, loss of methylation of GNAS DMRs (PHP-Ib) as iPPSD3, PRKAR1A mutations (acrodysostosis type 1) as iPPSD4, PDE4D mutations (acrodysostosis type 2) as iPPSD5 and PDE3A mutations (autosomal dominant hypertension with brachydactyly) as iPPSD6. iPPSDx is reserved for unknown molecular defects and iPPSDn+1 for new molecular defects which are yet to be described. With these new classifications, the aim is to clarify the borders of each different subtype of disease and make the classification

Legume-rhizobia signal exchange: promiscuity and environmental effects

Directory of Open Access Journals (Sweden)

Mario Andrade Lira Junior

2015-09-01

Full Text Available Although signal exchange between legumes and their rhizobia is among the best-known examples of this biological process, most of the more characterized data comes from just a few legume species and environmental stresses. Although a relative wealth of information is available for some model legumes and some of the major pulses such as soybean, little is known about tropical legumes. This relative disparity in current knowledge is also apparent in the research on the effects of environmental stress on signal exchange; cool-climate stresses, such as low-soil temperature, comprise a relatively large body of research, whereas high-temperature stresses and drought are not nearly as well understood. Both tropical legumes and their environmental stress-induced effects are increasingly important due to global population growth (the demand for protein, climate change (increasing temperatures and more extreme climate behavior, and urbanization (and thus heavy metals. This knowledge gap for both legumes and their environmental stresses is compounded because whereas most temperate legume-rhizobia symbioses are relatively specific and cultivated under relatively stable environments, the converse is true for tropical legumes, which tend to be promiscuous and grow in highly variable conditions. This review will clarify some of this missing information and highlight fields in which further research would benefit our current knowledge.

Stroke survivors' and relatives' negotiation of relational and activity changes: A qualitative study.

Science.gov (United States)

Arntzen, Cathrine; Hamran, Torunn

2016-01-01

This study explores stroke survivors' and relatives' negotiation of relational and activity change in their interrelated long-term meaning-making processes of everyday life and what it means for the experience of progress and well-being. Repeated retrospective in-depth interviews were conducted with both the stroke survivor and relatives. A Critical Psychological Perspective gives the frame of reference to study more closely what is going on in and across particular contexts in family members' ongoing social practices. An asymmetric problematic relationship can develop among the participants in the context of family life. However, the analysis identifies six beneficial relational and activity changes, which contribute to a reciprocal, balanced repositioning, and help the family move in a more positive direction. The repositioning processes facilitate a new transformation of family we-ness, which is important for the participants' experience of process and well-being. The comprehensive family work that has to be done is about managing the imbalance of everyday life, upholding separate activities outside the family sphere and dealing with the fact that peripheral others become more peripheral. The study addresses some arguments for taking a family-centred perspective in occupational therapy practice, as well as in a stroke rehabilitation service in general.

Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis

Directory of Open Access Journals (Sweden)

Erdi Sozen

2014-01-01

Full Text Available Atherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1 and modulates matrix metalloproteinase (MMP induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1 related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36 mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun.

Myasthenia Gravis Impairment Index: Responsiveness, meaningful change, and relative efficiency.

Science.gov (United States)

Barnett, Carolina; Bril, Vera; Kapral, Moira; Kulkarni, Abhaya V; Davis, Aileen M

2017-12-05

To study responsiveness and meaningful change of the Myasthenia Gravis Impairment Index (MGII) and its relative efficiency compared to other measures. We enrolled 95 patients receiving prednisone, IV immunoglobulin (IVIg), or plasma exchange (PLEX) and 54 controls. Patients were assessed with the MGII and other measures-including the Quantitative Myasthenia Gravis Score, Myasthenia Gravis Composite, and Myasthenia Gravis Activities of Daily Living-at baseline and 3-4 weeks after treatment. Statistical markers of responsiveness included between-groups and within-group differences, and we estimated the relative efficiency of the MGII compared to other measures. Patient-meaningful change was assessed with an anchor-based method, using the patient's impression of change. We determined the minimal detectable change (MDC) and the minimal important difference (MID) at the group and individual level. Treated patients had a higher change in MGII scores than controls (analysis of covariance p 1 favoring the MGII. The MGII demonstrated responsiveness to prednisone, IVIg, and PLEX in patients with myasthenia. There is a differential response in ocular and generalized symptoms to type of therapy. The MGII has higher relative efficiency than comparison measures and is viable for use in clinical trials. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.