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Sample records for activity increased rapidly

  1. Immobilization induces a very rapid increase in osteoclast activity

    NASA Astrophysics Data System (ADS)

    Heer, Martina; Baecker, Natalie; Mika, Claudia; Boese, Andrea; Gerzer, Rupert

    2005-07-01

    We studied in a randomized, strictly controlled cross-over design, the effects of 6 days 6° head-down tilt bed rest (HDT) in eight male healthy subjects in our metabolic ward. The study consisted of two periods (phases) of 11 days each in order to allow for the test subjects being their own controls. Both study phases were identical with respect to environmental conditions, study protocol and diet. Two days before arriving in the metabolic ward the subjects started with a diet. The diet was continued in the metabolic ward. The metabolic ward period (1l days) was divided into three parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers. On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers. Urinary calcium excretion was, as early as the first day in immobilization, increased (p<0.01). CTX- and NTX-excretion stayed unchanged in the first 24 h in HDT compared to the control. But already on the 2nd day of immobilization, both bone resorption markers significantly increased. We conclude from these results—pronounced rise of bone resorption markers—that already 24 h of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies as a first step for the development of countermeasures to immobilization.

  2. Muscle activity patterns during quick increase of movement amplitude in rapid elbow extensions.

    PubMed

    Takatoku, Nozomi; Fujiwara, Motoko

    2010-04-01

    In this study, we investigated a motor strategy for increasing the amplitude of movement in rapid extensions at the elbow joint. This study focused on the changes in a triphasic electromyographic (EMG) pattern, i.e., the first agonist burst (AG1), the second agonist burst (AG2) and the antagonist burst (ANT), for increasing the amplitude of movement required after the initiation of movement. Subjects performed 40 degrees (Basic task) and 80 degrees of extension (Wide task). These tasks were performed under two conditions; performing a predetermined task (SF condition) and performing a task in response to a visual stimulus immediately after movement commencement (ST condition). Kinematic parameters and EMG activity from the agonist (triceps brachii) and the antagonist (biceps brachii) muscles were recorded. As a result, the onset latency of AG1 and AG2 and the duration of AG1 were longer under the ST condition than the SF condition. No difference was observed between the SF and ST condition with respect to ANT activity. It is concluded that the motor strategy for increasing the amplitude of movement after the initiation of movement was to control the movement velocity and the timing to stop movement by the coactivation duration of AG1 and ANT and to stop the desired position accurately by AG2 activity.

  3. Insulin rapidly increases diacylglycerol by activating de novo phosphatidic acid synthesis.

    PubMed

    Farese, R V; Konda, T S; Davis, J S; Standaert, M L; Pollet, R J; Cooper, D R

    1987-05-01

    The mechanisms whereby insulin increases diacylglycerol in BC3H-1 myocytes were examined. When [3H]arachidonate labeling of phospholipids was used as an indicator of phospholipase C activation, transient increases in [3H]diacylglycerol were observed between 0.5 and 10 minutes after the onset of insulin treatment. With [3H]glycerol labeling as an indicator of de novo phospholipid synthesis, [3H]diacylglycerol was increased maximally at 1 minute and remained elevated for 20 minutes. [3H]Glycerol-labeled diacylglycerol was largely derived directly from phosphatidic acid. Insulin increased de novo phosphatidic acid synthesis within 5 to 10 seconds; within 1 minute, this synthesis was 60 times greater than that of controls. Thus, the initial increase in diacylglycerol is due to both increased hydrolysis of phospholipids and a burst of de novo phosphatidic acid synthesis. After 5 to 10 minutes, de novo phosphatidic acid synthesis continues as a major source of diacylglycerol. Both phospholipid effects of insulin seem important for generating diacylglycerol and other phospholipid-derived intracellular signaling substances.

  4. Increased neuroplasticity and hippocampal microglia activation in a mice model of rapid antidepressant treatment.

    PubMed

    Muzio, Luca; Brambilla, Valentina; Calcaterra, Lorenza; D'Adamo, Patrizia; Martino, Gianvito; Benedetti, Francesco

    2016-09-15

    The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects. Unbiased evaluation of the transcriptional responses were obtained in the hippocampus by Illumina Bead Chip Array system, then confirmed with real time PCR. Spine densities in granular neurons of the dentate gyrus (DG) were assayed by standard Golgi staining. Activation of Microglial/Macrophages cells was evaluated by immunufluorescence analysis for Iba1. Rates of cell proliferation was estimated pulsing mice with the S-phase tracer 5-Iodo-2'-deoxyuridine (IdU). All SD procedures caused a decreasing of floating time at FST, and increased expression of the immediate early gene Arc/Arg3.1. In addition, SSW also increased expression of the Microglia/Macrophages genes Iba-1 and chemokine receptors Cx3cR1 and CxcR4, of the canonical Wnt signaling gene Wnt7a, and of dendritic spines in CA4 neurons of the DG. SSW up-regulated both the number of Iba1+ cells and rates of cell proliferation in the subgranular region of the DG. The antidepressant-like effects of SD dissociated both, from hippocampal neuroplasticity in the DG (not occurring after ASD), and from microglial activation (not preventing behavioral response when occurring). The increase in dendritic spine density in the DG after SD and exercise was associated with an up-regulation of Wnt 7a, and with activation of the innate immune system of the brain. Increased Arc/Arg3.1 suggests however increased neuroplasticity, which could be common to all fast-acting antidepressants

  5. Rapid increase in aggressive behavior precedes the decrease in brain aromatase activity during socially mediated sex change in Lythrypnus dalli.

    PubMed

    Black, Michael P; Balthazart, Jacques; Baillien, Michelle; Grober, Matthew S

    2011-01-01

    In the bluebanded goby, Lythrypnus dalli, removal of the male from a social group results in a rapid behavioral response where one female becomes dominant and changes sex to male. In a previous study, within hours of male removal, aromatase activity in the brain (bAA) of dominant females was almost 50% lower than that of control females from a group in which the male had not been removed. For those females that displayed increased aggressive behavior after the male was removed, the larger the increase in aggressive behavior, the greater the reduction in bAA. To investigate whether decreased bAA leads to increased aggression, the present study used a more rapid time course of behavioral profiling and bAA assay, looking within minutes of male removal from the group. There were no significant differences in bAA between control females (large females from groups with the male still present), females that doubled their aggressive behavior by 10 or 20 min after male removal, or females that did not double their aggressive behavior within 30 min after male removal. Further, individual variation in bAA and aggressive behavior were not correlated in these fish. Whole brain decreases in aromatase activity thus appear to follow, rather than precede, rapid increases in aggressive behavior, which provides one potential mechanism underlying the rapid increase in androgens that follows aggressive interactions in many vertebrate species. For fish species that change sex from female to male, this increase in androgens could subsequently facilitate sex change.

  6. Optogenetic activation of melanin-concentrating hormone neurons increases non-rapid eye movement and rapid eye movement sleep during the night in rats.

    PubMed

    Blanco-Centurion, Carlos; Liu, Meng; Konadhode, Roda P; Zhang, Xiaobing; Pelluru, Dheeraj; van den Pol, Anthony N; Shiromani, Priyattam J

    2016-11-01

    Neurons containing melanin-concentrating hormone (MCH) are located in the hypothalamus. In mice, optogenetic activation of the MCH neurons induces both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep at night, the normal wake-active period for nocturnal rodents [R. R. Konadhode et al. (2013) J. Neurosci., 33, 10257-10263]. Here we selectively activate these neurons in rats to test the validity of the sleep network hypothesis in another species. Channelrhodopsin-2 (ChR2) driven by the MCH promoter was selectively expressed by MCH neurons after injection of rAAV-MCHp-ChR2-EYFP into the hypothalamus of Long-Evans rats. An in vitro study confirmed that the optogenetic activation of MCH neurons faithfully triggered action potentials. In the second study, in Long-Evans rats, rAAV-MCH-ChR2, or the control vector, rAAV-MCH-EYFP, were delivered into the hypothalamus. Three weeks later, baseline sleep was recorded for 48 h without optogenetic stimulation (0 Hz). Subsequently, at the start of the lights-off cycle, the MCH neurons were stimulated at 5, 10, or 30 Hz (1 mW at tip; 1 min on - 4 min off) for 24 h. Sleep was recorded during the 24-h stimulation period. Optogenetic activation of MCH neurons increased both REM and NREM sleep at night, whereas during the day cycle, only REM sleep was increased. Delta power, an indicator of sleep intensity, was also increased. In control rats without ChR2, optogenetic stimulation did not increase sleep or delta power. These results lend further support to the view that sleep-active MCH neurons contribute to drive sleep in mammals.

  7. Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids

    PubMed Central

    Limbourg, Florian P.; Huang, Zhihong; Plumier, Jean-Christophe; Simoncini, Tommaso; Fujioka, Masayuki; Tuckermann, Jan; Schütz, Günther; Moskowitz, Michael A.; Liao, James K.

    2002-01-01

    Many cellular responses to corticosteroids involve the transcriptional modulation of target genes by the glucocorticoid receptor (GR). A rapid, non-nuclear effect of GR was found to mediate neuroprotection. High-dose corticosteroids (20 mg/kg intraperitoneally), given within 2 hours of transient cerebral ischemia, acutely increased endothelial nitric oxide synthase (eNOS) activity, augmented regional cerebral blood flow (CBF) by 40% to 50%, and reduced cerebral infarct size by 32%. These neuroprotective effects of corticosteroids were abolished by the GR antagonist RU486 and by inhibition of phosphatidylinositol 3-kinase (PI3K), and were absent in eNOS–/– mice. To determine the mechanism by which GR activated eNOS, we measured the effect of corticosteroids on PI3K and the protein kinase Akt. In a ligand-dependent manner, GR activated PI3K and Akt in vitro and in vivo caused NO-dependent vasodilation, which was blocked by cotreatment with RU486 or the PI3K inhibitor LY294002 but not by transcriptional inhibitors. Indeed, a mutant GR, which cannot dimerize and bind to DNA, still activated PI3K and Akt in response to corticosteroids. These findings indicate that non-nuclear GR rapidly activates eNOS through the PI3K/Akt pathway and suggest that this mechanism mediates the acute neuroprotective effects of corticosteroids through augmentation of CBF. PMID:12464678

  8. Acute renal ischemia rapidly activates the energy sensor AMPK but does not increase phosphorylation of eNOS-Ser1177.

    PubMed

    Mount, Peter F; Hill, Rebecca E; Fraser, Scott A; Levidiotis, Vicki; Katsis, Frosa; Kemp, Bruce E; Power, David A

    2005-11-01

    A fundamental aspect of acute renal ischemia is energy depletion, manifest as a falling level of ATP that is associated with a simultaneous rise in AMP. The energy sensor AMP-activated protein kinase (AMPK) is activated by a rising AMP-to-ATP ratio, but its role in acute renal ischemia is unknown. AMPK is activated in the ischemic heart and is reported to phosphorylate both endothelial nitric oxide synthase (eNOS) and acetyl-CoA carboxylase. To study activation of AMPK in acute renal ischemia, the renal pedicle of anesthetized Sprague-Dawley rats was cross-clamped for increasing time intervals. AMPK was strongly activated within 1 min and remained so after 30 min. However, despite the robust activation of AMPK, acute renal ischemia did not increase phosphorylation of the AMPK phosphorylation sites eNOS-Ser(1177) or acetyl-CoA carboxylase-Ser(79). Activation of AMPK in bovine aortic endothelial cells by the ATP-depleting agent antimycin A and the antidiabetic drug phenformin also did not increase phosphorylation of eNOS-Ser(1177), confirming that AMPK activation and phosphorylation of eNOS are dissociated in some situations. Immunoprecipitation studies demonstrated that the dissociation between AMPK activation and phosphorylation of eNOS-Ser(1177) was not due to changes in the physical associations between AMPK, eNOS, or heat shock protein 90. In conclusion, acute renal ischemia rapidly activates the energy sensor AMPK, which is known to maintain ATP reserves during energy stress. The substrates it phosphorylates, however, are different from those in other organs such as the heart.

  9. Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera: Calliphoridae).

    PubMed

    Coleman, Paul C; Bale, Jeffrey S; Hayward, Scott A L

    2015-01-01

    Virtually all temperate insects survive the winter by entering a physiological state of reduced metabolic activity termed diapause. However, there is increasing evidence that climate change is disrupting the diapause response resulting in non-diapause life stages encountering periods of winter cold. This is a significant problem for adult life stages in particular, as they must remain mobile, periodically feed, and potentially initiate reproductive development at a time when resources should be diverted to enhance stress tolerance. Here we present the first evidence of protein/meat feeding restricting rapid cold hardening (RCH) ability and increasing low temperature activity thresholds. No RCH response was noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy) fed a sugar, water and liver (SWL) diet, while a strong RCH response was seen in females fed a diet of sugar and water (SW) only. The RCH response in SW flies was induced at temperatures as high as 10°C, but was strongest following 3h at 0°C. The CTmin (loss of coordinated movement) and chill coma (final appendage twitch) temperature of SWL females (-0.3 ± 0.5°C and -4.9 ± 0.5°C, respectively) was significantly higher than for SW females (-3.2 ± 0.8°C and -8.5 ± 0.6°C). We confirmed this was not directly the result of altered extracellular K+, as activity thresholds of alanine-fed adults were not significantly different from SW flies. Instead we suggest the loss of cold tolerance is more likely the result of diverting resource allocation to egg development. Between 2009 and 2013 winter air temperatures in Birmingham, UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively, suggesting differential exposure to chill injury depending on whether adults had access to meat or not. We conclude that disruption of diapause could significantly impact on winter survival through loss of synchrony in the timing of active feeding and reproductive development with favourable

  10. Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera: Calliphoridae)

    PubMed Central

    2015-01-01

    Virtually all temperate insects survive the winter by entering a physiological state of reduced metabolic activity termed diapause. However, there is increasing evidence that climate change is disrupting the diapause response resulting in non-diapause life stages encountering periods of winter cold. This is a significant problem for adult life stages in particular, as they must remain mobile, periodically feed, and potentially initiate reproductive development at a time when resources should be diverted to enhance stress tolerance. Here we present the first evidence of protein/meat feeding restricting rapid cold hardening (RCH) ability and increasing low temperature activity thresholds. No RCH response was noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy) fed a sugar, water and liver (SWL) diet, while a strong RCH response was seen in females fed a diet of sugar and water (SW) only. The RCH response in SW flies was induced at temperatures as high as 10°C, but was strongest following 3h at 0°C. The CTmin (loss of coordinated movement) and chill coma (final appendage twitch) temperature of SWL females (-0.3 ± 0.5°C and -4.9 ± 0.5°C, respectively) was significantly higher than for SW females (-3.2 ± 0.8°C and -8.5 ± 0.6°C). We confirmed this was not directly the result of altered extracellular K+, as activity thresholds of alanine-fed adults were not significantly different from SW flies. Instead we suggest the loss of cold tolerance is more likely the result of diverting resource allocation to egg development. Between 2009 and 2013 winter air temperatures in Birmingham, UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively, suggesting differential exposure to chill injury depending on whether adults had access to meat or not. We conclude that disruption of diapause could significantly impact on winter survival through loss of synchrony in the timing of active feeding and reproductive development with favourable

  11. RAPID KNEE-EXTENSIONS TO INCREASE QUADRICEPS MUSCLE ACTIVITY IN PATIENTS WITH TOTAL KNEE ARTHROPLASTY: A RANDOMIZED CROSS-OVER STUDY

    PubMed Central

    Wilquin, Lousia; Jakobsen, Thomas Linding; Holsgaard-Larsen, Anders; Bandholm, Thomas

    2017-01-01

    Background Inhibition of the quadriceps muscle and reduced knee-extension strength is common shortly following total knee arthroplasty (weeks to months), due to reduced voluntary activation of the quadriceps muscle. In healthy subjects, strength training with heavy loads is known to increase agonist muscle activity, especially if the exercise is conducted using rapid muscle contractions. Purpose The purpose of this study was to examine if patients with total knee arthroplasty could perform rapid knee-extensions using a 10 RM load four to eight weeks after surgery, and the degree to which rapid knee-extensions were associated with greater voluntary quadriceps muscle activity during an experimental strength training session, compared to that elicited using slow knee-extensions. Study Design A randomized cross-over study. Methods Twenty-four patients (age 66.5) 4-8 weeks post total knee arthroplasty randomly performed one set of five rapid, and one set of five slow knee-extensions with the operated leg, using a load of their 10 repetition maximum, while surface electromyography recordings were obtained from the vastus medialis and lateralis of the quadriceps muscle. Results Data from 23 of the 24 included patients were analyzed. Muscle activity was significantly higher during rapid knee-extensions (120.2% [10th-90th percentile: 98.3-149.1]) compared to slow knee-extensions (106.0% [88.8-140.8]) for the vastus lateralis (p<0.01), but not for the vastus medialis (120.8% [90.4-134.0]) and (121.8% [93.0-133.0]) (p = 0.17), respectively. Slow and rapid knee-extensions were performed at a median angular velocity of 19.7 degrees/sec (13.7-24.4) and 51.4 degrees/sec (28.9-63.1), respectively Conclusion Four to eight weeks after their total knee arthroplasty, the patients in the present study were able to conduct rapid knee-extensions according to the experimental protocol with an approximately doubled angular velocity compared to slow knee-extensions. This was associated with

  12. 17β-Estradiol Rapidly Increases KATP Activity in GnRH via a Protein Kinase Signaling Pathway

    PubMed Central

    Zhang, Chunguang; Kelly, Martin J.; Rønnekleiv, Oline K.

    2010-01-01

    17β-Estradiol (E2) both inhibits and excites GnRH neurons via presynaptic as well as postsynaptic mechanisms. Although it has been demonstrated that E2 can alter the excitability of GnRH neurons via direct actions, the intracellular signaling cascades mediating these actions are not well understood. Previously we have shown that the activity of one of the critical ion channels needed for maintaining GnRH neurons in a hyperpolarized state, the ATP-sensitive potassium channel (KATP) channel, is augmented by E2 in ovariectomized females. However, the mRNA expression of the KATP channel subunits Kir6.2 and SUR1 are unchanged with in vivo E2 treatment. Therefore, to elucidate the cellular signaling mechanism(s) modulating the channel activity, we did whole-cell patch-clamp recording of enhanced green fluorescent protein-GnRH neurons from ovariectomized female mice to study the acute effects of E2. E2 dose-dependently (EC50 = 0.6 nM) enhanced the diazoxide (channel opener)-activated KATP channel currents by 1.2- to 2.0-fold, which was antagonized by ICI 182,780. E2-BSA was equally as effective as E2, whereas E2 had no effect. The protein kinase A (PKA) activator forskolin mimicked the effects of E2, whereas the PKA inhibitor H89 and the protein kinase C (PKC) inhibitor bisindolylmaleimide I blocked the effects of E2. Similar to E2, STX, a membrane estrogen receptor (ER) agonist that does not bind to ERα or ERβ, also potentiated the diazoxide-induced KATP channel current by 1.5-fold. Therefore, E2 can potentiate KATP channel activity in GnRH neurons through a membrane ER-activated PKC-PKA signaling pathway. PMID:20660067

  13. Diminished neuronal activity increases neuron-neuron connectivity underlying silent synapse formation and the rapid conversion of silent to functional synapses.

    PubMed

    Nakayama, Kimiko; Kiyosue, Kazuyuki; Taguchi, Takahisa

    2005-04-20

    Neuronal activity regulates the synaptic strength of neuronal networks. However, it is still unclear how diminished activity changes connection patterns in neuronal circuits. To address this issue, we analyzed neuronal connectivity and relevant mechanisms using hippocampal cultures in which developmental synaptogenesis had occurred. We show that diminution of network activity in mature neuronal circuit promotes reorganization of neuronal circuits via NR2B subunit-containing NMDA-type glutamate receptors (NR2B-NMDARs), which mediate silent synapse formation. Simultaneous double whole-cell recordings revealed that diminishing neuronal circuit activity for 48 h increased the number of synaptically connected neuron pairs with both silent and functional synapses. This increase was accompanied by the specific expression of NR2B-NMDARs at synaptic sites. Analysis of miniature EPSCs (mEPSCs) showed that the frequency of NMDAR-mediated, but not AMPAR-mediated, mEPSCs increased, indicating that diminished neuronal activity promotes silent synapse formation via the surface delivering NR2B-NMDARs in mature neurons. After activation of neuronal circuit by releasing from TTX blockade (referred as circuit reactivation), the frequency of AMPAR-mediated mEPSCs increased instead, and this increase was prevented by ifenprodil. The circuit reactivation also caused an increased colocalization of glutamate receptor 1-specfic and synaptic NR2B-specific puncta. These results indicate that the circuit reactivation converts rapidly silent synapses formed during activity suppression to functional synapses. These data may provide a new example of homeostatic circuit plasticity that entails the modulation of neuron-neuron connectivity by synaptic activity.

  14. Stimulatory role of calcium in rapid eye movement sleep deprivation-induced noradrenaline-mediated increase in Na-K-ATPase activity in rat brain.

    PubMed

    Das, G; Gopalakrishnan, A; Faisal, M; Mallick, B N

    2008-07-31

    Rapid eye movement (REM) sleep deprivation elevates noradrenaline level, which upon acting on alpha1-adrenoceptors increases Na-K-ATPase activity; however, the detailed intracellular mechanism of action was unknown. Since membrane integrity is crucial for maintaining Na-K-ATPase activity as well as ionic exchange and noradrenaline affects membrane lipid-peroxidation, we proposed that the deprivation might modulate membrane lipid-peroxidation, which would modulate intracellular ionic concentration and thereby increase Na-K-ATPase activity. Hence, in this in vivo and in vitro study, rats were deprived of REM sleep for 4 days by the flowerpot method and suitable control experiments were conducted. The deprivation simultaneously decreased membrane lipid-peroxidation as well as increased Na-K-ATPase activity by its dephosphorylation and all the effects were induced by noradrenaline. Further, in vitro experiments showed that hydrogen peroxide (H(2)O(2))-induced enhanced lipid-peroxidation increased synaptosomal calcium (Ca(2+))-influx, which was also prevented by noradrenaline and nifidipine, an L-type Ca(2+)-channel blocker. Additionally, both nifidipine and cyclopiazonic acid, which have opposite effects on intracellular Ca(2+)-concentration, prevented deprivation induced increased Na-K-ATPase activity. We propose that REM sleep deprivation elevates noradrenaline level in the brain that acting on alpha1-adrenoceptor simultaneously reduces membrane lipid-peroxidation but activates phospholipase-C, resulting in closure of L-type Ca(2+)-channel and releasing membrane bound Ca(2+); the latter then dephosphorylates Na-K-ATPase, the active form, causing its increased activity.

  15. Rapid Active Sampling Package

    NASA Technical Reports Server (NTRS)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  16. Rapid Eye Movement Sleep Deprivation Associated Increase in Na-K ATPase Activity in the Rat Brain is Due to Noradrenaline Induced α1-Adrenoceptor Mediated Increased α-Subunit of the Enzyme.

    PubMed

    Amar, Megha; Mallick, Birendra Nath

    2015-08-01

    Rapid eye movement sleep (REMS) modulates Na-K ATPase activity and maintains brain excitability. REMS deprivation (REMSD)-associated increased Na-K ATPase activity is mediated by noradrenaline (NA) acting on α1-adrenoceptor (AR) in the brain. It was shown that NA-induced increased Na-K ATPase activity was due to allosteric modulation as well as increased turnover of the enzyme. Although the former has been studied in detail, our understanding on the latter was lacking, which we have studied. Male Wistar rats were REMS deprived for 4-days by classical flower-pot method; suitable control experiments were conducted. In another set, α1-AR antagonist prazosin (PRZ) was i.p. injected 48 h REMSD onward. At the end of experiments rats were sacrificed by cervical dislocation and brains were removed. Synaptosomes prepared from the brains were used to estimate Na-K ATPase activity as well as protein expressions of different isoforms of the enzyme subunits using western blot. REMSD significantly increased synaptosomal Na-K ATPase activity and that was due to differential increase in the expressions of α1-, α2- and α3-isoforms, but not that of β1- and β2-isoforms. PRZ reduced the REMSD-induced increased Na-K ATPase activity and protein expressions. We also observed that the increased Na-K ATPase subunit expression was not due to enhanced mRNA synthesis, which suggests the possibility of post-transcriptional regulation. Thus, the findings suggest that REMSD-associated increased Na-K ATPase activity is due to elevated level of α-subunit of the enzyme and that is induced by NA acting on α1-AR mediated mRNA-stabilization.

  17. Essential Roles of GABA Transporter-1 in Controlling Rapid Eye Movement Sleep and in Increased Slow Wave Activity after Sleep Deprivation

    PubMed Central

    Xu, Xin-Hong; Qu, Wei-Min; Bian, Min-Juan; Huang, Fang; Fei, Jian; Urade, Yoshihiro; Huang, Zhi-Li

    2013-01-01

    GABA is the major inhibitory neurotransmitter in the mammalian central nervous system that has been strongly implicated in the regulation of sleep. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites for GABA and regulates GABAergic transmission in the brain. However, the role of GAT1 in sleep-wake regulation remains elusive. In the current study, we characterized the spontaneous sleep-wake cycle and responses to sleep deprivation in GAT1 knock-out (KO) mice. GAT1 KO mice exhibited dominant theta-activity and a remarkable reduction of EEG power in low frequencies across all vigilance stages. Under baseline conditions, spontaneous rapid eye movement (REM) sleep of KO mice was elevated both during the light and dark periods, and non-REM (NREM) sleep was reduced during the light period only. KO mice also showed more state transitions from NREM to REM sleep and from REM sleep to wakefulness, as well as more number of REM and NREM sleep bouts than WT mice. During the dark period, KO mice exhibited more REM sleep bouts only. Six hours of sleep deprivation induced rebound increases in NREM and REM sleep in both genotypes. However, slow wave activity, the intensity component of NREM sleep was briefly elevated in WT mice but remained completely unchanged in KO mice, compared with their respective baselines. These results indicate that GAT1 plays a critical role in the regulation of REM sleep and homeostasis of NREM sleep. PMID:24155871

  18. Essential roles of GABA transporter-1 in controlling rapid eye movement sleep and in increased slow wave activity after sleep deprivation.

    PubMed

    Xu, Xin-Hong; Qu, Wei-Min; Bian, Min-Juan; Huang, Fang; Fei, Jian; Urade, Yoshihiro; Huang, Zhi-Li

    2013-01-01

    GABA is the major inhibitory neurotransmitter in the mammalian central nervous system that has been strongly implicated in the regulation of sleep. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites for GABA and regulates GABAergic transmission in the brain. However, the role of GAT1 in sleep-wake regulation remains elusive. In the current study, we characterized the spontaneous sleep-wake cycle and responses to sleep deprivation in GAT1 knock-out (KO) mice. GAT1 KO mice exhibited dominant theta-activity and a remarkable reduction of EEG power in low frequencies across all vigilance stages. Under baseline conditions, spontaneous rapid eye movement (REM) sleep of KO mice was elevated both during the light and dark periods, and non-REM (NREM) sleep was reduced during the light period only. KO mice also showed more state transitions from NREM to REM sleep and from REM sleep to wakefulness, as well as more number of REM and NREM sleep bouts than WT mice. During the dark period, KO mice exhibited more REM sleep bouts only. Six hours of sleep deprivation induced rebound increases in NREM and REM sleep in both genotypes. However, slow wave activity, the intensity component of NREM sleep was briefly elevated in WT mice but remained completely unchanged in KO mice, compared with their respective baselines. These results indicate that GAT1 plays a critical role in the regulation of REM sleep and homeostasis of NREM sleep.

  19. Rapid increase in Japanese life expectancy after World War II.

    PubMed

    Sugiura, Yasuo; Ju, Young-Su; Yasuoka, Junko; Jimba, Masamine

    2010-02-01

    Japanese life expectancy increased by about 13.7 years during the first decade after World War II, despite the country's post-war poverty. Although it is known that medical progress explains part of this increase, roles of non-medical factors have not been systematically studied. This study hypothesizes that non-medical factors, in addition to medical factors, are associated with the rapid increase in life expectancy in Japan. We analyzed the time trends of potential explanatory factors and used regression analysis with historical data from the Ministry of Internal Affairs and Communications' Historical Statistics of Japan during the period between 1946 and 1983. Time trends analysis revealed that the rapid increase in life expectancy preceded the dramatic growth of per capita Gross Domestic Product (GDP) by 10 years. In education, the nearly universal enrollment in elementary schools and increased advancement to upper secondary schools for both sexes were associated with better health. Regarding legislation, 32 health laws were passed in the first decade after the war and these laws were associated with improved health. Using regression analysis, we found that the enrollment rate in elementary schools, the number of health laws, and expansion of community-based activity staff were significantly associated with the increased life expectancy during the first decade after World War II. To conclude, in addition to medical factors, non-medical factors applied across the country, particularly education, community-based activities and legislation were associated with the rapid increase in Japanese life expectancy after World War II.

  20. 1alpha,25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC-beta activity via phospholipase A2-dependent production of lysophospholipid.

    PubMed

    Schwartz, Z; Shaked, D; Hardin, R R; Gruwell, S; Dean, D D; Sylvia, V L; Boyan, B D

    2003-05-01

    1alpha,25(OH)(2)D(3) activates protein kinase C (PKC) in rat growth plate chondrocytes via mechanisms involving phosphatidylinositol-specific phospholipase C (PI-PLC) and phospholipase A(2) (PLA(2)). The purpose of this study was to determine if 1alpha,25(OH)(2)D(3) activates PI-PLC directly or through a PLA(2)-dependent mechanism. We determined which PLC isoforms are present in the growth plate chondrocytes, and determined which isoform(s) of PLC is(are) regulated by 1alpha,25(OH)(2)D(3). Inhibitors and activators of PLA(2) were used to assess the inter-relationship between these two phospholipid-signaling pathways. PI-PLC activity in lysates of prehypertrophic and upper hypertrophic zone (growth zone) cells that were incubated with 1alpha,25(OH)(2)D(3), was increased within 30s with peak activity at 1-3 min. PI-PLC activity in resting zone cells was unaffected by 1alpha,25(OH)(2)D(3). 1beta,25(OH)(2)D(3), 24R,25(OH)(2)D(3), actinomycin D and cycloheximide had no effect on PLC in lysates of growth zone cells. Thus, 1alpha,25(OH)(2)D(3) regulation of PI-PLC enzyme activity is stereospecific, cell maturation-dependent, and nongenomic. PLA(2)-activation (mastoparan or melittin) increased PI-PLC activity to the same extent as 1alpha,25(OH)(2)D(3); PLA(2)-inhibition (quinacrine, oleyloxyethylphosphorylcholine (OEPC), or AACOCF(3)) reduced the effect of 1alpha,25(OH)(2)D(3). Neither arachidonic acid (AA) nor its metabolites affected PI-PLC. In contrast, lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) activated PI-PLC (LPE>LPC). 1alpha,25(OH)(2)D(3) stimulated PI-PLC and PKC activities via Gq; GDPbetaS inhibited activity, but pertussis toxin did not. RT-PCR showed that the cells express PLC-beta1a, PLC-beta1b, PLC-beta3 and PLC-gamma1 mRNA. Antibodies to PLC-beta1 and PLC-beta3 blocked the 1alpha,25(OH)(2)D(3) effect; antibodies to PLC-delta and PLC-gamma did not. Thus, 1alpha,25(OH)(2)D(3) regulates PLC-beta through PLA(2)-dependent production of

  1. Onset and Rapid Increase of Gamma-Ray activity from the Binary System PSR B1259-63 detected by Fermi LAT

    NASA Astrophysics Data System (ADS)

    Wood, K. S.; Caliandro, G. A.; Cheung, C. C.; Li, J.; Torres, D. F.; Fermi LAT Collaboration

    2014-06-01

    The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, is measuring rapid brightening of the binary system PSR B1259-63/SS 2883 in the GeV energy range. ...

  2. Uav Data Processing for Rapid Mapping Activities

    NASA Astrophysics Data System (ADS)

    Tampubolon, W.; Reinhardt, W.

    2015-08-01

    During disaster and emergency situations, geospatial data plays an important role to serve as a framework for decision support system. As one component of basic geospatial data, large scale topographical maps are mandatory in order to enable geospatial analysis within quite a number of societal challenges. The increasing role of geo-information in disaster management nowadays consequently needs to include geospatial aspects on its analysis. Therefore different geospatial datasets can be combined in order to produce reliable geospatial analysis especially in the context of disaster preparedness and emergency response. A very well-known issue in this context is the fast delivery of geospatial relevant data which is expressed by the term "Rapid Mapping". Unmanned Aerial Vehicle (UAV) is the rising geospatial data platform nowadays that can be attractive for modelling and monitoring the disaster area with a low cost and timely acquisition in such critical period of time. Disaster-related object extraction is of special interest for many applications. In this paper, UAV-borne data has been used for supporting rapid mapping activities in combination with high resolution airborne Interferometric Synthetic Aperture Radar (IFSAR) data. A real disaster instance from 2013 in conjunction with Mount Sinabung eruption, Northern Sumatra, Indonesia, is used as the benchmark test for the rapid mapping activities presented in this paper. On this context, the reliable IFSAR dataset from airborne data acquisition in 2011 has been used as a comparable dataset for accuracy investigation and assessment purpose in 3 D reconstructions. After all, this paper presents a proper geo-referencing and feature extraction method of UAV data to support rapid mapping activities.

  3. Rapid intracellular calcium changes in U937 monocyte cell line: transient increases in response to platelet-activating factor and chemotactic peptide but not interferon-gamma or lipopolysaccharide.

    PubMed Central

    Maudsley, D J; Morris, A G

    1987-01-01

    The dye fura-2, a potentially more sensitive successor to quin2 for measuring intracellular free calcium ion concentrations [(Ca2+]i), has been applied here to investigate the possible involvement of early changes in [Ca2+]i in the stimulation of the human monocyte-macrophage-like cell line U937. The calcium ionophores A23187 and ionomycin, known pharmacological stimuli for macrophages, were found to cause sharp rises in [Ca2+]i as expected. Responses analogous to those reported for a murine macrophage cell (J774) were obtained on stimulation of U937 cells with ATP which caused rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 200 mM). In addition to ATP, several agents known to activate macrophages were used as stimuli. In particular, platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was found to cause rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 400 nM) even at concentrations as low as 10(-10) M. This contrasts with responses to ATP that were markedly reduced at 10(-6) M compared with 10(-5) M or above, suggesting that PAF is a highly potent stimulus for intracellular calcium mobilization in macrophages. Similar responses were obtained with chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine). On the other hand, two agents known to be potent activators of macrophages, interferon gamma and lipopolysaccharide, had no rapid effect on [Ca2+]i. This may reflect differences in the kinetics of signal-response coupling or alternatively a different mechanism of action by-passing the need for rapid elevation of [Ca2+]i. PMID:3110054

  4. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  5. Increased Spreading Activation in Depression

    ERIC Educational Resources Information Center

    Foster, Paul S.; Yung, Raegan C.; Branch, Kaylei K.; Stringer, Kristi; Ferguson, Brad J.; Sullivan, William; Drago, Valeria

    2011-01-01

    The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of…

  6. Plant phenological synchrony increases under rapid within-spring warming

    NASA Astrophysics Data System (ADS)

    Wang, Cong; Tang, Yanhong; Chen, Jin

    2016-05-01

    Phenological synchrony influences many ecological processes. Recent climate change has altered the synchrony of phenology, but little is known about the underlying mechanisms. Here using in situ phenological records from Europe, we found that the standard deviation (SD, as a measure of synchrony) of first leafing day (FLD) and the SD of first flowering day (FFD) among local plants were significantly smaller in the years and/or in the regions with a more rapid within-spring warming speed (WWS, the linear slope of the daily mean temperature against the days during spring, in oC/day) with correlation coefficients of ‑0.75 and ‑0.48 for FLD and ‑0.55 and ‑0.23 for FFD. We further found that the SDs of temperature sensitivity of local plants were smaller under the rapid WWS conditions with correlation coefficients of ‑0.46 and ‑0.33 for FLD and FFD respectively. This study provides the first evidence that the within-season rate of change of the temperature but not the magnitude determines plant phenological synchrony. It implies that temporally, the asymmetric seasonal climatic warming may decrease the synchrony via increasing WWS, especially in arctic regions; spatially, plants in coastal and low latitude areas with low WWS would have more diverse spring phenological traits.

  7. Plant phenological synchrony increases under rapid within-spring warming

    PubMed Central

    Wang, Cong; Tang, Yanhong; Chen, Jin

    2016-01-01

    Phenological synchrony influences many ecological processes. Recent climate change has altered the synchrony of phenology, but little is known about the underlying mechanisms. Here using in situ phenological records from Europe, we found that the standard deviation (SD, as a measure of synchrony) of first leafing day (FLD) and the SD of first flowering day (FFD) among local plants were significantly smaller in the years and/or in the regions with a more rapid within-spring warming speed (WWS, the linear slope of the daily mean temperature against the days during spring, in oC/day) with correlation coefficients of −0.75 and −0.48 for FLD and −0.55 and −0.23 for FFD. We further found that the SDs of temperature sensitivity of local plants were smaller under the rapid WWS conditions with correlation coefficients of −0.46 and −0.33 for FLD and FFD respectively. This study provides the first evidence that the within-season rate of change of the temperature but not the magnitude determines plant phenological synchrony. It implies that temporally, the asymmetric seasonal climatic warming may decrease the synchrony via increasing WWS, especially in arctic regions; spatially, plants in coastal and low latitude areas with low WWS would have more diverse spring phenological traits. PMID:27145698

  8. Increase in composite binder activity

    NASA Astrophysics Data System (ADS)

    Fediuk, R.; Smoliakov, A.; Stoyushko, N.

    2016-11-01

    The binder of portland cement (51-59 wt.%), fly ash of thermal power stations (3644 wt.%), limestone crushing waste (4-9 wt.%) and dry hyper plasticizer (0.2 wt.%) has been created. It can be used in the building materials industry for production of high-strength concrete. The composite binder is obtained by co-milling of the components in vario-planetary mill to a specific surface area of 550-600 m2/kg. The technical result is the possibility of obtaining a composite binder with significant replacement of cement with industrial waste, cost-effective and superior to portland cement for construction and technical properties, increased activity. This allows producing concrete for walling with a compressive strength of 100 MPa, while using more than 50% of industrial waste.

  9. Human amygdala activation during rapid eye movements of rapid eye movement sleep: an intracranial study.

    PubMed

    Corsi-Cabrera, María; Velasco, Francisco; Del Río-Portilla, Yolanda; Armony, Jorge L; Trejo-Martínez, David; Guevara, Miguel A; Velasco, Ana L

    2016-10-01

    The amygdaloid complex plays a crucial role in processing emotional signals and in the formation of emotional memories. Neuroimaging studies have shown human amygdala activation during rapid eye movement sleep (REM). Stereotactically implanted electrodes for presurgical evaluation in epileptic patients provide a unique opportunity to directly record amygdala activity. The present study analysed amygdala activity associated with REM sleep eye movements on the millisecond scale. We propose that phasic activation associated with rapid eye movements may provide the amygdala with endogenous excitation during REM sleep. Standard polysomnography and stereo-electroencephalograph (SEEG) were recorded simultaneously during spontaneous sleep in the left amygdala of four patients. Time-frequency analysis and absolute power of gamma activity were obtained for 250 ms time windows preceding and following eye movement onset in REM sleep, and in spontaneous waking eye movements in the dark. Absolute power of the 44-48 Hz band increased significantly during the 250 ms time window after REM sleep rapid eye movements onset, but not during waking eye movements. Transient activation of the amygdala provides physiological support for the proposed participation of the amygdala in emotional expression, in the emotional content of dreams and for the reactivation and consolidation of emotional memories during REM sleep, as well as for next-day emotional regulation, and its possible role in the bidirectional interaction between REM sleep and such sleep disorders as nightmares, anxiety and post-traumatic sleep disorder. These results provide unique, direct evidence of increased activation of the human amygdala time-locked to REM sleep rapid eye movements.

  10. Increasing opportunities for physical activity.

    PubMed

    Buckley, Sue

    2007-07-01

    Being physically active can have a number of benefits - having fun, meeting with friends, keeping healthy and experiencing success. For children with Down syndrome the foundations need to be laid early if they are to keep active in school, teenage and adult years and parents ask for more help in this area from professionals.

  11. Local modulation of steroid action: rapid control of enzymatic activity

    PubMed Central

    Charlier, Thierry D.; Cornil, Charlotte A.; Patte-Mensah, Christine; Meyer, Laurence; Mensah-Nyagan, A. Guy; Balthazart, Jacques

    2015-01-01

    Estrogens can induce rapid, short-lived physiological and behavioral responses, in addition to their slow, but long-term, effects at the transcriptional level. To be functionally relevant, these effects should be associated with rapid modulations of estrogens concentrations. 17β-estradiol is synthesized by the enzyme aromatase, using testosterone as a substrate, but can also be degraded into catechol-estrogens via hydroxylation by the same enzyme, leading to an increase or decrease in estrogens concentration, respectively. The first evidence that aromatase activity (AA) can be rapidly modulated came from experiments performed in Japanese quail hypothalamus homogenates. This rapid modulation is triggered by calcium-dependent phosphorylations and was confirmed in other tissues and species. The mechanisms controlling the phosphorylation status, the targeted amino acid residues and the reversibility seem to vary depending of the tissues and is discussed in this review. We currently do not know whether the phosphorylation of the same amino acid affects both aromatase and/or hydroxylase activities or whether these residues are different. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues. PMID:25852459

  12. A rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease.

    PubMed

    Chang, Mary Y; Tanino, Yoshinori; Vidova, Veronika; Kinsella, Michael G; Chan, Christina K; Johnson, Pamela Y; Wight, Thomas N; Frevert, Charles W

    2014-02-01

    The goals of this study were to characterize the changes in chondroitin sulfate proteoglycans and hyaluronan in lungs in acute response to gram-negative bacterial infection and to identify cellular components responsible for these changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1 and 2 associated with increased immunohistochemical and histochemical staining for versican and hyaluronan in the lungs. Versican was associated with a subset of alveolar macrophages. To examine whether macrophages contribute to versican and hyaluronan accumulation, in vitro studies with primary cultures of bone marrow-derived and alveolar macrophages were performed. Unstimulated macrophages expressed very low levels of versican and hyaluronan synthase mRNA, with no detectible versican protein or hyaluronan product. Stimulation with LPS caused rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading enzymes. Hyaluronan could be detected following chloroquine pre-treatment, indicating rapid turnover and degradation of hyaluronan by macrophages. In addition, the effects of LPS, the M1 macrophage classical activation agonist, were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative activation agonists, respectively. Versican and Has1 increased only in response to M1 activation. Finally, the up-regulation of versican and Has1 in the whole lungs of wild-type mice following IT LPS was completely abrogated in TLR-4(-/-) mice. These findings suggest that versican and hyaluronan synthesis may play an important role in the innate immune response to gram-negative lung infection.

  13. Reprint of: A rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease.

    PubMed

    Chang, Mary Y; Tanino, Yoshinori; Vidova, Veronika; Kinsella, Michael G; Chan, Christina K; Johnson, Pamela Y; Wight, Thomas N; Frevert, Charles W

    2014-04-01

    The goals of this study were to characterize the changes in chondroitin sulfate proteoglycans and hyaluronan in lungs in acute response to gram-negative bacterial infection and to identify cellular components responsible for these changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1 and 2 associated with increased immunohistochemical and histochemical staining for versican and hyaluronan in the lungs. Versican was associated with a subset of alveolar macrophages. To examine whether macrophages contribute to versican and hyaluronan accumulation, in vitro studies with primary cultures of bone marrow-derived and alveolar macrophages were performed. Unstimulated macrophages expressed very low levels of versican and hyaluronan synthase mRNA, with no detectible versican protein or hyaluronan product. Stimulation with LPS caused rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading enzymes. Hyaluronan could be detected following chloroquine pre-treatment, indicating rapid turnover and degradation of hyaluronan by macrophages. In addition, the effects of LPS, the M1 macrophage classical activation agonist, were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative activation agonists, respectively. Versican and Has1 increased only in response to M1 activation. Finally, the up-regulation of versican and Has1 in the whole lungs of wild-type mice following IT LPS was completely abrogated in TLR-4(-/-) mice. These findings suggest that versican and hyaluronan synthesis may play an important role in the innate immune response to gram-negative lung infection.

  14. A Rapid Increase in Macrophage-Derived Versican and Hyaluronan in Infectious Lung Disease

    PubMed Central

    Chang, Mary Y.; Tanino, Yoshinori; Vidova, Veronika; Kinsella, Michael G.; Chan, Christina K.; Johnson, Pamela Y.; Wight, Thomas N.; Frevert, Charles W.

    2014-01-01

    The goals of this study were to characterize the changes to chondroitin sulfate proteoglycans and hyaluronan in lungs in the acute response to gram-negative bacterial infection, and to identify cellular components responsible for these changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1 and 2 associated with increased immunohistochemical and histochemical staining for versican and hyaluronan in the lungs. Versican was associated with a subset of alveolar macrophages. To examine whether macrophages contribute to versican and hyaluronan accumulation, in vitro studies with primary cultures of bone marrow-derived and alveolar macrophages were performed. Unstimulated macrophages expressed very low levels of versican and hyaluronan synthase mRNA, with no detectible versican protein or hyaluronan product. Stimulation with LPS caused rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading enzymes. Hyaluronan could be detected following chloroquine pre-treatment, indicating rapid turnover and degradation of hyaluronan by macrophages. In addition, the effects of LPS, the M1 macrophage classical activation agonist, were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative activation agonists, respectively. Versican and Has1 increased only in response to M1 activation. Finally, the up-regulation of versican and Has1 in the whole lungs of wild-type mice following IT LPS was completely abrogated in TLR-4−/− mice. These findings suggest that versican and hyaluronan synthesis may play an important role in the innate immune response to gram-negative lung infection. PMID:24472738

  15. A rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease

    PubMed Central

    Chang, Mary Y.; Tanino, Yoshinori; Vidova, Veronika; Kinsella, Michael G.; Chan, Christina K.; Johnson, Pamela Y.; Wight, Thomas N.; Frevert, Charles W.

    2014-01-01

    The goals of this study were to characterize the changes in chondroitin sulfate proteoglycans and hyaluronan in lungs in acute response to gram-negative bacterial infection and to identify cellular components responsible for these changes. Mice were treated with intratracheal (IT) live Escherichia coli, E. coli lipopolysaccharide (LPS), or PBS. Both E. coli and LPS caused rapid selective increases in mRNA expression of versican and hyaluronan synthase (Has) isoforms 1 and 2 associated with increased immunohistochemical and histochemical staining for versican and hyaluronan in the lungs. Versican was associated with a subset of alveolar macrophages. To examine whether macrophages contribute to versican and hyaluronan accumulation, in vitro studies with primary cultures of bone marrow-derived and alveolar macrophages were performed. Unstimulated macrophages expressed very low levels of versican and hyaluronan synthase mRNA, with no detectible versican protein or hyaluronan product. Stimulation with LPS caused rapid increases in versican mRNA and protein, a rapid increase in Has1 mRNA, and concomitant inhibition of hyaluronidases 1 and 2, the major hyaluronan degrading enzymes. Hyaluronan could be detected following chloroquine pre-treatment, indicating rapid turnover and degradation of hyaluronan by macrophages. In addition, the effects of LPS, the M1 macrophage classical activation agonist, were compared to those of IL-4/IL-13 or IL-10, the M2a and M2c alternative activation agonists, respectively. Versican and Has1 increased only in response to M1 activation. Finally, the up-regulation of versican and Has1 in the whole lungs of wild-type mice following IT LPS was completely abrogated in TLR-4−/− mice. These findings suggest that versican and hyaluronan synthesis may play an important role in the innate immune response to gram-negative lung infection. PMID:24727035

  16. Increased Saliva Cotinine Concentrations in Smokers during Rapid Weight Loss.

    ERIC Educational Resources Information Center

    Niaura, Raymond; And Others

    1992-01-01

    Examined association between saliva cotinine levels and weight loss in nine obese female smokers during participation in protein-sparing modified fast. A significant weight loss was noted at three and six months, yet cotinine level increased significantly during this time. Results suggest that smoking-related health risks may increase during…

  17. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  18. Scopolamine rapidly increases mTORC1 signaling, synaptogenesis, and antidepressant behavioral responses

    PubMed Central

    Voleti, Bhavya; Navarria, Andrea; Liu, Rong-Jian; Banasr, Mounira; Li, Nanxin; Terwilliger, Rose; Sanacora, Gerard; Eid, Tore; Aghajanian, George; Duman, Ronald S.

    2013-01-01

    Background Clinical studies report that scopolamine, an acetylcholine muscarinic receptor antagonist, produces rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic response have not been determined. The present study examines the role of the mammalian target of rapamycin complex 1 (mTORC1) and synaptogenesis, which have been implicated in the rapid actions of NMDA receptor antagonists. Methods The influence of scopolamine on mTORC1 signaling was determined by analysis of the phosphorylated and activated forms of mTORC1 signaling proteins in the prefrontal cortex (PFC). The numbers and function of spine synapses were analyzed by whole cell patch clamp recording and 2-photon image analysis of PFC neurons. The actions of scopolamine were examined in the forced swim test in the absence or presence of selective mTORC1 and AMPA receptor inhibitors. Results The results demonstrate that a single, low dose of scopolamine rapidly increases mTORC1 signaling and the number and function of spine synapses in layer V pyramidal neurons in the PFC. Scopolamine administration also produces an antidepressant response in the forced swim test that is blocked by pretreatment with the mTORC1 inhibitor or by a glutamate AMPA receptor antagonist. Conclusions Taken together, the results demonstrate that the antidepressant actions of scopolamine require mTORC1 signaling and are associated with increased glutamate transmission, and synaptogenesis, similar to NMDA receptor antagonists. These findings provide novel targets for safer and more efficacious rapid acting antidepressant agents. PMID:23751205

  19. The rapidly increasing trend of cannabis use in burn injury.

    PubMed

    Jehle, Charles Christopher; Nazir, Niaman; Bhavsar, Dhaval

    2015-01-01

    The use of cannabis is currently increasing according to U.S. Department of Health and Human Services (HHS). Surprisingly, cannabis use among burn patients is poorly reported in literature. In this study, rates of cannabis use in burn patients are compared with general population. Data from the National Burn Repository (NBR) were used to investigate incidence, demographics, and outcomes in relation to use of cannabis as evidenced by urine drug screen (UDS). Thousands of patients from the NBR from 2002 to 2011 were included in this retrospective study. Inclusion criteria were patients older than 12 years of age who received a drug screen. Data points analyzed were patients' age, sex, UDS status, mechanism of burn injury, total body surface area, length of stay, ICU days, and insurance characteristics. Incidence of cannabis use in burn patients from the NBR was compared against national general population rates (gathered by Health and Human Services) using chi-square tests. Additionally, the burn patient population was analyzed using bivariate analysis and t-tests to find differences in the characteristics of these patients as well as differences in outcomes. Seventeen thousand eighty out of over 112,000 patients from NBR had information available for UDS. The incidence of cannabis use is increasing among the general population, but the rate is increasing more quickly among patients in the burn patient population (P = .0022). In 2002, 6.0% of patients in burn units had cannabis+ UDS, which was comparable with national incidence of 6.2%. By 2011, 27.0% of burn patients tested cannabis+ while national incidence of cannabis use was 7.0%. Patients who test cannabis+ are generally men (80.1%, P < .0001) and are younger on average (35 years old vs 42, P < .0001). The most common mechanisms of injury among patients who test cannabis+ or cannabis- are similar. Flame injury makes up >60% of injuries, followed by scalds that are >15%. In comparing cannabis+/- patients

  20. A Rapid and Quantitative Recombinase Activity Assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present here a comparison between the recombinase systems FLP-FRT and Cre-loxP. A transient excision based dual luciferase expression assay is used for its rapid and repeatable nature. The detection system was designed within an intron to remove the remaining recombinase recognition site and no...

  1. Gonadal Hormones Rapidly Enhance Spatial Memory and Increase Hippocampal Spine Density in Male Rats

    PubMed Central

    Jacome, Luis F.; Barateli, Ketti; Buitrago, Dina; Lema, Franklin; Frankfurt, Maya

    2016-01-01

    17β-estradiol (E2) rapidly, within minutes, activates behaviors and cognition by binding to membrane estrogen receptors, activating cell signaling cascades and increasing dendritic spines. In female rodents, E2 enhances spatial memory within 2–4 hours, and spine density is increased in the CA1 area of the hippocampus within 30–60 minutes. Although chronic gonadal hormone treatments in male rats alter cognition and spines/spine synapses and acute hormone effects occur in hippocampal slices, effects of acute, in vivo hormone administration in males are unknown. Therefore, we assessed rapid effects of E2 (20 μg/kg) and testosterone (T) (750 μg/kg) on spatial memory using the object placement task and on hippocampal spine density using Golgi impregnation. Orchidectomized rats received hormones immediately after the training trial and were tested for retention 2 hours later. Vehicle-injected orchidectomized males spent equal time exploring objects in the old and new locations, but E2- or T-treated subjects spent more time exploring objects at the new location, suggesting enhanced memory. Both hormones also increased spine density in CA1, but not the dentate gyrus, by 20%–40% at 30 minutes and 2 hours after injections. This report is the first, to our knowledge, to show E2 and T enhancements of memory and spine density within such a short time frame in male rats. PMID:26844375

  2. Rapid increases in immature synapses parallel estrogen-induced hippocampal learning enhancements

    PubMed Central

    Phan, Anna; Suschkov, Sarah; Molinaro, Luke; Reynolds, Kathryn; Lymer, Jennifer M.; Bailey, Craig D. C.; Kow, Lee-Ming; MacLusky, Neil J.; Pfaff, Donald W.; Choleris, Elena

    2015-01-01

    Dramatic increases in hippocampal spine synapse density are known to occur within minutes of estrogen exposure. Until now, it has been assumed that enhanced spinogenesis increased excitatory input received by the CA1 pyramidal neurons, but how this facilitated learning and memory was unclear. Delivery of 17β-estradiol or an estrogen receptor (ER)-α (but not ER-β) agonist into the dorsal hippocampus rapidly improved general discrimination learning in female mice. The same treatments increased CA1 dendritic spines in hippocampal sections over a time course consistent with the learning acquisition phase. Surprisingly, estrogen-activated spinogenesis was associated with a decrease in CA1 hippocampal excitatory input, rapidly and transiently reducing CA1 AMPA activity via a mechanism likely reflecting AMPA receptor internalization and creation of silent or immature synapses. We propose that estrogens promote hippocampally mediated learning via a mechanism resembling some of the broad features of normal development, an initial overproduction of functionally immature connections being subsequently “pruned” by experience. PMID:26655342

  3. Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation.

    PubMed

    Jourdi, Hussam; Hsu, Yu-Tien; Zhou, Miou; Qin, Qingyu; Bi, Xiaoning; Baudry, Michel

    2009-07-08

    Brain-derived neurotrophic factor (BDNF) stimulates local dendritic mRNA translation and is involved in formation and consolidation of memory. 2H,3H,6aH-pyrrolidino[2'',1''-3',2']1,3-oxazino[6',5'-5,4]-benzo[e]1,4-dioxan-10-one (CX614), one of the best-studied positive AMPA receptor modulators (also known as ampakines), increases BDNF mRNA and protein and facilitates long-term potentiation (LTP) induction. Several other ampakines also improve performance in various behavioral and learning tasks. Since local dendritic protein synthesis has been implicated in LTP stabilization and in memory consolidation, this study investigated whether CX614 could influence synaptic plasticity by upregulating dendritic protein translation. CX614 treatment of primary neuronal cultures and acute hippocampal slices rapidly activated the translation machinery and increased local dendritic protein synthesis. CX614-induced activation of translation was blocked by K252a [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester], CNQX, APV, and TTX, and was inhibited in the presence of an extracellular BDNF scavenger, TrkB-Fc. The acute effect of CX614 on translation was mediated by increased BDNF release as demonstrated with a BDNF scavenging assay using TrkB-Fc during CX614 treatment of cultured primary neurons and was blocked by nifedipine, ryanodine, and lack of extracellular Ca(2+) in acute hippocampal slices. Finally, CX614, like BDNF, rapidly increased dendritic translation of an exogenous translation reporter. Together, our results demonstrate that positive modulation of AMPA receptors rapidly stimulates dendritic translation, an effect mediated by BDNF secretion and TrkB receptor activation. They also suggest that increased BDNF secretion and stimulation of local protein synthesis contribute to the effects of ampakines on synaptic plasticity.

  4. Exergames: Increasing Physical Activity through Effective Instruction

    ERIC Educational Resources Information Center

    Rudella, Jennifer L.; Butz, Jennifer V.

    2015-01-01

    Due to the growing obesity epidemic in the United States, educators must consider new ways to increase physical activity in an effort to address obesity. There are a variety of ways educators can increase physical activity in the classroom, and exergames--video games that require physical movement in order to play--are a modern-day approach to…

  5. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness.

    PubMed

    Maslin, M R D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J

    2015-10-01

    Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

  6. Dynamic powder compaction of rapidly solidified Path A alloy with increased carbon and titanium content

    SciTech Connect

    Megusar, J.; Imeson, D.; Vander Sande, J.B.; Grant, N.J.

    1982-01-01

    The objective of this study is to show the potential of the dynamic powder compaction technique to consolidate rapidly solidified Path A alloys and to develop microstructures with improved irradiation performance in the fusion environment. Samples of rapidly solidified and dynamically compacted Path A alloy with increased carbon and titanium content have been included in alloy development irradiation experiments.

  7. Rapid Environmental Change Drives Increased Land Use by an Arctic Marine Predator

    PubMed Central

    Atwood, Todd C.; Peacock, Elizabeth; McKinney, Melissa A.; Lillie, Kate; Wilson, Ryan; Douglas, David C.; Miller, Susanne; Terletzky, Pat

    2016-01-01

    In the Arctic Ocean’s southern Beaufort Sea (SB), the length of the sea ice melt season (i.e., period between the onset of sea ice break-up in summer and freeze-up in fall) has increased substantially since the late 1990s. Historically, polar bears (Ursus maritimus) of the SB have mostly remained on the sea ice year-round (except for those that came ashore to den), but recent changes in the extent and phenology of sea ice habitat have coincided with evidence that use of terrestrial habitat is increasing. We characterized the spatial behavior of polar bears spending summer and fall on land along Alaska’s north coast to better understand the nexus between rapid environmental change and increased use of terrestrial habitat. We found that the percentage of radiocollared adult females from the SB subpopulation coming ashore has tripled over 15 years. Moreover, we detected trends of earlier arrival on shore, increased length of stay, and later departure back to sea ice, all of which were related to declines in the availability of sea ice habitat over the continental shelf and changes to sea ice phenology. Since the late 1990s, the mean duration of the open-water season in the SB increased by 36 days, and the mean length of stay on shore increased by 31 days. While on shore, the distribution of polar bears was influenced by the availability of scavenge subsidies in the form of subsistence-harvested bowhead whale (Balaena mysticetus) remains aggregated at sites along the coast. The declining spatio-temporal availability of sea ice habitat and increased availability of human-provisioned resources are likely to result in increased use of land. Increased residency on land is cause for concern given that, while there, bears may be exposed to a greater array of risk factors including those associated with increased human activities. PMID:27249673

  8. Rapid Environmental Change Drives Increased Land Use by an Arctic Marine Predator.

    PubMed

    Atwood, Todd C; Peacock, Elizabeth; McKinney, Melissa A; Lillie, Kate; Wilson, Ryan; Douglas, David C; Miller, Susanne; Terletzky, Pat

    2016-01-01

    In the Arctic Ocean's southern Beaufort Sea (SB), the length of the sea ice melt season (i.e., period between the onset of sea ice break-up in summer and freeze-up in fall) has increased substantially since the late 1990s. Historically, polar bears (Ursus maritimus) of the SB have mostly remained on the sea ice year-round (except for those that came ashore to den), but recent changes in the extent and phenology of sea ice habitat have coincided with evidence that use of terrestrial habitat is increasing. We characterized the spatial behavior of polar bears spending summer and fall on land along Alaska's north coast to better understand the nexus between rapid environmental change and increased use of terrestrial habitat. We found that the percentage of radiocollared adult females from the SB subpopulation coming ashore has tripled over 15 years. Moreover, we detected trends of earlier arrival on shore, increased length of stay, and later departure back to sea ice, all of which were related to declines in the availability of sea ice habitat over the continental shelf and changes to sea ice phenology. Since the late 1990s, the mean duration of the open-water season in the SB increased by 36 days, and the mean length of stay on shore increased by 31 days. While on shore, the distribution of polar bears was influenced by the availability of scavenge subsidies in the form of subsistence-harvested bowhead whale (Balaena mysticetus) remains aggregated at sites along the coast. The declining spatio-temporal availability of sea ice habitat and increased availability of human-provisioned resources are likely to result in increased use of land. Increased residency on land is cause for concern given that, while there, bears may be exposed to a greater array of risk factors including those associated with increased human activities.

  9. Rapidly assessing the activation conditions and porosity of metal-organic frameworks using thermogravimetric analysis

    SciTech Connect

    McDonald, TM; Bloch, ED; Long, JR

    2015-01-01

    A methodology utilizing a thermogravimetric analyzer to monitor propane uptake following incremental increases of the temperature is demonstrated as a means of rapidly identifying porous materials and determining the optimum activation conditions of metal-organic frameworks.

  10. Rapid assessment of disaster damage using social media activity.

    PubMed

    Kryvasheyeu, Yury; Chen, Haohui; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel

    2016-03-01

    Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and an increasing intensity of natural disasters resulting from climate change. During such events, citizens turn to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. In addition, the spatiotemporal distribution of disaster-related messages helps with the real-time monitoring and assessment of the disaster itself. We present a multiscale analysis of Twitter activity before, during, and after Hurricane Sandy. We examine the online response of 50 metropolitan areas of the United States and find a strong relationship between proximity to Sandy's path and hurricane-related social media activity. We show that real and perceived threats, together with physical disaster effects, are directly observable through the intensity and composition of Twitter's message stream. We demonstrate that per-capita Twitter activity strongly correlates with the per-capita economic damage inflicted by the hurricane. We verify our findings for a wide range of disasters and suggest that massive online social networks can be used for rapid assessment of damage caused by a large-scale disaster.

  11. Rapid assessment of disaster damage using social media activity

    PubMed Central

    Kryvasheyeu, Yury; Chen, Haohui; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel

    2016-01-01

    Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and an increasing intensity of natural disasters resulting from climate change. During such events, citizens turn to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. In addition, the spatiotemporal distribution of disaster-related messages helps with the real-time monitoring and assessment of the disaster itself. We present a multiscale analysis of Twitter activity before, during, and after Hurricane Sandy. We examine the online response of 50 metropolitan areas of the United States and find a strong relationship between proximity to Sandy’s path and hurricane-related social media activity. We show that real and perceived threats, together with physical disaster effects, are directly observable through the intensity and composition of Twitter’s message stream. We demonstrate that per-capita Twitter activity strongly correlates with the per-capita economic damage inflicted by the hurricane. We verify our findings for a wide range of disasters and suggest that massive online social networks can be used for rapid assessment of damage caused by a large-scale disaster. PMID:27034978

  12. Mechanical stimulation evokes rapid increases in extracellular adenosine concentration in the prefrontal cortex.

    PubMed

    Ross, Ashley E; Nguyen, Michael D; Privman, Eve; Venton, B Jill

    2014-07-01

    Mechanical perturbations can release ATP, which is broken down to adenosine. In this work, we used carbon-fiber microelectrodes and fast-scan cyclic voltammetry to measure mechanically stimulated adenosine in the brain by lowering the electrode 50 μm. Mechanical stimulation evoked adenosine in vivo (average: 3.3 ± 0.6 μM) and in brain slices (average: 0.8 ± 0.1 μM) in the prefrontal cortex. The release was transient, lasting 18 ± 2 s. Lowering a 15-μm-diameter glass pipette near the carbon-fiber microelectrode produced similar results as lowering the actual microelectrode. However, applying a small puff of artificial cerebral spinal fluid was not sufficient to evoke adenosine. Multiple stimulations within a 50-μm region of a slice did not significantly change over time or damage cells. Chelating calcium with EDTA or blocking sodium channels with tetrodotoxin significantly decreased mechanically evoked adenosine, signifying that the release is activity dependent. An alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, did not affect mechanically stimulated adenosine; however, the nucleoside triphosphate diphosphohydrolase 1,2 and 3 (NTDPase) inhibitor POM-1 significantly reduced adenosine so a portion of adenosine is dependent on extracellular ATP metabolism. Thus, mechanical perturbations from inserting a probe in the brain cause rapid, transient adenosine signaling which might be neuroprotective. We have discovered immediate changes in adenosine concentration in the prefrontal cortex following mechanical stimulation. The adenosine increase lasts only about 20 s. Mechanically stimulated adenosine was activity dependent and mostly because of extracellular ATP metabolism. This rapid, transient increase in adenosine may help protect tissue and would occur during implantation of any electrode, such as during deep brain stimulation.

  13. Thermodynamic balance of photosynthesis and transpiration at increasing CO2 concentrations and rapid light fluctuations.

    PubMed

    Marín, Dolores; Martín, Mercedes; Serrot, Patricia H; Sabater, Bartolomé

    2014-02-01

    Experimental and theoretical flux models have been developed to reveal the influence of sun flecks and increasing CO2 concentrations on the energy and entropy balances of the leaf. The rapid and wide range of fluctuations in light intensity under field conditions were simulated in a climatic gas exchange chamber and we determined the energy and entropy balance of the leaf based on radiation and gas exchange measurements. It was estimated that the energy of photosynthetic active radiation (PAR) accounts for half of transpiration, which is the main factor responsible for the exportation of the entropy generated in photosynthesis (Sg) out of the leaf in order to maintain functional the photosynthetic machinery. Although the response of net photosynthetic production to increasing concentrations of CO2 under fluctuating light is similar to that under continuous light, rates of transpiration respond slowly to changes of light intensity and are barely affected by the concentration of CO2 in the range of 260-495 ppm, in which net photosynthesis increases by more than 100%. The analysis of the results confirms that future increases of CO2 will improve the efficiency of the conversion of radiant energy into biomass, but will not reduce the contribution of plant transpiration to the leaf thermal balance.

  14. Insight into the Physical and Dynamical Processes that Control Rapid Increases in Total Flash Rate

    NASA Technical Reports Server (NTRS)

    Schultz, Christopher J.; Carey, Lawrence D.; Schultz, Elise V.; Blakeslee, Richard J.; Goodman, Steven J.

    2015-01-01

    Rapid increases in total lightning (also termed "lightning jumps") have been observed for many decades. Lightning jumps have been well correlated to severe and hazardous weather occurrence. The main focus of lightning jump work has been on the development of lightning algorithms to be used in real-time assessment of storm intensity. However, in these studies it is typically assumed that the updraft "increases" without direct measurements of the vertical motion, or specification of which updraft characteristic actually increases (e.g., average speed, maximum speed, or convective updraft volume). Therefore, an end-to-end physical and dynamical basis for coupling rapid increases in total flash rate to increases in updraft speed and volume must be understood in order to ultimately relate lightning occurrence to severe storm metrics. Herein, we use polarimetric, multi-Doppler, and lightning mapping array measurements to provide physical context as to why rapid increases in total lightning are closely tied to severe and hazardous weather.

  15. Rapid increase in training load affects markers of skeletal muscle damage and mechanical performance.

    PubMed

    Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas; Aagaard, Per; Masiulis, Nerijus; Skurvydas, Albertas

    2012-11-01

    The aim of this study was to monitor the changes in indirect markers of muscle damage during 3 weeks (9 training sessions) of stretch-shortening (drop jump) exercise with constant load alternated with steep increases in load. Physically active men (n = 9, mean age 19.1 years) performed a program involving a rapid stepwise increase in the number of jumps, drop height, and squat depth, and the addition of weight. Concentric, isometric maximal voluntary contraction (MVC), and stimulated knee extension torque were measured before and 10 minutes after each session. Muscle soreness and plasma creatine kinase activity were assessed after each session. Steep increments in stretch-shortening exercise load in sessions 4 and 7 amplified the postexercise decrease in stimulated muscle torque and slightly increased muscle soreness but had a minimal effect on the recovery of MVC and stimulated torque. Maximal jump height increased by 7.8 ± 6.3% (p < 0.05), 11.4 ± 3.3% (p < 0.05), and 12.8 ± 3.6% (p < 0.05) at 3, 10, and 17 days after the final training session, respectively. Gains in isometric knee extension MVC (7.9 ± 8.2%) and 100-Hz-evoked torque (9.9 ± 9.6%) (both p < 0.05) were observed within 17 days after the end of the training. The magnitude of improvement was greater after this protocol than that induced by a continuous constant progression loading pattern with small gradual load increments in each training session. These findings suggest that plyometric training using infrequent but steep increases in loading intensity and volume may be beneficial to athletic performance.

  16. Increased Ribozyme Activity in Crowded Solutions*

    PubMed Central

    Desai, Ravi; Kilburn, Duncan; Lee, Hui-Ting; Woodson, Sarah A.

    2014-01-01

    Noncoding RNAs must function in the crowded environment of the cell. Previous small-angle x-ray scattering experiments showed that molecular crowders stabilize the structure of the Azoarcus group I ribozyme, allowing the ribozyme to fold at low physiological Mg2+ concentrations. Here, we used an RNA cleavage assay to show that the PEG and Ficoll crowder molecules increased the biochemical activity of the ribozyme, whereas sucrose did not. Crowding lowered the Mg2+ threshold at which activity was detected and increased total RNA cleavage at high Mg2+ concentrations sufficient to fold the RNA in crowded or dilute solution. After correcting for solution viscosity, the observed reaction rate was proportional to the fraction of active ribozyme. We conclude that molecular crowders stabilize the native ribozyme and favor the active structure relative to compact inactive folding intermediates. PMID:24337582

  17. Increased corrosion resistance of the AZ80 magnesium alloy by rapid solidification.

    PubMed

    Aghion, E; Jan, L; Meshi, L; Goldman, J

    2015-11-01

    Magnesium (Mg) and Mg-alloys are being considered as implantable biometals. Despite their excellent biocompatibility and good mechanical properties, their rapid corrosion is a major impediment precluding their widespread acceptance as implantable biomaterials. Here, we investigate the potential for rapid solidification to increase the corrosion resistance of Mg alloys. To this end, the effect of rapid solidification on the environmental and stress corrosion behavior of the AZ80 Mg alloy vs. its conventionally cast counterpart was evaluated in simulated physiological electrolytes. The microstructural characteristics were examined by optical microscopy, SEM, TEM, and X-ray diffraction analysis. The corrosion behavior was evaluated by immersion, salt spraying, and potentiodynamic polarization. Stress corrosion resistance was assessed by Slow Strain Rate Testing. The results indicate that the corrosion resistance of rapidly solidified ribbons is significantly improved relative to the conventional cast alloy due to the increased Al content dissolved in the α-Mg matrix and the correspondingly reduced presence of the β-phase (Mg17 Al12 ). Unfortunately, extrusion consolidated solidified ribbons exhibited a substantial reduction in the environmental performance and stress corrosion resistance. This was mainly attributed to the detrimental effect of the extrusion process, which enriched the iron impurities and increased the internal stresses by imposing a higher dislocation density. In terms of immersion tests, the average corrosion rate of the rapidly solidified ribbons was <0.4 mm/year compared with ∼2 mm/year for the conventionally cast alloy and 26 mm/year for the rapidly solidified extruded ribbons.

  18. Rapid bactericidal activity of sitafloxacin against Streptococcus pneumoniae.

    PubMed

    Kanda, Hiroko; Inoue, Kazue; Okumura, Ryo; Hoshino, Kazuki

    2013-02-01

    The initial bactericidal activity of quinolones against Streptococcus pneumoniae at the concentration equivalent to their respective peak serum concentration (C(max)) and free drug fraction of C(max) (fC(max)) were investigated. The bactericidal activity of sitafloxacin (STFX), levofloxacin (LVFX), moxifloxacin (MFLX), and garenoxacin (GRNX) were compared by determining the actual killing of bacteria at C(max) and fC(max) for 1 and 2 hours based on the Japanese maximum dose per administration (100, 500, 400, and 400 mg, respectively). Against 4 quinolone-susceptible clinical isolates (wild-type), STFX with C(max) and fC(max) exhibited the most rapid bactericidal activity resulting in an average reduction of > or = 3.0 log10 colony forming units (CFU)/ mL in 1 hour. STFX with C(max) and fC(max) also showed the most rapid and potent bactericidal activity against 9 clinical isolates with single par (C/E) mutation, resulting in > or = 3.0 log10 CFU/mL average reduction in viable cells in 1 hour. STFX showed a statistically significant advantage in initial bactericidal activity over other quinolones for single mutants (P < 0.001). The propensity that the difference in the initial bactericidal activity between STFX and other quinolones was higher in single mutants than wild-type strains, was confirmed using S. pneumoniae ATCC49619 (wild-type) and its laboratory single parC mutant. As a result, STFX showed a similar rapid and potent initial bactericidal activity against both strains, while initial bactericidal activity for other quinolones was significantly reduced in the single mutant (P < 0.05). In conclusion, STFX has the most rapid and potent initial bactericidal activity against wild-type and single mutants of S. pneumoniae and its bactericidal activity is not affected by the presence of a single par mutation compared to LVFX, MFLX, and GRNX.

  19. Peripheral sounds rapidly activate visual cortex: evidence from electrocorticography.

    PubMed

    Brang, David; Towle, Vernon L; Suzuki, Satoru; Hillyard, Steven A; Di Tusa, Senneca; Dai, Zhongtian; Tao, James; Wu, Shasha; Grabowecky, Marcia

    2015-11-01

    Neurophysiological studies with animals suggest that sounds modulate activity in primary visual cortex in the presence of concurrent visual stimulation. Noninvasive neuroimaging studies in humans have similarly shown that sounds modulate activity in visual areas even in the absence of visual stimuli or visual task demands. However, the spatial and temporal limitations of these noninvasive methods prevent the determination of how rapidly sounds activate early visual cortex and what information about the sounds is relayed there. Using spatially and temporally precise measures of local synaptic activity acquired from depth electrodes in humans, we demonstrate that peripherally presented sounds evoke activity in the anterior portion of the contralateral, but not ipsilateral, calcarine sulcus within 28 ms of sound onset. These results suggest that auditory stimuli rapidly evoke spatially specific activity in visual cortex even in the absence of concurrent visual stimulation or visual task demands. This rapid auditory-evoked activation of primary visual cortex is likely to be mediated by subcortical pathways or direct cortical projections from auditory to visual areas.

  20. Experience with family activation of rapid response teams.

    PubMed

    Bogert, Soudi; Ferrell, Carmen; Rutledge, Dana N

    2010-01-01

    Condition H allows family activation of a rapid response team in a hospital setting. Systematic implementation of Condition H at a 500-bed Magnet community hospital led to varied types of calls, all of which met the policy criteria. Many communication issues were discovered through this process.

  1. Increased nociceptive input rapidly modulates spinal GABAergic transmission through endogenously released glutamate.

    PubMed

    Zhou, Hong-Yi; Zhang, Hong-Mei; Chen, Shao-Rui; Pan, Hui-Lin

    2007-01-01

    Stimulation of nociceptive primary afferents elicits pain by promoting glutamatergic transmission in the spinal cord. Little is known about how increased nociceptive input controls GABAergic tone in the spinal dorsal horn. In this study, we determined how increased nociceptive inflow affects GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons by using whole cell recordings in rat spinal cord slices. Bath application of capsaicin for 3 min induced a long-lasting inhibition of sIPSCs in 50% of the neurons tested. In the other half of the neurons, capsaicin either increased the frequency of sIPSCs (34.6%) or had no effect on sIPSCs (15.4%). The GABA(A) current elicited by puff application of GABA was not altered by capsaicin. Capsaicin did not inhibit sIPSCs in rats treated with intrathecal pertussis toxin. Also, capsaicin failed to inhibit sIPSCs in the presence of ionotropic glutamate receptor antagonists or in the presence of both LY341495 and CPPG (group II and group III metabotropic glutamate receptor antagonists, respectively). However, when LY341495 or CPPG was used alone, capsaicin still decreased the frequency of sIPSCs in some neurons. Additionally, bradykinin significantly inhibited sIPSCs in a population of lamina II neurons and this inhibitory effect was also abolished by LY341495 and CPPG. Our study provides novel information that stimulation of nociceptive primary afferents rapidly suppresses GABAergic input to many dorsal horn neurons through endogenous glutamate and activation of presynaptic group II and group III metabotropic glutamate receptors. These findings extend our understanding of the microcircuitry of the spinal dorsal horn involved in nociception.

  2. Increased non-rapid eye movement sleep by cocaine withdrawal: possible involvement of A2A receptors.

    PubMed

    Yang, Shu-Long; Han, Jin-Yi; Kim, Yun-Bae; Nam, Sang-Yoon; Song, Sukgil; Hong, Jin Tae; Oh, Ki-Wan

    2011-02-01

    This study attempted to clarify whether cocaine withdrawal altered sleep architecture and the role of adenosine receptors in this process. Cocaine (20 mg/kg) was administered subcutaneously once per day for 7 days to rat implanted with sleep/wake recording electrode. Polygraphic signs of undisturbed sleep/wake activities were recorded for 24 h before cocaine administration (basal recording as control); withdrawal-day 1 (after 1 day of repeated cocaine administration), withdrawal-day 8 (after 8 days of repeated cocaine administration), and withdrawal-day 14 (after 14 days of repeated cocaine administration), respectively. On cocaine withdrawal-day 1, wakefulness was significantly increased, total sleep was decreased, non-rapid eye movement sleep was markedly reduced, and rapid eye movement sleep was enhanced. Sleep/wake cycles were also increased on cocaine withdrawal day 1. However, non-rapid eye movement sleep was increased on withdrawal-day 8 and 14, whereas rapid eye movement sleep was decreased and no significant changes were observed in the total sleep and sleep/wake cycles during these periods. Adenosine A(2A) receptors expression was increased on withdrawal-day 8 and 14, whereas A(1) receptors levels were reduced after 14 days of withdrawal and the A(2B) receptors remained unchanged. Our findings suggest that alterations of sleep and sleep architecture during cocaine subacute and subchronic withdrawals after repeated cocaine administration may be partially involved in A(2A) receptors over-expression in the rat hypothalamus.

  3. Rapid toxicity testing based on mitochondrial respiratory activity

    SciTech Connect

    Haubenstricker, M.E. ); Holodnick, S.E.; Mancy, K.H. ); Brabec, M.J. )

    1990-05-01

    The need exists for rapid and inexpensive methods to determine the health effects of environmental contaminants on biological systems. One of the current research approaches for assessing cytotoxicity is to monitor the respiratory activity of the mitochondrion, a sensitive, nonspecific subcellular target site. Detected changes in mitochondrial function after the addition of a test chemical could be correlated to toxic effects. Mitochondrial respiration can be characterized by three indices: state 3 and state 4 respiratory rates, and the respiratory control ratio (RCR). State 4, the idle or resting state, results when coupled mitochondrial respire in a medium containing inorganic phosphate and a Kreb's cycle substrate in the absence of a phosphate acceptor such as adenosine diphosphate (ADP). In the presence of ADP the respiration rate increases to a maximum (state 3), accompanied by phosphorylation of ADP to adenosine triphosphate (ATP). The ratio of state 3 to state 4, or RCR, indicates how tightly the oxidative phosphorylation process is coupled. The synthesis of ATP by mitochondria is influenced by a number of compounds, most of which are either uncouplers or inhibitors.

  4. Rapid weather changes are associated with increased ischemic stroke risk: a case-crossover study.

    PubMed

    Rakers, Florian; Schiffner, Rene; Rupprecht, Sven; Brandstädt, Antje; Witte, Otto W; Walther, Mario; Schlattmann, Peter; Schwab, Matthias

    2016-02-01

    Observational studies focusing on absolute meteorological values suggest an association between meteorological parameters and stroke risk but these results are inconsistent and conflicting. Since changes in weather can provoke atrial fibrillation, we examined the association between rapid weather changes and stroke risk in 1694 patients with determinable onset of stroke symptoms in a case-crossover study in central Germany. Days one to three before stroke onset were classified as hazard periods and day seven as the respective control period. Risk of ischemic stroke in relation to 24 h differences in mean ambient temperature, relative humidity and atmospheric pressure was determined. The association between temperature and stroke risk appears to be close to linear with an increase in stroke risk of 11 % (odds ratio 1.11, 95 % confidence interval 1.01-1.22) for each 2.9 °C temperature decrease over 24 h. In individuals with a higher cardiovascular risk, stroke risk increased by 30 % (1.30, 1.06-1.61). Risk for cardioembolic strokes increased by 26 % (1.26, 1.06-1.50). Rapid positive or negative changes in relative humidity (>5 %) and atmospheric pressure (>10 hPa) increased stroke risk by a maximum of 30 % (1.30, 1.02-1.66) and 63 % (1.63, 1.10-2.42). In individuals with a higher cardiovascular risk, rapid changes in atmospheric pressure were associated with a four-times higher stroke risk (4.56, 1.26-16.43). Our results suggest that rapid decreases in ambient temperature and rapid changes in relative humidity and atmospheric pressure increase stroke risk under temperate climate conditions. Individuals with a high cardiovascular risk profile seem to be at greater risk.

  5. Rapid increase in growth and productivity can aid invasions by a non-native tree.

    PubMed

    Dudeque Zenni, Rafael; Lacerda da Cunha, Wanderson; Sena, Guilherme

    2016-01-01

    Research on biological invasions has produced detailed theories describing range expansions of introduced populations. However, current knowledge of evolutionary factors associated with invasive range expansions, especially those related to rapid evolution of long-lived organisms, is still rudimentary. Here, we used a system of six 40-year-old invasive pine populations that originated from replicated introduction events to study evolution in productivity, growth, and chemical defence traits. We tested the hypotheses that invasive populations were undergoing rapid phenotypic change as populations spread, that populations exhibit trade-offs between evolution in growth and chemical defences, and that rates of rapid evolution in plant growth and productivity effect rates of invasion. Although all invasions started from replicated pools of genetic material and equal propagule pressure, we found divergence in mean values for the six invasive populations in the six traits measured. Not only were there between-population variations but also invasive populations were also rapidly changing along each invasive population expansion. Two populations displayed greater leaf areas (LAs) and smaller specific LAs (SLAs) during range expansion. Four populations had faster growth rates at the leading edge of the invasion front in comparison with plants at the rear edge. In terms of total plant defences, non-volatile resin increased in plants along one invasion gradient and decreased in a second, total needle phenolics increased in plants along one invasion gradient and total wood phenolics increased in plants along the one invasion gradient and decreased in a second. We found no trade-offs between investments in growth and chemical defence. Also, faster rates of change in growth rate and LA were positively associated with greater dispersal distances of invasive populations, suggesting rapid evolution may increase invasiveness. Understanding the roles of both natural and human

  6. Rapid increase in growth and productivity can aid invasions by a non-native tree

    PubMed Central

    Dudeque Zenni, Rafael; Lacerda da Cunha, Wanderson; Sena, Guilherme

    2016-01-01

    Research on biological invasions has produced detailed theories describing range expansions of introduced populations. However, current knowledge of evolutionary factors associated with invasive range expansions, especially those related to rapid evolution of long-lived organisms, is still rudimentary. Here, we used a system of six 40-year-old invasive pine populations that originated from replicated introduction events to study evolution in productivity, growth, and chemical defence traits. We tested the hypotheses that invasive populations were undergoing rapid phenotypic change as populations spread, that populations exhibit trade-offs between evolution in growth and chemical defences, and that rates of rapid evolution in plant growth and productivity effect rates of invasion. Although all invasions started from replicated pools of genetic material and equal propagule pressure, we found divergence in mean values for the six invasive populations in the six traits measured. Not only were there between-population variations but also invasive populations were also rapidly changing along each invasive population expansion. Two populations displayed greater leaf areas (LAs) and smaller specific LAs (SLAs) during range expansion. Four populations had faster growth rates at the leading edge of the invasion front in comparison with plants at the rear edge. In terms of total plant defences, non-volatile resin increased in plants along one invasion gradient and decreased in a second, total needle phenolics increased in plants along one invasion gradient and total wood phenolics increased in plants along the one invasion gradient and decreased in a second. We found no trade-offs between investments in growth and chemical defence. Also, faster rates of change in growth rate and LA were positively associated with greater dispersal distances of invasive populations, suggesting rapid evolution may increase invasiveness. Understanding the roles of both natural and human

  7. Rapid optical determination of β-lactamase and antibiotic activity

    PubMed Central

    2014-01-01

    Background The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect β-lactamase and thereby assess activity of β-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics. The methodology is centred on a fluorescence quenching based probe (β-LEAF – β-Lactamase Enzyme Activated Fluorophore) that mimics the structure of β-lactam antibiotics. Results The β-LEAF assay was performed for rapid determination of β-lactamase production and activity of β-lactam antibiotic (cefazolin) on a panel of Staphylococcus aureus ATCC strains and clinical isolates. Four of the clinical isolates were determined to be lactamase producers, with the capacity to inactivate cefazolin, out of the twenty-five isolates tested. These results were compared against gold standard methods, nitrocefin disk test for β-lactamase detection and disk diffusion for antibiotic susceptibility, showing results to be largely consistent. Furthermore, in the sub-set of β-lactamase producers, it was demonstrated and validated that multiple antibiotics (cefazolin, cefoxitin, cefepime) could be assessed simultaneously to predict the antibiotic that would be most active for a given bacterial isolate. Conclusions The study establishes the rapid β-LEAF assay for β-lactamase detection and prediction of antibiotic activity using S. aureus clinical isolates. Although the focus in the current study is β-lactamase-based resistance, the overall approach represents a broad diagnostic platform. In the long-term, these studies form the basis for the development of assays utilizing a broader variety of targets, pathogens and drugs. PMID:24708478

  8. Increased uptake by splenic red pulp macrophages contributes to rapid platelet turnover in WASP(-) mice.

    PubMed

    Prislovsky, Amanda; Strom, Ted S

    2013-09-01

    Thrombocytopenia caused by rapid platelet consumption contributes to the severe thrombocytopenia of Wiskott-Aldrich syndrome (WAS) and to the milder thrombocytopenia seen in murine WAS. We show that rapid clearance of ¹¹¹In-labeled murine WASP(-) platelets correlates with enhanced splenic uptake. Using platelets labeled with a pH-sensitive fluorescent marker (pHrodo), we quantify normal platelet uptake by red pulp macrophages (RPMs), and demonstrate its enhancement after in vivo opsonization of platelets. The spleens of WASP(-) mice contain an increased number of RPM, and rapid clearance of WASP(-) platelets in WASP(-) mice in turn generates an increased number of pHrodo(+) splenic RPMs. To separately assess the platelet intrinsic and recipient-dependent functions involved in the clearance and splenic phagocyte uptake of WASP(-) platelets, we performed "crossed" pHrodo(+) platelet injection studies (wild type [WT] to WASP(-), WASP(-) to WT). We show that an extrinsic effect of recipient WASP deficiency on the clearance of WASP(-) platelets correlates with increased platelet uptake by RPMs. An intrinsic effect of platelet WASP deficiency on platelet clearance does not, however, correlate with increased total uptake by WT or WASP(-) RPMs. In contrast to other published findings, we find no evidence of a baseline or antibody-induced increase in phosphatidyl serine exposure on WASP(-) platelets. Our findings suggest that an increased number of RPMs in WASP(-) mice contributes significantly to the increased platelet consumption rate in WASP(-) mice. This might explain the consistent efficacy of splenectomy in murine and clinical WAS.

  9. Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report

    PubMed Central

    Li, Hong-Jiang; Han, Hong-Xiu; Feng, Dong-Fu

    2016-01-01

    Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties. PMID:27698865

  10. Rapid increase of spines by dihydrotestosterone and testosterone in hippocampal neurons: Dependence on synaptic androgen receptor and kinase networks.

    PubMed

    Hatanaka, Yusuke; Hojo, Yasushi; Mukai, Hideo; Murakami, Gen; Komatsuzaki, Yoshimasa; Kim, Jonghyuk; Ikeda, Muneki; Hiragushi, Ayako; Kimoto, Tetsuya; Kawato, Suguru

    2015-09-24

    Rapid modulation of hippocampal synaptic plasticity by locally synthesized androgen is important in addition to circulating androgen. Here, we investigated the rapid changes of dendritic spines in response to the elevation of dihydrotestosterone (DHT) and testosterone (T), by using hippocampal slices from adult male rats, in order to clarify whether these signaling processes include synaptic/extranuclear androgen receptor (AR) and activation of kinases. We found that the application of 10nM DHT and 10nM T increased the total density of spines by approximately 1.3-fold within 2h, by imaging Lucifer Yellow-injected CA1 pyramidal neurons. Interestingly, DHT and T increased different head-sized spines. While DHT increased middle- and large-head spines, T increased small-head spines. Androgen-induced spinogenesis was suppressed by individually blocking Erk MAPK, PKA, PKC, p38 MAPK, LIMK or calcineurin. On the other hand, blocking CaMKII did not inhibit spinogenesis. Blocking PI3K altered the spine head diameter distribution, but did not change the total spine density. Blocking mRNA and protein synthesis did not suppress the enhancing effects induced by DHT or T. The enhanced spinogenesis by androgens was blocked by AR antagonist, which AR was localized postsynaptically. Taken together, these results imply that enhanced spinogenesis by DHT and T is mediated by synaptic/extranuclear AR which rapidly drives the kinase networks. This article is part of a Special Issue entitled SI: Brain and Memory.

  11. Rapid increase in southern elephant seal genetic diversity after a founder event.

    PubMed

    de Bruyn, Mark; Pinsky, Malin L; Hall, Brenda; Koch, Paul; Baroni, Carlo; Hoelzel, A Rus

    2014-03-22

    Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population.

  12. Exercise Sandals Increase Lower Extremity Electromyographic Activity During Functional Activities

    PubMed Central

    Hirth, Christopher J.; Guskiewicz, Kevin M.

    2003-01-01

    Objective: Anecdotal evidence suggests that use of Exercise Sandals results in a number of positive clinical outcomes. However, little research has been conducted to determine their efficacy objectively. Our purposes were to determine the effect of Exercise Sandals on lower leg electromyography (EMG) during activities in the Exercise Sandals and to compare EMG associated with Exercise Sandals with traditional lower extremity rehabilitation exercises. Design and Setting: Two within-subjects, repeated-measures designs were used to identify differences in lower extremity EMG: (1) between activities with and without Exercise Sandals and (2) between Exercise Sandals activities and traditional rehabilitation activities. All data were collected in the Sports Medicine Research Laboratory. Subjects: Eighteen subjects involved in rehabilitation using Exercise Sandals for at least 2 weeks within the year before data collection. Measurements: Mean EMG amplitudes from the tibialis anterior, peroneus longus, soleus, and lateral gastrocnemius muscles were measured during single-leg stance, side stepping, and “high knees,” all performed with and without the Exercise Sandals, as well as single-leg stance on a foam surface and T-band kicks in the sagittal and frontal planes. Results: Exercise Sandals increased lower leg EMG activity, particularly in the ankle invertors and evertors. Also, activities involving the Exercise Sandals resulted in EMG activity similar to or exceeding that associated with traditional ankle-rehabilitation exercises. Conclusions: These results, coupled with the fact that Exercise Sandals are used in a functional closed kinetic chain manner, suggest that they are an effective means of increasing lower extremity muscle activity. PMID:14608427

  13. Nest predation increases with parental activity: Separating nest site and parental activity effects

    USGS Publications Warehouse

    Martin, T.E.; Scott, J.; Menge, C.

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators have found similar results. We tested whether nest site effects might yield higher predation during incubation because the most obvious sites are depredated most rapidly. We conducted experiments using nest sites from the previous year to remove parental activity. Our results showed that nest sites have highly repeatable effects on nest predation risk; poor nest sites incurred rapid predation and caused predation rates to be greater during the incubation than nestling stage. This pattern also was exhibited in a bird species with similar (i.e. controlled) parental activity between nesting stages. Once nest site effects are taken into account, nest predation shows a strong proximate increase with parental activity during the nestling stage within and across species. Parental activity and nest sites exert antagonistic influences on current estimates of nest predation between nesting stages and both must be considered in order to understand current patterns of nest predation, which is an important source of natural selection.

  14. Nest predation increases with parental activity: separating nest site and parental activity effects.

    PubMed Central

    Martin, T E; Scott, J; Menge, C

    2000-01-01

    Alexander Skutch hypothesized that increased parental activity can increase the risk of nest predation. We tested this hypothesis using ten open-nesting bird species in Arizona, USA. Parental activity was greater during the nestling than incubation stage because parents visited the nest frequently to feed their young during the nestling stage. However, nest predation did not generally increase with parental activity between nesting stages across the ten study species. Previous investigators have found similar results. We tested whether nest site effects might yield higher predation during incubation because the most obvious sites are depredated most rapidly. We conducted experiments using nest sites from the previous year to remove parental activity. Our results showed that nest sites have highly repeatable effects on nest predation risk; poor nest sites incurred rapid predation and caused predation rates to be greater during the incubation than nestling stage. This pattern also was exhibited in a bird species with similar (i.e. controlled) parental activity between nesting stages. Once nest site effects are taken into account, nest predation shows a strong proximate increase with parental activity during the nestling stage within and across species. Parental activity and nest sites exert antagonistic influences on current estimates of nest predation between nesting stages and both must be considered in order to understand current patterns of nest predation, which is an important source of natural selection. PMID:11413645

  15. Sensor web enables rapid response to volcanic activity

    USGS Publications Warehouse

    Davies, Ashley G.; Chien, Steve; Wright, Robert; Miklius, Asta; Kyle, Philip R.; Welsh, Matt; Johnson, Jeffrey B.; Tran, Daniel; Schaffer, Steven R.; Sherwood, Robert

    2006-01-01

    Rapid response to the onset of volcanic activity allows for the early assessment of hazard and risk [Tilling, 1989]. Data from remote volcanoes and volcanoes in countries with poor communication infrastructure can only be obtained via remote sensing [Harris et al., 2000]. By linking notifications of activity from ground-based and spacebased systems, these volcanoes can be monitored when they erupt.Over the last 18 months, NASA's Jet Propulsion Laboratory (JPL) has implemented a Volcano Sensor Web (VSW) in which data from ground-based and space-based sensors that detect current volcanic activity are used to automatically trigger the NASA Earth Observing 1 (EO-1) spacecraft to make highspatial-resolution observations of these volcanoes.

  16. Boiling phenomenon due to quasi-steadily and rapidly increasing heat inputs in LN 2 and LHe I

    NASA Astrophysics Data System (ADS)

    Sakurai, A.; Shiotsu, M.; Hata, K.

    Dynamic boiling processes, including the transition from a single-phase non-boiling regime to film boiling caused by exponentially increasing heat inputs, Q 0e t/τ for a wide range of periods and pressures on horizontal wires in LN 2 and LHe I were investigated. The main problem is that there are no active cavities on the wire surfaces for initial boiling in the liquids. The heat transfer processes due to increasing heat inputs with increasing rates ranging from quasi-steady to rapidly increasing ones in LN 2 were classified into three types for the pressures. The dynamic boiling processes in LHe I due to rapidly increasing heat inputs at the pressures tested here correspond to Type 3 processes including semi-direct transitions in LN 2 at pressures higher than about 1 MPa. The lower limit temperatures of boiling initiation on the wire surfaces for initial boiling in liquids at pressures due to quasi-steadily increasing heat inputs are clearly lower than the homogeneous spontaneous nucleation temperatures corresponding to these pressures. Liquid superheat close to the solid surface in LHe I was evaluated from the value of the wire surface temperature, taking off the temperature drop due to Kapitza resistance. The initial boiling temperatures due to quasi-steady heat inputs at pressures in saturated LN 2 and LHe I agreed with the values derived from the theoretical model based on the heterogeneous spontaneous nucleation in flooded cavities on the solid surface.

  17. Rapid growth results in increased susceptibility to predation in Menidia menidia.

    PubMed

    Munch, Stephan B; Conover, David O

    2003-09-01

    Several recent studies have demonstrated that rapid growth early in life leads to decreased physiological performance. Nearly all involved experiments over short time periods (<1 day) to control for potentially confounding effects of size. This approach, however, neglects the benefits an individual accrues by growing. The net effect of growth can only be evaluated over a longer interval in which rapidly growing individuals are allowed the time required to attain the expected benefits of large size. We used two populations of Menidia menidia with disparate intrinsic growth rates to address this issue. We compared growth and survivorship among populations subject to predation in mesocosms under ambient light and temperature conditions for a period of up to 30 days to address two questions: Do the growth rates of fish in these populations respond differently to the presence of predators? Is the previously demonstrated survival cost of growth counterbalanced by the benefits of increased size? We found that growth was insensitive to predation risk: neither population appeared to modify growth rates in response to predation levels. Moreover, the fast-growing population suffered significantly higher mortality throughout the trials despite being 40% larger than the slow-growing population at the experiment's end. These results confirm that the costs of rapid growth extend over prolonged intervals and are not ameliorated merely by the attainment of large size.

  18. Rapid activation of gill Na+,K+-ATPase in the euryhaline teleost Fundulus heteroclitus

    USGS Publications Warehouse

    Mancera, J.M.; McCormick, S.D.

    2000-01-01

    The rapid activation of gill Na+,K+-ATPase was analyzed in the mummichog (Fundulus heteroclitus) and Atlantic salmon (Salmo salar) transferred from low salinity (0.1 ppt) to high salinity (25-35 ppt). In parr and presmolt, Salmo salar gill Na+,K+-ATPase activity started to increase 3 days after transfer. Exposure of Fundulus heteroclitus to 35 ppt seawater (SW) induced a rise in gill Na+,K+-ATPase activity 3 hr after transfer. After 12 hr, the values dropped to initial levels but showed a second significant increase 3 days after transfer. The absence of detergent in the enzyme assay resulted in lower values of gill Na+,K+-ATPase, and the rapid increase after transfer to SW was not observed. Na+,K+-ATPase activity of gill filaments in vitro for 3 hr increased proportionally to the osmolality of the culture medium (600 mosm/kg > 500 mosm/kg > 300 mosm/kg). Osmolality of 800 mosm/kg resulted in lower gill Na+,K+-ATPase activity relative to 600 mosm/kg. Increasing medium osmolality to 600 mosm/kg with mannitol also increased gill Na+,K+-ATPase. Cycloheximide inhibited the increase in gill Na+,K+-ATPase activity observed in hyperosmotic medium in a dose-dependent manner (10-4 M > 10-5 M > 10-6 M). Actinomycin D or bumetanide in the culture (doses of 10-4 M, 10-5 M, and 10-6 M) did not affect gill Na+,K+-ATPase. Injection of fish with actinomycin D prior to gill organ culture, however, prevented the increase in gill Na+,K+-ATPase activity in hyperosmotic media. The results show a very rapid and transitory increase in gill Na+,K+-ATPase activity in the first hours after the transfer of Fundulus heteroclitus to SW that is dependent on translational and transcriptional processes. (C) 2000 Wiley-Liss, Inc.

  19. Rapid increase in relativistic electron flux controlled by nonlinear phase trapping of whistler chorus elements

    NASA Astrophysics Data System (ADS)

    Saito, Shinji; Miyoshi, Yoshizumi; Seki, Kanako

    2016-07-01

    Wave-particle interactions with whistler chorus waves are believed to provide a primary acceleration for electrons in the outer radiation belt. Previous models for flux enhancement of the radiation belt have assumed the stochastic process as a diffusion manner of successive random-phase interactions, but physical mechanisms for the acceleration are not fully incorporated in these models because of the lack of a nonlinear scattering process. Here we report rapid increase in relativistic electron flux by using an innovative computer simulation model that incorporates not only diffusive process but also nonlinear scattering processes. The simulations show that three types of scattering simultaneously occur, which are diffusive, phase trapping, and phase bunching. It is found that the phase trapping is the most efficient mechanism to produce the MeV electrons rapidly in the scattering processes. The electrons are accelerated from 400 keV to over 1 MeV in time scale less than 60 s. On the other hand, as the phase trapping is suppressed by the breaking of relative phase angle between waves and gyrating electrons during the interaction, the increase of electron flux at MeV energy is clearly reduced. Our simulations conclude that the phase-trapping process causes a significant effect for the increase in relativistic electron flux and suggest that a quasi-linear diffusion model is not always valid to fully describe the relativistic electron acceleration.

  20. Fractionation of muscle activity in rapid responses to startling cues

    PubMed Central

    Dean, Lauren R.

    2017-01-01

    Movements in response to acoustically startling cues have shorter reaction times than those following less intense sounds; this is known as the StartReact effect. The neural underpinnings for StartReact are unclear. One possibility is that startling cues preferentially invoke the reticulospinal tract to convey motor commands to spinal motoneurons. Reticulospinal outputs are highly divergent, controlling large groups of muscles in synergistic patterns. By contrast the dominant pathway in primate voluntary movement is the corticospinal tract, which can access small groups of muscles selectively. We therefore hypothesized that StartReact responses would be less fractionated than standard voluntary reactions. Electromyogram recordings were made from 15 muscles in 10 healthy human subjects as they carried out 32 varied movements with the right forelimb in response to startling and nonstartling auditory cues. Movements were chosen to elicit a wide range of muscle activations. Multidimensional muscle activity patterns were calculated at delays from 0 to 100 ms after the onset of muscle activity and subjected to principal component analysis to assess fractionation. In all cases, a similar proportion of the total variance could be explained by a reduced number of principal components for the startling and the nonstartling cue. Muscle activity patterns for a given task were very similar in response to startling and nonstartling cues. This suggests that movements produced in the StartReact paradigm rely on similar contributions from different descending pathways as those following voluntary responses to nonstartling cues. NEW & NOTEWORTHY We demonstrate that the ability to activate muscles selectively is preserved during the very rapid reactions produced following a startling cue. This suggests that the contributions from different descending pathways are comparable between these rapid reactions and more typical voluntary movements. PMID:28003416

  1. High altitude simulation, substance P and airway rapidly adapting receptor activity in rabbits.

    PubMed

    Bhagat, R; Yasir, A; Vashisht, A; Kulshreshtha, R; Singh, S B; Ravi, K

    2011-09-15

    To investigate whether there is a change in airway rapidly adapting receptor (RAR) activity during high altitude exposure, rabbits were placed in a high altitude simulation chamber (barometric pressure, 429 mm Hg). With 12 h exposure, when there was pulmonary congestion, an increase in basal RAR activity was observed. With 36 h exposure, when there was alveolar edema, there was a further increase in basal RAR activity. In these backgrounds, there was an increase in the sensitivity of the RARs to substance P (SP). To assess whether there was an increase in lung SP level, neutral endopeptidase activity was determined which showed a decrease in low barometric pressure exposed groups. It is concluded that along with the SP released, pulmonary congestion and edema produced, respectively by different durations of low barometric pressure exposure cause a progressive increase in RAR activity which may account for the respiratory symptoms reported in climbers who are unacclimatized.

  2. School Programs to Increase Physical Activity

    ERIC Educational Resources Information Center

    Lee, Amelia; Solmon, Melinda

    2007-01-01

    A quality physical education program is at the heart of any plan to promote lifelong participation in physical activity, but it has become evident at many schools that physical education specialists alone cannot address the physical activity needs of children. This is why a series of studies were conducted to develop strategies for the…

  3. Rapid response of a hydrologic system to volcanic activity: Masaya volcano, Nicaragua

    USGS Publications Warehouse

    Pearson, S.C.P.; Connor, C.B.; Sanford, W.E.

    2008-01-01

    Hydrologic systems change in response to volcanic activity, and in turn may be sensitive indicators of volcanic activity. Here we investigate the coupled nature of magmatic and hydrologic systems using continuous multichannel time series of soil temperature collected on the flanks of Masaya volcano, Nicaragua, one of the most active volcanoes in Central America. The soil temperatures were measured in a low-temperature fumarole field located 3.5 km down the flanks of the volcano. Analysis of these time series reveals that they respond extremely rapidly, on a time scale of minutes, to changes in volcanic activity also manifested at the summit vent. These rapid temperature changes are caused by increased flow of water vapor through flank fumaroles during volcanism. The soil temperature response, ~5 °C, is repetitive and complex, with as many as 13 pulses during a single volcanic episode. Analysis of the frequency spectrum of these temperature time series shows that these anomalies are characterized by broad frequency content during volcanic activity. They are thus easily distinguished from seasonal trends, diurnal variations, or individual rainfall events, which triggered rapid transient increases in temperature during 5% of events. We suggest that the mechanism responsible for the distinctive temperature signals is rapid change in pore pressure in response to magmatism, a response that can be enhanced by meteoric water infiltration. Monitoring of distal fumaroles can therefore provide insight into coupled volcanic-hydrologic-meteorologic systems, and has potential as an inexpensive monitoring tool.

  4. Changing arctic ecosystems—What is causing the rapid increase of snow geese in northern Alaska?

    USGS Publications Warehouse

    Hupp, Jerry W.; Ward, David H.; Whalen, Mary E.; Pearce, John M.

    2015-09-10

    Through the Changing Arctic Ecosystems (CAE) initiative, the U.S. Geological Survey (USGS) informs key resource management decisions for Arctic Alaska by providing scientific information on current and future ecosystem response to a warming climate. The Arctic Coastal Plain (ACP) of northern Alaska is a key study area within the USGS CAE initiative. This region has experienced a warming trend over the past decades, leading to decreased sea ice, permafrost thaw, and an advancement of spring phenology. The number of birds on the ACP also is changing, marked by increased populations of the four species of geese that nest in the region. The Snow Goose (Chen caerulescens) is the most rapidly increasing of these species. USGS CAE research is quantifying these changes and their implications for management agencies.

  5. Rapid increase in the national treatment costs for hepatitis A infections in Korea.

    PubMed

    Park, Hee Suk; Choi, Bo Youl; Kwon, Young Dae

    2012-01-01

    The number of symptomatic hepatitis A cases has progressively been increasing during the last several years in Korea. Available cost estimates indicate a growing burden to the public. The purpose of this study was to determine the extent of treatment costs for patients with hepatitis A and to analyze the influential factors with nationwide data. We collected data on 72,921 patients with hepatitis A from 5-year National Health Insurance claim archives between 2004 and 2008. Multiple regression analyses were conducted to examine influential factors affecting treatment costs for hepatitis A. Total treatment costs for patients with hepatitis A during the 5-year period were US$47,902,087 and increased significantly each year. In total, 91.4% of treatment costs were used for hospitalization, and the proportion of inpatients increased gradually throughout the study period. The most influential factor on treatment costs was treatment duration. Our results show that the soaring number of patients with hepatitis A followed by the hospitalization-focused treatment practice is a major factor associated with the rapid increase in treatment costs. Appropriate policies should be promptly developed to control treatment costs and economic burden of hepatitis A infections.

  6. Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.

    PubMed

    Barouch, Dan H; Ghneim, Khader; Bosche, William J; Li, Yuan; Berkemeier, Brian; Hull, Michael; Bhattacharyya, Sanghamitra; Cameron, Mark; Liu, Jinyan; Smith, Kaitlin; Borducchi, Erica; Cabral, Crystal; Peter, Lauren; Brinkman, Amanda; Shetty, Mayuri; Li, Hualin; Gittens, Courtney; Baker, Chantelle; Wagner, Wendeline; Lewis, Mark G; Colantonio, Arnaud; Kang, Hyung-Joo; Li, Wenjun; Lifson, Jeffrey D; Piatak, Michael; Sekaly, Rafick-Pierre

    2016-04-21

    The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

  7. Increased ABCA1 activity protects against atherosclerosis.

    PubMed

    Singaraja, Roshni R; Fievet, Catherine; Castro, Graciela; James, Erick R; Hennuyer, Nathalie; Clee, Susanne M; Bissada, Nagat; Choy, Jonathan C; Fruchart, Jean-Charles; McManus, Bruce M; Staels, Bart; Hayden, Michael R

    2002-07-01

    The ABC transporter ABCA1 plays a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages. Previously, it was demonstrated that human ABCA1 overexpression in vivo in transgenic mice results in a mild elevation of plasma HDL levels and increased efflux of cholesterol from macrophages. In this study, we determined the effect of overexpression of ABCA1 on atherosclerosis development. Human ABCA1 transgenic mice (BAC(+)) were crossed with ApoE(-/-) mice, a strain that spontaneously develop atherosclerotic lesions. BAC(+)ApoE(-/-) mice developed dramatically smaller, less-complex lesions as compared with their ApoE(-/-) counterparts. In addition, there was increased efflux of cholesterol from macrophages isolated from the BAC(+)ApoE(-/-) mice. Although the increase in plasma HDL cholesterol levels was small, HDL particles from BAC(+)ApoE(-/-) mice were significantly better acceptors of cholesterol. Lipid analysis of HDL particles from BAC(+)ApoE(-/-) mice revealed an increase in phospholipid levels, which was correlated significantly with their ability to enhance cholesterol efflux.

  8. Changes in Indirect Markers of Muscle Damage and Tendons After Daily Drop Jumping Exercise with Rapid Load Increase

    PubMed Central

    Paleckis, Vidas; Mickevičius, Mantas; Snieckus, Audrius; Streckis, Vytautas; Pääsuke, Mati; Rutkauskas, Saulius; Steponavičiūtė, Rasa; Skurvydas, Albertas; Kamandulis, Sigitas

    2015-01-01

    The aim of this study was to assess changes in indirect markers of muscle damage and type I collagen degradation, as well as, patellar and Achilles tendon morphological differences during nine daily drop-jumps sessions with constant load alternated with rapid increases in load to test the hypothesis that frequent drop-jump training results in negative muscular and tendon adaptation. Young men (n = 9) performed daily drop jump workouts with progression every 3 days in terms of number of jumps, platform height and squat amplitude. Voluntary and electrically evoked knee extensor torque, muscle soreness, blood plasma creatine kinase (CK) activity and carboxyterminal cross-linked telopeptide (ICTP), patellar and Achilles tendon thickness and cross-sectional area (CSA) were assessed at different time points during the training period and again on days 1, 3, 10 and 17 after the training. The findings were as follows: (1) steady decline in maximal muscle strength with major recovery within 24 hours after the first six daily training sessions; (2) larger decline in electrically induced muscle torque and prolonged recovery during last three training sessions; (3) increase in patellar and Achilles tendons CSA without change in thickness towards the end of training period; (4) increase in jump height but not in muscle strength after whole training period. Our findings suggest that frequent drop-jump sessions with constant load alternated with rapid increases in load do not induce severe muscle damage or major changes in tendons, nonetheless, this type of loading is not advisable for muscle strength improvement. Key points Frequent drop jump training induces activation mode dependent muscle torque depression late in the training period. No significant changes in the thickness of patellar and Achilles tendons are observed during frequent training, while CSA increases towards the end of training period. Longitudinal effect for jump height but not for muscle strength is evident

  9. Small Projects Rapid Integration and Test Environment (SPRITE): Application for Increasing Robutness

    NASA Technical Reports Server (NTRS)

    Lee, Ashley; Rakoczy, John; Heather, Daniel; Sanders, Devon

    2013-01-01

    Over the past few years interest in the development and use of small satellites has rapidly gained momentum with universities, commercial, and government organizations. In a few years we may see networked clusters of dozens or even hundreds of small, cheap, easily replaceable satellites working together in place of the large, expensive and difficult-to-replace satellites now in orbit. Standards based satellite buses and deployment mechanisms, such as the CubeSat and Poly Pico-satellite Orbital Deployer (P-POD), have stimulated growth in this area. The use of small satellites is also proving to be a cost effective capability in many areas traditionally dominated by large satellites, though many challenges remain. Currently many of these small satellites undergo very little testing prior to flight. As these small satellites move from technology demonstration and student projects toward more complex operational assets, it is expected that the standards for verification and validation will increase.

  10. Rapid trait evolution drives increased speed and variance in experimental range expansions

    PubMed Central

    Weiss-Lehman, Christopher; Hufbauer, Ruth A; Melbourne, Brett A

    2017-01-01

    Range expansions are central to two ecological issues reshaping patterns of global biodiversity: biological invasions and climate change. Traditional theory considers range expansion as the outcome of the demographic processes of birth, death and dispersal, while ignoring the evolutionary implications of such processes. Recent research suggests evolution could also play a critical role in determining expansion speed but controlled experiments are lacking. Here we use flour beetles (Tribolium castaneum) to show experimentally that mean expansion speed and stochastic variation in speed are both increased by rapid evolution of traits at the expansion edge. We find that higher dispersal ability and lower intrinsic growth rates evolve at the expansion edge compared with spatially nonevolving controls. Furthermore, evolution of these traits is variable, leading to enhanced variance in speed among replicate population expansions. Our results demonstrate that evolutionary processes must be considered alongside demographic ones to better understand and predict range expansions. PMID:28128350

  11. Consistent abnormalities in metabolic network activity in idiopathic rapid eye movement sleep behaviour disorder.

    PubMed

    Wu, Ping; Yu, Huan; Peng, Shichun; Dauvilliers, Yves; Wang, Jian; Ge, Jingjie; Zhang, Huiwei; Eidelberg, David; Ma, Yilong; Zuo, Chuantao

    2014-12-01

    Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. 18F-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0±5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5±7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6±5.0 years) and 16 moderate parkinsonian patients (age 56.9±12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network characterized by increased activity in pons, thalamus, medial frontal and sensorimotor areas, hippocampus, supramarginal and inferior temporal gyri, and posterior cerebellum, with decreased activity in occipital and superior temporal regions. Compared to the healthy control subjects, network expressions were elevated (P<0.0001) in the patients with this disorder and in the parkinsonian cohorts but decreased with disease progression. Parkinson's disease-related network activity was also elevated (P<0.0001) in the patients with rapid eye movement sleep behaviour disorder but lower than in the hemi-parkinsonian cohort. Abnormal metabolic networks may provide markers of idiopathic rapid eye movement sleep behaviour disorder to identify those at higher risk to develop neurodegenerative parkinsonism.

  12. Repeated Administration of Korea Red Ginseng Extract Increases Non-Rapid Eye Movement Sleep via GABAAergic Systems.

    PubMed

    Lee, Chung-Il; Kim, Chung-Soo; Han, Jin-Yi; Oh, Eun-Hye; Oh, Ki-Wan; Eun, Jae Soon

    2012-10-01

    The current inquiry was conducted to assess the change in sleep architecture after long periods of administration to determine whether ginseng can be used in the therapy of sleeplessness. Following post-surgical recovery, red ginseng extract (RGE, 200 mg/ kg) was orally administrated to rats for 9 d. Data were gathered on the 1st, 5th, and 9th day, and an electroencephalogram was recorded 24 h after RGE administration. Polygraphic signs of unobstructed sleep-wake activities were simultaneously recorded with sleep-wake recording electrodes from 11:00 a.m. to 5:00 p.m. for 6 h. Rodents were generally tamed to freely moving polygraphic recording conditions. Although the 1st and 5th day of RGE treatment showed no effect on power densities in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, the 9th day of RGE administration showed augmented α-wave (8.0 to 13.0 Hz) power densities in NREM and REM sleep. RGE increased total sleep and NREM sleep. The total percentage of wakefulness was only decreased on the 9th day, and the number of sleep-wake cycles was reduced after the repeated administration of RGE. Thus, the repeated administration of RGE increased NREM sleep in rats. The α-wave activities in the cortical electroencephalograms were increased in sleep architecture by RGE. Moreover, the levels of both α- and β-subunits of the γ-aminobutyric acid (GABA)A receptor were reduced in the hypothalamus of the RGE-treated groups. The level of glutamic acid decarboxylase was over-expressed in the hypothalamus. These results demonstrate that RGE increases NREM sleep via GABAAergic systems.

  13. Rapid test for distinguishing membrane-active antibacterial agents.

    PubMed

    Prakash Singh, Maya

    2006-10-01

    In the search for antibacterial agents with a novel mode-of-action (MOA) many targeted cellular and cell-free assays are developed and used to screen chemical and natural product libraries. Frequently, hits identified by the primary screens include compounds with nonspecific activities that can affect the integrity and function of bacterial membrane. For a rapid dereplication of membrane-active compounds, a simple method was established using a commercially available Live/Dead(R) Bacterial Viability Kit. This method utilized two fluorescent nucleic acid stains, SYTO9 (stains all cells green) and propidium iodide (stains cells with damaged membrane red) for the drug-treated bacterial cells. The cells were then either examined visually by fluorescence microscopy or their fluorescence emissions were recorded using a multi-label plate reader set to measure emissions at two different wavelengths. The ratio of green versus red was compared to a standard curve indicating the percentage of live versus dead bacteria. Nine known antibiotics and 14 lead compounds from various antibacterial screens were tested with results consistent with their MOA.

  14. Rapid increase of carbonate in cortical bones of hens during laying period.

    PubMed

    Li, Z; Li, Q; Wang, S-J; Zhang, L; Qiu, J-Y; Wu, Y; Zhou, Z-L

    2016-12-01

    The incorporation of carbonate has been recognized as an evident change in bone mineral (bioapatite) during aging. Laying hens (Gushi layer) at 4 stages of age (8 hens each stage) were studied by Raman spectroscopy and X-ray radiography to investigate the mineralogical changes and bone density, respectively. Cortical bones of the humerus and femur show a rapid increase of carbonate (∼1.9 wt.%) from sexual maturity to the peak of hens' laying period, while the densities of the cortical bones are relatively stable. Before sexual maturity, the density of the cortical bones increases considerably during aging. However, after the peak of the laying period, only femoral density continues elevating. Carbonate contents in the cortical bones reach the maximum at the peak of the laying period. Two pathways (halted growth of density and Ca-release due to the CO3 incorporation) could both contribute to the intense Ca requirement for egg laying. Crystallization, however, has no significant changes during aging and the laying period. This study could shed light on the mechanism of mineral losses due to CO3 incorporation, and also shows the advantages of Raman spectroscopy in tracking mineral loss in poultry bone.

  15. Rapid warming increases survival of slow-frozen sibling oocytes: a step towards a single warming procedure irrespective of the freezing protocol?

    PubMed

    Parmegiani, Lodovico; Tatone, Carla; Cognigni, Graciela Estela; Bernardi, Silvia; Troilo, Enzo; Arnone, Alessandra; Maccarini, Antonio Manuel; Di Emidio, Giovanna; Vitti, Maurizio; Filicori, Marco

    2014-05-01

    Nowadays, human oocytes/embryos are cryopreserved via slow freezing or vitrification. The aim of this study was to evaluate a rapid warming protocol for slow-frozen human oocytes based on the standard warming procedure for vitrification. This was a prospective study on 216 sibling oocytes randomized for either conventional rapid thawing or rapid warming with vitrification warming solution. The primary endpoint was morphological assessment of survival at 2h. Surviving oocytes were divided into two subgroups: (i) parthenogenetically activated; and (ii) fixed and observed for spindle/chromosome configuration. Secondary endpoints were parthenogenetic development and spindle/metaphase configuration. Survival rate with rapid warming was higher (92/102, 90.2%) than with rapid thawing (85/114, 74.6%; P=0.005), and after 3d of culture the rapidly warmed parthenotes had more blastomeres compared with those rapidly thawed (P=0.042). Meiotic spindle and chromosomal configuration were not significantly influenced by rapid warming or rapid thawing. The finding of this study allows IVF centres to increase the efficiency of oocyte slow freezing, enabling survival rates comparable to vitrification protocols, and potentially to optimize costs by using the same warming protocol for both slow-frozen and vitrified reproductive cells.

  16. Trajectory Hunting: Analysis of UARS Measurements showing Rapid Chlorine Activation

    NASA Technical Reports Server (NTRS)

    Danilin, M.Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.

    1998-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the AER photochemical box model. In this study, we investigate rapid chlorine activation in the Arctic lower stratosphere on 29 Dec 1992 associated with a polar stratospheric cloud (PSC) event. Six air parcels that have been sampled twice were followed along 5-day trajectories at the 465 K (approximately 46 mb) and 585 K (approximately 22 mb) levels. A detailed sensitivity study with the AER. photochemical box model along these trajectories leads to the following conclusions for the episode considered: (1) model results are in better agreement with UARS measurements at these levels if the UKMO temperature is decreased by at least 1-2 K; (2) the NAT (nitric acid trihydrate) PSC formation scheme produces results in better agreement with observations than the STS (supercooled ternary solution) scheme; (3) the model can explain the UARS measurements at 585 K, but under-estimates the ClO abundance at 465 K, suggesting some inconsistency between the UARS measurements at this level.

  17. Trajectory Hunting: Analysis of UARS Measurements Showing Rapid Chlorine Activation

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.

    1998-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the AER photochemical box model. In this study, we investigate rapid chlorine activation in the Arctic lower stratosphere on 29 Dec. 1992 associated with a polar stratospheric cloud (PSC) event. Six air parcels that have been sampled twice were followed along 5-day trajectories at the 465 K (approx. 46 mb) and 585 K (approxi. 22 mb) levels. A detailed sensitivity study with the AER photochemical box model along these trajectories leads to the following conclusions for the episode considered: 1) model results are in better agreement with UARS measurements at these levels if the U.K. Meteorological Office (UKMO) temperature is decreased by at least 1-2 K; 2) the NAT (nitric acid trihydrate) PSC formation scheme produces results in better agreement with observations than the STS (supercooled ternary solution) scheme; 3) the model can explain the UARS measurements at 585 K, but under-estimates the ClO abundance at 465 K, suggesting some inconsistency between the UARS measurements at this level.

  18. Intracellular Ca2+ stores and Ca2+ influx are both required for BDNF to rapidly increase quantal vesicular transmitter release.

    PubMed

    Amaral, Michelle D; Pozzo-Miller, Lucas

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) is well known as a survival factor during brain development as well as a regulator of adult synaptic plasticity. One potential mechanism to initiate BDNF actions is through its modulation of quantal presynaptic transmitter release. In response to local BDNF application to CA1 pyramidal neurons, the frequency of miniature excitatory postsynaptic currents (mEPSC) increased significantly within 30 seconds; mEPSC amplitude and kinetics were unchanged. This effect was mediated via TrkB receptor activation and required both full intracellular Ca(2+) stores as well as extracellular Ca(2+). Consistent with a role of Ca(2+)-permeable plasma membrane channels of the TRPC family, the inhibitor SKF96365 prevented the BDNF-induced increase in mEPSC frequency. Furthermore, labeling presynaptic terminals with amphipathic styryl dyes and then monitoring their post-BDNF destaining in slice cultures by multiphoton excitation microscopy revealed that the increase in frequency of mEPSCs reflects vesicular fusion events. Indeed, BDNF application to CA3-CA1 synapses in TTX rapidly enhanced FM1-43 or FM2-10 destaining with a time course that paralleled the phase of increased mEPSC frequency. We conclude that BDNF increases mEPSC frequency by boosting vesicular fusion through a presynaptic, Ca(2+)-dependent mechanism involving TrkB receptors, Ca(2+) stores, and TRPC channels.

  19. Pointwise transinformation distinguishes a recurrent increase of synchronization in the rapid eye movement sleep electroencephalogram.

    PubMed

    Landwehr, Ralf; Jowaed, Ahmad

    2012-02-01

    The analysis of electroencephalogram (EEG) coupling patterns is essential for understanding how interrelations between cortical sites change with the wake-sleep cycle. Waking and sleep EEGs of 12 normal sleepers were analyzed by pointwise transinformation (PTI). Stage-dependent differences of PTI were assessed, and a spectral analysis of synchronized events was performed. A pattern of recurrent EEG synchronization was distinguished in all rapid eye movement (REM) sleep phases. The mean coupling of EEG leads differed regionally, with high coupling levels of frontal and occipital derivations and lower midtemporal and central coupling levels. Mean coupling levels were comparable in stages R, W, and N1 but were lower than in N2 and N3. An REM-specific pattern of low EEG synchronization was identified for F7-F8 and T3-T4, with lowest coupling levels during tonic REM sleep. Also, maximal intervals of uncoupled EEG were longer during tonic REM sleep. Because of these results, a new descriptive entity is proposed: the recurrent increase of synchronization in the EEG (RISE). This seems to reflect the dynamic aspects of spatiotemporal EEG synchronization on small time scales. A possibly specific low coupling pattern of the temporal leads may distinguish REM sleep from other states with a "desynchronized" EEG and, to some extent, tonic from phasic REM sleep.

  20. Rapid Drinking is Associated with Increases in Driving-Related Risk-Taking

    PubMed Central

    Bernosky-Smith, Kimberly A.; Aston, Elizabeth R.; Liguori, Anthony

    2014-01-01

    Objective The rate of alcohol drinking has been shown to predict impairment on cognitive and behavioral tasks. The current study assessed the influence of speed of alcohol consumption within a laboratory-administered binge on self-reported attitudes toward driving and simulated driving ability. Method Forty moderate drinkers (20 female, 20 male) were recruited from the local community via advertisements for individuals who drank alcohol at least once per month. The equivalent of four standard alcohol drinks was consumed at the participant’s desired pace within a two-hour session. Results Correlation analyses revealed that, after alcohol drinking, mean simulated driving speed, time in excess of speed limit, collisions, and reported confidence in driving were all associated with rapid alcohol drinking. Conclusion Fast drinking may coincide with increased driving confidence due to the extended latency between the conclusion of drinking and the commencement of driving. However, this latency did not reduce alcohol-related driving impairment, as fast drinking was also associated with risky driving. PMID:23027650

  1. Anthropogenic-driven rapid shifts in tree distribution lead to increased dominance of broadleaf species.

    PubMed

    Vayreda, Jordi; Martinez-Vilalta, Jordi; Gracia, Marc; Canadell, Josep G; Retana, Javier

    2016-12-01

    Over the past century, major shifts in the geographic distribution of tree species have occurred in response to changes in land use and climate. We analyse species distribution and abundance from about 33 000 forest inventory plots in Spain sampled twice over a period of 10-12 years. We show a dominance of range contraction (extinction), and demographic decline over range expansion (colonization), with seven of 11 species exhibiting extinction downhill of their distribution. Contrary to expectations, these dynamics are not always consistent with climate warming over the study period, but result from legacies in forest structure due to past land use change and fire occurrence. We find that these changes have led to the expansion of broadleaf species (i.e. family Fagaceae) over areas formerly dominated by conifer species (i.e. family Pinaceae), due to the greater capacity of the former to respond to most disturbances and their higher competitive ability. This recent and rapid transition from conifers to broadleaves has important implications in forest dynamics and ecosystem services they provide. The finding raises the question as to whether the increasing dominance of relatively drought-sensitive broadleaf species will diminish resilience of Mediterranean forests to very likely drier conditions in the future.

  2. Rapid Response Team Activations in Pediatric Surgical Patients.

    PubMed

    Acker, Shannon N; Wathen, Beth; Roosevelt, Genie E; Hill, Lauren R S; Schubert, Anna; Reese, Jenny; Bensard, Denis D; Kulungowski, Ann M

    2017-02-01

    Introduction The rapid response team (RRT) is a multidisciplinary team who evaluates hospitalized patients for concerns of nonemergent clinical deterioration. RRT evaluations are mandatory for children whose Pediatric Early Warning System (PEWS) score (assessment of child's behavior, cardiovascular and respiratory status) is ≥4. We aimed to determine if there were differences in characteristics of RRT calls between children who were admitted primarily to either medical or surgical services. We hypothesized that RRT activations would be called for less severely ill children with lower PEWS score on surgical services compared with children admitted to a medical service. Materials and Methods We performed a retrospective review of all children with RRT activations between January 2008 and April 2015 at a tertiary care pediatric hospital. We evaluated the characteristics of RRT calls and made comparisons between RRT calls made for children admitted primarily to medical or surgical services. Results A total of 2,991 RRT activations were called, and 324 (11%) involved surgical patients. Surgical patients were older than medical patients (median: 7 vs. 4 years; p < 0.001). RRT evaluations were called for lower PEWS score in surgical patients compared with medical (median: 3 vs. 4, p < 0.001). Surgical patients were more likely to remain on the inpatient ward following the RRT (51 vs. 39%, p < 0.001) and were less likely to require an advanced airway than medical patients (0.9 vs. 2.1%; p = 0.412). RRT evaluations did not differ between day and night shifts (52% day vs. 48% night; p = 0.17). All surgical patients and all but one medical patient survived the event; surgical patients were more likely to survive to hospital discharge (97 vs. 91%, p < 0.001) Conclusions RRT activations are rare events among pediatric surgical patients. When compared with medical patients, RRT evaluation is requested for surgical patients with a lower PEWS

  3. How Active Are Your Students? Increasing Physical Activity in Schools

    ERIC Educational Resources Information Center

    Avery, Marybell; Brandt, Janet

    2010-01-01

    The U. S. Department of Health and Human Services recommends that youth engage in at least 60 minutes of physical activity each day, most of which should be either moderate- or vigorous-intensity aerobic physical activity. Half of this amount (30 minutes) should be achieved during the school day. NASPE provides guidance in the form of a…

  4. Increasing use of rapid HIV testing in labor and delivery among women with no prenatal care: a local initiative.

    PubMed

    Levison, Judy; Williams, Lena T; Moore, Anna; McFarlane, Jenny; Davila, Jessica A

    2011-08-01

    Pregnant women who do not receive prenatal care and may not be aware of their HIV status are at greatest risk of transmitting HIV to their newborn. A multi-component intervention was designed and implemented to increase the use of rapid HIV testing among pregnant women with no prenatal care at labor and delivery in two county hospitals in Houston/Harris County, Texas. The intervention involved establishing a local task force including representatives from each hospital, assessing each hospital's readiness to implement rapid testing, providing educational presentations and materials, and offering individualized follow-up. Outcomes data were obtained and included the number of patients presenting with no prenatal care who received rapid HIV testing on admission. Before the intervention, both hospitals had rapid test kits available but were not using them consistently. Following the intervention, we observed a significant increase in the use of rapid HIV testing at both institutions (P < 0.001). In the 3 months immediately following the intervention, use of rapid testing at Hospital 1 increased from 7.4 to 35.3% and at Hospital 2 from 27.4 to 41.5%. At 1 year, almost 100% of women with no prenatal care at both hospitals received rapid testing. Educating staff and clinicians and implementing system-wide changes may facilitate behavior change regarding prenatal HIV testing.

  5. Using agent based modeling to assess the effect of increased Bus Rapid Transit system infrastructure on walking for transportation.

    PubMed

    Lemoine, Pablo D; Cordovez, Juan Manuel; Zambrano, Juan Manuel; Sarmiento, Olga L; Meisel, Jose D; Valdivia, Juan Alejandro; Zarama, Roberto

    2016-07-01

    The effect of transport infrastructure on walking is of interest to researchers because it provides an opportunity, from the public policy point of view, to increase physical activity (PA). We use an agent based model (ABM) to examine the effect of transport infrastructure on walking. Particular relevance is given to assess the effect of the growth of the Bus Rapid Transit (BRT) system in Bogotá on walking. In the ABM agents are assigned a home, work location, and socioeconomic status (SES) based on which they are assigned income for transportation. Individuals must decide between the available modes of transport (i.e., car, taxi, bus, BRT, and walking) as the means of reaching their destination, based on resources and needed travel time. We calibrated the model based on Bogota's 2011 mobility survey. The ABM results are consistent with previous empirical findings, increasing BRT access does indeed increase the number of minutes that individuals walk for transportation, although this effect also depends on the availability of other transport modes. The model indicates a saturation process: as more BRT lanes are added, the increment in minutes walking becomes smaller, and eventually the walking time decreases. Our findings on the potential contribution of the expansion of the BRT system to walking for transportation suggest that ABMs may prove helpful in designing policies to continue promoting walking.

  6. Dual specimens increase the diagnostic accuracy and reduce the reaction duration of rapid urease test

    PubMed Central

    Hsu, Wen-Hung; Wang, Sophie SW; Kuo, Chao-Hung; Chen, Chiao-Yun; Chang, Ching-Wen; Hu, Huang-Ming; Wang, Jaw-Yuan; Yang, Yuan-Chieh; Lin, Yu-Chun; Wang, Wen-Ming; Wu, Deng-Chyang; Wu, Ming-Tsang; Kuo, Fu-Chen

    2010-01-01

    AIM: To evaluate the influence of multiple samplings during esophagogastroduodenoscopy (EGD) on the accuracy of the rapid urease test, and the validity of newly developed rapid urease tests, HelicotecUT plus test and HelicotecUT test, CLO test and ProntoDry test. METHODS: A total of 355 patients undergoing EGD for dyspepsia were included. Their Helicobacter pylori (H. pylori) treatment status was either naïve or eradicated. Six biopsy specimens from antrum and gastric body, respectively, were obtained during EGD. Single antral specimens and dual (antrum + body) specimens were compared. Infection status of H. pylori was evaluated by three different tests: culture, histology, and four different commercially available rapid urease tests (RUTs)-including the newly developed HelicotecUT plus test and HelicotecUT test, and established CLO test and ProntoDry test. H. pylori status was defined as positive when the culture was positive or if there were concordant positive results among histology, CLO test and ProntoDry test. RESULTS: When dual specimens were applied, sensitivity was enhanced and RUT reaction time was significantly reduced, regardless of their treatment status. Thirty minutes were enough to achieve an agreeable positive rate in all the RUTs. Both newly developed RUTs showed comparable sensitivity, specificity and accuracy to the established RUTs, regardless of patient treatment status, RUT reaction duration, and EGD biopsy sites. CONCLUSION: Combination of antrum and body biopsy specimens greatly enhances the sensitivity of rapid urease test and reduces the reaction duration to 30 min. PMID:20556840

  7. Rapid activation of the bivalent gene Sox21 requires displacement of multiple layers of gene-silencing machinery

    PubMed Central

    Chakravarthy, Harini; Ormsbee, Briana D.; Mallanna, Sunil K.; Rizzino, Angie

    2011-01-01

    The rapid formation of numerous tissues during development is highly dependent on the swift activation of key developmental regulators. Recent studies indicate that many key regulatory genes are repressed in embryonic stem cells (ESCs), yet poised for rapid activation due to the presence of both activating (H3K4 trimethylation) and repressive (H3K27 trimethylation) histone modifications (bivalent genes). However, little is known about bivalent gene regulation. In this study, we investigated the regulation of the bivalent gene Sox21, which is activated rapidly when ESCs differentiate in response to increases in Sox2. Chromatin immunoprecipitation demonstrated that prior to differentiation, the Sox21 gene is bound by a complex array of repressive and activating transcriptional machinery. Upon activation, all identified repressive machinery and histone modifications associated with the gene are lost, but the activating modifications and transcriptional machinery are retained. Notably, these changes do not occur when ESCs differentiate in response to retinoic acid. Moreover, ESCs lacking a functional PRC2 complex fail to activate this gene, apparently due to its association with other repressive complexes. Together, these findings suggest that bivalent genes, such as Sox21, are silenced by a complex set of redundant repressive machinery, which exit rapidly in response to appropriate differentiation signals.—Chakravarthy, H., Ormsbee, B. D., Mallanna, S. K., Rizzino, A. Rapid activation of the bivalent gene Sox21 requires displacement of multiple layers of gene-silencing machinery. PMID:20876214

  8. Mitoenergetic Dysfunction Triggers a Rapid Compensatory Increase in Steady-State Glucose Flux

    PubMed Central

    Liemburg-Apers, Dania C.; Schirris, Tom J.J.; Russel, Frans G.M.; Willems, Peter H.G.M.; Koopman, Werner J.H.

    2015-01-01

    ATP can be produced in the cytosol by glycolytic conversion of glucose (GLC) into pyruvate. The latter can be metabolized into lactate, which is released by the cell, or taken up by mitochondria to fuel ATP production by the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS) system. Altering the balance between glycolytic and mitochondrial ATP generation is crucial for cell survival during mitoenergetic dysfunction, which is observed in a large variety of human disorders including cancer. To gain insight into the kinetic properties of this adaptive mechanism we determined here how acute (30 min) inhibition of OXPHOS affected cytosolic GLC homeostasis. GLC dynamics were analyzed in single living C2C12 myoblasts expressing the fluorescent biosensor FLII12Pglu-700μδ6 (FLII). Following in situ FLII calibration, the kinetic properties of GLC uptake (V1) and GLC consumption (V2) were determined independently and used to construct a minimal mathematical model of cytosolic GLC dynamics. After validating the model, it was applied to quantitatively predict V1 and V2 at steady-state (i.e., when V1 = V2 = Vsteady-state) in the absence and presence of OXPHOS inhibitors. Integrating model predictions with experimental data on lactate production, cell volume, and O2 consumption revealed that glycolysis and mitochondria equally contribute to cellular ATP production in control myoblasts. Inhibition of OXPHOS induced a twofold increase in Vsteady-state and glycolytic ATP production flux. Both in the absence and presence of OXPHOS inhibitors, GLC was consumed at near maximal rates, meaning that GLC consumption is rate-limiting under steady-state conditions. Taken together, we demonstrate here that OXPHOS inhibition increases steady-state GLC uptake and consumption in C2C12 myoblasts. This activation fully compensates for the reduction in mitochondrial ATP production, thereby maintaining the balance between cellular ATP supply and demand. PMID:26445438

  9. Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

    PubMed

    Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

    2011-09-01

    Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations.

  10. Light induces a rapid and transient increase in inositol-trisphosphate in toad rod outer segments

    SciTech Connect

    Brown, J.E.; Blazynski, C.; Cohen, A.I.

    1987-08-14

    The sub-second time course of changes in the content of (/sup 3/H)inositol-1,4,5-trisphosphate was determined in rod outer segments from very rapidly frozen Bufo retinas that had been incubated with (/sup 3/H)inositol. Rod outer segments were cut off frozen specimens with a cryostat microtome and the water soluble extracts were analyzed. The content of (/sup 3/H)inositol-1,4,5-trisphosphate rose after approximately 250 msec of bright illumination, but returned to the unstimulated level after 1 sec, whether the stimulus remained on or not. That is, there was rapid but transient change in the content of (/sup 3/H)inositol-1,4,5-trisphosphate after the onset of stimulation.

  11. Rapid intrusion of magma into wet rock: groundwater flow due to pore pressure increases.

    USGS Publications Warehouse

    Delaney, P.T.

    1982-01-01

    Analytical and numerical solutions are developed to simulate the pressurization, expansion, and flow of groundwater contained within saturated, intact host rocks subject to sudden heating from the planar surface of an igneous intrusion. For most rocks, water diffuses more rapidly than heat, assuring that groundwater is not heated along a constant-volume pressure path and that thermal expansion and pressurization adjacent to the intrusion drives a flow that extends well beyond the heated region. -from Author

  12. Rapid neurogenesis through transcriptional activation in human stem cells

    PubMed Central

    Busskamp, Volker; Lewis, Nathan E; Guye, Patrick; Ng, Alex HM; Shipman, Seth L; Byrne, Susan M; Sanjana, Neville E; Murn, Jernej; Li, Yinqing; Li, Shangzhong; Stadler, Michael; Weiss, Ron; Church, George M

    2014-01-01

    Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems-level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types. PMID:25403753

  13. Internal porosity of mineral coating supports microbial activity in rapid sand filters for groundwater treatment.

    PubMed

    Gülay, Arda; Tatari, Karolina; Musovic, Sanin; Mateiu, Ramona V; Albrechtsen, Hans-Jørgen; Smets, Barth F

    2014-11-01

    A mineral coating develops on the filter grain surface when groundwater is treated via rapid sand filtration in drinking water production. The coating changes the physical and chemical properties of the filter material, but little is known about its effect on the activity, colonization, diversity, and abundance of microbiota. This study reveals that a mineral coating can positively affect the colonization and activity of microbial communities in rapid sand filters. To understand this effect, we investigated the abundance, spatial distribution, colonization, and diversity of all and of nitrifying prokaryotes in filter material with various degrees of mineral coating. We also examined the physical and chemical characteristics of the mineral coating. The amount of mineral coating correlated positively with the internal porosity, the packed bulk density, and the biologically available surface area of the filter material. The volumetric NH4 (+) removal rate also increased with the degree of mineral coating. Consistently, bacterial 16S rRNA and amoA abundances positively correlated with increased mineral coating levels. Microbial colonization could be visualized mainly within the outer periphery (60.6 ± 35.6 μm) of the mineral coating, which had a thickness of up to 600 ± 51 μm. Environmental scanning electron microscopic (E-SEM) observations suggested an extracellular polymeric substance-rich matrix and submicron-sized bacterial cells. Nitrifier diversity profiles were similar irrespective of the degree of mineral coating, as indicated by pyrosequencing analysis. Overall, our results demonstrate that mineral coating positively affects microbial colonization and activity in rapid sand filters, most likely due to increased volumetric cell abundances facilitated by the large surface area of internal mineral porosity accessible for microbial colonization.

  14. The Older Woman: Increased Psychosocial Benefits from Physical Activity.

    ERIC Educational Resources Information Center

    Wakat, Diane; Odom, Sarah

    1982-01-01

    Older women who participate in physical activity programs find physical benefits in the improvement of cardiovascular and musculoskeletal systems. The psychosocial benefits which result from physical activity include an increase in self-esteem, increased social contacts, a counteraction to depression, and improved stress management. Suggestions…

  15. Best Practices and Recommendations for Increasing Physical Activity in Youth

    ERIC Educational Resources Information Center

    Erwin, Heather; Beets, Michael W.; Centeio, Erin; Morrow, James R., Jr.

    2014-01-01

    Many efforts to increase the physical activity levels of Americans have been introduced and implemented over the past 20 years. National Physical Activity Guidelines have been established, and the National Physical Activity Plan (NPAP) is now in place, which includes a specific sector dedicated to education. This article addresses the Education…

  16. School-Based Health Promotion Initiative Increases Children's Physical Activity

    ERIC Educational Resources Information Center

    Cluss, Patricia; Lorigan, Devin; Kinsky, Suzanne; Nikolajski, Cara; McDermott, Anne; Bhat, Kiran B.

    2016-01-01

    Background: Childhood obesity increases health risk, and modest physical activity can impact that risk. Schools have an opportunity to help children become more active. Purpose: This study implemented a program offering extra school-day activity opportunities in a rural school district where 37% of students were obese or overweight in 2005 and…

  17. Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium

    SciTech Connect

    Liu Zhiwei; Yu Xinyuan; Shaikh, Zahir A.

    2008-05-01

    Cadmium (Cd), an endocrine disruptor, can induce a variety of signaling events including the activation of ERK1/2 and AKT. In this study, the involvement of estrogen receptors (ER) in these events was evaluated in three human breast caner cell lines, MCF-7, MDA-MB-231, and SK-BR-3. The Cd-induced signal activation patterns in the three cell lines mimicked those exhibited in response to 17{beta}-estradiol. Specifically, treatment of MCF-7 cells, that express ER{alpha}, ER{beta} and GPR30, to 0.5-10 {mu}M Cd for only 2.5 min resulted in transient phosphorylation of ERK1/2. Cd also triggered a gradual increase and sustained activation of AKT during the 60 min treatment period. In SK-BR-3 cells, that express only GPR30, Cd also caused a transient activation of ERK1/2, but not of AKT. In contrast, in MDA-MB-231 cells, that express only ER{beta}, Cd was unable to cause rapid activation of either ERK1/2 or AKT. A transient phosphorylation of ER{alpha} was also observed within 2.5 min of Cd exposure in the MCF-7 cells. While the estrogen receptor antagonist, ICI 182,780, did not prevent the effect of Cd on these signals, specific siRNA against hER{alpha} significantly reduced Cd-induced activation of ERK1/2 and completely blocked the activation of AKT. It is concluded that Cd, like estradiol, can cause rapid activation of ERK1/2 and AKT and that these signaling events are mediated by possible interaction with membrane ER{alpha} and GPR30, but not ER{beta}.

  18. A bioluminescent caspase-1 activity assay rapidly monitors inflammasome activation in cells.

    PubMed

    O'Brien, Martha; Moehring, Danielle; Muñoz-Planillo, Raúl; Núñez, Gabriel; Callaway, Justin; Ting, Jenny; Scurria, Mike; Ugo, Tim; Bernad, Laurent; Cali, James; Lazar, Dan

    2017-03-04

    Inflammasomes are protein complexes induced by diverse inflammatory stimuli that activate caspase-1, resulting in the processing and release of cytokines, IL-1β and IL-18, and pyroptosis, an immunogenic form of cell death. To provide a homogeneous method for detecting caspase-1 activity, we developed a bioluminescent, plate-based assay that combines a substrate, Z-WEHD-aminoluciferin, with a thermostable luciferase in an optimized lytic reagent added directly to cultured cells. Assay specificity for caspase-1 is conferred by inclusion of a proteasome inhibitor in the lytic reagent and by use of a caspase-1 inhibitor to confirm activity. This approach enables a specific and rapid determination of caspase-1 activation. Caspase-1 activity is stable in the reagent thereby providing assay convenience and flexibility. Using this assay system, caspase-1 activation has been determined in THP-1 cells following treatment with α-hemolysin, LPS, nigericin, gramicidin, MSU, R848, Pam3CSK4, and flagellin. Caspase-1 activation has also been demonstrated in treated J774A.1 mouse macrophages, bone marrow-derived macrophages (BMDMs) from mice, as well as in human primary monocytes. Caspase-1 activity was not detected in treated BMDMs derived from Casp1(-/-) mice, further confirming the specificity of the assay. Caspase-1 activity can be measured directly in cultured cells using the lytic reagent, or caspase-1 activity released into medium can be monitored by assay of transferred supernatant. The caspase-1 assay can be multiplexed with other assays to monitor additional parameters from the same cells, such as IL-1β release or cell death. The caspase-1 assay in combination with a sensitive real-time monitor of cell death allows one to accurately establish pyroptosis. This assay system provides a rapid, convenient, and flexible method to specifically and quantitatively monitor caspase-1 activation in cells in a plate-based format. This will allow a more efficient and effective

  19. Re-presentation of Olfactory Exposure Therapy Success Cues during Non-Rapid Eye Movement Sleep did not Increase Therapy Outcome but Increased Sleep Spindles

    PubMed Central

    Rihm, Julia S.; Sollberger, Silja B.; Soravia, Leila M.; Rasch, Björn

    2016-01-01

    Exposure therapy induces extinction learning and is an effective treatment for specific phobias. Sleep after learning promotes extinction memory and benefits therapy success. As sleep-dependent memory-enhancing effects are based on memory reactivations during sleep, here we aimed at applying the beneficial effect of sleep on therapy success by cueing memories of subjective therapy success during non-rapid eye movement sleep after in vivo exposure-based group therapy for spider phobia. In addition, oscillatory correlates of re-presentation during sleep (i.e., sleep spindles and slow oscillations) were investigated. After exposure therapy, spider-phobic patients verbalized their subjectively experienced therapy success under presence of a contextual odor. Then, patients napped for 90 min recorded by polysomnography. Half of the sleep group received the odor during sleep while the other half was presented an odorless vehicle as control. A third group served as a wake control group without odor presentation. While exposure therapy significantly reduced spider-phobic symptoms in all subjects, these symptoms could not be further reduced by re-presenting the odor associated with therapy success, probably due to a ceiling effect of the highly effective exposure therapy. However, odor re-exposure during sleep increased left-lateralized frontal slow spindle (11.0–13.0 Hz) and right-lateralized parietal fast spindle (13.0–15.0 Hz) activity, suggesting the possibility of a successful re-presentation of therapy-related memories during sleep. Future studies need to further examine the possibility to enhance therapy success by targeted memory reactivation (TMR) during sleep. PMID:27445775

  20. Rapid intervention and treatment zone: redesigning nursing services to meet increasing emergency department demand.

    PubMed

    Considine, Julie; Lucas, Elspeth; Martin, Roslyn; Stergiou, Helen E; Kropman, Matthew; Chiu, Herman

    2012-02-01

    The impact of emergency nursing roles in demand management systems is poorly understood. The aim of this study was to evaluate emergency nurses' role in a specific emergency department (ED) demand management system: rapid intervention and treatment zone (RITZ). A descriptive exploratory approach was used. Data were collected from audit of 193 randomly selected patient records and 12 h of clinical practice observation. The median age of participants was 31 years, 51.8% were males and 99.5% were discharged home. Nurse qualifications or seniority had no significant effect on waiting time or length of stay (LOS). There were disparities between documented and observed nursing practice. The designation and qualifications of RITZ nurses made little difference to waiting times and ED LOS. Specific documentation and communication systems for areas of the ED that manage large numbers of low complexity patients warrant further research.

  1. Increasing Early Diagnosis of HIV through Rapid Testing in a Street Outreach Program in Spain

    PubMed Central

    Delgado, J.; Hoyos, J.; Belza, M.J.; Álvarez, J.; Gutiérrez, J.; Neira-León, M.; Suárez, M.

    2009-01-01

    Abstract Our goal was to analyze the results of a multicity program offering rapid HIV testing in a mobile unit in central locations. Between October 2006 and December 2007, 7138 persons were tested, providing a finger-prick blood sample and filling out a brief questionnaire while waiting for the results of the Determine® test. Seventy people were classified as reactive and 3 as indeterminate. Confirmatory test results were obtained for 83.6%. Of the 56 reactive persons contacted, 2 were confirmed as negative, giving a positive predictive value of 96.6%. Those tested were primarily men (60.6%), persons with university education (47.4%), and included a large percentage of immigrants (26.2%), especially from Latin America, and 37.3% were men who have sex with men (MSM). Forty-seven percent had ever been tested for HIV. Global HIV prevalence was 0.98% (confidence interval [CI]: 0.75–1.21), 1.59%, (CI: 1.21–1.97) in men and 0.19%, (CI: 0.02–0.35) in women. In the tree analysis the high prevalence node included Latin Americans with only primary studies (study level finished at least at the age of 12). Of the 64% HIV-positive tests in 2007 with available CD4 counts, 18.75% had CD4 counts under 350. Street-based mobile units offering rapid HIV testing in selected sites, may diagnose HIV at an earlier stage of infection than clinic-based sites, and have a low rate of false-positives. PMID:19591605

  2. Technology to promote and increase physical activity in heart failure.

    PubMed

    Franklin, Nina C

    2015-01-01

    Regular physical activity is firmly recommended as part of a multifaceted approach to heart failure (HF) self-management. Unfortunately, research indicates that most patients are less likely to engage in and adhere to such activities. The widespread use of information and communication technology tools and resources offers an innovative and potentially beneficial avenue for increasing physical activity levels in HF patients. This article presents specific ways in which advances in information and communication technologies, including Internet- and mobile-based communications, social media platforms, and self-monitoring health devices, can serve as a means to broadly promote increasing levels of physical activity to improve health outcomes in the HF population.

  3. Rapid increases of CO and H2O in the tropical lower stratosphere during January 2010 stratospheric sudden warming event

    NASA Astrophysics Data System (ADS)

    Eguchi, Nawo; Kodera, Kunihiko; Ueyama, Rei; Li, Qian

    2014-05-01

    A potential transport mechanism of various tracers from the tropical troposphere to the lower stratosphere (LS) across the tropical tropopause layer (TTL) is the overshooting convective clouds which inject air with tropospheric characteristics (high CO, high H2O, low O3) into the LS over a period of a few days. Evidence of such convective intrusions extending up to the 90 hPa level are observed over the southern African continent at the end of January 2010 in MLS and CALIOP satellite measurements. Rapid increases of CO and water vapor concentrations over Africa are associated with increased convective activity over the region a few days prior to the onset of stratospheric sudden warming (SSW) event and contribute to enhancements in their zonal tropical mean concentrations during January and February 2010. The modulation of tropical upwelling by SSW appears to force stronger and deeper tropical convection, particularly in the Southern Hemisphere tropics. The January 2010 SSW event induced the lowest recorded LS temperature in MLS history (2004-13), allowing an unprecedented clear detection of stratosphere-troposphere exchange process by way of CO, H2O and O3 intrusions. The present study suggests that short duration, overshooting clouds can have a large impact on the zonally averaged fields of LS composition (zonally-averaged tracer fields in the tropical LS). In this presentation, we present the simulated CO, water vapor and ozone mixing ratios during Jan 2010 SSW using GEOS-Chem model. We further investigate the transport pathways based on trajectory analysis of air parcels in convective regions of the tropics.

  4. Magnetic resonance imaging of the knee in Norway 2002–2004 (national survey): rapid increase, older patients, large geographic differences

    PubMed Central

    Espeland, Ansgar; Natvig, Nils L; Løge, Ingard; Engebretsen, Lars; Ellingsen, Jostein

    2007-01-01

    Background Magnetic resonance imaging (MRI) of the knee is the second most common MRI examination in Norway after head/brain MRI. Little has been published internationally on trends in the use of knee MRI after 1999. This study aimed to describe levels and trends in ambulant knee MRI utilisation in Norway 2002–2004 in relation to type of radiology service, geographic regions, number of MRI-scanners, patient age and gender, and type of referring health care provider. Methods We analysed administrative data on all claims for reimbursement of ambulant knee MRI performed in Norway in 2002, 2003 and 2004 and noted nominal reimbursement. We also recorded the referring health care provider from clinical requests of ambulant knee MRI done consecutively during two months in 2004 at one private institute and three hospitals. Number of MRI-scanners was given by manufacturers and radiology services. Results In Norway, the rate of knee MRI claims for 2004 was 15.6 per 1000 persons. This rate was 74% higher in East than in North region (18.4 vs. 10.6), slightly higher for men than women (16.4 vs. 14.7) and highest for ages 50–59 years (29.0) and 60–69 years (21.2). Most claims (76% for 2004) came from private radiology services. In 2004, the referring health care provider was a general practitioner in 63% of claims (unspecified in 24%) and in 83.5% (394/472) of clinical requests. From 2002 to 2004, the rate of knee MRI claims increased 64%. In the age group 50 years or above the increase was 86%. Rate of MRI-scanners increased 43% to 21 scanners per million persons in 2004. Reimbursement for knee MRI claims (nominal value) increased 80% to 70 million Norwegian kroner in 2004. Conclusion Ambulant knee MRI utilisation in Norway increases rapidly especially for patients over 50, and shows large geographic differences. Evaluation of clinical outcomes of this activity is needed together with clinical guidelines for use of knee MRI. PMID:17659090

  5. Asbestos exposure increases human bronchial epithelial cell fibrinolytic activity.

    PubMed

    Gross, T J; Cobb, S M; Gruenert, D C; Peterson, M W

    1993-03-01

    Chronic exposure to asbestos fibers results in fibrotic lung disease. The distal pulmonary epithelium is an early target of asbestos-mediated injury. Local plasmin activity may be important in modulating endoluminal inflammatory responses in the lung. We studied the effects of asbestos exposure on cell-mediated plasma clot lysis as a marker of pericellular plasminogen activation. Exposing human bronchial epithelial (HBE) cells to 100 micrograms/ml of asbestos fibers for 24 h resulted in increased plasma clot lysis. Fibrinolytic activity was augmented in a dose-dependent fashion, was not due to secreted protease, and occurred only when there was direct contact between the plasma clot and the epithelial monolayer. Further analysis showed that asbestos exposure increased HBE cell-associated urokinase-type plasminogen activator (uPA) activity in a time-dependent manner. The increased cell-associated PA activity could be removed by acid washing. The increase in PA activity following asbestos exposure required new protein synthesis because it was abrogated by treatment with either cycloheximide or actinomycin D. Therefore, asbestos exposure increases epithelial-mediated fibrinolysis by augmenting expression of uPA activity at the cell surface by mechanisms that require new RNA and protein synthesis. These observations suggest a novel mechanism whereby exposure of the distal epithelium to inhaled particulates may result in a chronic inflammatory response that culminates in the development of fibrotic lung disease.

  6. Increased sternocleidomastoid, but not trapezius, muscle activity in response to increased chewing load.

    PubMed

    Häggman-Henrikson, Birgitta; Nordh, Erik; Eriksson, Per-Olof

    2013-10-01

    Previous findings, during chewing, that boluses of larger size and harder texture result in larger amplitudes of both mandibular and head-neck movements suggest a relationship between increased chewing load and incremental recruitment of jaw and neck muscles. The present report evaluated jaw (masseter and digastric) and neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing of test foods of different sizes and textures by 10 healthy subjects. Muscle activity was recorded by surface electromyography and simultaneous mandibular and head movements were recorded using an optoelectronic technique. Each subject performed continuous jaw-opening/jaw-closing movements whilst chewing small and large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw closing without a bolus, SCM activity was recorded for jaw opening concomitantly with digastric activity. During chewing, SCM activity was recorded for jaw closing concomitantly with masseter activity. Trapezius activity was present in some, but not all, cycles. For the masseter and SCM muscles, higher activity was seen with larger test foods, suggesting increased demand and recruitment of these muscles in response to an increased chewing load. This result reinforces the previous notion of a close functional connection between the jaw and the neck motor systems in jaw actions and has scientific and clinical significance for studying jaw function and dysfunction.

  7. Rapid increase in human life expectancy: will it soon be limited by the aging of elastin?

    PubMed

    Robert, L; Robert, A M; Fülöp, T

    2008-04-01

    The postponement of the most frequent age-related diseases stimulated speculations of the possibility of "dying of old age". The selective decline of individual physiological functions-aging in spare-parts-indicates however the potential limitation of the life-span by the rapid decline of some of the vital parameters. We explored a possibility of such a limitation of maximal life-span by the age-related alteration of elastin, consisting in Ca-accumulation, lipid deposition and elastolytic degradation. The quantitative evaluation of these processes suggests an approximative upper limit for the elastic properties of the cardio-respiratory system of about 100-120 years, at least, as far as elastin is involved. This process, age-related alterations of elastic fibers, is however not the only one limiting the functional value of the cardiovascular system. Crosslinking of collagen fibers by advanced glycation end-products certainly contributes also to the age-dependent rigidification of the cardiovascular system. Therefore the answer to the initial question, can age-dependent alterations of a single matrix macromolecule be limiting such vital functions as the cardio-respiratory system-is a cautious yes, with however the caveat that other, independent mechanisms, such as the Maillard reaction, can also interfere with and limit further the functional value of such vital physiological functions.

  8. More rapid climate change promotes evolutionary rescue through selection for increased dispersal distance.

    PubMed

    Boeye, Jeroen; Travis, Justin M J; Stoks, Robby; Bonte, Dries

    2013-02-01

    Species can either adapt to new conditions induced by climate change or shift their range in an attempt to track optimal environmental conditions. During current range shifts, species are simultaneously confronted with a second major anthropogenic disturbance, landscape fragmentation. Using individual-based models with a shifting climate window, we examine the effect of different rates of climate change on the evolution of dispersal distances through changes in the genetically determined dispersal kernel. Our results demonstrate that the rate of climate change is positively correlated to the evolved dispersal distances although too fast climate change causes the population to crash. When faced with realistic rates of climate change, greater dispersal distances evolve than those required for the population to keep track of the climate, thereby maximizing population size. Importantly, the greater dispersal distances that evolve when climate change is more rapid, induce evolutionary rescue by facilitating the population in crossing large gaps in the landscape. This could ensure population persistence in case of range shifting in fragmented landscapes. Furthermore, we highlight problems in using invasion speed as a proxy for potential range shifting abilities under climate change.

  9. Detection of shigella in lettuce by the use of a rapid molecular assay with increased sensitivity

    PubMed Central

    Jiménez, Kenia Barrantes; McCoy², Clyde B.; Achí, Rosario

    2010-01-01

    A Multiplex Polymerase Chain Reaction (PCR) assay to be used as an alternative to the conventional culture method in detecting Shigella and enteroinvasive Escherichia coli (EIEC) virulence genes ipaH and ial in lettuce was developed. Efficacy and rapidity of the molecular method were determined as compared to the conventional culture. Lettuce samples were inoculated with different Shigella flexneri concentrations (from 10 CFU/ml to 107 CFU/ml). DNA was extracted directly from lettuce after inoculation (direct-PCR) and after an enrichment step (enrichment PCR). Multiplex PCR detection limit was 104CFU/ml, diagnostic sensitivity and specificity were 100% accurate. An internal amplification control (IAC) of 100 bp was used in order to avoid false negative results. This method produced results in 1 to 2 days while the conventional culture method required 5 to 6 days. Also, the culture method detection limit was 106 CFU/ml, diagnostic sensitivity was 53% and diagnostic specificity was 100%. In this study a Multiplex PCR method for detection of virulence genes in Shigella and EIEC was shown to be effective in terms of diagnostic sensitivity, detection limit and amount of time as compared to Shigella conventional culture. PMID:24031579

  10. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice

    PubMed Central

    Sidor, Michelle M.; Spencer, Sade M.; Dzirasa, Kafui; Parekh, Puja K.; Tye, Kay M.; Warden, Melissa R.; Arey, Rachel N.; Enwright, John F; Jacobsen, Jacob PR; Kumar, Sunil; Remillard, Erin M; Caron, Marc G.; Deisseroth, Karl; McClung, Colleen A

    2014-01-01

    Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels, and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviours in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behaviour. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder. PMID:25560763

  11. Mechanism of pyruvate dehydrogenase activation by increased cardiac work.

    PubMed

    Kobayashi, K; Neely, J R

    1983-06-01

    The effects of increased cardiac work, pyruvate and insulin on the state of pyruvate dehydrogenase (PDH) activation and rate of pyruvate decarboxylation was studied in the isolated perfused rat heart. At low levels of cardiac work, 61% of PDH was present in the active form when glucose was the only substrate provided. The actual rate of pyruvate decarboxylation was only 5% of the available capacity calculated from the percent of active PDH. Under this condition, the rate of pyruvate decarboxylation was restricted by the slow rate of pyruvate production from glycolysis. Increasing cardiac work accelerated glycolysis, but production of pyruvate remained rate limiting for pyruvate oxidation and only 40% of the maximal active PDH capacity was used. Addition of insulin along with glucose reduced the percent of active PDH to 16% of the total at low cardiac work. This effect of insulin was associated with increased mitochondria NADH/NAD and acetyl CoA/CoA ratios. With both glucose and insulin the calculated maximum capacity of active PDH was about the same as measured rates of pyruvate oxidation indicating that pyruvate oxidation was limited by the activation state of PDH. In this case, raising the level of cardiac work increased the active PDH to 85% and although pyruvate oxidation was accelerated, measured flux through PDH was only 73% of the maximal activity of active PDH. With pyruvate as added exogenous substrate, PDH was 82% of active at low cardiac work probably due to pyruvate inhibition of PDH kinase. In this case, the measured rate of pyruvate oxidation was 64% of the capacity of active PDH. However, increased cardiac work still caused further activation of PDH to 96% active. Thus, actual rates of pyruvate oxidation in the intact tissue were determined by (1) the supply of pyruvate in hearts receiving glucose alone, (2) by the percent of active PDH in hearts receiving both glucose and insulin at low work and (3) by end-product inhibition in hearts receiving

  12. Rapid activation of the bivalent gene Sox21 requires displacement of multiple layers of gene-silencing machinery.

    PubMed

    Chakravarthy, Harini; Ormsbee, Briana D; Mallanna, Sunil K; Rizzino, Angie

    2011-01-01

    The rapid formation of numerous tissues during development is highly dependent on the swift activation of key developmental regulators. Recent studies indicate that many key regulatory genes are repressed in embryonic stem cells (ESCs), yet poised for rapid activation due to the presence of both activating (H3K4 trimethylation) and repressive (H3K27 trimethylation) histone modifications (bivalent genes). However, little is known about bivalent gene regulation. In this study, we investigated the regulation of the bivalent gene Sox21, which is activated rapidly when ESCs differentiate in response to increases in Sox2. Chromatin immunoprecipitation demonstrated that prior to differentiation, the Sox21 gene is bound by a complex array of repressive and activating transcriptional machinery. Upon activation, all identified repressive machinery and histone modifications associated with the gene are lost, but the activating modifications and transcriptional machinery are retained. Notably, these changes do not occur when ESCs differentiate in response to retinoic acid. Moreover, ESCs lacking a functional PRC2 complex fail to activate this gene, apparently due to its association with other repressive complexes. Together, these findings suggest that bivalent genes, such as Sox21, are silenced by a complex set of redundant repressive machinery, which exit rapidly in response to appropriate differentiation signals.

  13. Factors significantly increasing or inhibiting early stages of malignant melanoma (M.M.) and non-invasive evaluation of new treatment by ingestion and external application of optimal doses of the most effective anti-M.M. substances: haritaki, cilantro, vitamin D3, nori, EPA with DHA, & application of special (+) solar energy stored paper, which reduced the M.M. active area & asbestos rapidly.

    PubMed

    Omura, Yoshiaki; Jones, Marilyn; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

    2013-01-01

    Sterilizing the pre-cancer skin of malignant melanoma (M.M.) with 70% Isopropyl alcohol intensified malignancy & the malignant response extended to surrounding normal looking skin, while sterilizing with 80% (vodka) or 12% (plum wine) ethyl alcohol completely inhibited M.M. in the area (both effects lasted for about 90 minutes initially). Burnt food (bread, vegetables, meat, and fish), a variety of smoked & non-smoked fish-skin, many animal's skin, pepper, Vitamin C over 75 mg, mango, pineapple, coconut, almond, sugars, Saccharine & Aspartame, garlic, onion, etc & Electromagnetic field from cellular phones worsened M.M. & induced abnormal M.M. response of surrounding skin. We found the following factors inhibit early stage of M.M. significantly: 1) Increasing normal cell telomere, by taking 500 mg Haritaki, often reached between 400-1150 ng& gradually diminished, but the M.M. response was completely inhibited until normal cell telomeres are reduced to 150 ng, which takes 6-8 hours. More than 70 mg Vitamin C, Orange Juice, & other high Vitamin C containing substances shouldn't be taken because they completely inhibit the effects of Haritaki. 2) We found Chrysotile asbestos & Tremolite asbestos (% of the Chrysotile amount) coexist. A special Cilantro tablet was used to remove asbestos & some toxic metals. 3) Vitamin D3 400 I.U. has a maximum inhibiting effect on M.M. but 800 I.U. or higher promotes malignancy. 4) Noricontaining Iodine, etc., was used. 5) EPA 180 mm with DHA 120 mg was most effectively used after metastasis to the surrounding skin was eliminated. When we combined 1 Cilantro tablet & Vitamin D3 400 I.U. withsmall Nori pieces & EPA with DHA, the effect of complete inhibition of M.M. lasted 9-11 hours. When these anti-M.M.substances (Haritaki, Vitamin D3, Cilantro, Nori, EPA. with DHA) were taken together, the effect lasted 12-14 hoursand M.M. involvement in surrounding normal-looking skin disappeared rapidly & original dark brown or black are as

  14. Rapid and reproducible determination of active gibberellins in citrus tissues by UPLC/ESI-MS/MS.

    PubMed

    Manzi, Matías; Gómez-Cadenas, Aurelio; Arbona, Vicent

    2015-09-01

    Phytohormone determination is crucial to explain the physiological mechanisms during growth and development. Therefore, rapid and precise methods are needed to achieve reproducible determination of phytohormones. Among many others, gibberellins (GAs) constitute a family of complex analytes as most of them share similar structure and chemical properties although only a few hold biological activity (namely GA1; GA3; GA4 and GA7). A method has been developed to extract GAs from plant tissues by mechanical disruption using ultrapure water as solvent and, in this way, ion suppression was reduced whereas sensitivity increased. Using this methodology, the four active GAs were separated and quantified by UPLC coupled to MS/MS using the isotope-labeled internal standards [(2)H2]-GA1 and [(2)H2]-GA4. To sum up, the new method provides a fast and reproducible protocol to determine bioactive GAs at low concentrations, using minimal amounts of sample and reducing the use of organic solvents.

  15. Herbivores cause a rapid increase in hereditary symbiosis and alter plant community composition

    PubMed Central

    Clay, Keith; Holah, Jenny; Rudgers, Jennifer A.

    2005-01-01

    Microbial symbioses are ubiquitous in nature. Hereditary symbionts warrant particular attention because of their direct effects on the evolutionary potential of their hosts. In plants, hereditary fungal endophytes can increase the competitive ability, drought tolerance, and herbivore resistance of their host, although it is unclear whether or how these ecological benefits may alter the dynamics of the endophyte symbiosis over time. Here, we demonstrate that herbivores alter the dynamics of a hereditary symbiont under field conditions. Also, we show that changes in symbiont frequency were accompanied by shifts in the overall structure of the plant community. Replicated 25-m2 plots were enriched with seed of the introduced grass, Lolium arundinaceum at an initial frequency of 50% infection by the systemic, seed-transmitted endophyte Neotyphodium coenophialum. Over 54 months, there was a significantly greater increase in endophyte-infection frequency in the presence of herbivores (30% increase) than where mammalian and insect herbivory were experimentally reduced by fencing and insecticide application (12% increase). Under ambient mammalian herbivory, the above-ground biomass of nonhost plant species was reduced compared with the mammal-exclusion treatment, and plant composition shifted toward greater relative biomass of infected, tall fescue grass. These results demonstrate that herbivores can drive plant–microbe dynamics and, in doing so, modify plant community structure directly and indirectly. PMID:16116093

  16. Herbivores cause a rapid increase in hereditary symbiosis and alter plant community composition.

    PubMed

    Clay, Keith; Holah, Jenny; Rudgers, Jennifer A

    2005-08-30

    Microbial symbioses are ubiquitous in nature. Hereditary symbionts warrant particular attention because of their direct effects on the evolutionary potential of their hosts. In plants, hereditary fungal endophytes can increase the competitive ability, drought tolerance, and herbivore resistance of their host, although it is unclear whether or how these ecological benefits may alter the dynamics of the endophyte symbiosis over time. Here, we demonstrate that herbivores alter the dynamics of a hereditary symbiont under field conditions. Also, we show that changes in symbiont frequency were accompanied by shifts in the overall structure of the plant community. Replicated 25-m2 plots were enriched with seed of the introduced grass, Lolium arundinaceum at an initial frequency of 50% infection by the systemic, seed-transmitted endophyte Neotyphodium coenophialum. Over 54 months, there was a significantly greater increase in endophyte-infection frequency in the presence of herbivores (30% increase) than where mammalian and insect herbivory were experimentally reduced by fencing and insecticide application (12% increase). Under ambient mammalian herbivory, the above-ground biomass of nonhost plant species was reduced compared with the mammal-exclusion treatment, and plant composition shifted toward greater relative biomass of infected, tall fescue grass. These results demonstrate that herbivores can drive plant-microbe dynamics and, in doing so, modify plant community structure directly and indirectly.

  17. Rapidly increasing methyl mercury in endangered ivory gull (Pagophila eburnea) feathers over a 130 year record.

    PubMed

    Bond, Alexander L; Hobson, Keith A; Branfireun, Brian A

    2015-04-22

    Mercury (Hg) is increasing in marine food webs, especially at high latitudes. The bioaccumulation and biomagnification of methyl mercury (MeHg) has serious effects on wildlife, and is most evident in apex predators. The MeHg body burden in birds is the balance of ingestion and excretion, and MeHg in feathers is an effective indicator of overall MeHg burden. Ivory gulls (Pagophila eburnea), which consume ice-associated prey and scavenge marine mammal carcasses, have the highest egg Hg concentrations of any Arctic bird, and the species has declined by more than 80% since the 1980s in Canada. We used feathers from museum specimens from the Canadian Arctic and western Greenland to assess whether exposure to MeHg by ivory gulls increased from 1877 to 2007. Based on constant feather stable-isotope (δ(13)C, δ(15)N) values, there was no significant change in ivory gulls' diet over this period, but feather MeHg concentrations increased 45× (from 0.09 to 4.11 µg g(-1) in adults). This dramatic change in the absence of a dietary shift is clear evidence of the impact of anthropogenic Hg on this high-latitude threatened species. Bioavailable Hg is expected to increase in the Arctic, raising concern for continued population declines in high-latitude species that are far from sources of environmental contaminants.

  18. Rapidly increasing methyl mercury in endangered ivory gull (Pagophila eburnea) feathers over a 130 year record

    PubMed Central

    Bond, Alexander L.; Hobson, Keith A.; Branfireun, Brian A.

    2015-01-01

    Mercury (Hg) is increasing in marine food webs, especially at high latitudes. The bioaccumulation and biomagnification of methyl mercury (MeHg) has serious effects on wildlife, and is most evident in apex predators. The MeHg body burden in birds is the balance of ingestion and excretion, and MeHg in feathers is an effective indicator of overall MeHg burden. Ivory gulls (Pagophila eburnea), which consume ice-associated prey and scavenge marine mammal carcasses, have the highest egg Hg concentrations of any Arctic bird, and the species has declined by more than 80% since the 1980s in Canada. We used feathers from museum specimens from the Canadian Arctic and western Greenland to assess whether exposure to MeHg by ivory gulls increased from 1877 to 2007. Based on constant feather stable-isotope (δ13C, δ15N) values, there was no significant change in ivory gulls' diet over this period, but feather MeHg concentrations increased 45× (from 0.09 to 4.11 µg g−1 in adults). This dramatic change in the absence of a dietary shift is clear evidence of the impact of anthropogenic Hg on this high-latitude threatened species. Bioavailable Hg is expected to increase in the Arctic, raising concern for continued population declines in high-latitude species that are far from sources of environmental contaminants. PMID:25788594

  19. Tropospheric Ozone Increases over the Southern Africa Region: Bellwether for Rapid Growth in Southern Hemisphere Pollution?

    NASA Technical Reports Server (NTRS)

    Thompson, Anne M.; Balashov, Nikolay V.; Witte, J. C.; Coetzee, J. G. R.; Thouret, V.; Posny, F.

    2014-01-01

    Increases in free-tropospheric (FT) ozone based on ozonesonde records from the early 1990s through 2008 over two subtropical stations, Irene (near Pretoria, South Africa) and Réunion (21 deg. S, 55 deg. E; approx. 2800 km NE of Irene in the Indian Ocean), have been reported. Over Irene a large increase in the urban-influenced boundary layer (BL, 1.5-4 km) was also observed during the 18-year period, equivalent to 30%decade-1. Here we show that the Irene BL trend is at least partly due to a gradual change in the sonde launch times from early morning to the midday period. The FT ozone profiles over Irene in 1990-2007 are re-examined, filling in a 1995-1999 gap with ozone profiles taken during the Measurements of Ozone by Airbus In-service Aircraft (MOZAIC) project over nearby Johannesburg. A multivariate regression model that accounts for the annual ozone cycle, El Niño-Southern Oscillation (ENSO) and possible tropopause changes was applied to monthly averaged Irene data from 4 to 11 km and to 1992-2011 Réunion sonde data from 4 to 15 km. Statistically significant trends appear predominantly in the middle and upper troposphere (UT; 4-11 km over Irene, 4-15 km over Réunion) in winter (June-August), with increases 1 ppbv yr(exp. -1) over Irene and approx. 2 ppbv yr(exp. -1) over Réunion. These changes are equivalent to approx. 25 and 35-45%decade( exp. -1), respectively. Both stations also display smaller positive trends in summer, with a 45%decade(exp. -1) ozone increase near the tropopause over Réunion in December. To explain the ozone increases, we investigated a time series of dynamical markers, e.g., potential vorticity (PV) at 330-350 K. PV affects UT ozone over Irene in November-December but displays little relationship with ozone over Réunion. A more likely reason for wintertime FT ozone increases over Irene and Réunion appears to be long-range transport of growing pollution in the Southern Hemisphere. The ozone increases are consistent with trajectory

  20. Building a better mousetrap (exergame) to increase youth physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While exergames have been demonstrated to induce moderate levels of physical activity (PA) if played as designed, there is conflicting evidence on use of exergaming leading to increased habitual PA. Exergames have increased PA in some home and school studies, but not others. Exergames have been us...

  1. New sensitizers and rapid monitoring of their photodynamic activity

    NASA Astrophysics Data System (ADS)

    Torshina, Nadezgda L.; Posypanova, Anna M.; Volkova, Anna I.

    1996-04-01

    At present, there are lots and lots of chemical compounds that are, to a certain extent, photodynamically active. Therefore, the task of carrying out the expressive screening of such compounds has been raised sharply enough. The primary screening in vitro of compounds, with the help of biological liquids, is notable for quickness and cheapness at the same time, it is possible to determine the comparative characteristics of compounds by their photodynamical activity. Decomposition of albumins of a mixture of photosensitizer and biological liquid when irradiating with light is the basis of this method. Efficiency of decomposition of components of biological liquids is determined using biochemical reactions (e.g., those for determining the total albumins or blood hemoglobin). Subsequently, with a sufficient efficiency of a photosensitizer, it will be possible to carry out a study in vivo, with the purpose of establishing accumulation of preparations in tumor.

  2. Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

    NASA Astrophysics Data System (ADS)

    Bailey, Andy M.; Alberti, Fabrizio; Kilaru, Sreedhar; Collins, Catherine M.; de Mattos-Shipley, Kate; Hartley, Amanda J.; Hayes, Patrick; Griffin, Alison; Lazarus, Colin M.; Cox, Russell J.; Willis, Christine L.; O’Dwyer, Karen; Spence, David W.; Foster, Gary D.

    2016-05-01

    Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.

  3. Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

    PubMed Central

    Bailey, Andy M.; Alberti, Fabrizio; Kilaru, Sreedhar; Collins, Catherine M.; de Mattos-Shipley, Kate; Hartley, Amanda J.; Hayes, Patrick; Griffin, Alison; Lazarus, Colin M.; Cox, Russell J.; Willis, Christine L.; O’Dwyer, Karen; Spence, David W.; Foster, Gary D.

    2016-01-01

    Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi. PMID:27143514

  4. Method and apparatus for rapid thrust increases in a turbofan engine

    NASA Technical Reports Server (NTRS)

    Cornett, J. E.; Corley, R. C.; Fraley, T. O.; Saunders, A. A., Jr. (Inventor)

    1980-01-01

    Upon a landing approach, the normal compressor stator schedule of a fan speed controlled turbofan engine is temporarily varied to substantially close the stators to thereby increase the fuel flow and compressor speed in order to maintain fan speed and thrust. This running of the compressor at an off-design speed substantially reduces the time required to subsequently advance the engine speed to the takeoff thrust level by advancing the throttle and opening the compressor stators.

  5. Socioeconomic status accounts for rapidly increasing geographic variation in the incidence of poor fetal growth.

    PubMed

    Ball, Stephen J; Jacoby, Peter; Zubrick, Stephen R

    2013-06-25

    Fetal growth is an important risk factor for infant morbidity and mortality. In turn, socioeconomic status is a key predictor of fetal growth; however, other sociodemographic factors and environmental effects may also be important. This study modelled geographic variation in poor fetal growth after accounting for socioeconomic status, with a fixed effect for socioeconomic status and a combination of spatially-correlated and spatially-uncorrelated random effects. The dataset comprised 88,246 liveborn singletons, aggregated within suburbs in Perth, Western Australia. Low socioeconomic status was strongly associated with an increased risk of poor fetal growth. An increase in geographic variation of poor fetal growth from 1999-2001 (interquartile odds ratio among suburbs = 1.20) to 2004-2006 (interquartile odds ratio = 1.40) indicated a widening risk disparity by socioeconomic status. Low levels of residual spatial patterns strengthen the case for targeting policies and practices in areas of low socioeconomic status for improved outcomes. This study indicates an alarming increase in geographic inequalities in poor fetal growth in Perth which warrants further research into the specific aspects of socioeconomic status that act as risk factors.

  6. Proton Pump Inhibition Increases Rapid Eye Movement Sleep in the Rat

    PubMed Central

    Jha, Sushil K.

    2014-01-01

    Increased bodily CO2 concentration alters cellular pH as well as sleep. The proton pump, which plays an important role in the homeostatic regulation of cellular pH, therefore, may modulate sleep. We investigated the effects of the proton pump inhibitor “lansoprazole” on sleep-wakefulness. Male Wistar rats were surgically prepared for chronic polysomnographic recordings. Two different doses of lansoprazole (low: 1 mg/kg; high: 10 mg/kg) were injected intraperitoneally in the same animal (n = 7) and sleep-wakefulness was recorded for 6 hrs. The changes in sleep-wakefulness were compared statistically. Percent REM sleep amount in the vehicle and lansoprazole low dose groups was 9.26 ± 1.03 and 9.09 ± 0.54, respectively, which increased significantly in the lansoprazole high dose group by 31.75% (from vehicle) and 34.21% (from low dose). Also, REM sleep episode numbers significantly increased in lansoprazole high dose group. Further, the sodium-hydrogen exchanger blocker “amiloride” (10 mg/kg; i.p.) (n = 5) did not alter sleep-wake architecture. Our results suggest that the proton pump plays an important role in REM sleep modulation and supports our view that REM sleep might act as a sentinel to help maintain normal CO2 level for unperturbed sleep. PMID:24701564

  7. Multi-modal characterization of rapid anterior hippocampal volume increase associated with aerobic exercise

    PubMed Central

    Thomas, Adam G.; Dennis, Andrea; Rawlings, Nancy B.; Stagg, Charlotte J.; Matthews, Lucy; Morris, Martyn; Kolind, Shannon H.; Foxley, Sean; Jenkinson, Mark; Nichols, Thomas E.; Dawes, Helen; Bandettini, Peter A.; Johansen-Berg, Heidi

    2016-01-01

    The hippocampus has been shown to demonstrate a remarkable degree of plasticity in response to a variety of tasks and experiences. For example, the size of the human hippocampus has been shown to increase in response to aerobic exercise. However, it is currently unknown what underlies these changes. Here we scanned sedentary, young to middle-aged human adults before and after a six-week exercise intervention using nine different neuroimaging measures of brain structure, vasculature, and diffusion. We then tested two different hypotheses regarding the nature of the underlying changes in the tissue. Surprisingly, we found no evidence of a vascular change as has been previously reported. Rather, the pattern of changes is better explained by an increase in myelination. Finally, we show hippocampal volume increase is temporary, returning to baseline after an additional six weeks without aerobic exercise. This is the first demonstration of a change in hippocampal volume in early to middle adulthood suggesting that hippocampal volume is modulated by aerobic exercise throughout the lifespan rather than only in the presence of age related atrophy. It is also the first demonstration of hippocampal volume change over a period of only six weeks, suggesting gross morphometric hippocampal plasticity occurs faster than previously thought. PMID:26654786

  8. Rapidly increasing macroalgal cover not related to herbivorous fishes on Mesoamerican reefs

    PubMed Central

    Suchley, Adam; McField, Melanie D.

    2016-01-01

    Long-term phase shifts from coral to macroalgal dominated reef systems are well documented in the Caribbean. Although the impact of coral diseases, climate change and other factors is acknowledged, major herbivore loss through disease and overfishing is often assigned a primary role. However, direct evidence for the link between herbivore abundance, macroalgal and coral cover is sparse, particularly over broad spatial scales. In this study we use a database of coral reef surveys performed at 85 sites along the Mesoamerican Reef of Mexico, Belize, Guatemala and Honduras, to examine potential ecological links by tracking site trajectories over the period 2005–2014. Despite the long-term reduction of herbivory capacity reported across the Caribbean, the Mesoamerican Reef region displayed relatively low macroalgal cover at the onset of the study. Subsequently, increasing fleshy macroalgal cover was pervasive. Herbivorous fish populations were not responsible for this trend as fleshy macroalgal cover change was not correlated with initial herbivorous fish biomass or change, and the majority of sites experienced increases in macroalgae browser biomass. This contrasts the coral reef top-down herbivore control paradigm and suggests the role of external factors in making environmental conditions more favourable for algae. Increasing macroalgal cover typically suppresses ecosystem services and leads to degraded reef systems. Consequently, policy makers and local coral reef managers should reassess the focus on herbivorous fish protection and consider complementary measures such as watershed management in order to arrest this trend. PMID:27280075

  9. Rapid increases and time-lagged declines in amphibian occupancy after wildfire

    USGS Publications Warehouse

    Hossack, Blake R.; Lowe, Winsor H.; Corn, Paul Stephen

    2013-01-01

    Climate change is expected to increase the frequency and severity of drought and wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be particularly vulnerable to these modified disturbance regimes because large wildfires often occur during extended droughts and thus may compound environmental threats. However, understanding of the effects of wildfires on amphibians in forests with long fire-return intervals is limited. Numerous stand-replacing wildfires have occurred since 1988 in Glacier National Park (Montana, U.S.A.), where we have conducted long-term monitoring of amphibians. We measured responses of 3 amphibian species to fires of different sizes, severity, and age in a small geographic area with uniform management. We used data from wetlands associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether burn extent and severity and interactions between wildfire and wetland isolation affected the distribution of breeding populations. We measured responses with models that accounted for imperfect detection to estimate occupancy during prefire (0-4 years) and different postfire recovery periods. For the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21 years after wildfire, occupancy for both species decreased ≥ 25% in areas where >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests burned. This increase in occupancy was followed by a gradual decline. Our results show that accounting for magnitude of change and time lags is critical to understanding population dynamics of amphibians after large disturbances. Our results also inform understanding of the potential threat of increases in wildfire frequency or severity to amphibians in the region.

  10. Rapid increases and time-lagged declines in amphibian occupancy after wildfire.

    PubMed

    Hossack, Blake R; Lowe, Winsor H; Corn, Paul Stephen

    2013-02-01

    Climate change is expected to increase the frequency and severity of drought and wildfire. Aquatic and moisture-sensitive species, such as amphibians, may be particularly vulnerable to these modified disturbance regimes because large wildfires often occur during extended droughts and thus may compound environmental threats. However, understanding of the effects of wildfires on amphibians in forests with long fire-return intervals is limited. Numerous stand-replacing wildfires have occurred since 1988 in Glacier National Park (Montana, U.S.A.), where we have conducted long-term monitoring of amphibians. We measured responses of 3 amphibian species to fires of different sizes, severity, and age in a small geographic area with uniform management. We used data from wetlands associated with 6 wildfires that burned between 1988 and 2003 to evaluate whether burn extent and severity and interactions between wildfire and wetland isolation affected the distribution of breeding populations. We measured responses with models that accounted for imperfect detection to estimate occupancy during prefire (0-4 years) and different postfire recovery periods. For the long-toed salamander (Ambystoma macrodactylum) and Columbia spotted frog (Rana luteiventris), occupancy was not affected for 6 years after wildfire. But 7-21 years after wildfire, occupancy for both species decreased ≥ 25% in areas where >50% of the forest within 500 m of wetlands burned. In contrast, occupancy of the boreal toad (Anaxyrus boreas) tripled in the 3 years after low-elevation forests burned. This increase in occupancy was followed by a gradual decline. Our results show that accounting for magnitude of change and time lags is critical to understanding population dynamics of amphibians after large disturbances. Our results also inform understanding of the potential threat of increases in wildfire frequency or severity to amphibians in the region.

  11. Kepler Observations of Rapid Optical Variability in Active Galactic Nuclei

    NASA Technical Reports Server (NTRS)

    Mushotzky, R. F.; Edelson, R.; Baumgartner, W. H.; Gandhi, P.

    2012-01-01

    Over three quarters in 2010 - 2011, Kepler monitored optical emission from four active galactic nuclei (AGN) with approx 30 min sampling, > 90% duty cycle and approx < 0.1% repeatability. These data determined the AGN optical fluctuation power spectral density functions (PSDs) over a wide range in temporal frequency. Fits to these PSDs yielded power law slopes of -2.6 to -3.3, much steeper than typically seen in the X-rays. We find evidence that individual AGN exhibit intrinsically different PSD slopes. The steep PSD fits are a challenge to recent AGN variability models but seem consistent with first order MRI theoretical calculations of accretion disk fluctuations.

  12. Rapid Increase in Scrub Typhus Incidence in Mainland China, 2006–2014

    PubMed Central

    Wu, Yi-Cheng; Qian, Quan; Soares Magalhaes, Ricardo J.; Han, Zhi-Hai; Haque, Ubydul; Weppelmann, Thomas A.; Hu, Wen-Biao; Liu, Yun-Xi; Sun, Yan-Song; Zhang, Wen-Yi; Li, Shen-Long

    2016-01-01

    Scrub typhus is a vector-borne disease, which has recently reemerged in China. In this study, we describe the distribution and incidence of scrub typhus cases in China from 2006 to 2014 and quantify differences in scrub typhus cases with respect to sex, age, and occupation. The results of our study indicate that the annual incidence of scrub typhus has increased during the study period. The number of cases peaked in 2014, which was 12.8 times greater than the number of cases reported in 2006. Most (77.97%) of the cases were reported in five provinces (Guangdong, Yunnan, Anhui, Fujian, and Shandong). Our study also demonstrates that the incidence rate of scrub typhus was significantly higher in females compared to males (P < 0.001) and was highest in the 60–69 year age group, and that farmers had a higher incidence rate than nonfarmers (P < 0.001). Different seasonal trends were identified in the number of reported cases between the northern and southern provinces of China. These findings not only demonstrate that China has experienced a large increase in scrub typhus incidence, but also document an expansion in the geographic distribution throughout the country. PMID:26711517

  13. Rapid increase in cuckoo egg matching in a recently parasitized reed warbler population.

    PubMed

    Avilés, J M; Stokke, B G; Moksnes, A; Røskaft, E; Asmul, M; Møller, A P

    2006-11-01

    Parasitic cuckoos lay eggs that mimic those of their hosts, and such close phenotypic matching may arise from coevolutionary interactions between parasite and host. However, cuckoos may also explicitly choose hosts in a way that increases degree of matching between eggs of cuckoos and parasites, with female preference for specific host phenotypes increasing the degree of matching. We tested for temporal change in degree of matching between eggs of the parasitic European cuckoo (Cuculus canorus) and its reed warbler (Acrocephalus scirpaceus) host during 24 consecutive years in a recently parasitized reed warbler population. Cuckoo-host egg matching in an ultraviolet-brownness component yielding most of the chromatic variance of eggs improved during the study period. Improved matching was not due to changes in cuckoo egg phenotype. Cuckoo eggs matched host eggs for ultraviolet-brownness within nests irrespective of duration of sympatry. Ultraviolet-brownness of cuckoo eggs was similar to that of reed warbler eggs at parasitized nests, but differed from that of reed warbler eggs at unparasitized nests. These findings provide tentative support for the cuckoo preference hypothesis suggesting that cuckoo-host egg matching could partially be due to cuckoo females selecting host nests based on the appearance of their eggs.

  14. [Increase of physical activity by improvement of the nutritional status].

    PubMed

    Torún, B

    1989-09-01

    Physical activity is affected by nutritional modifications and, in turn, influences growth, cognition, social behavior, work performance and other functions. Studies in preschool children showed that: 1. A decrease in energy intake during four to seven days reduced the time allocated to energy-demanding activities and increased sedentary activities. 2. Children with mild weight deficit were more sedentary than well-nourished counterparts. 3. Children became more active when nutritional status improved. 4. A 10% reduction in energy intake reduced total energy expenditure by 15% without affecting weight gain nor basal metabolism. Studies of men working in non-mechanized agriculture showed that: 1. Dietary improvements led to faster salaried work, reduction of napping time and greater physical activity after work. 2. An increase in energy intake increased total daily energy expenditure, tending to maintain energy balance and relatively stable body weight within the cyclic variations of the agricultural year. 3. Food supplementation did not necessarily improve productivity. Other labor incentives without dietary improvements increased energy expenditure during working hours, which resulted in weight loss. In conclusion, good health and nutrition provide the biological basis for adequate physical activity that may improve cognitive development, social interactions, economic productivity and the quality of life of an individual or a population, but other incentives are required for the optimal expression of that biologic potential.

  15. Rapid increase in fish numbers follows creation of world's largest marine reserve network.

    PubMed

    Russ, Garry R; Cheal, Alistair J; Dolman, Andrew M; Emslie, Michael J; Evans, Richard D; Miller, Ian; Sweatman, Hugh; Williamson, David H

    2008-06-24

    No-take marine reserves (NTMRs) are much advocated as a solution to managing marine ecosystems, protecting exploited species and restoring natural states of biodiversity [1,2]. Increasingly, it is becoming clear that effective marine conservation and management at ecosystem and regional scales requires extensive networks of NTMRs [1,2]. The world's largest network of such reserves was established on Australia's Great Barrier Reef (GBR) in 2004. Closing such a large area to all fishing has been socially and politically controversial, making it imperative that the effectiveness of this new reserve network be assessed. Here we report evidence, first, that the densities of the major target species of the GBR reef line fisheries were significantly higher in the new NTMRs, compared with fished sites, in just two years; and second, that the positive differences were consistent for multiple marine reserves over an unprecedented spatial scale (>1,000 km).

  16. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  17. Rapid rotation and mixing in active OB stars - Physical processes

    NASA Astrophysics Data System (ADS)

    Zahn, Jean-Paul

    2011-07-01

    In the standard description of stellar interiors, O and B stars possess a thoroughly mixed convective core surrounded by a stable radiative envelope in which no mixing occurs. But as is well known, this model disagrees strongly with the spectroscopic diagnostic of these stars, which reveals the presence at their surface of chemical elements that have been synthesized in the core. Hence the radiation zone must be the seat of some mild mixing mechanisms. The most likely to operate there are linked with the rotation: these are the shear instabilites triggered by the differential rotation, and the meridional circulation caused by the changes in the rotation profile accompanying the non-homologous evolution of the star. In addition to these hydrodynamical processes, magnetic stresses may play an important role in active stars, which host a magnetic field. These physical processes will be critically examined, together with some others that have been suggested.

  18. Activation of initiation factor 2 by ligands and mutations for rapid docking of ribosomal subunits

    PubMed Central

    Pavlov, Michael Y; Zorzet, Anna; Andersson, Dan I; Ehrenberg, Måns

    2011-01-01

    We previously identified mutations in the GTPase initiation factor 2 (IF2), located outside its tRNA-binding domain, compensating strongly (A-type) or weakly (B-type) for initiator tRNA formylation deficiency. We show here that rapid docking of 30S with 50S subunits in initiation of translation depends on switching 30S subunit-bound IF2 from its inactive to active form. Activation of wild-type IF2 requires GTP and formylated initiator tRNA (fMet-tRNAi). In contrast, extensive activation of A-type IF2 occurs with only GTP or with GDP and fMet-tRNAi, implying a passive role for initiator tRNA as activator of IF2 in subunit docking. The theory of conditional switching of GTPases quantitatively accounts for all our experimental data. We find that GTP, GDP, fMet-tRNAi and A-type mutations multiplicatively increase the equilibrium ratio, K, between active and inactive forms of IF2 from a value of 4 × 10−4 for wild-type apo-IF2 by factors of 300, 8, 80 and 20, respectively. Functional characterization of the A-type mutations provides keys to structural interpretation of conditional switching of IF2 and other multidomain GTPases. PMID:21151095

  19. Synthetic polymers in the marine environment: a rapidly increasing, long-term threat.

    PubMed

    Moore, Charles James

    2008-10-01

    Synthetic polymers, commonly known as plastics, have been entering the marine environment in quantities paralleling their level of production over the last half century. However, in the last two decades of the 20th Century, the deposition rate accelerated past the rate of production, and plastics are now one of the most common and persistent pollutants in ocean waters and beaches worldwide. Thirty years ago the prevailing attitude of the plastic industry was that "plastic litter is a very small proportion of all litter and causes no harm to the environment except as an eyesore" [Derraik, J.G.B., 2002. The pollution of the marine environment by plastic debris: a review. Mar. Pollut. Bull. 44(9), 842-852]. Between 1960 and 2000, the world production of plastic resins increased 25-fold, while recovery of the material remained below 5%. Between 1970 and 2003, plastics became the fastest growing segment of the US municipal waste stream, increasing nine-fold, and marine litter is now 60-80% plastic, reaching 90-95% in some areas. While undoubtedly still an eyesore, plastic debris today is having significant harmful effects on marine biota. Albatross, fulmars, shearwaters and petrels mistake floating plastics for food, and many individuals of these species are affected; in fact, 44% of all seabird species are known to ingest plastic. Sea turtles ingest plastic bags, fishing line and other plastics, as do 26 species of cetaceans. In all, 267 species of marine organisms worldwide are known to have been affected by plastic debris, a number that will increase as smaller organisms are assessed. The number of fish, birds, and mammals that succumb each year to derelict fishing nets and lines in which they become entangled cannot be reliably known; but estimates are in the millions. We divide marine plastic debris into two categories: macro, >5 mm and micro, <5 mm. While macro-debris may sometimes be traced to its origin by object identification or markings, micro

  20. Volume Transitions of Isolated Cell Nuclei Induced by Rapid Temperature Increase.

    PubMed

    Chan, Chii J; Li, Wenhong; Cojoc, Gheorghe; Guck, Jochen

    2017-03-28

    Understanding the physical mechanisms governing nuclear mechanics is important as it can impact gene expression and development. However, how cell nuclei respond to external cues such as heat is not well understood. Here, we studied the material properties of isolated nuclei in suspension using an optical stretcher. We demonstrate that isolated nuclei regulate their volume in a highly temperature-sensitive manner. At constant temperature, isolated nuclei behaved like passive, elastic and incompressible objects, whose volume depended on the pH and ionic conditions. When the temperature was increased suddenly by even a few degrees Kelvin, nuclei displayed a repeatable and reversible temperature-induced volume transition, whose sign depended on the valency of the solvent. Such phenomenon is not observed for nuclei subjected to slow heating. The transition temperature could be shifted by adiabatic changes of the ambient temperature, and the magnitude of temperature-induced volume transition could be modulated by modifying the chromatin compaction state and remodeling processes. Our findings reveal that the cell nucleus can be viewed as a highly charged polymer gel with intriguing thermoresponsive properties, which might play a role in nuclear volume regulation and thermosensing in living cells.

  1. Communication and general concern criterion prior to activation of the rapid response team: a grounded theory.

    PubMed

    Martland, Jarrad; Chamberlain, Diane; Hutton, Alison; Smigielski, Michael

    2015-11-30

    Objective Patients commonly show signs and symptoms of deterioration for hours or days before cardiorespiratory arrest. Rapid response teams (RRT) were created to improve recognition and response to patient deterioration in these situations. Activation criteria include vital signs or 'general concern' by a clinician or family member. The general concern criterion for RRT activation accounts for nearly one-third of all RRT activity, and although it is well established that communication deficits between staff can contribute to poorer outcomes for patients, there is little evidence pertaining to communication and its effects on the general concern RRT activation. Thus, the aim of the present study was to develop a substantive grounded theory related to the communication process between clinicians that preceded the activation of an RRT when general concern criterion was used.Methods Qualitative grounded theory involved collection of three types of data details namely personal notes from participants in focus groups with white board notes from discussions and audio recordings of the focus groups sessions. Focus groups were conducted with participants exploring issues associated with clinician communication and how it related to the activation of an RRT using the general concern criterion.Results The three main phases of coding (i.e. open, axial and selective coding) analysis identified 322 separate open codes. The strongest theme contributed to a theory of ineffective communication and decreased psychological safety, namely that 'In the absence of effective communication there is a subsequent increase in anxiety, fear or concern that can be directly attributed to the activation of an RRT using the 'general concern' criterion'. The RRT filled cultural and process deficiencies in the compliance with an escalation protocol. Issues such as 'not for resuscitation documentation' and 'inability to establish communication with and between medical or nursing personnel' rated

  2. The rapid increase of circulating adiponectin in neonatal calves depends on colostrum intake.

    PubMed

    Kesser, J; Hill, M; Heinz, J F L; Koch, C; Rehage, J; Steinhoff-Wagner, J; Hammon, H M; Mielenz, B; Sauerwein, H; Sadri, H

    2015-10-01

    blood concentrations of adiponectin and placental transfer of adiponectin to the bovine fetus is unlikely. In conclusion, colostrum intake is essential for the postnatal increase of circulating adiponectin in newborn calves.

  3. Rapid Changes on Sediment Accumulation Rates within Submarine Canyons Caused By Bottom Trawling Activities

    NASA Astrophysics Data System (ADS)

    Puig, P.; Masque, P.; Martin, J.; Paradis, S.; Juan, X.; Toro, M.; Palanques, A.

    2014-12-01

    The physical disturbance of the marine sedimentary environments by commercial bottom trawling is a matter of concern. The direct physical effects of this fishing technique include scraping and ploughing of the seabed and increases of the near-bottom water turbidity by sediment resuspension. However, the quantification of the sediment that has been resuspended by this anthropogenic activity over years and has been ultimately exported across the margin remains largely unaddressed. The analysis of sediment accumulation rates from sediment cores collected along the axes of several submarine canyons in the Catalan margin (northwestern Mediterranean) has allowed to estimate the contribution of this anthropogenic activity to the present-day sediment dynamics. 210Pb chronologies, occasionally supported by 137Cs dating, indicate a rapid increase of sediment accumulation rates since the 1970s, in coincidence with a strong impulse in the industrialization of the trawling fleets of this region. Such increase has been associated to the enhanced delivery of sediment resuspended by trawlers from the shelves and upper slope regions towards the canyon's interior, and to the rapid technical development at that time, in terms of engine power and gear size. This change has been observed in La Fonera (or Palamós) Canyon at depths greater than 1700 m, while in other canyons it is restricted to shallower regions (~1000 m in depth) closer to fishing grounds. Two sampling sites from La Fonera and Foix submarine canyons that exhibited high sediment accumulation rates (0.6-0.7 cm/y) were reoccupied several years after the first chronological analyses. These two new cores reveal a second and more rapid increase of sediment accumulation rates in both canyons occurring circa 2002 and accounting for about 2 cm/y. This second change at the beginning of the XXI century has been attributed to a preferential displacement of the trawling fleet towards slope fishing grounds surrounding submarine

  4. Increasing physical activity of children during school recess.

    PubMed

    Hayes, Lynda B; Van Camp, Carole M

    2015-09-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M = 1,956 steps) were 47% higher than in baseline (M = 1,326 steps), and the percentage of recess spent in moderate-to-vigorous physical activity was higher during intervention (M = 25%) than in baseline (M = 4%). These methods successfully increased steps during recess and could be used to increase steps in other settings.

  5. Fentanyl, clonidine, and repeated increases in desflurane concentration, but not nitrous oxide or esmolol, block the transient mydriasis caused by rapid increases in desflurane concentration.

    PubMed

    Daniel, M; Larson, M D; Eger, E I; Noorani, M; Weiskopf, R B

    1995-08-01

    Initial, but not subsequent, inhalation of 8% desflurane produces transient sympathetic stimulation. We hypothesized that initial but not subsequent increases should produce pupil dilation, and that N2O, fentanyl, and clonidine, but not esmolol, should blunt the response. In 10 volunteers, we maintained anesthesia with 4% end-tidal desflurane in oxygen for 32 min, then increased the concentration to 8% for 10 min. In nine of the volunteers, we twice repeated the increase to 8%, separating each increase by a 32-min period at 4%. On separate days, five volunteers received 4%-8% desflurane in 60% N2O; five received fentanyl 1.5 micrograms/kg or 4.5 micrograms/kg intravenously 5 min before 4%-8% desflurane; four received clonidine 4.3 micrograms/kg, orally, 90 min before 4% to 8%; and four received esmolol 0.75 mg/kg, intravenously, 1.5 min before 4%-8%. Without other drugs present, 4%-8% desflurane transiently increased pupil diameter to 5.4 +/- 0.5 mm (mean +/- SD), with subsequent 4%-8% increases producing attenuated responses (2.9 +/- 1.5 and 3.2 +/- 1.8 mm). N2O produced a higher peak (6.2 +/- 0.7 mm). Fentanyl 1.5 micrograms/kg and 4.5 micrograms/kg decreased peak diameter (2.3 +/- 0.9 and 1.6 +/- 0.3 mm), as did clonidine (2.3 +/- 1.7 mm) but not esmolol. We conclude that, concurrent with sympathetic stimulation, an initial rapid increase in desflurane concentration transiently increases pupil diameter, whereas repeated increases produce attenuated responses. N2O augments, fentanyl and clonidine attenuate, and esmolol does not affect the response.

  6. Local school policies increase physical activity in Norwegian secondary schools

    PubMed Central

    Haug, Ellen; Torsheim, Torbjørn; Samdal, Oddrun

    2010-01-01

    SUMMARY The implementation of school policies to support the adoption of physical activity is one of the main strategies recommended to increase physical activity levels among this age group. However, documentation of the effect of such policies is so far limited. The purpose of this study was to explore policy-related practices to support physical activity in Norwegian secondary schools and their association with recess physical activity. Emphasis was given to examine the association between policies and physical activity, over and beyond, individual level interests and environmental factors and to examine cross-level interaction effects. This cross-sectional study was based on a nationally representative sample of Norwegian secondary schools and grade 8 students who participated in the Health Behaviour in School-aged Children (HBSC) 2005/06 study. The final sample comprised 68 schools and 1347 students. Data were collected through questionnaires. The results showed that schools with a written policy for physical activity and schools offering organized non-curricular physical activity several times a week had a higher proportion of students reporting daily participation in recess physical activity. Multilevel logistic regression analysis demonstrated a cross-level main effect of the policy index after controlling for sex, socio-economic status, individual-level interests and the physical environment. A significant contribution of adding the policy index to the prediction of recess physical activity above that provided by the individual-level interests and the physical environment was demonstrated. The results are encouraging and give scientific support to policy documents recommending the implementation of school policies to increase physical activity. PMID:19884244

  7. Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.

    PubMed

    Nimjee, Shahid M; Lohrmann, Jens D; Wang, Haichen; Snyder, David J; Cummings, Thomas J; Becker, Richard C; Oney, Sabah; Sullenger, Bruce A

    2012-02-01

    Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agent's safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery.

  8. Semantic features and semantic categories: differences in rapid activation of the lexicon.

    PubMed

    Frenck-Mestre, C; Bueno, S

    Robust priming was shown in a semantic categorization task for prime-target pairs which shared semantic features (e.g., pumpkin-squash). Priming facilitation for these pairs was demonstrated at extremely rapid prime exposures (28 and 43 ms) and increased with prime duration. The onset and amount of facilitation differed significantly for these semantic, nonassociative pairs and for associative-semantic prime-target pairs (e.g., cow-bull). The latter pairs produced facilitation, but later (at prime-target SOAs of 70 and 200 ms) and of lesser magnitude. These results are discussed in relation to three current models of semantic memory: spreading activation, compound cue, and distributed models.

  9. Rapid ester biosynthesis screening reveals a high activity alcohol-O-acyltransferase (AATase) from tomato fruit.

    PubMed

    Lin, Jyun-Liang; Zhu, Jie; Wheeldon, Ian

    2016-05-01

    Ethyl and acetate esters are naturally produced in various yeasts, plants, and bacteria. The biosynthetic pathways that produce these esters share a common reaction step, the condensation of acetyl/acyl-CoA with an alcohol by alcohol-O-acetyl/acyltransferase (AATase). Recent metabolic engineering efforts exploit AATase activity to produce fatty acid ethyl esters as potential diesel fuel replacements as well as short- and medium-chain volatile esters as fragrance and flavor compounds. These efforts have been limited by the lack of a rapid screen to quantify ester biosynthesis. Enzyme engineering efforts have also been limited by the lack of a high throughput screen for AATase activity. Here, we developed a high throughput assay for AATase activity and used this assay to discover a high activity AATase from tomato fruit, Solanum lycopersicum (Atf-S.l). Atf1-S.l exhibited broad specificity towards acyl-CoAs with chain length from C4 to C10 and was specific towards 1-pentanol. The AATase screen also revealed new acyl-CoA substrate specificities for Atf1, Atf2, Eht1, and Eeb1 from Saccharomyces cerevisiae, and Atf-C.m from melon fruit, Cucumis melo, thus increasing the pool of characterized AATases that can be used in ester biosynthesis of ester-based fragrance and flavor compounds as well as fatty acid ethyl ester biofuels.

  10. P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2

    PubMed Central

    Adamczyk, Magdalena; Griffiths, Rhiannon; Dewitt, Sharon; Knäuper, Vera; Aeschlimann, Daniel

    2015-01-01

    ABSTRACT Transglutaminases (denoted TG or TGM) are externalized from cells via an unknown unconventional secretory pathway. Here, we show for the first time that purinergic signaling regulates active secretion of TG2 (also known as TGM2), an enzyme with a pivotal role in stabilizing extracellular matrices and modulating cell–matrix interactions in tissue repair. Extracellular ATP promotes TG2 secretion by macrophages, and this can be blocked by a selective antagonist against the purinergic receptor P2X7 (P2X7R, also known as P2RX7). Introduction of functional P2X7R into HEK293 cells is sufficient to confer rapid, regulated TG2 export. By employing pharmacological agents, TG2 release could be separated from P2X7R-mediated microvesicle shedding. Neither Ca2+ signaling alone nor membrane depolarization triggered TG2 secretion, which occurred only upon receptor membrane pore formation and without pannexin channel involvement. A gain-of-function mutation in P2X7R associated with autoimmune disease caused enhanced TG2 externalization from cells, and this correlated with increased pore activity. These results provide a mechanistic explanation for a link between active TG2 secretion and inflammatory responses, and aberrant enhanced TG2 activity in certain autoimmune conditions. PMID:26542019

  11. Using the Web to Increase Physical Activity in College Students

    ERIC Educational Resources Information Center

    Magoc, Dejan; Tomaka, Joe; Bridges-Arzaga, Amber

    2011-01-01

    Objectives: To evaluate the effectiveness of a theoretically based and Web-delivered intervention using common course technology for increasing physical activity in a college student sample. Methods: One hundred four students randomly participated in either a Web-based intervention involving 7 theory-based learning lessons or a control group that…

  12. Increased proteasome activity determines human embryonic stem cell identity

    PubMed Central

    Vilchez, David; Boyer, Leah; Morantte, Ianessa; Lutz, Margaret; Merkwirth, Carsten; Joyce, Derek; Spencer, Brian; Page, Lesley; Masliah, Eliezer; Berggren, W. Travis; Gage, Fred H.; Dillin, Andrew

    2016-01-01

    Embryonic stem cells are able to replicate continuously in the absence of senescence and, therefore, are immortal in culture1,2. While genome stability is central for survival of stem cells; proteome stability may play an equally important role in stem cell identity and function. Additionally, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. We hypothesized that stem cells have an increased proteostasis ability compared to their differentiated counterparts and asked whether proteasome activity differed among human embryonic stem cells (hESCs). Notably, hESC populations exhibit a high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11/RPN-63–5 and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. Proteasome inhibition affects pluripotency of hESCs inducing differentiation towards specific cell lineages. FOXO4, an insulin/IGF-1 responsive transcription factor associated with long lifespan in invertebrates6,7, regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Our results establish a novel regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates with hESC function and identity. PMID:22972301

  13. Texting to increase adolescent physical activity: Feasibility assessment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Feasibility trials assess whether a behavior change program warrants a definite trial evaluation. This paper reports the feasibility of an intervention consisting of Self Determination Theory-informed text messages, pedometers, and goal prompts to increase adolescent physical activity. A 4-group ran...

  14. Reduced Frontal Activation with Increasing 2nd Language Proficiency

    ERIC Educational Resources Information Center

    Stein, Maria; Federspiel, Andrea; Koenig, Thomas; Wirth, Miranka; Lehmann, Christoph; Wiest, Roland; Strik, Werner; Brandeis, Daniel; Dierks, Thomas

    2009-01-01

    The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second…

  15. Games for increasing physical activity: Mechanisms for change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A small conference was held in Houston, TX, in May 2014, to address how to enhance exergames to increase physical activity. Several leading researchers were asked to address specific topics. Attendees came from across the globe. This Games for Health Journal Special Issue is devoted to sharing the a...

  16. Hypocholesterolemia in chronic anemias with increased erythropoietic activity.

    PubMed

    Shalev, Hanna; Kapelushnik, Joseph; Moser, Asher; Knobler, Hilla; Tamary, Hannah

    2007-03-01

    Hypocholesterolemia of unknown etiology has been previously described in various chronic anemias. Few small studies also suggested that those patients have a lower incidence of atherosclerotic events. The aim of our study was to determine the extent of hypocholesterolemia in various types of anemias. We studied 59 patients with chronic anemias associated with high-erythropoietic activity (thalassemia intermedia, congenital dyserythropoietic anemia type I, congenital spherocytosis), 8 patients with low-erythropoietic activity anemias (acquired aplastic anemia, Fanconi anemia, and Diamond Blackfan anemia), and 20 healthy controls. Mean serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, hemoglobin, serum ferritin, soluble transferrin receptor (STR), and serum erythropoietin levels were determined in each patient. All patients with chronic anemia and increased erythropoietic activity had hypocholesterolemia, whereas none of those with low erythropoietic activity was hypocholesterolemic. Mean serum cholesterol, HDL cholesterol, and LDL cholesterol levels were found to be significantly lower in the high-erythropoietic activity group (80+/-19 mg/dl; 31+/-10 mg/dl; 35+/-14 mg/dl, respectively) compared with the control group (P<0.001; 0.001; 0.001, respectively) and the low-erythropoietic activity group (P<0.001; 0.001; 0.01, respectively). Significant inverse correlation (R2=0.507) was observed between serum cholesterol and STR levels, which in the absence of iron deficiency reflect bone marrow activity. Taken together, our results imply that hypocholesterolemia accompanies anemias with high-erythropoietic activity. We suggest that the high-erythropoitic activity-associated hypocholesterolemia is due to increased cholesterol requirements by the proliferating erythoid cells. Further studies are needed to elucidate the exact mechanism and the possible clinical consequences of this phenomenon.

  17. Increased matriptase zymogen activation in inflammatory skin disorders

    PubMed Central

    Chen, Cheng-Jueng; Wu, Bai-Yao; Tsao, Pai-In; Chen, Chi-Yung; Wu, Mei-Hsuan; Chan, Yee Lam E.; Lee, Herng-Sheng; Johnson, Michael D.; Eckert, Richard L.; Chen, Ya-Wen; Chou, Fengpai; Lin, Chen-Yong

    2011-01-01

    Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H2O2 and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases. PMID:21123732

  18. Chromosome 1 replacement increases brain orexins and antidepressive measures without increasing locomotor activity.

    PubMed

    Feng, Pingfu; Hu, Yufen; Vurbic, Drina; Akladious, Afaf; Strohl, Kingman P

    2014-12-01

    Decreased orexin level has been well demonstrated in patients suffering from narcolepsy, depression accompanied with suicide attempt; obstructive sleep apnea and comorbidity were also demonstrated in these diseases. As C57BL/6J (B6) mice are more "depressed" and have lower brain orexins than A/J mice, B6 mice having chromosome 1 replacement (B6A1 mice) might have restored orexin levels and less depressive behavior. We studied the behavior of 4-6 month old B6, A/J and B6A1 mice with forced swim, tail suspension, and locomotor activity tests. The animals were then sacrificed and hypothalamus and medullas dissected from brain tissue. Orexins-A and -B were determined by radioimmunoassay. Compared with A/J mice, B6 mice displayed several signs of depression, including increased immobility, increased locomotors activity, and decreased orexin A and -B levels in both the hypothalamus and medulla. Compared to B6 mice, B6A1 mice exhibited significantly higher levels of orexins-A and -B in both brain regions. B6A1 mice also exhibited antidepressive features in most of measured variables, including decreased locomotor activity, decreased immobility and increased swim in tail suspension test; compared with B6 mice, however. B6A1 mice also reversed immobility in the early phase of the swim test. In summary, B6 mice exhibited depressive attributes compared with A/J mice, including increased locomotor activity, greater immobility, and decreased brain orexins, these were largely reversed in B6A1 mice. We conclude that orexin levels modulate these B6 behaviors, likely due to expression of A/J alleles on Chromosome 1.

  19. Methods of increasing secretion of polypeptides having biological activity

    SciTech Connect

    Merino, Sandra

    2013-10-01

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  20. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-10-28

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  1. Methods of increasing secretion of polypeptides having biological activity

    DOEpatents

    Merino, Sandra

    2014-05-27

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  2. Methods of increasing secretion of polypeptides having biological activity

    SciTech Connect

    Merino, Sandra

    2015-04-14

    The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

  3. 20 CFR 665.300 - What are rapid response activities and who is responsible for providing them?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What are rapid response activities and who is responsible for providing them? 665.300 Section 665.300 Employees' Benefits EMPLOYMENT AND TRAINING... INVESTMENT ACT Rapid Response Activities § 665.300 What are rapid response activities and who is...

  4. 20 CFR 665.300 - What are rapid response activities and who is responsible for providing them?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false What are rapid response activities and who is responsible for providing them? 665.300 Section 665.300 Employees' Benefits EMPLOYMENT AND TRAINING... WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.300 What are rapid response activities and who...

  5. Plant species richness increases phosphatase activities in an experimental grassland

    NASA Astrophysics Data System (ADS)

    Hacker, Nina; Wilcke, Wolfgang; Oelmann, Yvonne

    2014-05-01

    Plant species richness has been shown to increase aboveground nutrient uptake requiring the mobilization of soil nutrient pools. For phosphorus (P) the underlying mechanisms for increased P release in soil under highly diverse grassland mixtures remain obscure because aboveground P storage and concentrations of inorganic and organic P in soil solution and differently reactive soil P pools are unrelated (Oelmann et al. 2011). The need of plants and soil microorganisms for P can increase the exudation of enzymes hydrolyzing organically bound P (phosphatases) which might represent an important release mechanism of inorganic P in a competitive environment such as highly diverse grassland mixtures. Our objectives were to test the effects of i) plant functional groups (legumes, grasses, non-leguminous tall and small herbs), and of (ii) plant species richness on microbial P (Pmic) and phosphatase activities in soil. In autumn 2013, we measured Pmic and alkaline phosphomonoesterase and phosphodiesterase activities in soil of 80 grassland mixtures comprising different community compositions and species richness (1, 2, 4, 8, 16, 60) in the Jena Experiment. In general, Pmic and enzyme activities were correlated (r = 0.59 and 0.46 for phosphomonoesterase and phosphodiesterase activities, respectively; p

  6. Exercising self-control increases relative left frontal cortical activation.

    PubMed

    Schmeichel, Brandon J; Crowell, Adrienne; Harmon-Jones, Eddie

    2016-02-01

    Self-control refers to the capacity to override or alter a predominant response tendency. The current experiment tested the hypothesis that exercising self-control temporarily increases approach motivation, as revealed by patterns of electrical activity in the prefrontal cortex. Participants completed a writing task that did vs did not require them to exercise self-control. Then they viewed pictures known to evoke positive, negative or neutral affect. We assessed electroencephalographic (EEG) activity while participants viewed the pictures, and participants reported their trait levels of behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivity at the end of the study. We found that exercising (vs not exercising) self-control increased relative left frontal cortical activity during picture viewing, particularly among individuals with relatively higher BAS than BIS, and particularly during positive picture viewing. A similar but weaker pattern emerged during negative picture viewing. The results suggest that exercising self-control temporarily increases approach motivation, which may help to explain the aftereffects of self-control (i.e. ego depletion).

  7. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.

    PubMed

    Klinge, Carolyn M; Blankenship, Kristy A; Risinger, Kelly E; Bhatnagar, Shephali; Noisin, Edouard L; Sumanasekera, Wasana K; Zhao, Lei; Brey, Darren M; Keynton, Robert S

    2005-03-04

    Vascular endothelial cells (EC) are an important target of estrogen action through both the classical genomic (i.e. nuclear-initiated) activities of estrogen receptors alpha and beta (ERalpha and ERbeta) and the rapid "non-genomic" (i.e. membrane-initiated) activation of ER that stimulates intracellular phosphorylation pathways. We tested the hypothesis that the red wine polyphenol trans-resveratrol activates MAPK signaling via rapid ER activation in bovine aortic EC, human umbilical vein EC, and human microvascular EC. We report that bovine aortic EC, human umbilical vein EC, and human microvascular EC express ERalpha and ERbeta. We demonstrate that resveratrol and estradiol (E(2)) rapidly activated MAPK in a MEK-1, Src, matrix metalloproteinase, and epidermal growth factor receptor-dependent manner. Importantly, resveratrol activated MAPK and endothelial nitric-oxide synthase (eNOS) at nm concentrations (i.e. an order of magnitude less than that required for ER genomic activity) and concentrations possibly achieved transiently in serum following oral red wine consumption. Co-treatment with ER antagonists ICI 182,780 or 4-hydroxytamoxifen blocked resveratrol- or E(2)-induced MAPK and eNOS activation, indicating ER dependence. We demonstrate for the first time that ERalpha-and ERbeta-selective agonists propylpyrazole triol and diarylpropionitrile, respectively, stimulate MAPK and eNOS activity. A red but not a white wine extract also activated MAPK, and activity was directly correlated with the resveratrol concentration. These data suggest that ER may play a role in the rapid effects of resveratrol in EC and that some of the atheroprotective effects of resveratrol may be mediated through rapid activation of ER signaling in EC.

  8. Increasing Arabian dust activity and the Indian summer monsoon

    NASA Astrophysics Data System (ADS)

    Solmon, F.; Nair, V. S.; Mallet, M.

    2015-07-01

    Over the past decade, aerosol optical depth (AOD) observations based on satellite and ground measurements have shown a significant increase over Arabia and the Arabian Sea, attributed to an intensification of regional dust activity. Recent studies have also suggested that west Asian dust forcing could induce a positive response of Indian monsoon precipitations on a weekly timescale. Using observations and a regional climate model including interactive slab-ocean and dust aerosol schemes, the present study investigates possible climatic links between the increasing June-July-August-September (JJAS) Arabian dust activity and precipitation trends over southern India during the 2000-2009 decade. Meteorological reanalysis and AOD observations suggest that the observed decadal increase of dust activity and a simultaneous intensification of summer precipitation trend over southern India are both linked to a deepening of JJAS surface pressure conditions over the Arabian Sea. In the first part of the study, we analyze the mean climate response to dust radiative forcing over the domain, discussing notably the relative role of Arabian vs. Indo-Pakistani dust regions. In the second part of the study, we show that the model skills in reproducing regional dynamical patterns and southern Indian precipitation trends are significantly improved only when an increasing dust emission trend is imposed on the basis of observations. We conclude that although interannual climate variability might primarily determine the observed regional pattern of increasing dust activity and precipitation during the 2000-2009 decade, the associated dust radiative forcing might in return induce a critical dynamical feedback contributing to enhancing regional moisture convergence and JJAS precipitations over southern India.

  9. Increased antitumor activity of tumor-specific peptide modified thymopentin.

    PubMed

    Lao, Xingzhen; Li, Bin; Liu, Meng; Chen, Jiao; Gao, Xiangdong; Zheng, Heng

    2014-12-01

    Thymopoietin pentapeptide (thymopentin, TP5), an immunomodulatory peptide, has been successfully used as an immune system enhancer for treating immune deficiency, cancer, and infectious diseases. However, poor penetration into tumors remains a key limitation to the efficacy and application of TP5. iRGD (CRGDK/RGPD/EC) has been introduced to certain anticancer agents, and increased specific tumor penetrability of drugs and cell internalization have been observed. In the present study, we fused this iRGD fragment with the C-terminal of TP5 to yield a new product, TP5-iRGD. Cell attachment assay showed that TP5-iRGD exhibits more extensive attachment to the melanoma cell line B16F10 than wild-type TP5. Tumor cell viability assay showed that iRGD conjugation with the TP5 C-terminus increases the basal antiproliferative activity of the pentapeptide against the melanoma cell line B16F10, the human lung cancer cell line H460, and the human breast cancer cell line MCF-7. Subsequent injections of TP5-iRGD inhibited in vivo melanoma progression more efficiently than the native TP5. Murine spleen lymphocyte proliferation assay also showed that TP5-iRGD and the parent pentapeptide feature nearly identical spleen lymphocyte proliferation activities. We built an integrin αvβ3 and TP5-iRGD computational binding model to investigate the mechanism by which TP5-iRGD promotes increased activity further. Conjugation with iRGD promotes binding to integrin αvβ3, thereby increasing the tumor-homing efficiency of the resultant peptide. These experimental and computational observations of increased TP5-iRGD activity help broaden the usage of TP5 and reflect the great application potential of the peptide as an anticancer agent.

  10. Plant diversity increases soil microbial activity and soil carbon storage.

    PubMed

    Lange, Markus; Eisenhauer, Nico; Sierra, Carlos A; Bessler, Holger; Engels, Christoph; Griffiths, Robert I; Mellado-Vázquez, Perla G; Malik, Ashish A; Roy, Jacques; Scheu, Stefan; Steinbeiss, Sibylle; Thomson, Bruce C; Trumbore, Susan E; Gleixner, Gerd

    2015-04-07

    Plant diversity strongly influences ecosystem functions and services, such as soil carbon storage. However, the mechanisms underlying the positive plant diversity effects on soil carbon storage are poorly understood. We explored this relationship using long-term data from a grassland biodiversity experiment (The Jena Experiment) and radiocarbon ((14)C) modelling. Here we show that higher plant diversity increases rhizosphere carbon inputs into the microbial community resulting in both increased microbial activity and carbon storage. Increases in soil carbon were related to the enhanced accumulation of recently fixed carbon in high-diversity plots, while plant diversity had less pronounced effects on the decomposition rate of existing carbon. The present study shows that elevated carbon storage at high plant diversity is a direct function of the soil microbial community, indicating that the increase in carbon storage is mainly limited by the integration of new carbon into soil and less by the decomposition of existing soil carbon.

  11. Rapid assessment of mosquitoes and arbovirus activity after floods in southeastern Kansas, 2007.

    PubMed

    Harrison, Bruce A; Whitt, Parker B; Roberts, Lesa F; Lehman, Jennifer A; Lindsey, Nicole P; Nasci, Roger S; Hansen, Gail R

    2009-09-01

    A rapid assessment was conducted in July-August 2007 to determine the impact of heavy rains and early summer floods on the mosquitoes and arbovirus activity in 4 southeastern Kansas counties. During 10 days and nights of collections using different types and styles of mosquito traps, a total of 10,512 adult female mosquitoes representing 29 species were collected, including a new species record for Kansas (Psorophora mathesoni). High numbers of Aedes albopictus were collected. Over 4,000 specimens of 4 Culex species in 235 species-specific pools were tested for the presence of West Nile, St. Louis, and western equine encephalitis viruses. Thirty pools representing 3 Culex species were positive for West Nile virus (WNV). No other arboviruses were detected in the samples. Infection rates of WNV in Culex pipiens complex in 2 counties (10.7/1,000 to 22.6/1,000) and in Culex salinarius in 1 county (6.0/1,000) were sufficiently high to increase the risk of transmission to humans. The infection rate of WNV in Culex erraticus was 1.9/1,000 in one county. Two focal hot spots of intense WNV transmission were identified in Montgomery and Wilson counties, where infection rates in Cx. pipiens complex were 26/ 1,000 and 19.9/1,000, respectively. Despite confirmed evidence of WNV activity in the area, there was no increase in human cases of arboviral disease documented in the 4 counties for the remainder of 2007.

  12. Rapid volumetric temporal focusing multiphoton microscopy of neural activity: theory, image processing, and experimental realization

    NASA Astrophysics Data System (ADS)

    Dana, Hod; Marom, Anat; Kruger, Nimrod; Ellman, Aviv; Shoham, Shy

    2012-03-01

    The development of rapid volumetric imaging systems for functional multiphoton microscopy is essential for dynamical imaging of large-scale neuronal network activity. Here, we introduce a line-illuminating temporal-focusing microscope capable of rapid three-dimensional imaging at 10-20 volumes/sec, and study the system's characteristics both theoretically and experimentally. We demonstrate that our system is capable of functional volumetric calcium imaging of distributed neuronal activity patterns, and introduce a computational strategy for activity reconstruction in strongly scattering media.

  13. Pupil fluctuations track rapid changes in adrenergic and cholinergic activity in cortex

    PubMed Central

    Reimer, Jacob; McGinley, Matthew J; Liu, Yang; Rodenkirch, Charles; Wang, Qi; McCormick, David A; Tolias, Andreas S

    2016-01-01

    Rapid variations in cortical state during wakefulness have a strong influence on neural and behavioural responses and are tightly coupled to changes in pupil size across species. However, the physiological processes linking cortical state and pupil variations are largely unknown. Here we demonstrate that these rapid variations, during both quiet waking and locomotion, are highly correlated with fluctuations in the activity of corticopetal noradrenergic and cholinergic projections. Rapid dilations of the pupil are tightly associated with phasic activity in noradrenergic axons, whereas longer-lasting dilations of the pupil, such as during locomotion, are accompanied by sustained activity in cholinergic axons. Thus, the pupil can be used to sensitively track the activity in multiple neuromodulatory transmitter systems as they control the state of the waking brain. PMID:27824036

  14. Active learning increases student performance in science, engineering, and mathematics.

    PubMed

    Freeman, Scott; Eddy, Sarah L; McDonough, Miles; Smith, Michelle K; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-06-10

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes--although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms.

  15. Active learning increases student performance in science, engineering, and mathematics

    PubMed Central

    Freeman, Scott; Eddy, Sarah L.; McDonough, Miles; Smith, Michelle K.; Okoroafor, Nnadozie; Jordt, Hannah; Wenderoth, Mary Pat

    2014-01-01

    To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes—although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms. PMID:24821756

  16. Rapid X-Ray Variability of Active Galaxies. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Tennant, A. F., Jr.

    1983-01-01

    Active galactic nuclei are luminous sources of X-rays. The thesis that the X-rays are generated within 10 gravitational radii from the central object is tested. A very sensitive search for rapid ( 1 day) X-ray variability from active galaxies was made.

  17. The population in China’s earthquake-prone areas has increased by over 32 million along with rapid urbanization

    NASA Astrophysics Data System (ADS)

    He, Chunyang; Huang, Qingxu; Dou, Yinyin; Tu, Wei; Liu, Jifu

    2016-07-01

    Accurate assessments of the population exposed to seismic hazard are crucial in seismic risk mapping. Recent rapid urbanization in China has resulted in substantial changes in the size and structure of the population exposed to seismic hazard. Using the latest population census data and seismic maps, this work investigated spatiotemporal changes in the exposure of the population in the most seismically hazardous areas (MSHAs) in China from 1990 to 2010. In the context of rapid urbanization and massive rural-to-urban migration, nearly one-tenth of the Chinese population in 2010 lived in MSHAs. From 1990 to 2010, the MSHA population increased by 32.53 million at a significantly higher rate of change (33.6%) than the national average rate (17.7%). The elderly population in MSHAs increased by 81.4%, which is much higher than the group’s national growth rate of 58.9%. Greater attention should be paid to the demographic changes in earthquake-prone areas in China.

  18. Self-etching adhesives increase collagenolytic activity in radicular dentin.

    PubMed

    Tay, Franklin R; Pashley, David H; Loushine, Robert J; Weller, R Norman; Monticelli, Francesca; Osorio, Raquel

    2006-09-01

    Endogenous matrix metalloproteinases (MMPs) release from crown dentin and their activation results in degradation of hybrid layers created by dentin adhesives. This study tested the hypothesis that instrumented intraradicular dentin possesses latent collagenolytic activity that is activated by mild self-etching adhesives. Root dentin shavings were produced from 50 cleaned and shaped, saline-irrigated root canals using Gates Glidden drills and rinsed with sodium azide to prevent bacterial growth. Dried dentin powder aliquots were treated with two clinically-relevant MMP inhibitors, 2% chlorhexidine for 10 minutes and 17% EDTA for 1 minute. Additional dentin powder was mixed with Clearfil Liner Bond 2V or Clearfil Tri-S Bond for 1 minute followed by extracting the adhesives with acetone. Dentin powder was also treated with 2% chlorhexidine for 10 minutes before or after adhesive application. Collagenolytic activities of the nine groups were assayed with a fluorometer in 96-well plates, by recording the changes in fluorescence before and after addition of fluorescein-labeled type I collagen. Epoxy resin-embedded powders were examined with TEM for the extent of demineralization. Instrumented, mineralized intraradicular dentin possessed low but detectable collagenolytic activity that was inhibited by chlorhexidine (p < 0.001) and EDTA (p < 0.001). Both adhesives partially demineralized the dentin powder and activated latent MMPs, with 14- to 15-fold increases in collagenolytic activities (p < 0.001) that were significantly (p < 0.001) but incompletely inactivated after 10 min application of chlorhexidine. Mild self-etching adhesives activate latent MMPs without denaturing these enzymes, and may adversely affect the longevity of bonded root canal fillings and posts.

  19. Rapid Response to Selection, Competitive Release and Increased Transmission Potential of Artesunate-Selected Plasmodium chabaudi Malaria Parasites

    PubMed Central

    Pollitt, Laura C.; Huijben, Silvie; Sim, Derek G.; Salathé, Rahel M.; Jones, Matthew J.; Read, Andrew F.

    2014-01-01

    The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain

  20. Rapid response to selection, competitive release and increased transmission potential of artesunate-selected Plasmodium chabaudi malaria parasites.

    PubMed

    Pollitt, Laura C; Huijben, Silvie; Sim, Derek G; Salathé, Rahel M; Jones, Matthew J; Read, Andrew F

    2014-04-01

    The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain

  1. Interactions Increase Forager Availability and Activity in Harvester Ants.

    PubMed

    Pless, Evlyn; Queirolo, Jovel; Pinter-Wollman, Noa; Crow, Sam; Allen, Kelsey; Mathur, Maya B; Gordon, Deborah M

    2015-01-01

    Social insect colonies use interactions among workers to regulate collective behavior. Harvester ant foragers interact in a chamber just inside the nest entrance, here called the 'entrance chamber'. Previous studies of the activation of foragers in red harvester ants show that an outgoing forager inside the nest experiences an increase in brief antennal contacts before it leaves the nest to forage. Here we compare the interaction rate experienced by foragers that left the nest and ants that did not. We found that ants in the entrance chamber that leave the nest to forage experienced more interactions than ants that descend to the deeper nest without foraging. Additionally, we found that the availability of foragers in the entrance chamber is associated with the rate of forager return. An increase in the rate of forager return leads to an increase in the rate at which ants descend to the deeper nest, which then stimulates more ants to ascend into the entrance chamber. Thus a higher rate of forager return leads to more available foragers in the entrance chamber. The highest density of interactions occurs near the nest entrance and the entrances of the tunnels from the entrance chamber to the deeper nest. Local interactions with returning foragers regulate both the activation of waiting foragers and the number of foragers available to be activated.

  2. Changes in baseball batters' brain activity with increased pitch choice.

    PubMed

    Ryu, Kwangmin; Kim, Jingu; Ali, Asif; Kim, Woojong; Radlo, Steven J

    2015-09-01

    In baseball, one factor necessary for batters to decide whether to swing or not depends on what type of pitch is thrown. Oftentimes batters will look for their pitch (i.e., waiting for a fastball). In general, when a pitcher has many types of pitches in his arsenal, batters will have greater difficulty deciding upon the pitch thrown. Little research has been investigated the psychophysiology of a batters decision-making processes. Therefore, the primary purpose of this study was to determine how brain activation changes according to an increase in the number of alternatives (NA) available. A total of 15 male college baseball players participated in this study. The stimuli used in this experiment were video clips of a right-handed pitcher throwing fastball, curve, and slider pitches. The task was to press a button after selecting the fastball as the target stimulus from two pitch choices (fastball and curve), and then from three possibilities (fastball, curve, and slider). Functional and anatomic image scanning magnetic resonance imaging (MRI) runs took 4 and 5[Formula: see text]min, respectively. According to our analysis, the right precentral gyrus, left medial frontal gyrus, and right fusiform gyrus were activated when the NA was one. The supplementary motor areas (SMA) and primary motor cortex were activated when there were two alternatives to choose from and the inferior orbitofrontal gyrus was specifically activated with three alternatives. Contrary to our expectations, the NA was not a critical factor influencing the activation of related decision making areas when the NA was compared against one another. These findings highlight that specific brain areas related to decision making were activated as the NA increased.

  3. Projecting climate-driven increases in North American fire activity

    NASA Astrophysics Data System (ADS)

    Wang, D.; Morton, D. C.; Collatz, G. J.

    2013-12-01

    Climate regulates fire activity through controls on vegetation productivity (fuels), lightning ignitions, and conditions governing fire spread. In many regions of the world, human management also influences the timing, duration, and extent of fire activity. These coupled interactions between human and natural systems make fire a complex component of the Earth system. Satellite data provide valuable information on the spatial and temporal dynamics of recent fire activity, as active fires, burned area, and land cover information can be combined to separate wildfires from intentional burning for agriculture and forestry. Here, we combined satellite-derived burned area data with land cover and climate data to assess fire-climate relationships in North America between 2000-2012. We used the latest versions of the Global Fire Emissions Database (GFED) burned area product and Modern-Era Retrospective Analysis for Research and Applications (MERRA) climate data to develop regional relationships between burned area and potential evaporation (PE), an integrated dryness metric. Logistic regression models were developed to link burned area with PE and individual climate variables during and preceding the fire season, and optimal models were selected based on Akaike Information Criterion (AIC). Overall, our model explained 85% of the variance in burned area since 2000 across North America. Fire-climate relationships from the era of satellite observations provide a blueprint for potential changes in fire activity under scenarios of climate change. We used that blueprint to evaluate potential changes in fire activity over the next 50 years based on twenty models from the Coupled Model Intercomparison Project Phase 5 (CMIP5). All models suggest an increase of PE under low and high emissions scenarios (Representative Concentration Pathways (RCP) 4.5 and 8.5, respectively), with largest increases in projected burned area across the western US and central Canada. Overall, near

  4. High Altitude Increases Alteration in Maximal Torque but Not in Rapid Torque Development in Knee Extensors after Repeated Treadmill Sprinting

    PubMed Central

    Girard, Olivier; Brocherie, Franck; Millet, Grégoire P.

    2016-01-01

    We assessed knee extensor neuromuscular adjustments following repeated treadmill sprints in different normobaric hypoxia conditions, with special reference to rapid muscle torque production capacity. Thirteen team- and racquet-sport athletes undertook 8 × 5-s “all-out” sprints (passive recovery = 25 s) on a non-motorized treadmill in normoxia (NM; FiO2 = 20.9%), at low (LA; FiO2 = 16.8%) and high (HA; FiO2 = 13.3%) normobaric hypoxia (simulated altitudes of ~1800 m and ~3600 m, respectively). Explosive (~1 s; “fast” instruction) and maximal (~5 s; “hard” instruction) voluntary isometric contractions (MVC) of the knee extensors (KE), with concurrent electromyographic (EMG) activity recordings of the vastus lateralis (VL) and rectus femoris (RF) muscles, were performed before and 1-min post-exercise. Rate of torque development (RTD) and EMG (i.e., Root Mean Square or RMS) rise from 0 to 30, −50, −100, and −200 ms were recorded, and were also normalized to maximal torque and EMG values, respectively. Distance covered during the first 5-s sprint was similar (P > 0.05) in all conditions. A larger (P < 0.05) sprint decrement score and a shorter (P < 0.05) cumulated distance covered over the eight sprints occurred in HA (−8 ± 4% and 178 ± 11 m) but not in LA (−7 ± 3% and 181 ± 10 m) compared to NM (−5 ± 2% and 183 ± 9 m). Compared to NM (−9 ± 7%), a larger (P < 0.05) reduction in MVC torque occurred post-exercise in HA (−14 ± 9%) but not in LA (-12 ± 7%), with no difference between NM and LA (P > 0.05). Irrespectively of condition (P > 0.05), peak RTD (−6 ± 11%; P < 0.05), and normalized peak RMS activity for VL (−8 ± 11%; P = 0.07) and RF (−14 ± 11%; P < 0.01) muscles were reduced post-exercise, whereas reductions (P < 0.05) in absolute RTD occurred within the 0–100 (−8 ± 9%) and 0–200 ms (−10 ± 8%) epochs after contraction onset. After normalization to MVC torque, there was no difference in RTD values

  5. Serotonin increases synaptic activity in olfactory bulb glomeruli.

    PubMed

    Brill, Julia; Shao, Zuoyi; Puche, Adam C; Wachowiak, Matt; Shipley, Michael T

    2016-03-01

    Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range.

  6. Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription

    SciTech Connect

    Waldron, Elaine; Isbert, Simone; Kern, Andreas; Jaeger, Sebastian; Martin, Anne M.; Hebert, Sebastien S.; Behl, Christian; Weggen, Sascha; De Strooper, Bart; Pietrzik, Claus U.

    2008-08-01

    A sequence of amyloid precursor protein (APP) cleavages culminates in the sequential release of the APP intracellular domain (AICD) and the amyloid {beta} peptide (A{beta}) and/or p3 fragment. One of the environmental factors favouring the accumulation of AICD appears to be a rise in intracellular pH. Here we further identified the metabolism and subcellular localization of artificially expressed constructs under such conditions. We also co-examined the mechanistic lead up to the AICD accumulation and explored possible significances for its increased expression. We found that most of the AICD generated under pH neutralized conditions is likely cleaved from C83. While the AICD surplus was unable to further activate transcription of a luciferase reporter via a Gal4-DNA-binding domain, it failed entirely via the endogenous promoter regions of proposed target genes, APP and KAI1. The lack of a specific transactivation potential was also demonstrated by the unchanged levels of target gene mRNA. However, rather than translocating to the nucleus, the AICD surplus remains membrane tethered or free in the cytosol where it interacts with Fe65. Therefore we provide strong evidence that an increase in AICD generation does not directly promote gene activation of previously proposed target 0011gen.

  7. A ketogenic diet increases succinic dehydrogenase activity in aging cardiomyocytes.

    PubMed

    Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Solazzi, Moreno; Platano, Daniela; Aicardi, Giorgio; Bertoni-Freddari, Carlo

    2009-08-01

    Impairment of energy metabolism and an increase of reactive oxygen species (ROS) production seem to play a major role in age-related apoptotic loss of cardiomyocytes. Succinic dehydrogenase (SDH) is an important marker of the mitochondrial capability to provide an adequate amount of ATP. Moreover, because of its unique redox properties, SDH activity contributes to maintain the reduced state of the ubiquinone pool. Recent reports have shown that ketone body intake improves cardiac metabolic efficiency and exerts a cardioprotective antioxidant action, we therefore performed a cytochemical investigation of SDH activity in cardiomyocytes of late-adult (19-month-old) rats fed for 8 weeks with a medium-chain triglycerides ketogenic diet (MCT-KD). Young, age-matched and old animals fed with a standard chow were used as controls. The overall area of the precipitates (PA) from SDH activity and the area of the SDH-positive mitochondria (MA) were measured. The percent ratios PA/MA and MA/total myocardial tissue area (MA/TA) were the parameters taken into account. We found that PA/MA was significantly higher in young control rats and in MCT-KD-fed rats versus late-adult and old control rats and in young control versus MCT-KD-fed rats. MA/TA of MCT-KD-fed rats was significantly higher versus age-matched and old control rats and tended to be higher versus young control rats; this parameter was significantly higher in young versus old control rats. Thus, MCT-KD intake partially recovers age-related decrease of SDH activity and increases the myocardial area occupied by metabolically active mitochondria. These effects might counteract metabolic alterations leading to apoptosis-induced myocardial atrophy and failure during aging.

  8. BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

    PubMed Central

    Tyler, William J; Zhang, Xiao-lei; Hartman, Kenichi; Winterer, Jochen; Muller, Wolfgang; Stanton, Patric K; Pozzo-Miller, Lucas

    2006-01-01

    Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity. PMID:16709633

  9. Targeting Reductions in Sitting Time to Increase Physical Activity and Improve Health.

    PubMed

    Keadle, Sarah K; Conroy, David E; Buman, Matthew P; Dunstan, David W; Matthews, Charles E

    2017-03-08

    New evidence suggests that reductions in sedentary behavior may increase physical activity and improve health. These findings point to new behavioral targets for intervention and new ways to think about intervening to increase overall physical activity in the population. This report provides a knowledge update reflecting the rapid accumulation of new evidence related to sedentary behavior and health among adults. Recent observational studies suggest that leveraging the time-inverse relationship between sedentary and active behaviors by replacing sitting with standing, light or moderate-intensity activity can have important health benefits, particularly among less active adults. Clinical studies are providing evidence of the probable physiologic mechanisms underlying these associations, as well as insights into the cardiometabolic impact of breaking up and reducing sedentary behavior. In contrast to the well-established behavioral theories that guide the development and dissemination of evidence-based interventions to increase moderate-vigorous intensity physical activity (MVPA), much less is known about how to reduce sedentary time in order to increase daily activities. It has become clear that the environmental, social and individual level-determinants for sedentary time are distinct from those linked to the adoption and maintenance of MVPA. As a result, novel intervention strategies that focus on sitting and lower intensity activities by leveraging the surrounding environment (e.g., workplace, school, home) as well as individual-level cues and habits of sedentary behavior are being tested to increase the potency of interventions designed to increase overall physical activity. Herein we summarize the solutions-oriented research across the behavioral research framework, with a focus on highlighting areas of synergy across disciplines and identifying gaps for future research.

  10. Betaine increases the butyrylcholinesterase activity in rat plasma.

    PubMed

    Šišková, K; Dubničková, M; Pašková, Ľ; Rajdl, D; Ďuračková, Z; Muchová, J; Pauliková, I; Racek, J

    2016-01-01

    The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; p<0.001 and 0.41+/-0.11 (B) vs. 0.22+/-0.04 (control) O.D./min/mg; p=0.001). In conclusion, betaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account.

  11. Active salt deformation and rapid, transient incision along the Colorado River near Moab, Utah

    NASA Astrophysics Data System (ADS)

    Jochems, Andrew P.; Pederson, Joel L.

    2015-04-01

    In certain settings, erosion is driven by and balanced with tectonic uplift, but the evolution of many landscapes is dominated by other factors such as geologic substrate, drainage history, and transient incision. The Colorado Plateau is an example where these controls are debated and where salt deformation is hypothesized to be locally active and driven by differential unloading, although this is unconfirmed and unquantified in most places. We use luminescence-dated Colorado River terraces upstream of Moab, Utah, to quantify rates of salt-driven subsidence and uplift at the local scale. Active deformation in the study area is also supported by patterns of concavity along tributary drainages crossing salt structures. Subsidence in Professor Valley at a time-averaged rate of ~500 m/Myr (meters/million years) is superimposed upon rapid bedrock incision rates that increase from ~600 to ~900 m/Myr upstream through the study area. Such high rates are unexpected given the absence of sources of regional tectonic uplift here. Instead, the incision rate pattern across the greater area is consistent with a transient signal, perhaps still from ancient drainage integration through Grand Canyon far downstream, and then amplified by unloading at both the broad regional scale and at the local canyon scale.

  12. Obstruction increases activation in the right inferior frontal gyrus.

    PubMed

    Liu, Tao; Saito, Hirofumi; Oi, Misato

    2016-01-01

    The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions.

  13. Both novelty and expertise increase action observation network activity

    PubMed Central

    Liew, Sook-Lei; Sheng, Tong; Margetis, John L.; Aziz-Zadeh, Lisa

    2013-01-01

    Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON), is modulated by one's expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal) on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices), 11 experienced occupational therapists (OTs) who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ), as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing—similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ) and extreme novelty (novices) can result in the greatest AON activity. PMID:24062656

  14. Flavone deglycosylation increases their anti-inflammatory activity and absorption

    PubMed Central

    Hostetler, Gregory; Riedl, Ken; Cardenas, Horacio; Diosa-Toro, Mayra; Arango, Daniel; Schwartz, Steven; Doseff, Andrea I.

    2014-01-01

    Scope Flavones have reported anti-inflammatory activities, but the ability of flavone-rich foods to reduce inflammation is unclear. Here, we report the effect of flavone glycosylation in the regulation of inflammatory mediators in vitro and the absorption of dietary flavones in vivo. Methods and results The anti-inflammatory activities of celery extracts, some rich in flavone aglycones and others rich in flavone glycosides, were tested on the inflammatory mediators tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lipopolysaccharide-stimulated macrophages. Pure flavone aglycones and aglycone-rich extracts effectively reduced TNF-α production and inhibited the transcriptional activity of NF-κB, while glycoside-rich extracts showed no significant effects. Deglycosylation of flavones increased cellular uptake and cytoplasmic localization as shown by high-performance liquid chromatography (HPLC) and microscopy using the flavonoid fluorescent dye diphenyl-boric acid 2-aminoethyl ester (DPBA). Celery diets with different glycoside or aglycone contents were formulated and absorption was evaluated in mice fed with 5 or 10% celery diets. Relative absorption in vivo was significantly higher in mice fed with aglycone-rich diets as determined by HPLC-MS/MS (where MS/MS is tandem mass spectrometry). Conclusion These results demonstrate that deglycosylation increases absorption of dietary flavones in vivo and modulates inflammation by reducing TNF-α and NF-κB, suggesting the potential use of functional foods rich in flavones for the treatment and prevention of inflammatory diseases. PMID:22351119

  15. Increased β-cyanoalanine nitrilase activity improves cyanide tolerance and assimilation in Arabidopsis.

    PubMed

    O'Leary, Brendan; Preston, Gail M; Sweetlove, Lee J

    2014-01-01

    Plants naturally produce cyanide (CN) which is maintained at low levels in their cells by a process of rapid assimilation. However, high concentrations of environmental CN associated with activities such as industrial pollution are toxic to plants. There is thus an interest in increasing the CN detoxification capacity of plants as a potential route to phytoremediation. Here, Arabidopsis seedlings overexpressing the Pseudomonas fluorescens β-cyanoalanine nitrilase pinA were compared with wild-type and a β-cyanoalanine nitrilase knockout line (ΔAtnit4) for growth in the presence of exogenous CN. After incubation with CN, +PfpinA seedlings had increased root length, increased fresh weight, and decreased leaf bleaching compared with wild-type, indicating increased CN tolerance. The increased tolerance was achieved without an increase in β-cyanoalanine synthase activity, the other enzyme in the cyanide assimilation pathway, suggesting that nitrilase activity is the limiting factor for cyanide detoxification. Labeling experiments with [¹³C]KCN demonstrated that the altered CN tolerance could be explained by differences in flux from CN to Asn caused by altered β-cyanoalanine nitrilase activity. Metabolite profiling after CN treatment provided new insight into downstream metabolism, revealing onward metabolism of Asn by the photorespiratory nitrogen cycle and accumulation of aromatic amino acids.

  16. Rapid Increase in Serum Low-Density Lipoprotein Cholesterol Concentration during Hepatitis C Interferon-Free Treatment

    PubMed Central

    Abiru, Seigo; Komori, Atsumasa; Nagaoka, Shinya; Saeki, Akira; Uchida, Shinjiro; Bekki, Shigemune; Kugiyama, Yuki; Nagata, Kazuyoshi; Nakamura, Minoru; Migita, Kiyoshi; Nakao, Kazuhiko

    2016-01-01

    Background & Aim We performed lipid analyses at the early period of therapy in patients with chronic hepatitis C who underwent interferon (IFN)-free direct-acting antiviral (DAA) treatment, and we attempted to identify the factors that contributed to a rapid increase in the patients’ serum low-density lipoprotein cholesterol (LDL-C) concentration. Methods We retrospectively analyzed the cases of 100 consecutive patients with HCV infection treated at the National Hospital Organization Nagasaki Medical Center: 24 patients underwent daclatasvir (DCV) and asunaprevir (ASV) combination therapy (DCV/ASV) for 24 weeks, and the other 76 patients underwent ledipasvir and sofosbuvir combination therapy (LDV/SOF) for 12 weeks. ΔLDL-C was defined as the changed in LDL-C level at 28 days from the start of therapy. To determine whether ΔLDL-C was associated with several kinds of factors including viral kinetics, we performed a stepwise multiple linear regression analysis. Results The LDL-C levels in patients treated with LDV/SOF were markedly and significantly elevated (87.45 to 122.5 mg/dl; p<10−10) compared to those in the DCV/ASV-treated patients (80.15 to 87.8 mg/dl; p = 0.0056). The median levels of ΔLDL-C in the LDV/SOF and DCV/ASV groups were 33.2 and 13.1, respectively. LDV/SOF combination therapy as an IFN-free regimen (p<0.001) and ΔHCV core antigen (0–1 day drop) (p<0.044) were identified as independent factors that were closely related to the ΔLDL-C. Conclusions A rapid increase in the serum LDL-C concentration during the IFN-free treatment of hepatitis C was associated with the type of HCV therapy and a decline of HCV core protein. PMID:27680885

  17. Sensitization of depressive-like behavior during repeated maternal separation is associated with more-rapid increase in core body temperature and reduced plasma cortisol levels.

    PubMed

    Yusko, Brittany; Hawk, Kiel; Schiml, Patricia A; Deak, Terrence; Hennessy, Michael B

    2012-02-01

    Infant guinea pigs exhibit a 2-stage response to maternal separation: an initial active stage, characterized by vocalizing, and a second passive stage marked by depressive-like behavior (hunched posture, prolonged eye-closure, extensive piloerection) that appears to be mediated by proinflammatory activity. Recently we found that pups showed an enhanced (i.e., sensitized) depressive-like behavioral response during repeated separation. Further, core body temperature was higher during the beginning of a second separation compared to the first, suggesting a more-rapid stress-induced febrile response to separation the second day, though the possibility that temperature was already elevated prior to the second separation could not be ruled out. Therefore, the present study examined temperature prior to, and during, 2 daily separations. We also examined the temperature response to a third separation conducted 3 days after the second, and assessed the effect of repeated separation on plasma cortisol levels. Core temperature did not differ just prior to the separations, but showed a more-rapid increase and then decline during both a second and third separation than during a first. Temperature responses were not associated with changes in motor activity. Depressive-like behavior was greater during the second and third separations. Pups separated a first time showed a larger plasma cortisol response at the conclusion of separation than did animals of the same age separated a third time. In all, the results indicate that the sensitization of depressive-like behavior during repeated separations over several days is accompanied by a more-rapid febrile response that may be related to a reduction of glucocorticoid suppression.

  18. [Increased fibrinolytic activity during cardiopulmonary bypass is caused by activated protein C system].

    PubMed

    Gando, S; Tedo, I; Masio, H; Goda, Y; Kawahigashi, H

    1994-06-01

    To examine the hypothesis that activated protein C system during cardiopulmonary bypass surgery may increase fibrinolytic activity during cardiopulmonary bypass, protein C activity, protein C antigen and thrombomodulin of sixteen patients undergoing elective cardiopulmonary bypass surgery were investigated after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of operation. Protein C activity decreased and thrombomodulin increased significantly after the cardiopulmonary bypass. There were no significant correlations of thrombomodulin with protein C activity and protein C antigen. In conclusion, we have demonstrated that protein C system is activated and circulating thrombomodulin appears in the systemic circulation during cardiopulmonary bypass surgery and this enhanced activation of protein C system is possibly related to the reported increase of fibrinolytic activity during cardiopulmonary bypass.

  19. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    PubMed Central

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  20. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  1. Pulmonary vascular pressures of thoroughbreds increase rapidly and to a higher level with rapid onset of high-intensity exercise than slow onset.

    PubMed

    Manohar, M

    1994-11-01

    Previous studies of pulmonary vascular pressures have utilised gradual incremental step exercise protocols, but in competitive racing at the track, horses perform rapid acceleration high-intensity exercise. The rate of rise in pulmonary vascular pressures under conditions of quick onset high-intensity exercise is unknown. Catheter mounted manometers, whose in vivo signals were matched with pressure signals obtained via transducers connected to fluid-filled lumens from same cardiovascular sites, were used to compare right heart and pulmonary vascular pressures in 8 healthy Thoroughbreds performing 2 separate exercise protocols on a high speed treadmill (gradually incremental vs. rapid acceleration exercise protocol where the belt speed was raised from 8 m/s to 15 m/s in 8 s). Heart rate, right atrial and pulmonary vascular pressures at rest were similar for the 2 protocols. Rapid acceleration of horses from 8 to 15 m/s was attended by an equally rapid escalation in the right heart and pulmonary vascular pressures such that these pressures reached their zenith as belt speed approached 15 m/s. Although exercise at 15 m/s resulted in similar heart rate in the 2 protocols, the mean +/- s.e. values of mean right atrial pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure and mean pulmonary capillary pressure (91.5 +/- 3.9 mmHg) in the rapid acceleration exercise were significantly (P < 0.05) higher than respective values at 15 m/s in the gradual incremental step exercise protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Doxepin and diphenhydramine increased non-rapid eye movement sleep through blockade of histamine H1 receptors.

    PubMed

    Wang, Yi-Qun; Takata, Yohko; Li, Rui; Zhang, Ze; Zhang, Meng-Qi; Urade, Yoshihiro; Qu, Wei-Min; Huang, Zhi-Li

    2015-02-01

    Histaminergic neurons have been reported to play an important role in the regulation of sleep-wake behavior through the histamine H1 receptor (R, H1R). First generation H1R antagonists, such as doxepin and diphenhydramine, produce drowsiness in humans, and are occasionally used to treat insomnia. However, if H1R antagonists function via physically blocking the H1R remains unclear. In the current study, we used H1R knockout (KO) mice to investigate if the sleep-promoting effects of doxepin and diphenhydramine are dependent on blockade of the H1R. When doxepin was administered, non-rapid eye movement (NREM) sleep in wild type (WT) mice increased for 4h, with an increase in the numbers of NREM sleep bouts of 256-512 s and 512-1024 s. These effects were not observed in the H1R KO mice. Furthermore, diphenhydramine increased NREM sleep for 6h in WT, and not in the H1R KO mice after the injection. These results indicate that both doxepin at 15 mg/kg and diphenhydramine at 10 mg/kg induce NREM sleep through blockade of H1R.

  3. Cytokinin activity increases stomatal density and transpiration rate in tomato

    PubMed Central

    Farber, Mika; Attia, Ziv; Weiss, David

    2016-01-01

    Previous studies on cytokinin (CK) and drought have suggested that the hormone has positive and negative effects on plant adaptation to restrictive conditions. This study examined the effect of CK on transpiration, stomatal activity, and response to drought in tomato (Solanum lycopersicum) plants. Transgenic tomato plants overexpressing the Arabidopsis thaliana CK-degrading enzyme CK oxidase/dehydrogenase 3 (CKX3) maintained higher leaf water status under drought conditions due to reduced whole-plant transpiration. The reduced transpiration could be attributed to smaller leaf area and reduced stomatal density. CKX3-overexpressing plants contained fewer and larger pavement cells and fewer stomata per leaf area than wild-type plants. In addition, wild-type leaves treated with CK exhibited enhanced transpiration and had more pavement cells and increased numbers of stomata per leaf area than untreated leaves. Manipulation of CK levels did not affect stomatal movement or abscisic acid-induced stomatal closure. Moreover, we found no correlation between stomatal aperture and the activity of the CK-induced promoter Two-Component Signaling Sensor (TCS) in guard cells. Previous studies have shown that drought reduces CK levels, and we propose this to be a mechanism of adaptation to water deficiency: the reduced CK levels suppress growth and reduce stomatal density, both of which reduce transpiration, thereby increasing tolerance to prolonged drought conditions. PMID:27811005

  4. Prescribed Active Learning Increases Performance in Introductory Biology

    PubMed Central

    O'Connor, Eileen; Parks, John W.; Cunningham, Matthew; Hurley, David; Haak, David; Dirks, Clarissa; Wenderoth, Mary Pat

    2007-01-01

    We tested five course designs that varied in the structure of daily and weekly active-learning exercises in an attempt to lower the traditionally high failure rate in a gateway course for biology majors. Students were given daily multiple-choice questions and answered with electronic response devices (clickers) or cards. Card responses were ungraded; clicker responses were graded for right/wrong answers or participation. Weekly practice exams were done as an individual or as part of a study group. Compared with previous versions of the same course taught by the same instructor, students in the new course designs performed better: There were significantly lower failure rates, higher total exam points, and higher scores on an identical midterm. Attendance was higher in the clicker versus cards section; attendance and course grade were positively correlated. Students did better on clicker questions if they were graded for right/wrong answers versus participation, although this improvement did not translate into increased scores on exams. In this course, achievement increases when students get regular practice via prescribed (graded) active-learning exercises. PMID:17548875

  5. Obesity-induced increases in sympathetic nerve activity: sex matters.

    PubMed

    Brooks, Virginia L; Shi, Zhigang; Holwerda, Seth W; Fadel, Paul J

    2015-01-01

    Abundant evidence obtained largely from male human and animal subjects indicates that obesity increases sympathetic nerve activity (SNA), which contributes to hypertension development. However, recent studies that included women reported that the strong relationships between muscle SNA and waist circumference or body mass index (BMI) found in men are not present in overweight and obese women. A similar sex difference in the association between adiposity and hypertension development has been identified in animal models of obesity. In this brief review, we consider two possible mechanisms for this sex difference. First, visceral adiposity, leptin, insulin, and angiotensin II have been identified as potential culprits in obesity-induced sympathoexcitation in males. We explore if these factors wield the same impact in females. Second, we consider if sex differences in vascular reactivity to sympathetic activation contribute. Our survey of the literature suggests that premenopausal females may be able to resist obesity-induced sympathoexcitation and hypertension in part due to differences in adipose disposition as well as its muted inflammatory response and reduced production of pressor versus depressor components of the renin-angiotensin system. In addition, vascular responsiveness to increased SNA may be reduced. However, more importantly, we identify the urgent need for further study, not only of sex differences per se, but also of the mechanisms that may mediate these differences. This information is required not only to refine treatment options for obese premenopausal women but also to potentially reveal new therapeutic avenues in obese men and women.

  6. Cytokinin activity increases stomatal density and transpiration rate in tomato.

    PubMed

    Farber, Mika; Attia, Ziv; Weiss, David

    2016-12-01

    Previous studies on cytokinin (CK) and drought have suggested that the hormone has positive and negative effects on plant adaptation to restrictive conditions. This study examined the effect of CK on transpiration, stomatal activity, and response to drought in tomato (Solanum lycopersicum) plants. Transgenic tomato plants overexpressing the Arabidopsis thaliana CK-degrading enzyme CK oxidase/dehydrogenase 3 (CKX3) maintained higher leaf water status under drought conditions due to reduced whole-plant transpiration. The reduced transpiration could be attributed to smaller leaf area and reduced stomatal density. CKX3-overexpressing plants contained fewer and larger pavement cells and fewer stomata per leaf area than wild-type plants. In addition, wild-type leaves treated with CK exhibited enhanced transpiration and had more pavement cells and increased numbers of stomata per leaf area than untreated leaves. Manipulation of CK levels did not affect stomatal movement or abscisic acid-induced stomatal closure. Moreover, we found no correlation between stomatal aperture and the activity of the CK-induced promoter Two-Component Signaling Sensor (TCS) in guard cells. Previous studies have shown that drought reduces CK levels, and we propose this to be a mechanism of adaptation to water deficiency: the reduced CK levels suppress growth and reduce stomatal density, both of which reduce transpiration, thereby increasing tolerance to prolonged drought conditions.

  7. Geometric complexity is increased in in vitro activated platelets.

    PubMed

    Bianciardi, Giorgio

    2015-06-01

    This article investigates the use of computerized fractal analysis for objective characterization of the complexity of platelets in vitro stimulated by low level thrombin (0.02 U mL(-1) ), collected from healthy individuals and observed by means of transmission electron microscopy. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension was evaluated by the box-counting technique (measure of geometric complexity of the platelet outline). The results showed that the platelet boundary is fractal when observed by transmission electron microscopy and that, after an in vitro platelet activation test, the shape of platelets present increased geometric complexity in comparison to the no stimulated platelets (P < 0.001), with 100% correct classification. Computerized fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation. The results may play important roles in the evaluation of the platelets status in pathological conditions, like as atherosclerosis and diabetes mellitus, where in in vivo activated platelets have been described.

  8. NOX Activity Is Increased in Mild Cognitive Impairment

    PubMed Central

    Gupta, Sunita; Parrino, Taryn E.; Knight, Alecia G.; Ebenezer, Philip J.; Weidner, Adam M.; LeVine, Harry; Keller, Jeffrey N.; Markesbery, William R.

    2010-01-01

    Abstract This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47phox and the catalytic subunit gp91phox was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91phox, moderate levels of gp91phox also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD. Antioxid. Redox Signal. 12, 1371–1382. PMID:19929442

  9. Increased nitrite reductase activity of fetal versus adult ovine hemoglobin

    PubMed Central

    Blood, Arlin B.; Tiso, Mauro; Verma, Shilpa T.; Lo, Jennifer; Joshi, Mahesh S.; Azarov, Ivan; Longo, Lawrence D.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Power, Gordon G.

    2009-01-01

    Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus. PMID:19028797

  10. The Potential for Pocket Parks to Increase Physical Activity

    PubMed Central

    Cohen, Deborah A.; Marsh, Terry; Williamson, Stephanie; Han, Bing; Derose, Kathryn Pitkin; Golinelli, Daniella; McKenzie, Thomas L.

    2014-01-01

    Purpose To assess the use of new pocket parks in low-income neighborhoods. Setting Los Angeles Subjects Parks users and residents living within ½ mile of 3 pocket parks and 15 neighborhood parks Intervention The creation of pocket parks Design Quasi-experimental post-only comparison Measures We used the System of Observing Play and Recreation in Communities (SOPARC) to measure park use and park-based physical activity and surveyed park users and residents about their park use. Analysis We surveyed 392 and 432 household members within one-half mile of the 3 pocket parks before and after park construction, respectively, as well as 71 pocket park users and compared them to 992 neighborhood park users and 342 residents living within ½ mile of other neighborhood parks. We compared pocket park use to playground area use in the larger neighborhood parks. We used descriptive statistics and Generalized Estimating Equations for the analysis. Results Overall, pocket park use compared favorably in promoting moderate-to-vigorous physical activity with that of existing playground space in nearby parks and they were cost-effective at $0.73/MET hour gained. Pocket park visitors walked an average of 0.25 miles to get there. Conclusions Pocket parks, when perceived as attractive and safe destinations, may increase physical activity by encouraging families with children to walk there. Additional strategies and programs may be needed to encourage more residents to use the parks. PMID:24380461

  11. Effect of increasing the choice of active options on children’s physical activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives: To determine whether increasing the choice of physical activity options increases the duration and intensity of children’s physical activity. Design: This cross-sectional laboratory study included gender (male, female) and choice group [single toy (no choice), three toys (low choice...

  12. Rapid and MR-Independent IK1 Activation by Aldosterone during Ischemia-Reperfusion

    PubMed Central

    Puddu, Paolo Emilio; Rouet, René; Guinamard, Romain; Manrique, Alain; Beygui, Farzin; Sallé, Laurent; Milliez, Paul

    2015-01-01

    . In this ischemia-reperfusion context, aldosterone induced rapid and MR-independent deleterious effects including an arrhythmia substrate (increased APD90 dispersion) and triggered activities (increased premature ventricular contractions occurrence on reperfusion) possibly related to direct IK1 activation. PMID:26222262

  13. Functional Brain Activation Differences in Stuttering Identified with a Rapid fMRI Sequence

    ERIC Educational Resources Information Center

    Loucks, Torrey; Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech…

  14. Chemical Genetics: receptor-ligand pairs for rapid manipulation of neuronal activity

    PubMed Central

    Wulff, Peer; Arenkiel, Benjamin R.

    2012-01-01

    Towards the functional dissection of neuronal circuits, a number of new genetic tools have been developed that enable rapid and reversible manipulation of genetically defined neuronal subtypes in intact mammalian brain circuits. Alongside the breakthrough technology of optogenetics, receptor-ligand pairs provide complementary approaches to modulate neuronal activity using chemical-genetics. PMID:22119143

  15. Use of active video games to increase physical activity in children: a (virtual) reality?

    PubMed

    Foley, Louise; Maddison, Ralph

    2010-02-01

    There has been increased research interest in the use of active video games (in which players physically interact with images onscreen) as a means to promote physical activity in children. The aim of this review was to assess active video games as a means of increasing energy expenditure and physical activity behavior in children. Studies were obtained from computerized searches of multiple electronic bibliographic databases. The last search was conducted in December 2008. Eleven studies focused on the quantification of the energy cost associated with playing active video games, and eight studies focused on the utility of active video games as an intervention to increase physical activity in children. Compared with traditional nonactive video games, active video games elicited greater energy expenditure, which was similar in intensity to mild to moderate intensity physical activity. The intervention studies indicate that active video games may have the potential to increase free-living physical activity and improve body composition in children; however, methodological limitations prevent definitive conclusions. Future research should focus on larger, methodologically sound intervention trials to provide definitive answers as to whether this technology is effective in promoting long-term physical activity in children.

  16. Method of rapid assessment of photocatalytic activities of self-cleaning films.

    PubMed

    Mills, Andrew; Wang, Jishun; McGrady, Mark

    2006-09-21

    An ink, comprising the redox dye resazurin (Rz) and the sacrificial electron donor glycerol, is shown to be capable of the rapid assessment of the photocatalytic activities of self-cleaning films. In the key initial stage of photocatalysis the ink changes from blue to pink. Prolonged irradiation bleaches the ink and eventually mineralizes it. The kinetics of the initial photoinduced color change is studied as a function of UV irradiance, [glycerol], [Rz], and temperature. The results reveal an apparent approximate quantum yield of 3.5 x 10(-3) and an initial rate, r(i), which increases with [glycerol] and decreases with [Rz]. It is proposed that the reduction of Rz, dispersed throughout the thick (ca. 590 nm) indicator film, may take place either via the diffusion of the dye molecules in the ink film to the surface of the underlying semiconductor layer and their subsequent reaction with photogenerated electrons and/or via the diffusion of alpha-hydroxyalkyl radicals, produced by the oxidation of the glycerol by photogenerated holes, or hydroxy radicals, away from the surface of the semiconductor into the ink film and their subsequent reaction with the dye molecules therein. The decrease in r(i) with [Rz] appears to be due to dimer formation, with the latter impeding the reduction process. The activation energy for the initial color-change process is low, ca. 9.1 +/- 0.1 kJ mol(-1) and not unlike many other photocatalytic processes. The initial rate of dye reduction appears to be directly related to the rate of destruction of stearic acid. The ink can be applied by spin-coating, stamping, or writing, using a felt-tip pen. The efficacy of such an ink for assessing the photocatalytic activity of any photocatalytic film, including those employed on commercial self-cleaning glasses, tiles, and paving stones, is discussed briefly.

  17. Departure from optimal O2 level for mouse trophoblast stem cell proliferation and potency leads to most rapid AMPK activation

    PubMed Central

    YANG, Yu; JIANG, Zhongliang; BOLNICK, Alan; DAI, Jing; PUSCHECK, Elizabeth E; RAPPOLEE, Daniel A

    2016-01-01

    Previous studies showed that cultured mouse trophoblast stem cells (mTSCs) have the most rapid proliferation, normal maintenance of stemness/potency, the least spontaneous differentiation, and the lowest level of stress-activated protein kinase (SAPK) when incubated at 2% O2 rather than at the traditional 20% O2 or hypoxic (0.5% and 0% O2) conditions. Switching from 2% O2 induced fast SAPK responses. Here we tested the dose response of AMP-activated protein kinase (AMPK) in its active form (pAMPK Thr172P) at O2 levels from 20–0%, and also tested whether pAMPK levels show similar rapid changes when mTSC cultures were switched from the optimal 2% O2 to other O2 conditions. There was a delayed increase in pAMPK levels ~6–8 h after switching conditions from 20% to 2%, 0.5%, or 0% O2. Altering O2 conditions from 2% to either 20%, 0.5%, or 0% led to rapid increase in pAMPK levels within 1 h, similar to the previously reported SAPK response in mTSC cells removed from 2% O2. Twelve hours of 0.5% O2 exposure led to cell program changes in terms of potency loss and suppressed biosynthesis, as indicated by levels of phosphorylated inactive acetyl CoA carboxylase (pACC). Phosphorylation of ACC was inhibited by the AMPK inhibitor Compound C. However, unlike other stressors, AMPK does not mediate hypoxia-induced potency loss in mTSCs. These results suggest an important aspect of stem cell biology, which demands rapid stress enzyme activation to cope with sudden changes in external environment, e.g., from least stressful (2% O2) to more stressful conditions. PMID:27867161

  18. Small platform sleep deprivation selectively increases the average duration of rapid eye movement sleep episodes during sleep rebound.

    PubMed

    Kitka, Tamas; Katai, Zita; Pap, Dorottya; Molnar, Eszter; Adori, Csaba; Bagdy, Gyorgy

    2009-12-28

    The single platform-on-water (flower pot) method is extensively used for depriving rapid eye movement sleep (REMS). Detailed comparison of sleep-wake architecture, recorded during the rebound period after spending three days on either a small or large platform, could separate the effects of REMS deficit from other stress factors caused by the procedure. A further aim of the study was to find the most characteristic REMS parameter of the rebound originating from REMS deficit. Rats were kept on a small or large platform for 72 h. Their fronto-parietal electroencephalogram, electromyogram and motility were recorded during the 24 h rebound at the beginning of the passive phase. A similar period of a home cage group was also recorded. The most typical differences between the two rebound groups were the increased cumulative time and longer average duration of REMS episodes without significant change in the number of these episodes of the small platform animals during the passive phase. Results obtained by cosinor analysis were in accordance with the findings above. Since we did not find any difference in the average duration of REMS episodes comparing the large platform rebound group and the home cage group, we concluded that the increased mean duration of REMS episodes is a selective marker for the rebound caused by small platform sleep deprivation, while other changes in sleep architecture may be the consequence of stress and also some sleep deficit.

  19. ClpB1 overproduction in Synechocystis sp. strain PCC 6803 increases tolerance to rapid heat shock.

    PubMed

    Gonzalez-Esquer, C Raul; Vermaas, Wim F J

    2013-10-01

    ClpB1 is a heat shock protein known to disaggregate large protein complexes. Constitutive, 16-fold ClpB1 overproduction in the cyanobacterium Synechocystis sp. strain PCC 6803 increased cell survival by 20-fold when cultures were heated quickly (1°C/s) to 50°C and delayed cell death by an average of 3 min during incubation at high temperatures (>46°C). Cooverexpression of ClpB1 and another heat shock protein, DnaK2, further increased cell survival. According to immunocytochemistry results, ClpB1 is dispersed throughout the cytoplasm but is concentrated in specific areas and is more prevalent near thylakoid membranes. However, ClpB1 overproduction does not lead to a change in the morphology, chlorophyll content, or photosystem ratio. Whereas electron microscopy demonstrated that apparent protein aggregation occurred after heat treatment in the control strain, protein aggregate size was maintained in the ClpB1 overexpresser. Constitutive ClpB1 overproduction allows an earlier response to heat shock and protects from rapid heating of cultures.

  20. NIMS Observes Increased Activity at Loki Patera, Io

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Loki Patera, historically the most active and persistent hot spot on Io, is located on the hemisphere of Io always facing Jupiter. Loki Patera was the site of two plumes during the Voyager encounters, which were not seen during the early orbits of Galileo. Ground-based observers reported Loki Patera to be unusually dim during this time, marking a period of low volcanic activity.

    On 21 February 1997, during Galileo's sixth orbit, the Near Infrared Mapping Spectrometer (NIMS) on the Galileo spacecraft observed Io in daylight from a range of approximately 703,000 km (440,000 miles). The image on the left shows Io at a wavelength of 2.95 microns. Loki Patera is seen to be relatively quiescent (at longer wavelengths which are more sensitive to thermal emission, Loki Patera is more noticeable).

    A few weeks later, on March 12th 1997, ground based observers using the Infra-Red Telescope Facility (IRTF) on Mauna Kea, Hawaii, observed an intense brightening in the Loki region, so much that Loki was contributing 75% of Io's in-eclipse flux for this hemisphere. A large eruption was taking place! Other ground-based observations through March, April and May tracked the course of the activity and confirmed its location at Loki Patera.

    On 4 April 1997, NIMS again observed Io during the seventh orbit from a range of 556,000 km (348,000 miles), with Loki Patera positioned in darkness, close to the limb. The image on the right shows the increase in activity at Loki Patera, again at 2.95 microns. A preliminary single temperature fit to NIMS orbit seven Loki Patera hot spot data yields a temperature of 500 K and an area of over 800 square kilometers. That the image is so bright at this wavelength is an indication of the areal extent of the activity. It is also probable that some part of the volcanic material being erupted or exposed is at considerably higher temperatures than that of the 500 K single-temperature fit.

    Io is under observation by ground-based observers under

  1. Increased microglial catalase activity in multiple sclerosis grey matter.

    PubMed

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.

  2. Writer's cramp: increased dorsal premotor activity during intended writing.

    PubMed

    Delnooz, Cathérine C S; Helmich, Rick C; Medendorp, W P; Van de Warrenburg, Bart P C; Toni, Ivan

    2013-03-01

    Simple writer's cramp (WC) is a task-specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task-specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task-specificity. We used fMRI to isolate cerebral alterations associated with the task-specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task-specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task-specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing.

  3. Rapid Forgetting of Social Transmission of Food Preferences in Aged Rats: Relationship to Hippocampal CREB Activation

    ERIC Educational Resources Information Center

    Countryman, Renee A.; Gold, Paul E.

    2007-01-01

    A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the…

  4. Rapid mechanochemical synthesis of VOx/TiO2 as highly active catalyst for HCB removal.

    PubMed

    Zhang, Shuzhen; Huang, Jun; Yang, Yang; Li, Yuancheng; Wang, Bin; Wang, Yujue; Deng, Shubo; Yu, Gang

    2015-12-01

    A rapid (1.5h) one-step ball milling (BM) method was developed to synthesize VOx/TiO2 (VTi-BM) and WOx or MoOx doped VOx/TiO2 (VWTi-BM or VMoTi-BM). Catalytic activity on gaseous POPs removal was tested using hexachlorobenzene (HCB) as surrogate. Catalytic performance decreased in the order of VWTi-BM (T50%=230°C)>VMoTi-BM (260°C)>VTi-BM (270°C)>VTi-WI (300°C; VOx/TiO2 synthesized by wetness impregnation method). The intermediates from oxidation of HCB were analyzed by off gas analysis, from which 2,2,4,5-tetrachloro-4-cyclopentene-1,3-dione (TCCD), dichloromaleic anhydride (DCMA) and tetrachloro-1,4-bezoquinone (TCBQ) were identified. Furthermore, a possible mechanism for the oxidation of HCB over VOx/TiO2 catalysts was proposed. Mechanism studies showed that BM samples possess better dispersion of the VOx species and more surface chemisorbed oxygen. Doping WOx or MoOx into VOx/TiO2 by ball milling can further enhance catalytic performance by increasing surface acid sites.

  5. Rapid and direct estimation of active biomass on granular activated carbon through adenosine tri-phosphate (ATP) determination.

    PubMed

    Velten, Silvana; Hammes, Frederik; Boller, Markus; Egli, Thomas

    2007-05-01

    Granular activated carbon (GAC) filtration is used during drinking water treatment for the removal of micropollutants such as taste and odour compounds, halogenated hydrocarbons, pesticides and pharmaceuticals. In addition, the active microbial biomass established on GAC is responsible for the removal of biodegradable dissolved organic carbon compounds present in water or formed during oxidation (e.g., ozonation and chlorination) processes. In order to conduct correct kinetic evaluations of DOC removal during drinking water treatment, and to assess the state and performance of full-scale GAC filter installations, an accurate and sensitive method for active biomass determination on GAC is required. We have developed a straight-forward method based on direct measurement of the total adenosine tri-phosphate (ATP) content of a GAC sample and other support media. In this method, we have combined flow-cytometric absolute cell counting and ATP analysis to derive case-specific ATP/cell conversion values. In this study, we present the detailed standardisation of the ATP method. An uncertainty assessment has shown that heterogeneous colonisation of the GAC particles makes the largest contribution to the combined standard uncertainty of the method. The method was applied for the investigation of biofilm formation during the start-up period of a GAC pilot-scale plant treating Lake Zurich water. A rapid increase in the biomass of up to 1.1 x 10(10)cells/g GAC dry weight (DW) within the first 33 days was observed, followed by a slight decrease to an average steady-state concentration of 7.9 x 10(9)cells/g GAC DW. It was shown that the method can be used to determine the biomass attached to the GAC for both stable and developing biofilms.

  6. Cocaine increases dopaminergic neuron and motor activity via midbrain α1 adrenergic signaling.

    PubMed

    Goertz, Richard Brandon; Wanat, Matthew J; Gomez, Jorge A; Brown, Zeliene J; Phillips, Paul E M; Paladini, Carlos A

    2015-03-13

    Cocaine reinforcement is mediated by increased extracellular dopamine levels in the forebrain. This neurochemical effect was thought to require inhibition of dopamine reuptake, but cocaine is still reinforcing even in the absence of the dopamine transporter. Here, we demonstrate that the rapid elevation in dopamine levels and motor activity elicited by cocaine involves α1 receptor activation within the ventral midbrain. Activation of α1 receptors increases dopaminergic neuron burst firing by decreasing the calcium-activated potassium channel current (SK), as well as elevates dopaminergic neuron pacemaker firing through modulation of both SK and the hyperpolarization-activated cation currents (Ih). Furthermore, we found that cocaine increases both the pacemaker and burst-firing frequency of rat ventral-midbrain dopaminergic neurons through an α1 adrenergic receptor-dependent mechanism within the ventral tegmental area and substantia nigra pars compacta. These results demonstrate the mechanism underlying the critical role of α1 adrenergic receptors in the regulation of dopamine neurotransmission and behavior by cocaine.

  7. Increased oscillatory theta activation evoked by violent digital game events.

    PubMed

    Salminen, Mikko; Ravaja, Niklas

    2008-04-11

    The authors examined electroencephalographic (EEG) oscillatory responses to two violent events, the player character wounding and killing an opponent character with a gun, in the digital game James Bond 007: NightFire. EEG was recorded from 25 (16 male) right-handed healthy young adults. EEG data were segmented into one 1-s baseline epoch before each event and two 1-s epochs after event onset. Power estimates (microV(2)) were derived with the fast Fourier transform (FFT) for each artefact free event. Both of the studied events evoked increased occipital theta (4-6Hz) responses as compared to the pre-event baseline. The wounding event evoked also increased occipital high theta (6-8Hz) response and the killing event evoked low alpha (8-10Hz) asymmetry over the central electrodes, both relative to the pre-event baseline. The results are discussed in light of facial electromyographic and electrodermal activity responses evoked by these same events, and it is suggested that the reported EEG responses may be attributable to affective processes related to these violent game events.

  8. Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains

    PubMed Central

    Beatty, Kimberly E.; Williams, Monique; Carlson, Brian L.; Swarts, Benjamin M.; Warren, Robin M.; van Helden, Paul D.; Bertozzi, Carolyn R.

    2013-01-01

    Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)–sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. This assay revealed that mycobacterial strains have distinct sulfatase fingerprints that can be used to judge both the species and lineage. Our results demonstrate the potential of enzyme-activated probes for rapid pathogen discrimination for infectious diseases. PMID:23878250

  9. Rapid direct methods for enumeration of specific, active bacteria in water and biofilms

    NASA Technical Reports Server (NTRS)

    McFeters, G. A.; Pyle, B. H.; Lisle, J. T.; Broadaway, S. C.

    1999-01-01

    Conventional methods for detecting indicator and pathogenic bacteria in water may underestimate the actual population due to sublethal environmental injury, inability of the target bacteria to take up nutrients and other physiological factors which reduce bacterial culturability. Rapid and direct methods are needed to more accurately detect and enumerate active bacteria. Such a methodological advance would provide greater sensitivity in assessing the microbiological safety of water and food. The principle goal of this presentation is to describe novel approaches we have formulated for the rapid and simultaneous detection of bacteria plus the determination of their physiological activity in water and other environmental samples. The present version of our method involves the concentration of organisms by membrane filtration or immunomagnetic separation and combines an intracellular fluorochrome (CTC) for assessment of respiratory activity plus fluorescent-labelled antibody detection of specific bacteria. This approach has also been successfully used to demonstrate spatial and temporal heterogeneities of physiological activities in biofilms when coupled with cryosectioning. Candidate physiological stains include those capable of determining respiratory activity, membrane potential, membrane integrity, growth rate and cellular enzymatic activities. Results obtained thus far indicate that immunomagnetic separation can provide a high degree of sensitivity in the recovery of seeded target bacteria (Escherichia coli O157:H7) in water and hamburger. The captured and stained target bacteria are then enumerated by either conventional fluorescence microscopy or ChemScan(R), a new instrument that is very sensitive and rapid. The ChemScan(R) laser scanning instrument (Chemunex, Paris, France) provides the detection of individual fluorescently labelled bacterial cells using three emission channels in less than 5 min. A high degree of correlation has been demonstrated between

  10. Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia.

    PubMed

    Schwarzer, Christian; Fu, Zhu; Patanwala, Maria; Hum, Lauren; Lopez-Guzman, Mirielle; Illek, Beate; Kong, Weidong; Lynch, Susan V; Machen, Terry E

    2012-05-01

    Pseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis (CF) patients, a process regulated by quorum-sensing molecules including N-(3-oxododecanoyl)-l-homoserine lactone (C12). C12 (10-100 µM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CF ΔF508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (Δψ(mito)) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca(2+) and ER-targeted GFP and oxidized contents into the cytosol). Effects began within 5 min and were complete in 1-2 h. C12 caused similar activation of caspases and release of cytoC from mitos in Calu-3 (wtCFTR, bronchial gland) cells, showing that C12-triggered responses occurred similarly in different airway epithelial types. C12 had nearly identical effects on three key aspects of the apoptosis response (caspase 3/7, depolarization of Δψ(mito) and reduction of redox potential in the ER) in JME and CFTR-corrected JME cells (adenoviral expression), showing that CFTR was likely not an important regulator of C12-triggered apoptosis in airway epithelia. Exposure of airway cultures to biofilms from PAO1wt caused depolarization of Δψ(mito) and increases in Ca(cyto) like 10-50 µM C12. In contrast, biofilms from PAO1ΔlasI (C12 deficient) had no effect, suggesting that C12 from P. aeruginosa biofilms may contribute to accumulation of apoptotic cells that cannot be cleared from CF lungs. A model to explain the effects of C12 is proposed.

  11. TransMilenio, a Scalable Bus Rapid Transit System for Promoting Physical Activity.

    PubMed

    Lemoine, Pablo D; Sarmiento, Olga L; Pinzón, Jose David; Meisel, Jose D; Montes, Felipe; Hidalgo, Dario; Pratt, Michael; Zambrano, Juan Manuel; Cordovez, Juan Manuel; Zarama, Roberto

    2016-04-01

    Transport systems can play an important role in increasing physical activity (PA). Bogotá has been recognized for its bus rapid transit (BRT) system, TransMilenio (TM). To date, BRTs have been implemented in over 160 cities worldwide. The aim of this study was to assess the association between PA and the use of TM among adults in Bogotá. The study consists of a cross-sectional study conducted from 2010 to 2011 with 1000 adults. PA was measured using the International Physical Activity Questionnaire. In a subsample of 250 adults, PA was objectively measured using ActiGraph accelerometers. Analyses were conducted using multilevel logistic regression models. The use of TM was associated with meeting moderate-to-vigorous PA (MVPA). TM users were more likely to complete an average of >22 min a day of MVPA (odds ratio [OR] = 3.1, confidence interval [CI] = 95 % 1.4-7.1) and to walk for transportation for ≥150 min per week (OR = 1.5; CI = 95 % 1.1-2.0). The use of TM was associated with 12 or more minutes of MVPA (95 % CI 4.5-19.4, p < 0.0001). Associations between meeting PA recommendations and use of TM did not differ by socioeconomic status (p value = 0.106) or sex (p value = 0.288). The use of TM is a promising strategy for enhancing public health efforts to reduce physical inactivity through walking for transport. Given the expansion of BRTs, these results could inform the development of transport PA programs in low- to high-income countries.

  12. Increased intracellular levels of lysosomal beta-glucuronidase in peripheral blood PMNs from humans with rapidly progressive periodontitis.

    PubMed

    Pippin, D J; Cobb, C M; Feil, P

    1995-01-01

    Release of potent lysosomal enzymes by degranulation of polymorphonuclear leukocytes (PMNs) in host gingiva may contribute significantly to tissue destruction and the pathogenesis of periodontal disease. A pilot study established that peripheral blood PMNs from humans with rapidly progressive periodontitis (RPP) contained significantly increased amounts of intracellular lysosomal beta-glucuronidase as compared to healthy controls. This investigation gained insight into the question: are the increased levels of beta-glucuronidase in persons with RPP an a priori genetically determined PMN characteristic, or a reactive phenomenon induced by the periodontal disease process during granulopoiesis? Twelve healthy controls and twelve otherwise healthy individuals with RPP participated in a repeated measures design to T0 (initial, baseline), T1 (four weeks after disease control therapy), and T2 (two months later). At each visit clinical indices (GI, pocket depths, GCF flow, plaque index) were performed and peripheral blood obtained. PMNs were isolated and suspended as 5 x 10(6) cells in 2.0 ml of HBSS. PMN suspensions were tested for total intracellular beta-glucuronidase, degranulation induced by 1 x 10(-6)M and 5 x 10(-7) M FMLP challenges, and unchallenged for non-specific enzyme release. PMNs from individuals with RPP contained significantly higher absolute amounts of beta-glucuronidase and released greater absolute amounts at FMLP challenge at T0, T1, and T2 compared to controls. No relationship was found between any of the clinical indices and beta-glucuronidase levels and no pattern was discovered relating to the repeated measures over time. We conclude that RPP peripheral blood PMNs contain elevated levels of beta-glucuronidase that are not induced by the periodontal disease process.

  13. Caffeine ingestion after rapid weight loss in judo athletes reduces perceived effort and increases plasma lactate concentration without improving performance.

    PubMed

    Lopes-Silva, Joao P; Felippe, Leandro J C; Silva-Cavalcante, Marcos D; Bertuzzi, Romulo; Lima-Silva, Adriano E

    2014-07-22

    The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this "loading period", subjects ingested a capsule containing either caffeine (6 mg·kg-1) or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (-3.9% ± 1.6% and -4.0% ± 2.3% from control, respectively, p < 0.05). At three hours after weigh-in, body weight had increased with both treatments but remained below the control (-3.0% ± 1.3% and -2.7% ± 2.2%). There were no significant differences in the number of throws between the control, caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p < 0.05). In conclusion, caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

  14. Increases in Calmodulin Abundance and Stabilization of Activated iNOS Mediate Bacterial Killing in RAW 264.7 Macrophages

    SciTech Connect

    Smallwood, Heather S.; Shi, Liang; Squier, Thomas C.

    2006-08-01

    The rapid activation of macrophages in response to bacterial antigens is central to the innate immune system that permits the recognition and killing of pathogens to limit infection. To understand regulatory mechanisms underlying macrophage activation, we have investigated changes in the abundance of calmodulin (CaM) and iNOS in response to the bacterial cell wall component lipopolysaccharide (LPS) using RAW 264.7 macrophages. Critical to these measurements was the ability to differentiate free iNOS from the CaM-bound (active) form of iNOS associated with nitric oxide generation. We observe a rapid two-fold increase in CaM abundance during the first 30 minutes that is blocked by inhibition of NF?B nuclear translocation or protein synthesis. A similar two-fold increase in the abundance of the complex between CaM and iNOS is observed with the same time dependence. In contrast, there are no detectable increases in the CaM-free (i.e., inactive) form of iNOS within the first hour; it remains at a very low abundance during the initial phase of macrophage activation. Increasing cellular CaM levels in stably transfected cells results in a corresponding increase in the abundance of the CaM/iNOS complex that promotes effective bacterial killing following challenge by Salmonella typhimurium. Thus, LPS-dependent increases in CaM abundance function in the stabilization and activation of iNOS on the rapid time-scale associated with macrophage activation and bacterial killing. These results explain how CaM and iNOS coordinately function to form a stable complex that is part of a rapid host-response that functions within the first 30 minutes following bacterial infection to up-regulate the innate immune system involving macrophage activation.

  15. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils.

  16. One-year-old fear memories rapidly activate human fusiform gyrus

    PubMed Central

    Pizzagalli, Diego A.

    2016-01-01

    Fast threat detection is crucial for survival. In line with such evolutionary pressure, threat-signaling fear-conditioned faces have been found to rapidly (<80 ms) activate visual brain regions including the fusiform gyrus on the conditioning day. Whether remotely fear conditioned stimuli (CS) evoke similar early processing enhancements is unknown. Here, 16 participants who underwent a differential face fear-conditioning and extinction procedure on day 1 were presented the initial CS 24 h after conditioning (Recent Recall Test) as well as 9-17 months later (Remote Recall Test) while EEG was recorded. Using a data-driven segmentation procedure of CS evoked event-related potentials, five distinct microstates were identified for both the recent and the remote memory test. To probe intracranial activity, EEG activity within each microstate was localized using low resolution electromagnetic tomography analysis (LORETA). In both the recent (41–55 and 150–191 ms) and remote (45–90 ms) recall tests, fear conditioned faces potentiated rapid activation in proximity of fusiform gyrus, even in participants unaware of the contingencies. These findings suggest that rapid processing enhancements of conditioned faces persist over time. PMID:26416784

  17. Real-Time Patient Survey Data During Routine Clinical Activities for Rapid-Cycle Quality Improvement

    PubMed Central

    Jones, Robert E

    2015-01-01

    Background Surveying patients is increasingly important for evaluating and improving health care delivery, but practical survey strategies during routine care activities have not been available. Objective We examined the feasibility of conducting routine patient surveys in a primary care clinic using commercially available technology (Web-based survey creation, deployment on tablet computers, cloud-based management of survey data) to expedite and enhance several steps in data collection and management for rapid quality improvement cycles. Methods We used a Web-based data management tool (survey creation, deployment on tablet computers, real-time data accumulation and display of survey results) to conduct four patient surveys during routine clinic sessions over a one-month period. Each survey consisted of three questions and focused on a specific patient care domain (dental care, waiting room experience, care access/continuity, Internet connectivity). Results Of the 727 available patients during clinic survey days, 316 patients (43.4%) attempted the survey, and 293 (40.3%) completed the survey. For the four 3-question surveys, the average time per survey was overall 40.4 seconds, with a range of 5.4 to 20.3 seconds for individual questions. Yes/No questions took less time than multiple choice questions (average 9.6 seconds versus 14.0). Average response time showed no clear pattern by order of questions or by proctor strategy, but monotonically increased with number of words in the question (<20 words, 21-30 words, >30 words)—8.0, 11.8, 16.8, seconds, respectively. Conclusions This technology-enabled data management system helped capture patient opinions, accelerate turnaround of survey data, with minimal impact on a busy primary care clinic. This new model of patient survey data management is feasible and sustainable in a busy office setting, supports and engages clinicians in the quality improvement process, and harmonizes with the vision of a learning health

  18. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    SciTech Connect

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  19. Deciphering The Speed of Link: Experimental Evidence of a Rapid Increase in Soil Respiration Following the Onset of Photosynthesis

    NASA Astrophysics Data System (ADS)

    Kayler, Z. E.; Keitel, C.; Jansen, K.; Gessler, A.

    2011-12-01

    labeled CO2 is carboxylated through photosynthesis and after transport, is respired below-ground. During the experiment we monitored the carbon isotopic composition of CO2 and the CO2 flux from the soil. We observed in our control trees (no darkness treatment), a rapid increase in soil respiration after the exposure to light that occurred on the order of minutes. For the same trees the label arrived three to five hours later. The concentration increase of the rapid CO2 release was on the order of 100- 200ppm above background while the labeled assimilates increased this value by about 50ppm. Two concentrations peaks were clearly observed each displaying unique kinetic responses. We have taken stem samples after the experiment to analyse the anatomical properties as well as leaf and root samples for carbohydrate analyses. Results from the trees placed in the dark are forthcoming. With these experiments we show experimental evidence for both mechanisms, pressure concentration waves and molecular diffusion, that are behind assimilate flow between the plant and the rhizosphere and we characterize their dynamics.

  20. Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia.

    PubMed

    Baker, E A; Tian, Y; Adler, S; Verbalis, J G

    2000-10-01

    In previous studies we developed a rat model in which demyelination is reproducibly produced following rapid correction of chronic hyponatremia and demonstrated that the development of demyelination in this model is strongly associated with NMR indices of blood-brain barrier (BBB) disruption. Because complement is toxic to oligodendrocytes, we evaluated the hypothesis that BBB disruption precipitated by correction of hypoosmolality is followed by an influx of complement into the brain, which then contributes to the demyelination that occurs under these conditions. We studied four groups of rats with immunocytochemical analysis using primary antibodies to IgG and the C3d split-fragment of activated complement: (1) normal rats; (2) rats in which hyponatremia was maintained for 7 days; (3) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 20 h prior to perfusion; and (4) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 5 days prior to perfusion. In normonatremic and uncorrected hyponatremic rats only background staining was observed in areas lacking a BBB and in blood vessel walls, whereas marked increases in IgG and C3d staining were seen in the brains of rats both 20 h and 5 days after rapid correction of hyponatremia. The staining intensity was significantly correlated with the degree of neurological impairment. These results provide evidence for functional BBB disruption following rapid correction of hyponatremia and support the hypothesis that complement activation may be involved in the pathogenesis of osmotic demyelination.

  1. Activity-induced internalization and rapid degradation of sodium channels in cultured fetal neurons

    PubMed Central

    1996-01-01

    A regulatory mechanism for neuronal excitability consists in controlling sodium channel density at the plasma membrane. In cultured fetal neurons, activation of sodium channels by neurotoxins, e.g., veratridine and alpha-scorpion toxin (alpha-ScTx) that enhance the channel open state probability induced a rapid down-regulation of surface channels. Evidence that the initial step of activity-induced sodium channel down-regulation is mediated by internalization was provided by using 125I-alpha-ScTx as both a channel probe and activator. After its binding to surface channels, the distribution of 125I-alpha-ScTx into five subcellular compartments was quantitatively analyzed by EM autoradiography. 125I-alpha-ScTx was found to accumulate in tubulovesicular endosomes and disappear from the cell surface in a time-dependent manner. This specific distribution was prevented by addition of tetrodotoxin (TTX), a channel blocker. By using a photoreactive derivative to covalently label sodium channels at the surface of cultured neurons, we further demonstrated that they are degraded after veratridine-induced internalization. A time-dependent decrease in the amount of labeled sodium channel alpha subunit was observed after veratridine treatment. After 120 min of incubation, half of the alpha subunits were cleaved. This degradation was prevented totally by TTX addition and was accompanied by the appearance of an increasing amount of a 90-kD major proteolytic fragment that was already detected after 45-60 min of veratridine treatment. Exposure of the photoaffinity-labeled cells to amphotericin B, a sodium ionophore, gave similar results. In this case, degradation was prevented when Na+ ions were substituted by choline ions and not blocked by TTX. After veratridine- or amphotericin B-induced internalization of sodium channels, breakdown of the labeled alpha subunit was inhibited by leupeptin, while internalization was almost unaffected. Thus, cultured fetal neurons are capable of

  2. Altered behavior in spotted hyenas associated with increased human activity

    USGS Publications Warehouse

    Boydston, Erin E.; Kapheim, Karen M.; Watts, Heather E.; Szykman, Micaela; Holekamp, Kay E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996–98 with that observed several years earlier and found many differences. Female hyenas in 1996–98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988–90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988–90. Finally, hyenas occurred in smaller groups in 1996–98 than in 1988–90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction.

  3. Platelet-activating factor-induced increases in glucose kinetics

    SciTech Connect

    Lang, C.H.; Dobrescu, C.; Hargrove, D.M.; Bagby, G.J.; Spitzer, J.J. )

    1988-02-01

    Platelet-activating factor (PAF) is a postulated mediator of many of the early hemodynamic effects of endotoxin. The aim of the present study was to determine whether in vivo administration of PAF could produce alterations in whole-body glucose metabolism that would mimic those seen during endotoxemia. Glucose kinetics were assessed in chronically catheterized conscious rats by the constant infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose before and for 4 h after either a bolus injection or a constant infusion of PAF. The bolus injection of PAF elevated the rate of glucose appearance (R{sub a}; 44%) for 1.5 h. The lower PAF infusion rate decreased blood pressure 11% to 104 mmHg, whereas the higher infusion rate decreased pressure 34% to 77 mmHg. Both PAF infusion rates produced elevations in plasma glucose and glucose R{sub a} throughout the 4-h infusion period in a dose-related manner. The PAF infusions also induced dose-related increases in plasma glucagon and catecholamine levels throughout the infusion period. Because the constant infusion of PAF did stimulate many of the hemodynamic and metabolic alterations produced by endotoxin, this study provides additional support for the potential importance of PAF as a mediator of the early hemodynamic and metabolic sequela of endotoxin shock. Furthermore, the PAF-induced changes in glucose metabolism appear to be mediated by the resultant elevation in plasma catecholamines.

  4. Increasing SK2 channel activity impairs associative learning

    PubMed Central

    McKay, Bridget M.; Oh, M. Matthew; Galvez, Roberto; Burgdorf, Jeffrey; Kroes, Roger A.; Weiss, Craig; Adelman, John P.; Moskal, Joseph R.

    2012-01-01

    Enhanced intrinsic neuronal excitability of hippocampal pyramidal neurons via reductions in the postburst afterhyperpolarization (AHP) has been hypothesized to be a biomarker of successful learning. This is supported by considerable evidence that pharmacologic enhancement of neuronal excitability facilitates learning. However, it has yet to be demonstrated that pharmacologic reduction of neuronal excitability restricted to the hippocampus can retard acquisition of a hippocampus-dependent task. Thus, the present study was designed to address this latter point using a small conductance potassium (SK) channel activator NS309 focally applied to the dorsal hippocampus. SK channels are important contributors to intrinsic excitability, as measured by the medium postburst AHP. NS309 increased the medium AHP and reduced excitatory postsynaptic potential width of CA1 neurons in vitro. In vivo, NS309 reduced the spontaneous firing rate of CA1 pyramidal neurons and impaired trace eyeblink conditioning in rats. Conversely, trace eyeblink conditioning reduced levels of SK2 channel mRNA and protein in the hippocampus. Therefore, the present findings indicate that modulation of SK channels is an important cellular mechanism for associative learning and further support postburst AHP reductions in hippocampal pyramidal neurons as a biomarker of successful learning. PMID:22552186

  5. β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle

    PubMed Central

    Nuber, Susanne; Zabel, Ulrike; Lorenz, Kristina; Nuber, Andreas; Milligan, Graeme; Tobin, Andrew B.; Lohse, Martin J.; Hoffmann, Carsten

    2016-01-01

    (β-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs)1–3. They bind to active, phosphorylated GPCRs and thereby shut off ‘classical’ signalling to G proteins3,4, trigger internalization of GPCRs via interaction with the clathrin machinery5–7 and mediate signalling via ‘non-classical’ pathways1,2. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) β-arrestin proteins (β-arrestin1 and β-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs)1,3,4. The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (β-)arrestins that have recently been solved by X-ray crystallography8–10. Here we investigate both the interaction of β-arrestin with GPCRs, and the β-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based β-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in β-arrestin2 that occur rapidly after the receptor–β-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and β-arrestins. They further indicate that β-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of β-arrestins, which permits their active signalling. PMID:27007855

  6. Rapid parallel flow cytometry assays of active GTPases using effector beads.

    PubMed

    Buranda, Tione; BasuRay, Soumik; Swanson, Scarlett; Agola, Jacob; Bondu, Virginie; Wandinger-Ness, Angela

    2013-11-15

    We describe a rapid assay for measuring the cellular activity of small guanine triphosphatases (GTPases) in response to a specific stimulus. Effector-functionalized beads are used to quantify in parallel multiple GTP-bound GTPases in the same cell lysate by flow cytometry. In a biologically relevant example, five different Ras family GTPases are shown for the first time to be involved in a concerted signaling cascade downstream of receptor ligation by Sin Nombre hantavirus.

  7. Rapid activation of specific phospholipase(s) D by cytokinin in Amaranthus assay system.

    PubMed

    Kravets, Volodymir S; Kolesnikov, Yaroslav S; Kretynin, Sergey V; Getman, Irina A; Romanov, Georgy A

    2010-03-01

    The suggested link between intracellular cytokinin signaling and phospholipase D (PLD, EC 3.1.4.4.) activity (Romanov et al. 2000, 2002) was investigated. The activity of PLD in the early period of cytokinin action was studied in vivo in derooted Amaranthus caudatus seedlings, using the level of phosphatidylbutanol production as a measure of PLD activity. Rapid activation of phosphatidylbutanol synthesis was demonstrated as early as within 5 min of cytokinin administration. Neomycin, a known phosphatidylinositol-4,5-bisphosphate (PIP(2)) antagonist, strongly repressed both physiological cytokinin effect and cytokinin-dependent PLD activation. N-acylethanolamine (NAE 12), an inhibitor of alpha-class PLD, did not influence significantly cytokinin effect on Amaranthus seedlings. Together, results suggest the involvement of PIP(2)-dependent non-class alpha-PLD in the molecular mechanism of cytokinin action.

  8. Activation of metabotropic GABA receptors increases the energy barrier for vesicle fusion.

    PubMed

    Rost, Benjamin R; Nicholson, Patrick; Ahnert-Hilger, Gudrun; Rummel, Andreas; Rosenmund, Christian; Breustedt, Joerg; Schmitz, Dietmar

    2011-09-15

    Neurotransmitter release from presynaptic terminals is under the tight control of various metabotropic receptors. We report here that in addition to the regulation of Ca(2+) channel activity, metabotropic GABA(B) receptors (GABA(B)Rs) at murine hippocampal glutamatergic synapses utilize an inhibitory pathway that directly targets the synaptic vesicle release machinery. Acute application of the GABA(B)R agonist baclofen rapidly and reversibly inhibits vesicle fusion, which occurs independently of the SNAP-25 C-terminus. Using applications of hypertonic sucrose solutions, we find that the size of the readily releasable pool remains unchanged by GABA(B)R activation, but the sensitivity of primed vesicles to hypertonic stimuli appears lowered as the response amplitudes at intermediate sucrose concentrations are smaller and release kinetics are slowed. These data show that presynaptic GABA(B)Rs can inhibit neurotransmitter release directly by increasing the energy barrier for vesicle fusion.

  9. Reduced Sensory Oscillatory Activity during Rapid Auditory Processing as a Correlate of Language-Learning Impairment

    PubMed Central

    Heim, Sabine; Friedman, Jennifer Thomas; Keil, Andreas; Benasich, April A.

    2010-01-01

    Successful language acquisition has been hypothesized to involve the ability to integrate rapidly presented, brief acoustic cues in sensory cortex. A body of work has suggested that this ability is compromised in language-learning impairment (LLI). The present research aimed to examine sensory integration during rapid auditory processing by means of electrophysiological measures of oscillatory brain activity using data from a larger longitudinal study. Twenty-nine children with LLI and control participants with typical language development (n=18) listened to tone doublets presented at a temporal interval that is essential for accurate speech processing (70-ms interstimulus interval). The children performed a deviant (pitch change of second tone) detection task, or listened passively. The electroencephalogram was recorded from 64 electrodes. Data were source-projected to the auditory cortices and submitted to wavelet analysis, resulting in time-frequency representations of electrocortical activity. Results show significantly reduced amplitude and phase-locking of early (45–75 ms) oscillations in the gamma-band range (29–52 Hz), specifically in the LLI group, for the second stimulus of the tone doublet. This suggests altered temporal organization of sensory oscillatory activity in LLI when processing rapid sequences. PMID:21822356

  10. Immunochromatographic IgG/IgM Test for Rapid Diagnosis of Active Tuberculosis▿

    PubMed Central

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-01-01

    For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary TB [epTB]), (ii) 73 patients with pulmonary non-TB diseases, and (iii) two leprosy patients. The sensitivities of IgG and IgM in patients with active TB (pTB and epTB) were 68.4% and 2.3%, respectively. IgG had the best performance characteristics, with sensitivities of 78.1% and 39.5% in sera from patients with active pTB and epTB, respectively, and a specificity of 100%. The sensitivities of IgM were poor and were similar for pTB and epTB (2.3%). In contrast, specificity was very elevated (100%). The combination of IgG with IgM did not improve its sensitivity. IgG-mediated responses against the mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens might constitute a clinically useful tool for presumptive diagnosis and discrimination of active pTB from other pulmonary diseases. Moreover, based on its simplicity and rapidity of application, it could be a screening tool for active pTB in poorly equipped laboratories. PMID:21994352

  11. Immunochromatographic IgG/IgM test for rapid diagnosis of active tuberculosis.

    PubMed

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-12-01

    For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary TB [epTB]), (ii) 73 patients with pulmonary non-TB diseases, and (iii) two leprosy patients. The sensitivities of IgG and IgM in patients with active TB (pTB and epTB) were 68.4% and 2.3%, respectively. IgG had the best performance characteristics, with sensitivities of 78.1% and 39.5% in sera from patients with active pTB and epTB, respectively, and a specificity of 100%. The sensitivities of IgM were poor and were similar for pTB and epTB (2.3%). In contrast, specificity was very elevated (100%). The combination of IgG with IgM did not improve its sensitivity. IgG-mediated responses against the mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens might constitute a clinically useful tool for presumptive diagnosis and discrimination of active pTB from other pulmonary diseases. Moreover, based on its simplicity and rapidity of application, it could be a screening tool for active pTB in poorly equipped laboratories.

  12. Activation of protease activated receptor 1 increases the excitability of the dentate granule neurons of hippocampus

    PubMed Central

    2011-01-01

    Protease activated receptor-1 (PAR1) is expressed in multiple cell types in the CNS, with the most prominent expression in glial cells. PAR1 activation enhances excitatory synaptic transmission secondary to the release of glutamate from astrocytes following activation of astrocytically-expressed PAR1. In addition, PAR1 activation exacerbates neuronal damage in multiple in vivo models of brain injury in a manner that is dependent on NMDA receptors. In the hippocampal formation, PAR1 mRNA appears to be expressed by a subset of neurons, including granule cells in the dentate gyrus. In this study we investigate the role of PAR activation in controlling neuronal excitability of dentate granule cells. We confirm that PAR1 protein is expressed in neurons of the dentate cell body layer as well as in astrocytes throughout the dentate. Activation of PAR1 receptors by the selective peptide agonist TFLLR increased the intracellular Ca2+ concentration in a subset of acutely dissociated dentate neurons as well as non-neuronal cells. Bath application of TFLLR in acute hippocampal slices depolarized the dentate gyrus, including the hilar region in wild type but not in the PAR1-/- mice. PAR1 activation increased the frequency of action potential generation in a subset of dentate granule neurons; cells in which PAR1 activation triggered action potentials showed a significant depolarization. The activation of PAR1 by thrombin increased the amplitude of NMDA receptor-mediated component of EPSPs. These data suggest that activation of PAR1 during normal function or pathological conditions, such as during ischemia or hemorrhage, can increase the excitability of dentate granule cells. PMID:21827709

  13. Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha.

    PubMed

    LoVerme, Jesse; Russo, Roberto; La Rana, Giovanna; Fu, Jin; Farthing, Jesse; Mattace-Raso, Giuseppina; Meli, Rosaria; Hohmann, Andrea; Calignano, Antonio; Piomelli, Daniele

    2006-12-01

    Severe pain remains a major area of unmet medical need. Here we report that agonists of the nuclear receptor PPAR-alpha (peroxisome proliferator-activated receptor-alpha) suppress pain behaviors induced in mice by chemical tissue injury, nerve damage, or inflammation. The PPAR-alpha agonists GW7647 [2-(4-(2-(1-cyclohexanebutyl)-3-cyclohexylureido)ethyl)phenylthio)-2-methylpropionic acid], Wy-14643 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid], and palmitoylethanolamide (PEA) reduced nocifensive behaviors elicited in mice by intraplantar (i.pl.) injection of formalin or i.p. injection of magnesium sulfate. These effects were absent in PPAR-alpha-null mice yet occurred within minutes of agonist administration in wild-type mice, suggesting that they were mediated through a transcription-independent mechanism. Consistent with this hypothesis, blockade of calcium-operated IK(ca) (K(Ca)3.1) and BK(ca) (K(Ca)1.1) potassium channels prevented the effects of GW7647 and PEA in the formalin test. Three observations suggest that PPAR-alpha agonists may inhibit nocifensive responses by acting on peripheral PPAR-alpha. (i) PEA reduced formalin-induced pain at i.pl. doses that produced no increase in systemic PEA levels; (ii) PPAR-alpha was expressed in dorsal root ganglia neurons of wild-type but not PPAR-alpha-null mice; and (ii) GW7647 and PEA prevented formalin-induced firing of spinal cord nociceptive neurons in rats. In addition to modulating nociception, GW7647 and PEA reduced hyperalgesic responses in the chronic constriction injury model of neuropathic pain; these effects were also contingent on PPAR-alpha expression and were observed following either acute or subchronic PPAR-alpha agonist administration. Finally, acute administration of GW7647 and PEA reduced hyperalgesic responses in the complete Freund's adjuvant and carrageenan models of inflammatory pain. Our results suggest that PPAR-alpha agonists may represent a novel class of analgesics.

  14. Increased dietary protein elevates plasma uric acid and is associated with decreased oxidative stress in rapidly-growing broilers.

    PubMed

    Machín, M; Simoyi, M F; Blemings, K P; Klandorf, H

    2004-03-01

    Uric acid is an important antioxidant and methods to elevate its plasma concentration may be important in animal health. In a first study, the effect of dietary protein on plasma uric acid (PUA) and glucose concentrations were determined in 3-week-old chicks. Twenty-four broiler chicks were randomly assigned to four diets: a commercial control diet (C, 20% crude protein), low protein (LP) containing 10% casein, medium protein (MP) containing 20% casein or high protein (HP) containing 45% casein for a 3-week experiment. PUA concentration increased (P<0.05) in chicks fed HP diet and declined (P<0.05) in chicks fed LP while plasma glucose concentrations were lower (P<0.05) in chicks fed the LP diet at the end of the study. In a second study, PUA and leukocyte oxidative activity (LOA) were determined in broilers fed C, LP, MP or HP diets for 4 weeks. As in the first study, dietary protein directly affected PUA concentrations. In birds consuming HP diets, PUA was negatively correlated (P=0.06) with lowered LOA. These data support the view that increases in dietary protein can increase PUA concentrations, which can ameliorate oxidative stress.

  15. Rapid Increases in proBDNF after Pilocarpine-Induced Status Epilepticus in Mice Are Associated with Reduced proBDNF Cleavage Machinery123

    PubMed Central

    Cruz Del Angel, Yasmin; Gonzalez, Marco I.; Carrel, Andrew J.; Carlsen, Jessica; Lam, Philip M.; Hempstead, Barbara L.; Russek, Shelley. J.

    2016-01-01

    Abstract Brain-derived neurotrophic factor (BDNF) levels are elevated after status epilepticus (SE), leading to activation of multiple signaling pathways, including the janus kinase/signal transducer and activator of transcription pathway that mediates a decrease in GABAA receptor α1 subunits in the hippocampus (Lund et al., 2008). While BDNF can signal via its pro or mature form, the relative contribution of these forms to signaling after SE is not fully known. In the current study, we investigate changes in proBDNF levels acutely after SE in C57BL/6J mice. In contrast to previous reports (Unsain et al., 2008; Volosin et al., 2008; VonDran et al., 2014), our studies found that levels of proBDNF in the hippocampus are markedly elevated as early as 3 h after SE onset and remain elevated for 7 d. Immunohistochemistry studies indicate that seizure-induced BDNF localizes to all hippocampal subfields, predominantly in principal neurons and also in astrocytes. Analysis of the proteolytic machinery that cleaves proBDNF to produce mature BDNF demonstrates that acutely after SE there is a decrease in tissue plasminogen activator and an increase in plasminogen activator inhibitor-1 (PAI-1), an inhibitor of extracellular and intracellular cleavage, which normalizes over the first week after SE. In vitro treatment of hippocampal slices from animals 24 h after SE with a PAI-1 inhibitor reduces proBDNF levels. These findings suggest that rapid proBDNF increases following SE are due in part to reduced cleavage, and that proBDNF may be part of the initial neurotrophin response driving intracellular signaling during the acute phase of epileptogenesis. PMID:27057559

  16. Rapid suppression of 7-dehydrocholesterol reductase activity in keratinocytes by vitamin D.

    PubMed

    Zou, Ling; Porter, Todd D

    2015-04-01

    7-Dehydrocholesterol (7DHC) serves as the sterol substrate for both cholesterol and vitamin D3 (cholecalciferol) synthesis. The pivotal enzyme in these two pathways is 7-dehydrocholesterol reductase (DHCR7), which converts 7DHC to cholesterol. Treatment of adult human epidermal keratinocytes (HEKa) with 10μM cholecalciferol resulted in a rapid decrease in DHCR7 activity (19% of control activity at 2h). This loss of activity was observed only in HEKa cells, a primary cell line cultured from normal human skin, and not in an immortalized skin cell line (HaCaT cells) nor in two hepatoma cell lines. The decrease in DHCR7 activity was not due to direct inhibition or to dephosphorylation of the enzyme, and enzyme protein levels were not decreased. 25-Hydroxyvitamin D3 had a lesser effect on DHCR7 activity, while 1α,25-dihydroxyvitamin D3 had no effect on DHCR7, indicating that the vitamin D receptor is not involved. Treatment with cholecalciferol did not lead to the accumulation of 7-dehydrocholesterol, and a 50% decrease in lanosterol synthesis in these cells suggests that cholecalciferol down-regulates the entire cholesterolgenic pathway. As vitamin D has been reported to be an inhibitor of hedgehog (Hh) signaling through Smo, we tested the effect of cyclopamine, an established inhibitor of the Hh pathway, on DHCR7 activity. Cyclopamine (10μM) also rapidly decreased DHCR7 activity (50% of control activity at 3h), suggesting that vitamin D3 may modulate DHCR7 activity and cholesterol/vitamin D3 synthesis by inhibiting hedgehog signaling. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  17. Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.

    PubMed

    Heidegger, Simon; Anz, David; Stephan, Nicolas; Bohn, Bernadette; Herbst, Tina; Fendler, Wolfgang Peter; Suhartha, Nina; Sandholzer, Nadja; Kobold, Sebastian; Hotz, Christian; Eisenächer, Katharina; Radtke-Schuller, Susanne; Endres, Stefan; Bourquin, Carole

    2013-10-10

    Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process, but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphologic changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B-cell subset. We demonstrate that the disruption is entirely dependent on type I interferon (IFN). At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such rerouted lymphocyte trafficking may impact the development of B-cell immunity to systemic viral pathogens.

  18. Rapid Detection of Glycogen Synthase Kinase-3 Activity in Mouse Sperm Using Fluorescent Gel Shift Electrophoresis

    PubMed Central

    Choi, Hoseok; Choi, Bomi; Seo, Ju Tae; Lee, Kyung Jin; Gye, Myung Chan; Kim, Young-Pil

    2016-01-01

    Assaying the glycogen synthase kinase-3 (GSK3) activity in sperm is of great importance because it is closely implicated in sperm motility and male infertility. While a number of studies on GSK3 activity have relied on labor-intensive immunoblotting to identify phosphorylated GSK3, here we report the simple and rapid detection of GSK3 activity in mouse sperm using conventional agarose gel electrophoresis and a fluorescent peptide substrate. When a dye-tethered and prephosphorylated (primed) peptide substrate for GSK3 was employed, a distinct mobility shift in the fluorescent bands on the agarose was observed by GSK3-induced phosphorylation of the primed peptides. The GSK3 activity in mouse testes and sperm were quantifiable by gel shift assay with low sample consumption and were significantly correlated with the expression levels of GSK3 and p-GSK3. We suggest that our assay can be used for reliable and rapid detection of GSK3 activity in cells and tissue extracts. PMID:27092510

  19. Rapid Detection of Glycogen Synthase Kinase-3 Activity in Mouse Sperm Using Fluorescent Gel Shift Electrophoresis.

    PubMed

    Choi, Hoseok; Choi, Bomi; Seo, Ju Tae; Lee, Kyung Jin; Gye, Myung Chan; Kim, Young-Pil

    2016-04-16

    Assaying the glycogen synthase kinase-3 (GSK3) activity in sperm is of great importance because it is closely implicated in sperm motility and male infertility. While a number of studies on GSK3 activity have relied on labor-intensive immunoblotting to identify phosphorylated GSK3, here we report the simple and rapid detection of GSK3 activity in mouse sperm using conventional agarose gel electrophoresis and a fluorescent peptide substrate. When a dye-tethered and prephosphorylated (primed) peptide substrate for GSK3 was employed, a distinct mobility shift in the fluorescent bands on the agarose was observed by GSK3-induced phosphorylation of the primed peptides. The GSK3 activity in mouse testes and sperm were quantifiable by gel shift assay with low sample consumption and were significantly correlated with the expression levels of GSK3 and p-GSK3. We suggest that our assay can be used for reliable and rapid detection of GSK3 activity in cells and tissue extracts.

  20. Non-invasive administration of 17β-estradiol rapidly increases aggressive behavior in non-breeding, but not breeding, male song sparrows.

    PubMed

    Heimovics, Sarah A; Ferris, Jennifer K; Soma, Kiran K

    2015-03-01

    17β-Estradiol (E2) acts in the brain via genomic and non-genomic mechanisms to influence physiology and behavior. There is seasonal plasticity in the mechanisms by which E2 activates aggression, and non-genomic mechanisms appear to predominate during the non-breeding season. Male song sparrows (Melospiza melodia) display E2-dependent territorial aggression throughout the year. Field studies show that song sparrow aggression during a territorial intrusion is similar in the non-breeding and breeding seasons, but aggression after an intrusion ends differs seasonally. Non-breeding males stop behaving aggressively within minutes whereas breeding males remain aggressive for hours. We hypothesize that this seasonal plasticity in the persistence of aggression relates to seasonal plasticity in E2 signaling. We used a non-invasive route of E2 administration to compare the non-genomic (within 20min) effects of E2 on aggressive behavior in captive non-breeding and breeding season males. E2 rapidly increased barrier contacts (attacks) during an intrusion by 173% in non-breeding season males only. Given that these effects were observed within 20min of E2 administration, they likely occurred via a non-genomic mechanism of action. The present data, taken together with past work, suggest that environmental cues associated with the non-breeding season influence the molecular mechanisms through which E2 influences behavior. In song sparrows, transient expression of aggressive behavior during the non-breeding season is highly adaptive: it minimizes energy expenditure and maximizes the amount of time available for foraging. In all, these data suggest the intriguing possibility that aggression in the non-breeding season may be activated by a non-genomic E2 mechanism due to the fitness benefits associated with rapid and transient expression of aggression.

  1. Engaging parents to increase youth physical activity: A systematic review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Parents are often involved in interventions to engage youth in physical activity, but it is not clear which methods for involving parents are effective. A systematic review was conducted of interventions with physical activity and parental components among healthy youth to identify how best to invol...

  2. Opportunities for Public Health to Increase Physical Activity Among Youths

    PubMed Central

    Dorn, Joan M.; Fulton, Janet E.; Janz, Kathleen F.; Lee, Sarah M.; McKinnon, Robin A.; Pate, Russell R.; Pfeiffer, Karin A.; Young, Deborah Rohm; Troiano, Richard P.; Lavizzo-Mourey, Risa

    2015-01-01

    Despite the well-known benefits of youths engaging in 60 or more minutes of daily physical activity, physical inactivity remains a significant public health concern. The 2008 Physical Activity Guidelines for Americans (PAG) provides recommendations on the amount of physical activity needed for overall health; the PAG Midcourse Report (2013) describes effective strategies to help youths meet these recommendations. Public health professionals can be dynamic change agents where youths live, learn, and play by changing environments and policies to empower youths to develop regular physical activity habits to maintain throughout life. We have summarized key findings from the PAG Midcourse Report and outlined actions that public health professionals can take to ensure that all youths regularly engage in health-enhancing physical activity. PMID:25602864

  3. Pharmacological modulations of cardiac ultra-rapid and slowly activating delayed rectifier currents: potential antiarrhythmic approaches.

    PubMed

    Islam, Mohammed A

    2010-01-01

    Despite the emerging new insights into our understandings of the cellular mechanisms underlying cardiac arrhythmia, medical therapy for this disease remains unsatisfactory. Atrial fibrillation (AF), the most prevalent arrhythmia, is responsible for significant morbidity and mortality. On the other hand, ventricular fibrillation results in sudden cardiac deaths in many instances. Prolongation of cardiac action potential (AP) is a proven principle of antiarrhythmic therapy. Class III antiarrhythmic agents prolong AP and QT interval by blocking rapidly activating delayed rectifier current (I(Kr)). However, I(Kr) blocking drugs carry the risk of life-threatening proarrhythmia. Recently, modulation of atrial-selective ultra-rapid delayed rectifier current (I(Kur)), has emerged as a novel therapeutic approach to treat AF. A number of I(Kur) blockers are being evaluated for the treatment of AF. The inhibition of slowly activating delayed rectifier current (I(Ks)) has also been proposed as an effective and safer antiarrhythmic approach because of its distinguishing characteristics that differ in remarkable ways from other selective class III agents. Selective I(Ks) block may prolong AP duration (APD) at rapid rates without leading to proarrhythmia. This article reviews the pathophysiological roles of I(Kur) and I(Ks) in cardiac repolarization and the implications of newly developed I(Kur) and I(Ks) blocking agents as promising antiarrhythmic approaches. Several recent patents pertinent to antiarrhythmic drug development have been discussed. Further research will be required to evaluate the efficacy and safety of these agents in the clinical setting.

  4. A RAPID Method for Blood Processing to Increase the Yield of Plasma Peptide Levels in Human Blood.

    PubMed

    Teuffel, Pauline; Goebel-Stengel, Miriam; Hofmann, Tobias; Prinz, Philip; Scharner, Sophie; Körner, Jan L; Grötzinger, Carsten; Rose, Matthias; Klapp, Burghard F; Stengel, Andreas

    2016-04-28

    Research in the field of food intake regulation is gaining importance. This often includes the measurement of peptides regulating food intake. For the correct determination of a peptide's concentration, it should be stable during blood processing. However, this is not the case for several peptides which are quickly degraded by endogenous peptidases. Recently, we developed a blood processing method employing Reduced temperatures, Acidification, Protease inhibition, Isotopic exogenous controls and Dilution (RAPID) for the use in rats. Here, we have established this technique for the use in humans and investigated recovery, molecular form and circulating concentration of food intake regulatory hormones. The RAPID method significantly improved the recovery for (125)I-labeled somatostatin-28 (+39%), glucagon-like peptide-1 (+35%), acyl ghrelin and glucagon (+32%), insulin and kisspeptin (+29%), nesfatin-1 (+28%), leptin (+21%) and peptide YY3-36 (+19%) compared to standard processing (EDTA blood on ice, p <0.001). High performance liquid chromatography showed the elution of endogenous acyl ghrelin at the expected position after RAPID processing, while after standard processing 62% of acyl ghrelin were degraded resulting in an earlier peak likely representing desacyl ghrelin. After RAPID processing the acyl/desacyl ghrelin ratio in blood of normal weight subjects was 1:3 compared to 1:23 following standard processing (p = 0.03). Also endogenous kisspeptin levels were higher after RAPID compared to standard processing (+99%, p = 0.02). The RAPID blood processing method can be used in humans, yields higher peptide levels and allows for assessment of the correct molecular form.

  5. Acute exposure to cold rapidly increases the number of nucleotide binding sites, but not proton conductance, in BAT mitochondria

    SciTech Connect

    Swick, A.G.; Swick, R.W.

    1986-03-01

    Studies on the effect of acute cold exposure of rats on brown adipose tissue (BAT) thermogenic activity have produced equivocal results. Therefore, the authors have reexamined the response of BAT mitochondria to abrupt changes in environmental temperature. /sup 3/H-GDP binding to BAT mitochondria increased more than 2-fold in 20 min when rats were moved from 27/sup 0/C to 4/sup 0/C. When rats housed at 4/sup 0/C for 2 h were returned to 27/sup 0/C, GDP binding decreased sharply in 20 min and returned to control levels in 2 h. On the other hand, GDP-inhibitable proton conductance, as measured by passive swelling in isotonic K-acetate of KCl buffers, was unaffected by brief cold exposure but more than doubled in rats kept at 4/sup 0/C for 10 days. The authors conclude that GDP-inhibitable swelling may be more indicative of uncoupling protein concentration whereas thermogenic activity is more appropriately indicated by GDP binding. GDP binding to BAT mitochondria from warm and acutely cold treated rats was not altered by prior swelling of the mitochondria nor by freeze-thawing the mitochondria before assay. Therefore, alterations of the number of GDP binding sites may not be a result of conformational changes of the mitochondril membrane.

  6. Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux

    PubMed Central

    Vrins, Carlos L. J.; van der Velde, Astrid E.; van den Oever, Karin; Levels, Johannes H. M.; Huet, Stephane; Oude Elferink, Ronald P. J.; Kuipers, Folkert; Groen, Albert K.

    2009-01-01

    Peroxisome proliferator-activated receptor delta (PPARδ) is involved in regulation of energy homeostasis. Activation of PPARδ markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary cholesterol secretion, nor by reduced cholesterol absorption. To test the hypothesis that PPARδ activation leads to stimulation of transintestinal cholesterol efflux (TICE), we quantified it by intestine perfusions in FVB mice treated with PPARδ agonist GW610742. To exclude the effects on cholesterol absorption, mice were also treated with cholesterol absorption inhibitor ezetimibe or ezetimibe/GW610742. GW601742 treatment had little effect on plasma lipid levels but stimulated both fecal neutral sterol excretion (∼200%) and TICE (∼100%). GW610742 decreased intestinal Npc1l1 expression but had no effect on Abcg5/Abcg8. Interestingly, expression of Rab9 and LIMPII, encoding proteins involved in intracellular cholesterol trafficking, was increased upon PPARδ activation. Although treatment with ezetimibe alone had no effect on TICE, it reduced the effect of GW610742 on TICE. These data show that activation of PPARδ stimulates fecal cholesterol excretion in mice, primarily by the two-fold increase in TICE, indicating that this pathway provides an interesting target for the development of drugs aiming at the prevention of atherosclerosis. PMID:19439761

  7. Analysis of rapid increase in the plasma density during the ramp-up phase in a radio frequency negative ion source by large-scale particle simulation.

    PubMed

    Yasumoto, M; Ohta, M; Kawamura, Y; Hatayama, A

    2014-02-01

    Numerical simulations become useful for the developing RF-ICP (Radio Frequency Inductively Coupled Plasma) negative ion sources. We are developing and parallelizing a two-dimensional three velocity electromagnetic Particle-In-Cell code. The result shows rapid increase in the electron density during the density ramp-up phase. A radial electric field due to the space charge is produced with increase in the electron density and the electron transport in the radial direction is suppressed. As a result, electrons stay for a long period in the region where the inductive electric field is strong, and this leads efficient electron acceleration and a rapid increasing of the electron density.

  8. Real-time PCR for rapidly detecting aniline-degrading bacteria in activated sludge.

    PubMed

    Kayashima, Takakazu; Suzuki, Hisako; Maeda, Toshinari; Ogawa, Hiroaki I

    2013-05-01

    We developed a detection method that uses quantitative real-time PCR (qPCR) and the TaqMan system to easily and rapidly assess the population of aniline-degrading bacteria in activated sludge prior to conducting a biodegradability test on a chemical compound. A primer and probe set for qPCR was designed by a multiple alignment of conserved amino acid sequences encoding the large (α) subunit of aniline dioxygenase. PCR amplification tests showed that the designed primer and probe set targeted aniline-degrading strains such as Acidovorax sp., Gordonia sp., Rhodococcus sp., and Pseudomonas putida, thereby suggesting that the developed method can detect a wide variety of aniline-degrading bacteria. There was a strong correlation between the relative copy number of the α-aniline dioxygenase gene in activated sludge obtained with the developed qPCR method and the number of aniline-degrading bacteria measured by the Most Probable Number method, which is the conventional method, and a good correlation with the lag time of the BOD curve for aniline degradation produced by the biodegradability test in activated sludge samples collected from eight different wastewater treatment plants in Japan. The developed method will be valuable for the rapid and accurate evaluation of the activity of inocula prior to conducting a ready biodegradability test.

  9. ROFA INCREASES CASPASE-3 ACTIVITY IN HUMAN ALVEOLAR MACRAPHAGE

    EPA Science Inventory

    Exposure to air pollution particles produces pulmonary inflammation and injury, but the mechanisms of this injury are unclear. Apoptosis, involving activation of caspases, may be one potential mechanism. In this study, we hypothesized that ROFA, a constituent of air pollution...

  10. State Legislation Related to Increasing Physical Activity: 2006-2012

    PubMed Central

    Eyler, Amy A.; Budd, Elizabeth; Camberos, Gabriela J.; Yan, Yan; Brownson, Ross C.

    2016-01-01

    Background Strategies to improve physical activity prevalence often include policy and environmental changes. State-level policies can be influential in supporting access and opportunities for physical activity in schools and communities. The purpose of this study was to explore the prevalence of state legislation related to physical activity and identify the correlates of enactment of this legislation. Methods An online legislative database was used to collect bills from 50 states in the U.S. from 2006-2012 for ten topics related to physical activity. Bills were coded for content and compiled into a database with state-level variables (e.g., obesity prevalence). With enactment status as the outcome, bivariate and multivariate analyses were conducted. Results Of the 1542 bills related to physical activity introduced, 30% (N=460) were enacted. Bills on public transportation and trails were more likely to be enacted than those without these topics. Primary sponsorship by the Republican Party, bipartisan sponsorship, and mention of specific funding amounts were also correlates of enactment. Conclusion Policy surveillance of bills and correlates of enactment are important for understanding patterns in legislative support for physical activity. This information can be used to prioritize advocacy efforts and identify ways for research to better inform policy. PMID:26104603

  11. Testing the applicability of rapid on-site enzymatic activity detection for surface water monitoring

    NASA Astrophysics Data System (ADS)

    Stadler, Philipp; Vogl, Wolfgang; Juri, Koschelnik; Markus, Epp; Maximilian, Lackner; Markus, Oismüller; Monika, Kumpan; Peter, Strauss; Regina, Sommer; Gabriela, Ryzinska-Paier; Farnleitner Andreas, H.; Matthias, Zessner

    2015-04-01

    On-site detection of enzymatic activities has been suggested as a rapid surrogate for microbiological pollution monitoring of water resources (e.g. using glucuronidases, galactosidases, esterases). Due to the possible short measuring intervals enzymatic methods have high potential as near-real time water quality monitoring tools. This presentation describes results from a long termed field test. For twelve months, two ColiMinder devices (Vienna Water Monitoring, Austria) for on-site determination of enzymatic activity were tested for stream water monitoring at the experimental catchment HOAL (Hydrological Open Air Laboratory, Center for Water Resource Systems, Vienna University of Technology). The devices were overall able to follow and reflect the diverse hydrological and microbiological conditions of the monitored stream during the test period. Continuous data in high temporal resolution captured the course of enzymatic activity in stream water during diverse rainfall events. The method also proofed sensitive enough to determine diurnal fluctuations of enzymatic activity in stream water during dry periods. The method was able to capture a seasonal trend of enzymatic activity in stream water that matches the results gained from Colilert18 analysis for E. coli and coliform bacteria of monthly grab samples. Furthermore the comparison of ColiMinder data with measurements gained at the same test site with devices using the same method but having different construction design (BACTcontrol, microLAN) showed consistent measuring results. Comparative analysis showed significant differences between measured enzymatic activity (modified fishman units and pmol/min/100ml) and cultivation based analyses (most probable number, colony forming unit). Methods of enzymatic activity measures are capable to detect ideally the enzymatic activity caused by all active target bacteria members, including VBNC (viable but nonculturable) while cultivation based methods cannot detect VBNC

  12. Complete inactivation of photosynthetic activity during desiccation and rapid recovery by rehydration in the aerial microalga Trentepohlia jolithus.

    PubMed

    Zhang, L; Li, Y; Liu, J

    2016-11-01

    Aerial microalgae are more exposed to harsh and rapidly changing environmental conditions, including desiccation and radiation. Under high light, aerial algae in the desiccated state would be highly subject to photodamage. Therefore, aerial algae need effective protective mechanisms to dissipate excess excitation energy. In this study, the changes in photosynthetic behaviors during desiccation and after rehydration in Trentepohlia jolithus were confirmed using chlorophyll a fluorescence (OJIP) transient, allowing determination of the photoprotection mechanisms of this aerial alga. The filaments of T. jolithus cells at 25% relative air humidity (RH) are significantly shrunken compared with those at 100% and 87% RH, decreasing the surface area for light absorption. At 25% RH, the shape and intensity of the OJIP transient disappeared, but recovered rapidly to the level at 100% RH after 5 s of rehydration. Compared with 100% RH, the maximum quantum yield of PSII (φPo ), phenomenological energy fluxes for absorption (ABS/CSm) and active PSII reaction centers (RCs) at 25% RH decreased significantly, the specific energy fluxes for absorption (ABS/RC) increased significantly, but the specific energy fluxes for trapping (TRo/RC) at 25% RH did not change. These parameters at 25% RH recovered rapidly to the level at 100% RH after 5 s of rehydration. These results suggest that the efficiency of PSII light absorption and activities of PSII RCs were reversibly down-regulated in desiccated T. jolithus, which may be a special adaptive mechanism for the survivability of aerial microalgae in habitats with rapidly changing water availability.

  13. Laser Activation of Rapid Absorption Changes in Spinach Chloroplasts and Chlorella 1

    PubMed Central

    Hildreth, W. W.; Avron, M.; Chance, B.

    1966-01-01

    The kinetics of the 520 mμ absorption change in spinach chloroplasts and Chlorella vulgaris following a flash from the ruby laser have been determined as follows: rise halftime ≤ 0.3 × 10−6 second; rapid recovery halftime = 5 to 6 × 10−6 second; intermediate recovery halftime = 4 × 10−4 second (spinach chloroplasts only); slow recovery halftime = 12 to 170 × 10−3 second, dependent on the measuring light intensity and aerobicity of the suspension. The rapid phase of the 520 mμ reaction is approximately independent of temperature, from 295° to 77° Absolute. With increasing oxygenation of the sample, the extent of the rapid phase decreases, the extent of the slow phase increases, while the extent of the intermediate phase in spinach chloroplasts remains constant. In spinach chloroplasts, no recovery halftime of the 3 recovery phases for the 520 mμ absorption change was observed to correspond to the halftime for oxidation of cytochrome f (t½ = 1.3 × 10−3 second). PMID:16656366

  14. Eating 'Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction.

    PubMed

    Oginsky, Max F; Goforth, Paulette B; Nobile, Cameron W; Lopez-Santiago, Luis F; Ferrario, Carrie R

    2016-12-01

    Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after 'junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by 'junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general 'read out' of mesolimbic function after 'junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a 'junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating 'junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after 'junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction.

  15. Eating ‘Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

    PubMed Central

    Oginsky, Max F; Goforth, Paulette B; Nobile, Cameron W; Lopez-Santiago, Luis F; Ferrario, Carrie R

    2016-01-01

    Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after ‘junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by ‘junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general ‘read out' of mesolimbic function after ‘junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a ‘junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating ‘junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after ‘junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction. PMID:27383008

  16. Rapid adaptation of activated sludge bacteria into a glycogen accumulating biofilm enabling anaerobic BOD uptake.

    PubMed

    Hossain, Md Iqbal; Paparini, Andrea; Cord-Ruwisch, Ralf

    2017-03-01

    Glycogen accumulating organisms (GAO) are known to allow anaerobic uptake of biological oxygen demand (BOD) in activated sludge wastewater treatment systems. In this study, we report a rapid transition of suspended activated sludge biomass to a GAO dominated biofilm by selective enrichment using sequences of anaerobic loading followed by aerobic exposure of the biofilm to air. The study showed that within eight weeks, a fully operational, GAO dominated biofilm had developed, enabling complete anaerobic BOD uptake at a rate of 256mg/L/h. The oxygen uptake by the biofilm directly from the atmosphere had been calculated to provide significant energy savings. This study suggests that wastewater treatment plant operators can convert activated sludge systems readily into a "passive aeration" biofilm that avoids costly oxygen transfer to bulk wastewater solution. The described energy efficient BOD removal system provides an opportunity to be coupled with novel nitrogen removal processes such as anammox.

  17. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    PubMed

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  18. Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running

    NASA Technical Reports Server (NTRS)

    Fluck, M.; Waxham, M. N.; Hamilton, M. T.; Booth, F. W.

    2000-01-01

    Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca(2+)/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca(2+), we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca(2+)-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca(2+)/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca(2+)-independent and Ca(2+)/CaM-dependent forms of Ca(2+)/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca(2+)-independent form of CaMKII was increased, like the Ca(2+)-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca(2+)-independent SRF kinase was increased, no alteration occurred in Ca(2+)/CaM-dependent SRF kinase activity. Thus any role of Ca(2+)-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.

  19. Rapid Cell-Based Assay for Detection and Quantification of Active Staphylococcal Enterotoxin Type D.

    PubMed

    Rasooly, Reuven; Do, Paula M; Hernlem, Bradley J

    2017-03-01

    Food poisoning by Staphylococcus aureus is a result of ingestion of Staphylococcal enterotoxins (SEs) produced by this bacterium and is a major source of foodborne illness. Staphylococcal enterotoxin D (SED) is one of the predominant enterotoxins recovered in Staphylococcal food poisoning incidences, including a recent outbreak in Guam affecting 300 children. Current immunology methods for SED detection cannot distinguish between the biologically active form of the toxin, which poses a threat, from the inactive form, which poses no threat. In vivo bioassays that measure emetic activity in kitten and monkeys have been used, but these methods rely upon expensive procedures using live animals and raising ethical concerns. A rapid (5 h) quantitative bioluminescence assay, using a genetically engineered T-cell Jurkat cell line expressing luciferase under regulation of nuclear factor of activated T cells response elements, in combination with the lymphoblastoid B-cell line Raji for antigen presentation, was developed. In this assay, the detection limit of biologically active SED is 100 ng/mL, which is 10 times more sensitive than the splenocyte proliferation assay, and 10(5) times more sensitive than monkey or kitten bioassay. Pasteurization or repeated freeze-thaw cycles had no effect on SED activity, but reduction in SED activity was shown with heat treatment at 100°C for 5 min. It was also shown that milk exhibits a protective effect on SED. This bioluminescence assay may also be used to rapidly evaluate antibodies to SED for potential therapeutic application as a measurement of neutralizing biological effects of SED.

  20. Rapid structural alterations of the active zone lead to sustained changes in neurotransmitter release.

    PubMed

    Matz, Jacob; Gilyan, Andrew; Kolar, Annette; McCarvill, Terrence; Krueger, Stefan R

    2010-05-11

    The likelihood with which an action potential elicits neurotransmitter release, the release probability (p(r)), is an important component of synaptic strength. Regulatory mechanisms controlling several steps of synaptic vesicle (SV) exocytosis may affect p(r), yet their relative importance in determining p(r) and eliciting temporal changes in neurotransmitter release at individual synapses is largely unknown. We have investigated whether the size of the active zone cytomatrix is a major determinant of p(r) and whether changes in its size lead to corresponding alterations in neurotransmitter release. We have used a fluorescent sensor of SV exocytosis, synaptophysin-pHluorin, to measure p(r) at individual synapses with high accuracy and employed a fluorescently labeled cytomatrix protein, Bassoon, to quantify the amount of active zone cytomatrix present at these synapses. We find that, for synapses made by a visually identified presynaptic neuron, p(r) is indeed strongly correlated with the amount of active zone cytomatrix present at the presynaptic specialization. Intriguingly, active zone cytomatrices are frequently subject to synapse-specific changes in size on a time scale of minutes. These spontaneous alterations in active zone size are associated with corresponding changes in neurotransmitter release. Our results suggest that the size of the active zone cytomatrix has a large influence on the reliability of synaptic transmission. Furthermore, they implicate mechanisms leading to rapid structural alterations at active zones in synapse-specific forms of plasticity.

  1. Soil disturbance increases soil microbial enzymatic activity in arid ecoregion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional diversity of the soil microbial community is commonly used in the assessment of soil health as it relates to the activity of soil microflora involved in carbon cycling. Soil microbes in different microenvironments will have varying responses to different substrates, thus catabolic fingerp...

  2. Increasing Pupil Physical Activity: A Comprehensive Professional Development Effort

    ERIC Educational Resources Information Center

    Kulinna, Pamela Hodges

    2012-01-01

    Study aim: To determine if pupil physical activity and Body Mass Index classifications maintained or improved after a one-year professional development program involving both classroom and physical education teachers. Guskey's model of teacher change guided this study. Material and methods: Indigenous children from ten schools (N = 320) in grades…

  3. Texting to increase physical activity in teens: Development & preliminary

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our purpose was to present formative research and preliminary results for a self-determination-theory (SDT)-based text messages to promote physical activity (PA) among teens. Thirty 14- to 17-year olds, stratified by gender and race/ethnicity (Black, Hispanic, White), were recruited to participate i...

  4. Increasing Physical Activity of Children during School Recess

    ERIC Educational Resources Information Center

    Hayes, Lynda B.; Van Camp, Carole M.

    2015-01-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M?=?1,956 steps) were 47% higher than in baseline (M?=?1,326 steps), and the…

  5. Somatosensory Anticipatory Alpha Activity Increases to Suppress Distracting Input

    ERIC Educational Resources Information Center

    Haegens, Saskia; Luther, Lisa; Jensen, Ole

    2012-01-01

    Effective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top-down modulation of oscillatory alpha band activity (8-14 Hz) serves to allocate resources to various regions, depending on task…

  6. Human P2X7 receptor activation induces the rapid shedding of CXCL16.

    PubMed

    Pupovac, Aleta; Foster, Christopher M; Sluyter, Ronald

    2013-03-22

    Activation of the purinergic P2X7 receptor by extracellular ATP induces the shedding of cell-surface molecules including the low-affinity IgE receptor, CD23 from leukocytes. CD23 is a known substrate of a disintegrin and metalloprotease (ADAM)10. The aim of the current study was to determine if P2X7 activation induced the shedding of the chemokine CXCL16, an ADAM10 substrate. Using immunolabelling and flow cytometry we demonstrate that human RPMI 8226 multiple myeloma B cells, which have been previously shown to express P2X7, also express CXCL16. Flow cytometric and ELISA measurements of ATP-induced loss of cell-surface CXCL16 showed that ATP treatment of RPMI 8226 cells induced the rapid shedding of CXCL16. Treatment of RPMI 8226 cells with the specific P2X7 antagonists, AZ10606120 and KN-62 impaired ATP-induced CXCL16 shedding by ~86% and ~90% respectively. RT-PCR demonstrated that ADAM10 is expressed in these cells and treatment of cells with the ADAM10 inhibitor, GI254023X, impaired ATP-induced CXCL16 shedding by ~87%. GI254023X also impaired P2X7-induced CD23 shedding by ∼57%. This data indicates that human P2X7 activation induces the rapid shedding of CXCL16 and that this process involves ADAM10.

  7. Activation of Transient Receptor Potential Vanilloid 4 Increases NMDA-Activated Current in Hippocampal Pyramidal Neurons

    PubMed Central

    Li, Lin; Qu, Weijun; Zhou, Libin; Lu, Zihong; Jie, Pinghui; Chen, Lei; Chen, Ling

    2013-01-01

    The glutamate excitotoxicity, mediated through N-methyl-d-aspartate receptors (NMDARs), plays an important role in cerebral ischemia injury. Transient receptor potential vanilloid 4 (TRPV4) can be activated by multiple stimuli that may happen during stroke. The present study evaluated the effect of TRPV4 activation on NMDA-activated current (INMDA) and that of blocking TRPV4 on brain injury after focal cerebral ischemia in mice. We herein report that activation of TRPV4 by 4α-PDD and hypotonic stimulation increased INMDA in hippocampal CA1 pyramidal neurons, which was sensitive to TRPV4 antagonist HC-067047 and NMDAR antagonist AP-5, indicating that TRPV4 activation potentiates NMDAR response. In addition, the increase in INMDA by hypotonicity was sensitive to the antagonist of NMDAR NR2B subunit, but not of NR2A subunit. Furthermore, antagonists of calcium/calmodulin-dependent protein kinase II (CaMKII) significantly attenuated hypotonicity-induced increase in INMDA, while antagonists of protein kinase C or casein kinase II had no such effect, indicating that phosphorylation of NR2B subunit by CaMKII is responsible for TRPV4-potentiated NMDAR response. Finally, we found that intracerebroventricular injection of HC-067047 after 60 min middle cerebral artery occlusion reduced the cerebral infarction with at least a 12 h efficacious time-window. These findings indicate that activation of TRPV4 increases NMDAR function, which may facilitate glutamate excitotoxicity. Closing TRPV4 may exert potent neuroprotection against cerebral ischemia injury through many mechanisms at least including the prevention of NMDAR-mediated glutamate excitotoxicity. PMID:23459987

  8. Fast voltammetry of metals at carbon-fiber microelectrodes: copper adsorption onto activated carbon aids rapid electrochemical analysis.

    PubMed

    Pathirathna, Pavithra; Samaranayake, Srimal; Atcherley, Christopher W; Parent, Kate L; Heien, Michael L; McElmurry, Shawn P; Hashemi, Parastoo

    2014-09-21

    Rapid, in situ trace metal analysis is essential for understanding many biological and environmental processes. For example, trace metals are thought to act as chemical messengers in the brain. In the environment, some of the most damaging pollution occurs when metals are rapidly mobilized and transported during hydrologic events (storms). Electrochemistry is attractive for in situ analysis, primarily because electrodes are compact, cheap and portable. Electrochemical techniques, however, do not traditionally report trace metals in real-time. In this work, we investigated the fundamental mechanisms of a novel method, based on fast-scan cyclic voltammetry (FSCV), that reports trace metals with sub-second temporal resolution at carbon-fiber microelectrodes (CFMs). Electrochemical methods and geochemical models were employed to find that activated CFMs rapidly adsorb copper, a phenomenon that greatly advances the temporal capabilities of electrochemistry. We established the thermodynamics of surface copper adsorption and the electrochemical nature of copper deposition onto CFMs and hence identified a unique adsorption-controlled electrochemical mechanism for ultra-fast trace metal analysis. This knowledge can be exploited in the future to increase the sensitivity and selectivity of CFMs for fast voltammetry of trace metals in a variety of biological and environmental models.

  9. Activated paper surfaces for the rapid hybridization of DNA through capillary transport.

    PubMed

    Araújo, Ana Catarina; Song, Yajing; Lundeberg, Joakim; Ståhl, Patrik L; Brumer, Harry

    2012-04-03

    The development of low-cost, accurate, and equipment-free diagnostic tests is crucial to many clinical, laboratory, and field applications, including forensics and medical diagnostics. Cellulose fiber-based paper is an inexpensive, biodegradable, and renewable resource, the use of which as a biomolecule detection matrix and support confers several advantages compared to traditional materials such as glass. In this context, a new, facile method for the preparation of surface functionalized papers bearing single-stranded probe DNA (ssDNA) for rapid target hybridization via capillary transport is presented. Optimized reaction conditions were developed that allowed the direct, one-step activation of standard laboratory filters by the inexpensive and readily available bifunctional linking reagent, 1,4-phenylenediisothiocyanate. Such papers were thus amenable to subsequent coupling of amine-labeled ssDNA under standard conditions widely used for glass-based supports. The intrinsic wicking ability of the paper matrix facilitated rapid sample elution through arrays of probe DNA, leading to significant, detectable hybridization in the time required for the sample liquid to transit the vertical length of the strip (less than 2 min). The broad applicability of these paper test strips as rapid and specific diagnostics in "real-life" situations was exemplified by the discrimination of amplicons generated from canine and human mitochondrial and genomic DNA in mock forensic samples.

  10. Rapid In-Situ Measurement of Gamma Activity in Soil for Environmental Assessment

    NASA Astrophysics Data System (ADS)

    Honeycutt, T. K.

    2003-12-01

    In-situ measurements of gamma radiation in soil are used as a rapid, low-cost, non-intrusive alternative to conventional sampling and analysis methods in the preliminary assessment of environmental impacts to watersheds at the Savannah River Site (SRS). The method resolves the ambient gamma-radiation field near ground surface into background and residual components and provides radionuclide-specific soil activity determination. The efficacy of the method has been evaluated and compares favorably with conventional gamma-PHA soil analyses and aerial survey data. The method has garnered regulatory approval and is being successfully deployed to evaluate the impact of Cs-137 contamination from CERCLA sites.

  11. Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour

    PubMed Central

    De Marco, Rodrigo J.; Thiemann, Theresa; Groneberg, Antonia H.; Herget, Ulrich; Ryu, Soojin

    2016-01-01

    The anterior pituitary is the major link between nervous and hormonal systems, which allow the brain to generate adequate and flexible behaviour. Here, we address its role in mediating behavioural adjustments that aid in coping with acutely threatening environments. For this we combine optogenetic manipulation of pituitary corticotroph cells in larval zebrafish with newly developed assays for measuring goal-directed actions in very short timescales. Our results reveal modulatory actions of corticotroph cell activity on locomotion, avoidance behaviours and stimulus responsiveness directly after the onset of stress. Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments. PMID:27646867

  12. Activation of the motor cortex during phasic rapid eye movement sleep

    PubMed Central

    De Carli, Fabrizio; Proserpio, Paola; Morrone, Elisa; Sartori, Ivana; Ferrara, Michele; Gibbs, Steve Alex; De Gennaro, Luigi; Lo Russo, Giorgio

    2016-01-01

    When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder. Ann Neurol 2016;79:326–330 PMID:26575212

  13. Peptide Inhibitor of Complement C1 (PIC1) Rapidly Inhibits Complement Activation after Intravascular Injection in Rats

    PubMed Central

    Sharp, Julia A.; Hair, Pamela S.; Pallera, Haree K.; Kumar, Parvathi S.; Mauriello, Clifford T.; Nyalwidhe, Julius O.; Phelps, Cody A.; Park, Dalnam; Thielens, Nicole M.; Pascal, Stephen M.; Chen, Waldon; Duffy, Diane M.; Lattanzio, Frank A.; Cunnion, Kenji M.; Krishna, Neel K.

    2015-01-01

    The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1). In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator molecule MBL as well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory activity occurs via binding to the collagen-like tails of these collectin molecules. We further analyzed the effect of arginine and glutamic acid residue substitution on the complement inhibitory activity of our lead derivative in a hemolytic assay and found that the original sequence demonstrated superior inhibitory activity. To improve upon the solubility of the lead derivative, a pegylated, water soluble variant was developed, structurally characterized and demonstrated to inhibit complement activation in mouse plasma, as well as rat, non-human primate and human serum in vitro. After intravenous injection in rats, the pegylated derivative inhibited complement activation in the blood by 90% after 30 seconds, demonstrating extremely rapid function. Additionally, no adverse toxicological effects were observed in limited testing. Together these results show that PIC1 rapidly inhibits classical complement activation in vitro and in vivo and is functional for a variety of animal species, suggesting its utility in animal models of classical complement-mediated diseases. PMID:26196285

  14. T Lymphocyte Activation Threshold is Increased in Reduced Gravity

    NASA Technical Reports Server (NTRS)

    Adams, Charley L.; Gonzalez, M.; Sams, C. F.

    2000-01-01

    There have been substantial advances in molecular and cellular biology that have provided new insight into the biochemical and genetic basis of lymphocyte recognition, activation and expression of distinct functional phenotypes. It has now become evident that for both T and B cells, stimuli delivered through their receptors can result in either clonal expansion or apoptosis. In the case of T cells, clonal expansion of helper cells is accompanied by differentiation into two major functional subsets which regulate the immune response. The pathways between the membrane and the nucleus and their molecular components are an area of very active investigation. This meeting will draw together scientists working on diverse aspects of this problem, including receptor ligand interactions, intracellular pathways that transmit receptor mediated signals and the effect of such signal transduction pathways on gene regulation. The aim of this meeting is to integrate the information from these various experimental approaches into a new synthesis and molecular explanation of T cell activation, differentiation and death.

  15. PAR1 activation induces rapid changes in glutamate uptake and astrocyte morphology

    PubMed Central

    Sweeney, Amanda M.; Fleming, Kelsey E.; McCauley, John P.; Rodriguez, Marvin F.; Martin, Elliot T.; Sousa, Alioscka A.; Leapman, Richard D.; Scimemi, Annalisa

    2017-01-01

    The G-protein coupled, protease-activated receptor 1 (PAR1) is a membrane protein expressed in astrocytes. Fine astrocytic processes are in tight contact with neurons and blood vessels and shape excitatory synaptic transmission due to their abundant expression of glutamate transporters. PAR1 is proteolytically-activated by bloodstream serine proteases also involved in the formation of blood clots. PAR1 activation has been suggested to play a key role in pathological states like thrombosis, hemostasis and inflammation. What remains unclear is whether PAR1 activation also regulates glutamate uptake in astrocytes and how this shapes excitatory synaptic transmission among neurons. Here we show that, in the mouse hippocampus, PAR1 activation induces a rapid structural re-organization of the neuropil surrounding glutamatergic synapses, which is associated with faster clearance of synaptically-released glutamate from the extracellular space. This effect can be recapitulated using realistic 3D Monte Carlo reaction-diffusion simulations, based on axial scanning transmission electron microscopy (STEM) tomography reconstructions of excitatory synapses. The faster glutamate clearance induced by PAR1 activation leads to short- and long-term changes in excitatory synaptic transmission. Together, these findings identify PAR1 as an important regulator of glutamatergic signaling in the hippocampus and a possible target molecule to limit brain damage during hemorrhagic stroke. PMID:28256580

  16. Temperature dependence of rapidly adapting mechanically activated currents in rat dorsal root ganglion neurons.

    PubMed

    Jia, Zhanfeng; Ling, Jennifer; Gu, Jianguo G

    2012-08-01

    Rapidly adapting mechanically activated channels (RA) are expressed on somatosensory neurons and thought to play a role in mechanical transduction. Because mechanical sensations can be significantly affected by temperatures, we examined thermal sensitivity of RA currents in cultured dorsal root ganglion (DRG) neurons to see if RA channel activity is highly temperature-dependent. RA currents were evoked from DRG neurons by membrane displacements and recorded by the whole-cell patch-clamp recording technique. We found that RA currents were significantly enhanced by warming temperatures from 22 to 32 °C and reduced by cooling temperatures from 24 to 14 °C. RA channel activation exhibited steep temperature-dependence with a large temperature coefficient (Q10>5) and a high activation energy (Ea>30 kcal/mol). We further showed that RA channel activation by mechanical stimulation led to membrane depolarization, which could result in action potential firing at 22 °C or 32 °C but not at 14 °C. Taken together, our results provide the measurements of thermal dynamics and activation energy of RA channels, and suggest that a high energy barrier is present for RA channels to open. These findings are in agreement with temperature sensitivity of mechanical sensations in mammals.

  17. Balance recovery is compromised and trunk muscle activity is increased in chronic obstructive pulmonary disease.

    PubMed

    Smith, Michelle D; Chang, Angela T; Hodges, Paul W

    2016-01-01

    Increased respiration in chronic obstructive pulmonary disease (COPD) requires greater abdominal muscle activation, which may impact on contribution of the trunk to postural control. This study aimed to determine whether recovery of balance from postural perturbations and trunk muscle activity differs in people with and without COPD before and/or after exercise. Electromyography (EMG) of the obliquus internus (OI) and externus (OE) abdominis, rectus abdominis (RA), erector spinae (ES) and deltoid muscles was recorded with surface electrodes during rapid shoulder flexion and extension. Time taken to regain baseline centre of pressure velocity (vCOP) and the number of postural adjustments following arm movement was calculated from force plate data. Time to recover balance in the direction of postural disturbance (anteroposterior vCOP) was longer in COPD, particularly more severe COPD, than controls. Mediolateral vCOP (perpendicular to the perturbation) and the number of postural adjustments did not differ between groups, but people with more severe COPD were less successful at returning their mediolateral vCOP to baseline. Abdominal muscle EMG was similar between groups, but controls had greater ES EMG during arm movements. Individuals with more severe COPD had greater OE and RA EMG both before and during arm movement compared to those with less severe COPD and controls. Following exercise, OE and ES EMG increased in people with less severe COPD. This study shows that severe COPD is associated with impaired ability to recover balance and greater trunk muscle activity during postural challenges. Augmented trunk muscle activity may limit the contribution of trunk movements to balance recovery and could contribute to increased falls risk.

  18. Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

    PubMed

    Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

    2013-01-01

    Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

  19. Rapid and enhanced activation of microporous coordination polymers by flowing supercritical CO.sub.2

    DOEpatents

    Matzger, Adam J.; Liu, Baojian; Wong-Foy, Antek G.

    2016-07-19

    Flowing supercritical CO.sub.2 is used to activate metal organic framework materials (MOF). MOFs are activated directly from N,N-dimethylformamide (DMF) thus avoiding exchange with a volatile solvent. Most MCPs display increased surface areas directly after treatment although those with coordinatively unsaturated metal centers benefit from additional heating.

  20. Density increase due to active feedback in mirror machine

    NASA Astrophysics Data System (ADS)

    Seemann, Omri; Be'Ery, Ilan

    2014-10-01

    Mirror machines are one of the schemes for future fusion systems. Its main drawbacks are the flute instability and being open ended which results in plasma losses. A feedback system is used to stabilize the flute instability in a table top mirror machine with a continuous plasma source and RF heating. Under certain source density and temperature conditions, although the plasma was stabilized, plasma density increase was not measured. After decreasing the source density and increasing the temperature, Plasma density increase was achieved. It is theorized that these results are due to transition of the plasma main loss mechanism from collision dominated to instability dominated. In the former, the main density loss is through diffusion and In the latter, it is through flute instability which drives the plasma to the edge of the vacuum chamber. Future research directions are discussed for a planned machine which should achieve higher temperatures and better diagnostic capabilities. The research will focus on magnetic actuators and passive RF stabilization.

  1. Can turbidity caused by Corophium volutator (Pallas) activity be used to assess sediment toxicity rapidly?

    PubMed

    Briggs, Andrew D; Greenwood, Naomi; Grant, Alastair

    2003-04-01

    The standard toxicity test organism, Corophium volutator, exhibits a behavioural response to contaminated sediments that causes increased turbidity of overlying water. We quantify the effects of this response to an estuarine sediment spiked with copper and hydrocarbon contaminated sediments from an oil installation in the North Sea. Turbidity measured 24 h after the start of a toxicity test shows a strong relationship with contaminant concentrations and with mortality after 10 days. Turbidity measurements can therefore give a rapid indication of sediment toxicity, permitting a reduction in storage time of sediments to be used in dilution series and toxicity identification evaluation (TIE) tests, reducing the likelihood of contaminants degrading prior to testing.

  2. Rapid Temporal Dynamics of Transcription, Protein Synthesis, and Secretion during Macrophage Activation*

    PubMed Central

    Eichelbaum, Katrin; Krijgsveld, Jeroen

    2014-01-01

    Macrophages provide the first line of host defense with their capacity to react to an array of cytokines and bacterial components requiring tight regulation of protein expression and secretion to invoke a properly tuned innate immune response. To capture the dynamics of this system, we introduce a novel method combining pulsed stable isotope labeling with amino acids in cell culture (SILAC) with pulse labeling using the methionine analog azidohomoalanine that allows the enrichment of newly synthesized proteins via click-chemistry followed by their identification and quantification by mass spectrometry. We show that this permits the analysis of proteome changes on a rapid time scale, as evidenced by the detection of 4852 newly synthesized proteins after only a 20-min SILAC pulse. We have applied this methodology to study proteome response during macrophage activation in a time-course manner. We have combined this with full proteome, transcriptome, and secretome analyses, producing an integrative analysis of the first 3 h of lipopolysaccharide-induced macrophage activation. We observed the rapid induction of multiple processes well known to TLR4 signaling, as well as anti-inflammatory proteins and proteins not previously associated with immune response. By correlating transcriptional, translational, and secretory events, we derived novel mechanistic principles of processes specifically induced by lipopolysaccharides, including ectodomain shedding and proteolytic processing of transmembrane and extracellular proteins and protein secretion independent of transcription. In conclusion, we demonstrate that the combination of pulsed azidohomoalanine and pulsed SILAC permits the detailed characterization of proteomic events on a rapid time scale. We anticipate that this approach will be very useful in probing the immediate effects of cellular stimuli and will provide mechanistic insight into cellular perturbation in multiple biological systems. The data have been deposited

  3. Rapid in situ assessment of physiological activities in bacterial biofilms using fluorescent probes

    NASA Technical Reports Server (NTRS)

    Yu, F. P.; McFeters, G. A.

    1994-01-01

    Two rapid in situ enumeration methods using fluorescent probes were used to assess the physiological activities of Klebsiella pneumoniae biofilms on stainless steel. Fluorescent dyes, 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and rhodamine 123 (Rh 123), were chosen to perform this study. CTC is a soluble redox indicator which can be reduced by respiring bacteria to fluorescent CTC-formazan crystals. Rh 123 is incorporated into bacteria with respect to cellular proton motive force. The intracellular accumulation of these fluorescent dyes can be determined using epifluorescence microscopy. The results obtained with these two fluorescent probes in situ were compared to the plate count (PC) and in situ direct viable count (DVC) methods. Viable cell densities within biofilms determined by the three in situ methods were comparable and always showed approximately 2-fold higher values than those obtained with the PC method. As an additional advantage, the results were observed after 2 h, which was shorter than the 4 h incubation time required for the DVC method and 24 h for colony formation. The results indicate that staining with CTC and Rh 123 provides rapid information regarding cell numbers and physiological activities of bacteria within biofilms.

  4. Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry

    SciTech Connect

    Stiles, Katie M.; Krummenacher, Claude

    2010-03-30

    Entry of herpes simplex virus (HSV) occurs either by fusion at the plasma membrane or by endocytosis and fusion with an endosome. Binding of glycoprotein D (gD) to a receptor such as nectin-1 is essential in both cases. We show that virion gD triggered the rapid down-regulation of nectin-1 with kinetics similar to those of virus entry. In contrast, nectin-1 was not constitutively recycled from the surface of uninfected cells. Both the nectin-1alpha and beta isoforms were internalized in response to gD despite having different cytoplasmic tails. However, deletion of the nectin-1 cytoplasmic tail slowed down-regulation of nectin-1 and internalization of virions. These data suggest that nectin-1 interaction with a cytoplasmic protein is not required for its down-regulation. Overall, this study shows that gD binding actively induces the rapid internalization of various forms of nectin-1. We suggest that HSV activates a nectin-1 internalization pathway to use for endocytic entry.

  5. A rapid test for chitinase activity that uses 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide.

    PubMed Central

    O'Brien, M; Colwell, R R

    1987-01-01

    A total of 101 strains of bacteria from environmental and clinical sources, most of which were gram negative, were tested for chitobiase activity by using a filter paper spot test with 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide as the substrate. The results were compared with those obtained by a conventional plate method for chitinase activity by using colloidal chitin as the substrate. There was excellent agreement in the results for both methods. The filter paper spot test with 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide has the advantages of being rapid, simple to perform, and inexpensive. This method should be adaptable to a wider range of microorganisms, particularly those with unusual growth requirements. PMID:3662513

  6. Rapid, parallel path planning by propagating wavefronts of spiking neural activity.

    PubMed

    Ponulak, Filip; Hopfield, John J

    2013-01-01

    Efficient path planning and navigation is critical for animals, robotics, logistics and transportation. We study a model in which spatial navigation problems can rapidly be solved in the brain by parallel mental exploration of alternative routes using propagating waves of neural activity. A wave of spiking activity propagates through a hippocampus-like network, altering the synaptic connectivity. The resulting vector field of synaptic change then guides a simulated animal to the appropriate selected target locations. We demonstrate that the navigation problem can be solved using realistic, local synaptic plasticity rules during a single passage of a wavefront. Our model can find optimal solutions for competing possible targets or learn and navigate in multiple environments. The model provides a hypothesis on the possible computational mechanisms for optimal path planning in the brain, at the same time it is useful for neuromorphic implementations, where the parallelism of information processing proposed here can fully be harnessed in hardware.

  7. Rapid, parallel path planning by propagating wavefronts of spiking neural activity

    PubMed Central

    Ponulak, Filip; Hopfield, John J.

    2013-01-01

    Efficient path planning and navigation is critical for animals, robotics, logistics and transportation. We study a model in which spatial navigation problems can rapidly be solved in the brain by parallel mental exploration of alternative routes using propagating waves of neural activity. A wave of spiking activity propagates through a hippocampus-like network, altering the synaptic connectivity. The resulting vector field of synaptic change then guides a simulated animal to the appropriate selected target locations. We demonstrate that the navigation problem can be solved using realistic, local synaptic plasticity rules during a single passage of a wavefront. Our model can find optimal solutions for competing possible targets or learn and navigate in multiple environments. The model provides a hypothesis on the possible computational mechanisms for optimal path planning in the brain, at the same time it is useful for neuromorphic implementations, where the parallelism of information processing proposed here can fully be harnessed in hardware. PMID:23882213

  8. Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes

    PubMed Central

    Uwechue, Nneka M; Marx, Mari-Carmen; Chevy, Quentin; Billups, Brian

    2012-01-01

    Stimulation of astrocytes by neuronal activity and the subsequent release of neuromodulators is thought to be an important regulator of synaptic communication. In this study we show that astrocytes juxtaposed to the glutamatergic calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB) are stimulated by the activation of glutamate transporters and consequently release glutamine on a very rapid timescale. MNTB principal neurones express electrogenic system A glutamine transporters, and were exploited as glutamine sensors in this study. By simultaneous whole-cell voltage clamping astrocytes and neighbouring MNTB neurones in brainstem slices, we show that application of the excitatory amino acid transporter (EAAT) substrate d-aspartate stimulates astrocytes to rapidly release glutamine, which is detected by nearby MNTB neurones. This release is significantly reduced by the toxins l-methionine sulfoximine and fluoroacetate, which reduce glutamine concentrations specifically in glial cells. Similarly, glutamine release was also inhibited by localised inactivation of EAATs in individual astrocytes, using internal dl-threo-β-benzyloxyaspartic acid (TBOA) or dissipating the driving force by modifying the patch-pipette solution. These results demonstrate that astrocytes adjacent to glutamatergic synapses can release glutamine in a temporally precise, controlled manner in response to glial glutamate transporter activation. Since glutamine can be used by neurones as a precursor for glutamate and GABA synthesis, this represents a potential feedback mechanism by which astrocytes can respond to synaptic activation and react in a way that sustains or enhances further communication. This would therefore represent an additional manifestation of the tripartite relationship between synapses and astrocytes. PMID:22411007

  9. A model for the rapid evaluation of active magnetic shielding designs

    NASA Astrophysics Data System (ADS)

    Washburn, Scott Allen

    The use of active magnetic radiation shielding designs has the potential to reduce the radiation exposure received by astronauts on deep-space missions at a significantly lower mass penalty than designs that utilize only passive shielding. One of the common techniques for assessing the effectiveness of active or passive shielding designs is the use of Monte Carlo analysis to determine crew radiation exposure. Unfortunately, Monte Carlo analysis is a lengthy and computationally intensive process, and the associated time requirements to generate results make a broad analysis of the active magnetic shield design trade space impractical using this method. The ability to conduct a broad analysis of system design variables would allow the selection of configurations suited to specific mission goals, including mission radiation exposure limits, duration, and destination. Therefore, a rapid analysis method is required in order to effectively assess active shielding design parameters, and this body of work was developed in order to address this need. Any shielding analysis should also use complete representations of the radiation environment and detailed transport analyses to account for secondary particle production mechanisms. This body of work addresses both of these issues by utilizing the full Galactic Cosmic Radiation GCR flux spectrum and a detailed transport analysis to account for secondary particle effects due to mass interactions. Additionally, there is a complex relationship between the size and strength of an active shielding design and the amount and type of mass required to create it. This mass can significantly impact the resulting flux and radiation exposures inside the active shield, and any shielding analysis should not only include passive mass, but should attempt to provide a reasonable estimate of the actual mass associated with a given design. Therefore, a survey of active shielding systems is presented so that reasonable mass quantity and composition

  10. Rapid regulation of sialidase activity in response to neural activity and sialic acid removal during memory processing in rat hippocampus.

    PubMed

    Minami, Akira; Meguro, Yuko; Ishibashi, Sayaka; Ishii, Ami; Shiratori, Mako; Sai, Saki; Horii, Yuuki; Shimizu, Hirotaka; Fukumoto, Hokuto; Shimba, Sumika; Taguchi, Risa; Takahashi, Tadanobu; Otsubo, Tadamune; Ikeda, Kiyoshi; Suzuki, Takashi

    2017-04-07

    Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based sialic acid derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for sialic acid removal on the extracellular cell surface during neural excitation, the extracellular free sialic acid level in the hippocampus was monitored using in vivo microdialysis. The free sialic acid level was increased by high-K(+)-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing.

  11. Mice Expressing Activated PI3K Rapidly Develop Advanced Colon Cancer

    PubMed Central

    Leystra, Alyssa A.; Deming, Dustin A.; Zahm, Christopher D.; Farhoud, Mohammed; Paul Olson, Terrah J.; Hadac, Jamie N.; Nettekoven, Laura A.; Albrecht, Dawn M.; Clipson, Linda; Sullivan, Ruth; Washington, Mary Kay; Torrealba, Jose R.; Weichert, Jamey P.; Halberg, Richard B.

    2012-01-01

    Aberrations in the phosphatidylinositide-3-kinase (PI3K) signaling pathway play a key role in the pathogenesis of numerous cancers by altering cellular growth, metabolism, proliferation, and apoptosis (1). Mutations in the catalytic domain of PI3K that generate a dominantly active kinase are commonly found in human colorectal cancers and have been thought to drive tumor progression, but not initiation (2). However, the effects of constitutively activated PI3K upon the intestinal mucosa have not been previously studied in animal models. Here, we demonstrate that the expression of a dominantly active form of the PI3K protein in the mouse intestine results in hyperplasia and advanced neoplasia. Mice expressing constitutively active PI3K in the epithelial cells of the distal small bowel and colon rapidly developed invasive adenocarcinomas in the colon that spread into the mesentery and adjacent organs. The histological characteristics of these tumors were strikingly similar to invasive mucinous colon cancers in humans. Interestingly, these tumors formed without a benign polypoid intermediary, consistent with the lack of aberrant WNT signaling observed. Together, our findings indicate a non-canonical mechanism of colon tumor initiation that is mediated through activation of PI3K. This unique model has the potential to further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification. PMID:22525701

  12. Rapid and quantitative measuring of telomerase activity using an electrochemiluminescent sensor

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaoming; Xing, Da; Zhu, Debin; Jia, Li

    2007-11-01

    Telomerase, a ribonucleoprotein enzyme that adds telomeric repeats to the 3'end of chromosomal DNA for maintaining chromosomal integrity and stability. This strong association of telomerase activity with tumors establishing it is the most widespread cancer marker. A number of assays based on the polymerase chain reaction (PCR) have been developed for the evaluation of telomerase activity. However, those methods require gel electrophoresis and some staining procedures. We developed an electrochemiluminescent (ECL) sensor for the measuring of telomerase activity to overcome these problems such as troublesome post-PCR procedures and semi-quantitative assessment in the conventional method. In this assay 5'-biotinylated telomerase synthesis (TS) primer serve as the substrate for the extension of telomeric repeats under telomerase. The extension products were amplified with this TS primer and a tris-(2'2'-bipyridyl) ruthenium (TBR)-labeled reversed primer. The amplified products was separated and enriched in the surface of electrode by streptavidin-coated magnetic beads, and detected by measuring the ECL signals of the TBR labeled. Measuring telomerase activity use the sensor is easy, sensitive, rapid, and applicable to quantitative analysis, should be clinically useful for the detection and monitoring of telomerase activity.

  13. Dexamethasone rapidly suppresses IL-33-stimulated mast cell function by blocking transcription factor activity.

    PubMed

    Paranjape, Anuya; Chernushevich, Oksana; Qayum, Amina Abdul; Spence, Andrew J; Taruselli, Marcela T; Abebayehu, Daniel; Barnstein, Brian O; McLeod, Jamie Josephine Avila; Baker, Bianca; Bajaj, Gurjas S; Chumanevich, Alena P; Oskeritzian, Carole A; Ryan, John J

    2016-12-01

    Mast cells are critical effectors of allergic disease and can be activated by IL-33, a proinflammatory member of the IL-1 cytokine family. IL-33 worsens the pathology of mast cell-mediated diseases, but therapies to antagonize IL-33 are still forthcoming. Because steroids are the mainstay of allergic disease treatment and are well known to suppress mast cell activation by other stimuli, we examined the effects of the steroid dexamethasone on IL-33-mediated mast cell function. We found that dexamethasone potently and rapidly suppressed cytokine production elicited by IL-33 from murine bone marrow-derived and peritoneal mast cells. IL-33 enhances IgE-mediated mast cell cytokine production, an activity that was also antagonized by dexamethasone. These effects were consistent in human mast cells. We additionally observed that IL-33 augmented migration of IgE-sensitized mast cells toward antigen. This enhancing effect was similarly reversed by dexamethasone. Simultaneous addition of dexamethasone with IL-33 had no effect on the phosphorylation of MAP kinases or NFκB p65 subunit; however, dexamethasone antagonized AP-1- and NFκB-mediated transcriptional activity. Intraperitoneal administration of dexamethasone completely abrogated IL-33-mediated peritoneal neutrophil recruitment and prevented plasma IL-6 elevation. These data demonstrate that steroid therapy may be an effective means of antagonizing the effects of IL-33 on mast cells in vitro and in vivo, acting partly by suppressing IL-33-induced NFκB and AP-1 activity.

  14. Hemorrhage induces rapid in vivo activation of CREB and NF-kappaB in murine intraparenchymal lung mononuclear cells.

    PubMed

    Shenkar, R; Abraham, E

    1997-02-01

    Increased expression of proinflammatory cytokines appears to be an important factor contributing to the development of acute lung injury. In murine models, mRNA levels of proinflammatory and immunoregulatory cytokines, including IL-1alpha, IL-1beta, TGF-beta1, and TNF-alpha, are increased in intraparenchymal lung mononuclear cells 1 h after hemorrhage. Binding elements for the nuclear transcriptional regulatory factors, nuclear factor kappaB (NF-kappaB), CCAAT/enhancer binding protein beta (C/EBPbeta), serum protein 1 (Sp1), activator protein 1 (AP-1), and the cyclic AMP response-element binding protein (CREB) are present in the promoter regions of numerous cytokine genes, including those whose expression is increased after blood loss. To investigate early transcriptional mechanisms which may be involved in regulating pulmonary cytokine expression after hemorrhage, we examined in vivo activation of these five nuclear transcriptional factors among intraparenchymal lung mononuclear cells obtained in the immediate post-hemorrhage period. Activation of NF-kappaB and CREB, but not C/EBPbeta, Sp1, or AP-1, was present in lung mononuclear cells isolated from mice 15 min after hemorrhage. Inhibition of xanthine oxidase by prior feeding with either an allopurinol-supplemented or a tungsten-enriched diet prevented hemorrhage-induced activation of CREB, but not NF-kappaB. These results demonstrate that hemorrhage leads to rapid in vivo activation in the lung of CREB through a xanthine oxidase-dependent mechanism and of NF-kappaB through other pathways, and suggest that the activation of these transcriptional factors may have an important role in regulating pulmonary cytokine expression and the development of acute lung injury after blood loss.

  15. Active commuting to school in Finland, the potential for physical activity increase in different seasons

    PubMed Central

    Kallio, Jouni; Turpeinen, Salla; Hakonen, Harto; Tammelin, Tuija

    2016-01-01

    Background Active commuting to school (ACS) can be a significant source of physical activity and provide many health benefits. Objective This study identified the potential to increase physical activity levels by promoting ACS in Finnish schools and evaluated the effects of season, distance and age on ACS. Design Data were collected with a questionnaire from 5,107 students, aged 10–16, in 45 comprehensive schools in Finland. The distance and the mode of transport to school in different seasons were self-reported. Results The prevalence of ACS was over 80% during spring/fall for those living 0–5 km from school. ACS was inversely associated with the distance to school and was lower in winter compared to spring and fall. Cycling is less common in winter, especially among girls and younger students. The potential for increasing students’ physical activity levels via ACS seems to be largest in winter, especially among students living 1–5 km from school. The variation in the prevalence of ACS between schools was large, especially in winter. Conclusions When planning interventions to promote ACS, one is encouraged to acknowledge and evaluate the potential in the selected target schools in different seasons. The potential varies largely between schools and seasons and is highly dependent on students’ commuting distances. PMID:27924739

  16. Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications

    PubMed Central

    Sjogren, M; Folkesson, S; Blennow, K; Tarkowski, E

    2004-01-01

    Objective: Immunological mechanisms may be part of the pathophysiological mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of such mechanisms has been presented. The aim of this study was to compare the cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, and the anti-inflammatory cytokine transforming growth factor (TGF)-ß in patients with FTD and normal controls. Furthermore, serum levels of TNF-α, TGF-ß, and IL-1ß were measured in FTD patients. Methods: The CSF levels of IL-1ß, TNFα, and TGF-ß were measured using ELISA in 19 patients with FTD and 24 sex and age matched healthy controls. Results: The CSF levels of TNF-α (FTD 0.6 pg/mL (median: lower, upper quartile 0.3, 0.7); controls: 0.0 pg/mL (0.0, 0.0); p = 0.008) and TGF-ß (FTD 266 pg/mL (157, 371), controls: 147 pg/mL (119, 156); p = 0.0001) were significantly increased in FTD patients compared with controls. No correlations were found between CSF and serum levels of the cytokines. In the controls, but not in the FTD patients, a positive correlation was found between the CSF levels of TGF-ß and age (r = 0.42, p<0.05). No correlation was found between any of the cytokines and degree of brain atrophy or white matter changes. No differences between the groups were found for age, gender, or CSF/serum albumin ratio. Conclusions: The results suggest an increased intrathecal production of both pro- and anti-inflammatory cytokines in FTD. As no correlations were found with the albumin ratio, and no correlations between CSF and serum levels of the cytokines were found, these changes in the CSF cannot be explained by a systemic overproduction of cytokines. PMID:15258209

  17. Role of membrane depolarization and extracellular calcium in increased complement receptor expression during neutrophil (PMN) activation

    SciTech Connect

    Berger, M.; Wetzler, E.; Birx, D.L.

    1986-03-05

    During PMN activation the surface expression of receptors (R) for C3b and C3bi increases rapidly. This is necessary for optimal cell adhesion, migration, and phagocytosis. Following stimulation with fMLP or LTB-4, the increased expression of C3bR depends only on the Ca/sup + +/ released from intracellular stores and is not inhibited by 5mM EDTA, while the increase in C3biR also requires extracellular Ca/sup + +/. CR expression also increases when the PMN are depolarized with 140 mM K/sup +/, but with this stimulus, EDTA inhibits C3bR by 67% and C3biR 100%, suggesting that intracellular Ca/sup + +/ stores may not be released. Pertussis toxin caused dose-dependent inhibition of both CR responses to fMLP and also inhibited the increases in both CR induced by K/sup +/. Membrane depolarization (monitored by di-O-C5 fluorescence) due to fMLP was similarly inhibited by toxin but the depolarization due to K/sup +/ was not. The dose of phorbol myristate acetate that maximally increased CR expression, 0.1 ng/ml, did not depolarize the membrane. These results suggest that membrane depolarization is neither necessary nor sufficient for increased CR expression. A Ca/sup + +/ and GTP binding protein-dependent enzyme such as phospholipase C is necessary to the amplify initial signals generated either by release of Ca/sup + +/ stores or by opening voltage dependent Ca/sup + +/ channels following membrane depolarization.

  18. A decrease in S-adenosylmethionine synthetase activity increases the probability of spontaneous sporulation.

    PubMed Central

    Ochi, K; Freese, E

    1982-01-01

    Starting with a relaxed (relA) strain, mutants with reduced activity of adenosine triphosphate:L-methionine S-adenosyl transferase (EC 2.5.1.6; SAM synthetase) were isolated in Bacillus subtilis. One such mutant (gene symbol metE1) had only 3% of the normal SAM synthetase activity but grew almost as well as the parent strain. Another mutant was isolated (gene symbol spdC1) as being able to sporulate continually at a high frequency; it had one-half the normal SAM synthetase activity at 33 degrees C. Both mutants continually and spontaneously entered spore development at a higher frequency than the parent strain in a medium containing excess glucose, ammonium ions, and phosphate. Sporulation was prevented by a high concentration of SAM (1 mM or more) or by the combination of adenosine and methionine (0.5 mM or more each), both of which are precursors of SAM. In contrast to this continual increase in the spore titer, addition of decoyinine, an inhibitor of GMP synthetase, rapidly initiated massive sporulation. Various amino acid analogs also induced sporulation in the relA strain, the methionine analogs ethionine and selenomethionine being most effective. PMID:6811558

  19. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity.

    PubMed

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-02-23

    The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer-methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  20. Rapid increase in total torquetenovirus (TTV) plasma viremia load reveals an apparently transient superinfection by a TTV of a novel group 2 genotype.

    PubMed

    Maggi, Fabrizio; Andreoli, Elisabetta; Lanini, Letizia; Meschi, Silvia; Rocchi, Jara; Fornai, Claudia; Vatteroni, Maria Linda; Pistello, Mauro; Bendinelli, Mauro

    2006-07-01

    An apparently transient infection by a superimposed torquetenovirus (TTV) in a subject who already carried three different genotypes of the virus is described. The superinfection induced a rapid increase in the plasma TTV load and a decline in immunocomplexed virus. The superinfecting TTV was a novel group 2 genotype.

  1. Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate.

    PubMed

    Waung, Maggie W; Pfeiffer, Brad E; Nosyreva, Elena D; Ronesi, Jennifer A; Huber, Kimberly M

    2008-07-10

    Salient stimuli that modify behavior induce transcription of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and transport Arc mRNA into dendrites, suggesting that local Arc translation mediates synaptic plasticity that encodes such stimuli. Here, we demonstrate that long-term synaptic depression (LTD) in hippocampal neurons induced by group 1 metabotropic glutamate receptors (mGluRs) relies on rapid translation of Arc. mGluR-LTD induction causes long-term increases in AMPA receptor endocytosis rate and dendritic synthesis of Arc, a component of the AMPAR endocytosis machinery. Knockdown of Arc prevents mGluRs from triggering AMPAR endocytosis or LTD, and acute blockade of new Arc synthesis with antisense oligonucleotides blocks mGluR-LTD and AMPAR trafficking. In contrast, LTD induced by NMDA receptors does not persistently alter AMPAR endocytosis rate, induce Arc synthesis, or require Arc protein. These data demonstrate a role for local Arc synthesis specifically in mGluR-LTD and suggest that mGluR-LTD may be one consequence of Arc mRNA induction during experience.

  2. An ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na(+)-Activated K(+) Channels in Aplysia Neurons.

    PubMed

    Zhang, Yalan; Ni, Weiming; Horwich, Arthur L; Kaczmarek, Leonard K

    2017-02-22

    Mutations that alter levels of Slack (KCNT1) Na(+)-activated K(+) current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica, a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp. In contrast, outward potassium currents were significantly reduced by microinjection of mutant G85R SOD1YFP that had been preincubated at 37°C or of cross-linked dimers of G85R SOD1YFP. Reduction of potassium current was also seen with multimeric G85R SOD1YFP of ∼300 kDa or >300 kDa that had been cross-linked. In current clamp recordings, microinjection of cross-linked 300 kDa increased excitability by depolarizing the resting membrane potential, and decreasing the latency of action potentials triggered by depolarization. The effect of cross-linked 300 kDa on potassium current was reduced by removing Na(+) from the bath solution, or by knocking down levels of Slack using siRNA. It was also prevented by pharmacological inhibition of ASK1 (apoptosis signal-regulating kinase 1) or of c-Jun N-terminal kinase, but not by an inhibitor of p38 mitogen-activated protein kinase. These results suggest that soluble mutant SOD1 oligomers rapidly trigger a kinase pathway that regulates the activity of Na(+)-activated K(+) channels in neurons.SIGNIFICANCE STATEMENT Slack Na(+)-activated K(+) channels (KCNT1, KNa1.1) regulate neuronal excitability but are also linked to cytoplasmic signaling pathways that control neuronal protein translation. Mutations that alter the amplitude of these currents have devastating effects on neuronal

  3. Noradrenergic modulation of masseter muscle activity during natural rapid eye movement sleep requires glutamatergic signalling at the trigeminal motor nucleus.

    PubMed

    Schwarz, Peter B; Mir, Saba; Peever, John H

    2014-08-15

    Noradrenergic neurotransmission in the brainstem is closely coupled to changes in muscle activity across the sleep-wake cycle, and noradrenaline is considered to be a key excitatory neuromodulator that reinforces the arousal-related stimulus on motoneurons to drive movement. However, it is unknown if α-1 noradrenoceptor activation increases motoneuron responsiveness to excitatory glutamate (AMPA) receptor-mediated inputs during natural behaviour. We studied the effects of noradrenaline on AMPA receptor-mediated motor activity at the motoneuron level in freely behaving rats, particularly during rapid eye movement (REM) sleep, a period during which both AMPA receptor-triggered muscle twitches and periods of muscle quiescence in which AMPA drive is silent are exhibited. Male rats were subjected to electromyography and electroencephalography recording to monitor sleep and waking behaviour. The implantation of a cannula into the trigeminal motor nucleus of the brainstem allowed us to perfuse noradrenergic and glutamatergic drugs by reverse microdialysis, and thus to use masseter muscle activity as an index of motoneuronal output. We found that endogenous excitation of both α-1 noradrenoceptor and AMPA receptors during waking are coupled to motor activity; however, REM sleep exhibits an absence of endogenous α-1 noradrenoceptor activity. Importantly, exogenous α-1 noradrenoceptor stimulation cannot reverse the muscle twitch suppression induced by AMPA receptor blockade and nor can it elevate muscle activity during quiet REM, a phase when endogenous AMPA receptor activity is subthreshold. We conclude that the presence of an endogenous glutamatergic drive is necessary for noradrenaline to trigger muscle activity at the level of the motoneuron in an animal behaving naturally.

  4. The RCN1-encoded A subunit of protein phosphatase 2A increases phosphatase activity in vivo

    NASA Technical Reports Server (NTRS)

    Deruere, J.; Jackson, K.; Garbers, C.; Soll, D.; Delong, A.; Evans, M. L. (Principal Investigator)

    1999-01-01

    Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic C subunit and two distinct regulatory subunits, A and B. The RCN1 gene encodes one of three A regulatory subunits in Arabidopsis thaliana. A T-DNA insertion mutation at this locus impairs root curling, seedling organ elongation and apical hypocotyl hook formation. We have used in vivo and in vitro assays to gauge the impact of the rcn1 mutation on PP2A activity in seedlings. PP2A activity is decreased in extracts from rcn1 mutant seedlings, and this decrease is not due to a reduction in catalytic subunit expression. Roots of mutant seedlings exhibit increased sensitivity to the phosphatase inhibitors okadaic acid and cantharidin in organ elongation assays. Shoots of dark-grown, but not light-grown seedlings also show increased inhibitor sensitivity. Furthermore, cantharidin treatment of wild-type seedlings mimics the rcn1 defect in root curling, root waving and hypocotyl hook formation assays. In roots of wild-type seedlings, RCN1 mRNA is expressed at high levels in root tips, and accumulates to lower levels in the pericycle and lateral root primordia. In shoots, RCN1 is expressed in the apical hook and the basal, rapidly elongating cells in etiolated hypocotyls, and in the shoot meristem and leaf primordia of light-grown seedlings. Our results show that the wild-type RCN1-encoded A subunit functions as a positive regulator of the PP2A holoenzyme, increasing activity towards substrates involved in organ elongation and differential cell elongation responses such as root curling.

  5. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex

    PubMed Central

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B. H.

    2015-01-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this “reversed” size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys. PMID:25480358

  6. Increased Visual Stimulation Systematically Decreases Activity in Lateral Intermediate Cortex.

    PubMed

    Nasr, Shahin; Stemmann, Heiko; Vanduffel, Wim; Tootell, Roger B H

    2015-10-01

    Previous studies have attributed multiple diverse roles to the posterior superior temporal cortex (STC), both visually driven and cognitive, including part of the default mode network (DMN). Here, we demonstrate a unifying property across this multimodal region. Specifically, the lateral intermediate (LIM) portion of STC showed an unexpected feature: a progressively decreasing fMRI response to increases in visual stimulus size (or number). Such responses are reversed in sign, relative to well-known responses in classic occipital temporal visual cortex. In LIM, this "reversed" size function was present across multiple object categories and retinotopic eccentricities. Moreover, we found a significant interaction between the LIM size function and the distribution of subjects' attention. These findings suggest that LIM serves as a part of the DMN. Further analysis of functional connectivity, plus a meta-analysis of previous fMRI results, suggests that LIM is a heterogeneous area including different subdivisions. Surprisingly, analogous fMRI tests in macaque monkeys did not reveal a clear homolog of LIM. This interspecies discrepancy supports the idea that self-referential thinking and theory of mind are more prominent in humans, compared with monkeys.

  7. Radiometric macrophage culture assay for rapid evaluation of antileprosy activity of rifampin

    SciTech Connect

    Mittal, A.; Seshadri, P.S.; Prasad, H.K.; Sathish, M.; Nath, I.

    1983-10-01

    The antileprosy effect of rifampin was evaluated by a newly developed rapid in vitro assay wherein 31 human-derived strains and 1 armadillo-derived strain of Mycobacterium leprae were maintained for 2 and 3 weeks, respectively, in murine and human macrophages in the presence of (3H)thymidine. Of these strains, 27 showed significant incorporation of the radiolabel in cultures of live bacilli as compared with control cultures of heat-killed bacilli of the same strain. Consistent and significant inhibition of (3H)thymidine uptake was observed in M. leprae resident cultures with 3 to 200 ng of rifampin per ml as compared with similar cultures without the drug. In general, an increase in percent inhibition was seen from 3 to 20 ng/ml, with marginal increases at 40, 50, and 100 ng/ml. M. leprae strains appear to be remarkably susceptible to this drug in the in vitro assay.

  8. Rapid, Specific, No-wash, Far-red Fluorogen Activation in Subcellular Compartments by Targeted Fluorogen Activating Proteins

    PubMed Central

    2015-01-01

    Live cell imaging requires bright photostable dyes that can target intracellular organelles and proteins with high specificity in a no-wash protocol. Organic dyes possess the desired photochemical properties and can be covalently linked to various protein tags. The currently available fluorogenic dyes are in the green/yellow range where there is high cellular autofluorescence and the near-infrared (NIR) dyes need to be washed out. Protein-mediated activation of far-red fluorogenic dyes has the potential to address these challenges because the cell-permeant dye is small and nonfluorescent until bound to its activating protein, and this binding is rapid. In this study, three single chain variable fragment (scFv)-derived fluorogen activating proteins (FAPs), which activate far-red emitting fluorogens, were evaluated for targeting, brightness, and photostability in the cytosol, nucleus, mitochondria, peroxisomes, and endoplasmic reticulum with a cell-permeant malachite green analog in cultured mammalian cells. Efficient labeling was achieved within 20–30 min for each protein upon the addition of nM concentrations of dye, producing a signal that colocalized significantly with a linked mCerulean3 (mCer3) fluorescent protein and organelle specific dyes but showed divergent photostability and brightness properties dependent on the FAP. These FAPs and the ester of malachite green dye (MGe) can be used as specific, rapid, and wash-free labels for intracellular sites in live cells with far-red excitation and emission properties, useful in a variety of multicolor experiments. PMID:25650487

  9. Rapid estimation of activation enthalpies for cytochrome-P450-mediated hydroxylations.

    PubMed

    Mayeno, Arthur N; Robinson, Jonathan L; Reisfeld, Brad

    2011-03-01

    Cytochrome P450 (CYP) enzymes play a critical role in detoxication and bioactivation of xenobiotics; thus, the ability to predict the biotransformation rates and regioselectivity of CYP enzymes toward substrates is an important goal in toxicology and pharmacology. Here, we present the use of the semiempirical quantum chemistry method SAM1 to rapidly estimate relative activation enthalpies (ΔH(‡)) for the hydroxylation of aliphatic carbon centers of various substrates. The ΔH(‡) were determined via a reaction path calculation, in the reverse direction (RRP), using the iron-hydroxo-porphine intermediate and the substrate radical. The SAM1 ΔH(‡) were calculated via unrestricted Hartree-Fock (UHF) and configuration interaction (CI) formalisms for both the doublet and quartet spin states. The SAM1 RRP ΔH(‡), after subtracting a correction factor, were compared with density functional theory (DFT) B3LYP activation energies for two sets of substrates and showed R(2) ranging from 0.69 to 0.89, and mean absolute differences ranging from 1.2 ± 1.0 to 1.7 ± 1.5 kcal/mol. SAM1 UHF and CI RRP calculation times were, on average, more than 200 times faster than those for the corresponding forward reaction path DFT calculations. Certain key transition-state (TS) geometry measurements, such as the forming O···H bond length, showed good correlation with the DFT values. These results suggest that the SAM1 RRP approach can be used to rapidly estimate the DFT activation energy and some key TS geometry measurements and can potentially be applied to estimate substrate hydroxylation rates and regioselectivity by CYP enzymes.

  10. Rapid maxillary expansion causes neuronal activation in brain structures of rats.

    PubMed

    Joviliano, P; Junqueira, A A; Stabile, A C; Leite-Panissi, C R A; Rocha, M J A

    2008-07-01

    A correlation between pain sensation and neuronal c-fos expression has been analyzed following experimental rapid maxillar expansion (RME). Adult male Wistar rats were anaesthetized and divided into three groups: animals that received an orthodontic apparatus, which was immediately removed after the insertion (control), animals that received an inactivated orthodontic apparatus (without force), and animals that received an orthodontic apparatus previously activated (140 g force). After 6, 24, 48, or 72 h, the animals were re-anaesthetized, and perfused with 4% paraformaldehyde. The brains were removed, fixed, and sections containing brain structures related to nociception were processed for Fos protein immunohistochemistry (IHC). The insertion of the orthodontic apparatus with 140 g was able to cause RME that could be seen by radiography. The IHC results showed that the number of activated neurons in the different nuclei changed according to the duration of appliance insertion and followed a temporal pattern similar to that of sensations described in clinics. The animals that received the orthodontic apparatus without force did not show RME but a smaller c-fos expression in the same brain structures. In conclusion, we demonstrate that orthodontic force used for palate disjunction activates brain structures that are related to nociception, and that this activation is related to the pain sensation described during orthodontic treatment.

  11. Effect of surgically assisted rapid maxillary expansion on masticatory muscle activity: A pilot study

    PubMed Central

    Sverzut, Cássio E.; Martorelli, Karinna; Jabur, Roberto; Petri, Alice D.; Trivellato, Alexandre E.; Siéssere, Selma; Regalo, Simone C. H.

    2011-01-01

    Background: The aim of the present study was to analyze the electromyographic (EMG) activity of masseter and temporal muscles of adult patients submitted to surgically assisted rapid maxillary expansion (SARME) before and after the surgery. Materials and Methods: The sample consisted of 19 adults, with ages ranging from 20 to 47 years (mean 25.4 years), with bilateral posterior cross bite requiring SARME treatment. The electromyographic activity of masseter and temporal muscles was analyzed before treatment (T1) and after the surgical procedure (T2). The mean interval between the two electromyographic analyses was 15 days. Results: The muscular active was electromyographically analyzed during the clinical situation of habitual gum chewing (10 sec), dental clenching (4 sec), mouth opening and closing (10 sec), rest (10 sec), protrusion (10 sec), and right and left laterality (10 sec). The measured differences between T1 and T2 data were evaluated using the paired t-test (SPSS 17.0 for Windows). The electromyographic analysis showed that the activity of the masseter and temporal muscles decreased significantly after the SARME in all the clinical situations after the surgery. Conclusion: According to the results of the present study, individuals after SARME surgery presented patterns of electromyographic contraction similar to those developed by dentate individuals during the movements of mandibular excursion. PMID:23482404

  12. A rapidly activating sustained K+ current modulates repolarization and excitation-contraction coupling in adult mouse ventricle.

    PubMed Central

    Fiset, C; Clark, R B; Larsen, T S; Giles, W R

    1997-01-01

    1. The K+ currents which control repolarization in adult mouse ventricle, and the effects of changes in action potential duration on excitation-contraction coupling in this tissue, have been studied with electrophysiological methods using single cell preparations and by recording mechanical parameters from an in vitro working heart preparation. 2. Under conditions where Ca(2+)-dependent currents were eliminated by buffering intracellular Ca2+ with EGTA, depolarizing voltage steps elicited two rapidly activating outward K+ currents: (i) a transient outward current, and (ii) a slowly inactivating or 'sustained' delayed rectifier. 3. These two currents were separated pharmacologically by the K+ channel blocker 4-amino-pyridine (4-AP). 4-AP at concentrations between 3 and 200 microM resulted in (i) a marked increase in action potential duration and a large decrease in the sustained K+ current at plateau potentials, as well as (ii) a significant increase in left ventricular systolic pressure in the working heart preparation. 4. The current-voltage (I-V) relation, kinetics, and block by low concentrations of 4-AP strongly suggest that the rapid delayed rectifier in adult mouse ventricles is the same K+ current (Kv1.5) that has been characterized in detail in human and canine atria. 5. These results show that the 4-AP-sensitive rapid delayed rectifier is a very important repolarizing current in mouse ventricle. The enhanced contractility produced by 4-AP (50 microM) in the working heart preparation demonstrates that modulation of the action potential duration, by blocking a K+ current, is a very significant inotropic variable. PMID:9401964

  13. Rapidly inactivating and non-inactivating calcium-activated potassium currents in frog saccular hair cells

    PubMed Central

    Armstrong, Cecilia E; Roberts, William M

    2001-01-01

    Using a semi-intact epithelial preparation we examined the Ca2+-activated K+ (KCa) currents of frog (Rana pipiens) saccular hair cells. After blocking voltage-dependent K+ (KV) currents with 4-aminopyridine (4-AP) an outward current containing inactivating (Itransient) and non-inactivating (Isteady) components remained.The contribution of each varied greatly from cell to cell, with Itransient contributing from 14 to 90 % of the total outward current. Inactivation of Itransient was rapid (τ≈ 2–3 ms) and occurred within the physiological range of membrane potentials (V1/2=−63 mV). Recovery from inactivation was also rapid (τ≈ 10 ms).Suppression of both Itransient and Isteady by depolarizations that approached the Ca2+ equilibrium potential and by treatments that blocked Ca2+ influx (application Ca2+-free saline or Cd2+), suggest both are Ca2+ dependent. Both were blocked by iberiotoxin, a specific blocker of large-conductance KCa channels (BK), but not by apamin, a specific blocker of small-conductance KCa channels.Ensemble-variance analysis showed that Itransient and Isteady flow through two distinct populations of channels, both of which have a large single-channel conductance (∼100 pS in non-symmetrical conditions). Together, these data indicate that both Itransient and Isteady are carried through BK channels, one of which undergoes rapid inactivation while the other does not.Inactivation of Itransient could be removed by extracellular papain and could later be restored by intracellular application of the ‘ball’ domain of the auxiliary subunit (β2) thought to mediate BK channel inactivation in rat chromaffin cells. We hypothesize that Itransient results from the association of a similar β subunit with some of the BK channels and that papain removes inactivation by cleaving extracellular sites required for this association. PMID:11579156

  14. Forest response to increasing typhoon activity on the Korean peninsula: evidence from oak tree-rings.

    PubMed

    Altman, Jan; Doležal, Jiří; Cerný, Tomáš; Song, Jong-Suk

    2013-02-01

    The globally observed trend of changing intensity of tropical cyclones over the past few decades emphasizes the need for a better understanding of the effects of such disturbance events in natural and inhabited areas. On the Korean Peninsula, typhoon intensity has increased over the past 100 years as evidenced by instrumental data recorded from 1904 until present. We examined how the increase in three weather characteristics (maximum hourly and daily precipitation, and maximum wind speed) during the typhoon activity affected old-growth oak forests. Quercus mongolica is a dominant species in the Korean mountains and the growth releases from 220 individuals from three sites along a latitudinal gradient (33-38°N) of decreasing typhoon activity were studied. Growth releases indicate tree-stand disturbance and improved light conditions for surviving trees. The trends in release events corresponded to spatiotemporal gradients in maximum wind speed and precipitation. A high positive correlation was found between the maximum values of typhoon characteristics and the proportion of trees showing release. A higher proportion of disturbed trees was found in the middle and southern parts of the Korean peninsula where typhoons are most intense. This shows that the releases are associated with typhoons and also indicates the differential impact of typhoons on the forests. Finally, we present a record of the changing proportion of trees showing release based on tree-rings for the period 1770-1979. The reconstruction revealed no trend during the period 1770-1879, while the rate of forest disturbances increased rapidly from 1880 to 1979. Our results suggest that if typhoon intensity rises, as is projected by some climatic models, the number of forest disturbance events will increase thus altering the disturbance regime and ecosystem processes.

  15. Rapid recruitment and activation of macrophages by anti-Gal/α-Gal liposome interaction accelerates wound healing.

    PubMed

    Wigglesworth, Kim M; Racki, Waldemar J; Mishra, Rabinarayan; Szomolanyi-Tsuda, Eva; Greiner, Dale L; Galili, Uri

    2011-04-01

    Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galα1-3Galβ1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ∼1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95-100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.

  16. Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells.

    PubMed

    Lushnikova, Irina; Skibo, Galina; Muller, Dominique; Nikonenko, Irina

    2011-04-01

    Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic inhibitory inputs triggered by a brief oxygen-glucose deprivation (OGD) episode, a condition associated with a synaptic enhancement referred to as anoxic LTP and a structural remodeling of excitatory synapses. Three-dimensional reconstruction of inhibitory axo-somatic synapses at different times before and after brief OGD revealed important morphological changes. The PSD area significantly and markedly increased at synapses with large and complex PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of PSD size and presynaptic bouton volume developed in a strongly correlated manner. Analyses of single and serial sections further showed that the density of inhibitory synaptic contacts on the cell soma did not change within 1 h after OGD. In contrast, the proportion of the cell surface covered with inhibitory PSDs, as well as the complexity of these PSDs significantly increased, with less macular PSDs and more complex, segmented shapes. Together, these data reveal a rapid activity-related restructuring of somatic inhibitory synapses characterized by an enlargement and increased complexity of inhibitory PSDs, providing a new mechanism for a quick adjustment of the excitatory-inhibitory balance. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

  17. Rapid monitoring of RNA degradation activity in vivo for mammalian cells.

    PubMed

    Tani, Hidenori; Sato, Hiroaki; Torimura, Masaki

    2017-04-01

    We have developed a rapid fluorescence assay based on fluorescence resonance energy transfer (FRET) for the monitoring of RNA degradation activity in mammalian cells. In this technique, double-stranded RNA (dsRNA) fluorescent probes are used. The dsRNA fluorescent probes consist of a 5' fluorophore-labeled strand hybridized to a 3' quencher-labeled strand, and the fluorescent dye is quenched by a quencher dye. When the dsRNA is degraded by nascent RNases in cells, the fluorescence emission of the fluorophore is induced following the degradation of the double strands. The degradation rates of the dsRNA are decelerated in response to chemical or environmental toxicity; therefore, in the case of cellular toxicity, the dsRNA is not degraded and remains intact, thus quenching the fluorescence. Unlike in conventional cell-counting assays, this new assay eliminates time-consuming steps, and can be used to simply evaluate the cellular toxicity via a single reaction. Our results demonstrate that this assay can rapidly quantify the RNA degradation rates in vivo within 4 h for three model chemicals. We propose that this assay will be useful for monitoring cellular toxicity in high-throughput applications.

  18. Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons

    PubMed Central

    Nörenberg, Anja; Hu, Hua; Vida, Imre; Bartos, Marlene; Jonas, Peter

    2009-01-01

    Fast-spiking, parvalbumin-expressing basket cells (BCs) play a key role in feedforward and feedback inhibition in the hippocampus. However, the dendritic mechanisms underlying rapid interneuron recruitment have remained unclear. To quantitatively address this question, we developed detailed passive cable models of BCs in the dentate gyrus based on dual somatic or somatodendritic recordings and complete morphologic reconstructions. Both specific membrane capacitance and axial resistivity were comparable to those of pyramidal neurons, but the average somatodendritic specific membrane resistance (Rm) was substantially lower in BCs. Furthermore, Rm was markedly nonuniform, being lowest in soma and proximal dendrites, intermediate in distal dendrites, and highest in the axon. Thus, the somatodendritic gradient of Rm was the reverse of that in pyramidal neurons. Further computational analysis revealed that these unique cable properties accelerate the time course of synaptic potentials at the soma in response to fast inputs, while boosting the efficacy of slow distal inputs. These properties will facilitate both rapid phasic and efficient tonic activation of BCs in hippocampal microcircuits. PMID:20080772

  19. Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons.

    PubMed

    Nörenberg, Anja; Hu, Hua; Vida, Imre; Bartos, Marlene; Jonas, Peter

    2010-01-12

    Fast-spiking, parvalbumin-expressing basket cells (BCs) play a key role in feedforward and feedback inhibition in the hippocampus. However, the dendritic mechanisms underlying rapid interneuron recruitment have remained unclear. To quantitatively address this question, we developed detailed passive cable models of BCs in the dentate gyrus based on dual somatic or somatodendritic recordings and complete morphologic reconstructions. Both specific membrane capacitance and axial resistivity were comparable to those of pyramidal neurons, but the average somatodendritic specific membrane resistance (R(m)) was substantially lower in BCs. Furthermore, R(m) was markedly nonuniform, being lowest in soma and proximal dendrites, intermediate in distal dendrites, and highest in the axon. Thus, the somatodendritic gradient of R(m) was the reverse of that in pyramidal neurons. Further computational analysis revealed that these unique cable properties accelerate the time course of synaptic potentials at the soma in response to fast inputs, while boosting the efficacy of slow distal inputs. These properties will facilitate both rapid phasic and efficient tonic activation of BCs in hippocampal microcircuits.

  20. A rapid transcriptional activation is induced by the dormancy-breaking chemical hydrogen cyanamide in kiwifruit (Actinidia deliciosa) buds

    PubMed Central

    Walton, Eric F.; Wu, Rong-Mei; Richardson, Annette C.; Davy, Marcus; Hellens, Roger P.; Thodey, Kate; Janssen, Bart J.; Gleave, Andrew P.; Rae, Georgina M.; Wood, Marion; Schaffer, Robert J.

    2009-01-01

    Budbreak in kiwifruit (Actinidia deliciosa) can be poor in locations that have warm winters with insufficient winter chilling. Kiwifruit vines are often treated with the dormancy-breaking chemical hydrogen cyanamide (HC) to increase and synchronize budbreak. This treatment also offers a tool to understand the processes involved in budbreak. A genomics approach is presented here to increase our understanding of budbreak in kiwifruit. Most genes identified following HC application appear to be associated with responses to stress, but a number of genes appear to be associated with the reactivation of growth. Three patterns of gene expression were identified: Profile 1, an HC-induced transient activation; Profile 2, an HC-induced transient activation followed by a growth-related activation; and Profile 3, HC- and growth-repressed. One group of genes that was rapidly up-regulated in response to HC was the glutathione S-transferase (GST) class of genes, which have been associated with stress and signalling. Previous budbreak studies, in three other species, also report up-regulated GST expression. Phylogenetic analysis of these GSTs showed that they clustered into two sub-clades, suggesting a strong correlation between their expression and budbreak across species. PMID:19651683

  1. A rapid transcriptional activation is induced by the dormancy-breaking chemical hydrogen cyanamide in kiwifruit (Actinidia deliciosa) buds.

    PubMed

    Walton, Eric F; Wu, Rong-Mei; Richardson, Annette C; Davy, Marcus; Hellens, Roger P; Thodey, Kate; Janssen, Bart J; Gleave, Andrew P; Rae, Georgina M; Wood, Marion; Schaffer, Robert J

    2009-01-01

    Budbreak in kiwifruit (Actinidia deliciosa) can be poor in locations that have warm winters with insufficient winter chilling. Kiwifruit vines are often treated with the dormancy-breaking chemical hydrogen cyanamide (HC) to increase and synchronize budbreak. This treatment also offers a tool to understand the processes involved in budbreak. A genomics approach is presented here to increase our understanding of budbreak in kiwifruit. Most genes identified following HC application appear to be associated with responses to stress, but a number of genes appear to be associated with the reactivation of growth. Three patterns of gene expression were identified: Profile 1, an HC-induced transient activation; Profile 2, an HC-induced transient activation followed by a growth-related activation; and Profile 3, HC- and growth-repressed. One group of genes that was rapidly up-regulated in response to HC was the glutathione S-transferase (GST) class of genes, which have been associated with stress and signalling. Previous budbreak studies, in three other species, also report up-regulated GST expression. Phylogenetic analysis of these GSTs showed that they clustered into two sub-clades, suggesting a strong correlation between their expression and budbreak across species.

  2. A rapid quantitative assay for the detection of mammalian heparanase activity.

    PubMed Central

    Freeman, C; Parish, C R

    1997-01-01

    Heparan sulphate (HS) is an important component of the extracellular matrix and the vasculature basal laminar which functions as a barrier to the extravasation of metastatic and inflammatory cells. Cleavage of HS by endoglycosidase or heparanase activity produced by invading cells may assist in the disassembly of the extracellular matrix and basal laminar, and thereby facilitate cell migration. Heparanase activity has previously been shown to be related to the metastatic potential of murine and human melanoma cell lines [Nakajima, Irimura and Nicolson (1988) J. Cell. Biochem. 36, 157-167]. To determine heparanase activity, porcine mucosal HS was partially de-N-acetylated and re-N-acetylated with [3H]acetic anhydride to yield a radiolabelled substrate. This procedure prevented the masking of, or possible formation of, new heparanase-sensitive cleavage sites as has been observed with previous methods of radiolabelling. Heparanase activity in a variety of tissues and cell homogenates including human platelets, colonic carcinoma cells, umbilical vein endothelial cells and rat mammary adenocarcinoma cells (both metastatic and non-metastatic variants) and liver homogenates all degraded the substrate in a stepwise fashion from 18.5 to approximately 13, 8 and finally to 4.5 kDa fragments, as assessed by gel-filtration analysis, confirming the substrate as suitable for the detection of heparanase activity present in a variety of cells and tissues. A rapid quantitative assay was developed with the HS substrate using a novel method for separating degradation products from the substrate by taking advantage of the decreased affinity of the heparanase-cleaved products for the HS-binding plasma protein chicken histidine-rich glycoprotein (cHRG). Incubation mixtures were applied to cHRG-Sepharose columns, with unbound material corresponding to heparanase-degradation products. Heparanase activity was determined for a variety of human, rat and murine cell and tissue homogenates. The

  3. Rapid decadal convective precipitation increase over Eurasia during the last three decades of the 20th century

    PubMed Central

    Ye, Hengchun; Fetzer, Eric J.; Wong, Sun; Lambrigtsen, Bjorn H.

    2017-01-01

    Convective precipitation—localized, short-lived, intense, and sometimes violent—is at the root of challenges associated with observation, simulation, and prediction of precipitation. The understanding of long-term changes in convective precipitation characteristics and their role in precipitation extremes and intensity over extratropical regions are imperative to future water resource management; however, they have been studied very little. We show that annual convective precipitation total has been increasing astonishingly fast, at a rate of 18.4%/°C, of which 16% is attributable to an increase in convective precipitation occurrence, and 2.4% is attributable to increased daily intensity based on the 35 years of two (combined) historical data sets of 3-hourly synoptic observations and daily precipitation. We also reveal that annual daily precipitation extreme has been increasing at a rate of about 7.4%/°C in convective events only. Concurrently, the overall increase in mean daily precipitation intensity is mostly due to increased convective precipitation, possibly at the expanse of nonconvective precipitation. As a result, transitional seasons are becoming more summer-like as convective becomes the dominant precipitation type that has accompanied higher daily extremes and intensity since the late 1980s. The data also demonstrate that increasing convective precipitation and daily extremes appear to be directly linearly associated with higher atmospheric water vapor accompanying a warming climate over northern Eurasia. PMID:28138545

  4. Rapid decadal convective precipitation increase over Eurasia during the last three decades of the 20th century.

    PubMed

    Ye, Hengchun; Fetzer, Eric J; Wong, Sun; Lambrigtsen, Bjorn H

    2017-01-01

    Convective precipitation-localized, short-lived, intense, and sometimes violent-is at the root of challenges associated with observation, simulation, and prediction of precipitation. The understanding of long-term changes in convective precipitation characteristics and their role in precipitation extremes and intensity over extratropical regions are imperative to future water resource management; however, they have been studied very little. We show that annual convective precipitation total has been increasing astonishingly fast, at a rate of 18.4%/°C, of which 16% is attributable to an increase in convective precipitation occurrence, and 2.4% is attributable to increased daily intensity based on the 35 years of two (combined) historical data sets of 3-hourly synoptic observations and daily precipitation. We also reveal that annual daily precipitation extreme has been increasing at a rate of about 7.4%/°C in convective events only. Concurrently, the overall increase in mean daily precipitation intensity is mostly due to increased convective precipitation, possibly at the expanse of nonconvective precipitation. As a result, transitional seasons are becoming more summer-like as convective becomes the dominant precipitation type that has accompanied higher daily extremes and intensity since the late 1980s. The data also demonstrate that increasing convective precipitation and daily extremes appear to be directly linearly associated with higher atmospheric water vapor accompanying a warming climate over northern Eurasia.

  5. Does plasticity in plant physiological traits explain the rapid increase in water use efficiency? An ecohydrological modeling approach

    NASA Astrophysics Data System (ADS)

    Mastrotheodoros, Theodoros; Fatichi, Simone; Pappas, Christoforos; Molnar, Peter; Burlando, Paolo

    2016-04-01

    The rise of atmospheric CO2 concentration is expected to stimulate plant productivity by enhancing photosynthesis and reducing stomatal conductance and thus increasing plant water use efficiency (WUE) worldwide. An analysis of eddy covariance flux tower data from 21 forested ecosystems across the north hemisphere detected an unexpectedly large increase in WUE (Keenan et al, 2013), which was six times larger than the increase found by most previous studies based on controlled experiments (e.g., FACE), leaf-scale analyses, and numerical modelling. This increase could be solely attributed to the increase in atmospheric CO2 since other confounding factors were ruled out. Here, we investigate the potential contribution of plant plasticity, reflected in the temporal adjustment of major plant physiological traits, on changes in WUE using the ecohydrological model Tethys and Chloris (T&C). We hypothesize that the increase in WUE can be attributed to small variations in plant physiological traits, undetectable through observations, eventually triggered by the atmospheric CO2 increase. Data from the 21 sites in the above mentioned study are used to force the model. Simulation results with and without plasticity in the physiological traits (i.e., model parameters in our numerical experiments) are compared with the observed trends in WUE. We test several plant adaptation strategies in being effective in explaining the observed increase in WUE using a multifactorial numerical experiment in which we perturb in a systematic way selected plant parameters. Keenan, T. F., Hollinger, D. Y., Bohrer, G., Dragoni, D., Munger, J. W., Schmid, H. P., and Richardson, A. D. (2013). Increase in forest water-use efficiency as atmospheric carbon dioxide concentrations rise. Nature, 499(7458), 324-7.

  6. Sustaining rapid vesicular release at active zones: potential roles for vesicle tethering

    PubMed Central

    Hallermann, Stefan; Silver, R. Angus

    2016-01-01

    Rapid information processing in our nervous system relies on high-frequency fusion of transmitter-filled vesicles at chemical synapses. Some sensory synapses possess prominent electron-dense ribbon structures that provide a scaffold for tethering synaptic vesicles at the active zone (AZ), enabling sustained vesicular release. Here, we review functional data indicating that some central and neuromuscular synapses can also sustain vesicle-fusion rates that are comparable to those of ribbon-type sensory synapses. Comparison of the ultrastructure across these different types of synapses, together with recent work showing that cytomatrix proteins can tether vesicles and speed vesicle reloading, suggests that filamentous structures may play a key role in vesicle supply. We discuss potential mechanisms by which vesicle tethering could contribute to sustained high rates of vesicle fusion across ribbon-type, central, and neuromuscular synapses. PMID:23164531

  7. Can Rapid Diagnostic Testing for Malaria Increase Adherence to Artemether-Lumefantrine?: A Randomized Controlled Trial in Uganda.

    PubMed

    Saran, Indrani; Yavuz, Elif; Kasozi, Howard; Cohen, Jessica

    2016-04-01

    Most patients with suspected malaria do not receive diagnostic confirmation before beginning antimalarial treatment. We investigated the extent to which uncertainty about malaria diagnosis contributes to patient nonadherence to artemether-lumefantrine (AL) treatment through a randomized controlled trial in central Uganda. Among 1,525 patients purchasing a course of AL at private drug shops, we randomly offered 37.6% a free malaria rapid diagnostic test (RDT) and then assessed adherence through home visits 3 days later. Of these subjects, 68.4% tested positive for malaria and 65.8% adhered overall. Patients who tested positive did not have significantly higher odds of adherence than those who were not offered the test (adjusted odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.734-1.57,P= 0.719). Patients who received a positive malaria test had 0.488 fewer pills remaining than those not offered the test (95% CI: -1.02 to 0.043,P= 0.072). We found that patients who felt relatively healthy by the second day of treatment had lower odds of completing treatment (adjusted OR: 0.532, 95% CI: 0.394-0.719,P< 0.001). Our results suggest that diagnostic testing may not improve artemisinin-based combination therapy adherence unless efforts are made to persuade patients to continue taking the full course of drugs even if symptoms have resolved.

  8. Rapid regulation of thyroid sodium-iodide symporter activity by thyrotrophin and iodine.

    PubMed

    Ferreira, Andrea C F; Lima, Lívia P; Araújo, Renata L; Müller, Glaucia; Rocha, Renata P; Rosenthal, Doris; Carvalho, Denise P

    2005-01-01

    Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium-iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

  9. A Rapid and Sensitive Method to Measure the Functional Activity of Shiga Toxins in Human Serum

    PubMed Central

    Arfilli, Valentina; Carnicelli, Domenica; Ardissino, Gianluigi; Torresani, Erminio; Scavia, Gaia; Brigotti, Maurizio

    2015-01-01

    Shiga toxins (Stx) have a definite role in the development of hemolytic uremic syndrome in children with hemorrhagic colitis caused by pathogenic Stx-producing Escherichia coli (STEC) strains. The dramatic effects of these toxins on the microvasculature of different organs, particularly of the kidney, are well known, whereas there is no consensus on the mechanism by which Stx reach the endothelia of target organs and/or indirectly injure these body sites. We hereby describe a quick (4 h), radioactive, Raji cell-based method designed for the detection of Stx in human sera. The assay monitors the translation impairment induced by these powerful inhibitors of protein synthesis, which are identified properly by neutralizing their activity with specific monoclonal antibodies. By this method, we detected for the first time the functional activity of Stx in sera of STEC-infected patients during hemorrhagic colitis. Recent research has pointed to a dynamic process of Stx-induced renal intoxication in which concurrent and interactive steps are involved. Our rapid and specific method could be useful for studying the kinetics of Stx during the natural course of STEC infection and the interplay between Stx activity in serum and Stx presence in different blood fractions (neutrophils, monocytes, platelets, leukocyte-platelet aggregates, microvesicles, lipoproteins). PMID:26556372

  10. A rapid bioluminescence assay for measuring myeloperoxidase activity in human plasma

    PubMed Central

    Goiffon, Reece J.; Martinez, Sara C.; Piwnica-Worms, David

    2015-01-01

    Myeloperoxidase (MPO) is a circulating cardiovascular disease (CVD) biomarker used to estimate clinical risk and patient prognosis. Current enzyme-linked immunosorbent assays (ELISA) for MPO concentration are costly and time-intensive. Here we report a novel bioluminescence assay, designated MPO activity on a polymer surface (MAPS), for measuring MPO activity in human plasma samples using the bioluminescent substrate L-012. The method delivers a result in under an hour and is resistant to confounding effects from endogenous MPO inhibitors. In a pilot clinical study, we compared MAPS and two clinical ELISAs using 72 plasma samples from cardiac catheterization patients. Results from parallel MAPS and ELISAs were concordant within 2±11 μg l−1 MPO with similar uncertainty and reproducibility. Results between parallel MAPS and ELISA were in better agreement than those between independent ELISAs. MAPS may provide an inexpensive and rapid assay for determining MPO activity in plasma samples from patients with CVD or potentially other immune and inflammatory disorders. PMID:25666092

  11. Active root-inhabiting microbes identified by rapid incorporation of plant-derived carbon into RNA

    PubMed Central

    Vandenkoornhuyse, Philippe; Mahé, Stéphane; Ineson, Philip; Staddon, Phil; Ostle, Nick; Cliquet, Jean-Bernard; Francez, André-Jean; Fitter, Alastair H.; Young, J. Peter W.

    2007-01-01

    Plant roots harbor a large diversity of microorganisms that have an essential role in ecosystem functioning. To better understand the level of intimacy of root-inhabiting microbes such as arbuscular mycorrhizal fungi and bacteria, we provided 13CO2 to plants at atmospheric concentration during a 5-h pulse. We expected microbes dependent on a carbon flux from their host plant to become rapidly labeled. We showed that a wide variety of microbes occurred in roots, mostly previously unknown. Strikingly, the greatest part of this unsuspected diversity corresponded to active primary consumers. We found 17 bacterial phylotypes co-occurring within roots of a single plant, including five potentially new phylotypes. Fourteen phylotypes were heavily labeled with the 13C. Eight were phylogenetically close to Burkholderiales, which encompass known symbionts; the others were potentially new bacterial root symbionts. By analyzing unlabeled and 13C-enriched RNAs, we demonstrated differential activity in C consumption among these root-inhabiting microbes. Arbuscular mycorrhizal fungal RNAs were heavily labeled, confirming the high carbon flux from the plant to the fungal compartment, but some of the fungi present appeared to be much more active than others. The results presented here reveal the possibility of uncharacterized root symbioses. PMID:17939995

  12. A potential tipping point in tropical agriculture: Avoiding rapid increases in nitrous oxide fluxes from agricultural intensification in Kenya

    NASA Astrophysics Data System (ADS)

    Hickman, Jonathan E.; Tully, Katherine L.; Groffman, Peter M.; Diru, Willy; Palm, Cheryl A.

    2015-05-01

    There are national and regional efforts aimed at increasing fertilizer use in sub-Saharan Africa, where nitrogen (N) inputs must be increased by an order of magnitude or more to reach recommended rates. Fertilizer inputs increase N availability and cycling rates and subsequently emissions of nitrous oxide (N2O), a powerful greenhouse gas and the primary catalyst of stratospheric ozone depletion. We established experimental maize (Zea mays L.) plots in western Kenya to quantify the relationship between N inputs and N2O emissions. Mean N2O emissions were marginally, but not significantly, better described by an exponential model relating emissions to N input rate in 2011; in 2012, an exponential relationship provided the best fit compared to linear and other nonlinear models. Most N2O fluxes occurred during the 30 days following the second fertilizer application. Estimates of fertilizer N lost as N2O annually were well below the 1% Intergovernmental Panel on Climate Change default emission factor, ranging from 0.07% to 0.11% in 2011 and from 0.01% to 0.09% in 2012. In both years, the largest impact on annual N2O emissions occurred when inputs increased from 100 to 150 kg N ha-1: fluxes increased from 203 to 294 g N2O-N ha-1 yr-1 in 2011 and from 168 to 254 kg N ha-1 in 2012. Our results suggest that exponential emission responses are present in tropical systems and that agricultural intensification in western Kenya may be managed for increasing crop yields without immediate large increases in N2O emissions if application rates remain at or below 100 kg N ha-1.

  13. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase

    PubMed Central

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  14. Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase.

    PubMed

    Zhao, Yixiu; Zhang, Xin; Li, Jiannan; Bian, Yu; Sheng, Miaomiao; Liu, Bin; Fu, Zidong; Zhang, Yan; Yang, Baofeng

    2016-01-01

    Jujuboside B has been reported to have protective effect on many cardiovascular diseases. However, the effects of Jujuboside B on vascular tension and endothelial function are unknown. The present study investigated the effects of Jujuboside B on reducing vascular tension, protecting endothelial function and the potential mechanisms. The tension of isolated rat thoracic aorta ring was measured by Wire myograph system. The concentration of nitric oxide (NO) and the activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells (HAECs) were determined by Griess reagent method and enzyme-linked immune sorbent assay. The protein levels of eNOS and p-eNOS at Serine-1177 were determined by western blot analysis. Intracellular Ca2+ concentration in HAECs was measured by laser confocal imaging microscopy. Results showed that Jujuboside B reduced the tension of rat thoracic aorta rings with intact endothelium in a dose-dependent manner. L-NAME, KN93, EGTA, SKF96365, iberiotoxin and glibenclamide significantly attenuated Jujuboside B-induced vasodilation in endothelium-intact tissues. In contrast, indometacin and 4-DAMP had no such effects. Jujuboside B also promoted NO generation and increased eNOS activity, which were attenuated by L-NAME, EGTA and SKF96365. Moreover, Jujuboside B increased intracellular Ca2+ concentration dose-dependently, which was inhibited by EGTA and SKF96365. Besides, Jujuboside B induced a rapid Ca2+ influx instantaneously after depleting intracellular Ca2+ store, which was significantly inhibited by SKF96365. In conclusion, this study preliminarily confirmed that Jujuboside B reduced vascular tension endothelium-dependently. The underlying mechanisms involved that Jujuboside B increased extracellular Ca2+ influx through endothelial transient receptor potential cation (TRPC) channels, phosphorylated eNOS and promoted NO generation in vascular endothelial cells. In addition, Jujuboside B-induced vasodilation involved

  15. Mercuric reductase activity and evidence of broad-spectrum mercury resistance among clinical isolates of rapidly growing mycobacteria

    SciTech Connect

    Steingrube, V.A.; Wallace, R.J. Jr.; Steele, L.C.; Pang, Y.J. )

    1991-05-01

    Resistance to mercury was evaluated in 356 rapidly growing mycobacteria belonging to eight taxonomic groups. Resistance to inorganic Hg2+ ranged from 0% among the unnamed third biovariant complex of Mycobacterium fortuitum to 83% among M. chelonae-like organisms. With cell extracts and 203Hg(NO3)2 as the substrate, mercuric reductase (HgRe) activity was demonstrable in six of eight taxonomic groups. HgRe activity was inducible and required NADPH or NADH and a thiol donor for optimai activity. Species with HgRe activity were also resistant to organomercurial compounds, including phenylmercuric acetate. Attempts at intraspecies and intragenus transfer of HgRe activity by conjugation or transformation were unsuccessful. Mercury resistance is common in rapidly growing mycobacteria and appears to function via the same inducible enzyme systems already defined in other bacterial species. This system offers potential as a strain marker for epidemiologic investigations and for studying genetic systems in rapidly growing mycobacteria.

  16. Rapid Increases in Forest Understory Diversity and Productivity following a Mountain Pine Beetle (Dendroctonus ponderosae) Outbreak in Pine Forests

    PubMed Central

    Pec, Gregory J.; Karst, Justine; Sywenky, Alexandra N.; Cigan, Paul W.; Erbilgin, Nadir; Simard, Suzanne W.; Cahill, James F.

    2015-01-01

    The current unprecedented outbreak of mountain pine beetle (Dendroctonus ponderosae) in lodgepole pine (Pinus contorta) forests of western Canada has resulted in a landscape consisting of a mosaic of forest stands at different stages of mortality. Within forest stands, understory communities are the reservoir of the majority of plant species diversity and influence the composition of future forests in response to disturbance. Although changes to stand composition following beetle outbreaks are well documented, information on immediate responses of forest understory plant communities is limited. The objective of this study was to examine the effects of D. ponderosae-induced tree mortality on initial changes in diversity and productivity of understory plant communities. We established a total of 110 1-m2 plots across eleven mature lodgepole pine forests to measure changes in understory diversity and productivity as a function of tree mortality and below ground resource availability across multiple years. Overall, understory community diversity and productivity increased across the gradient of increased tree mortality. Richness of herbaceous perennials increased with tree mortality as well as soil moisture and nutrient levels. In contrast, the diversity of woody perennials did not change across the gradient of tree mortality. Understory vegetation, namely herbaceous perennials, showed an immediate response to improved growing conditions caused by increases in tree mortality. How this increased pulse in understory richness and productivity affects future forest trajectories in a novel system is unknown. PMID:25859663

  17. Rapid Increases in forest understory diversity and productivity following a mountain pine beetle (Dendroctonus ponderosae) outbreak in pine forests.

    PubMed

    Pec, Gregory J; Karst, Justine; Sywenky, Alexandra N; Cigan, Paul W; Erbilgin, Nadir; Simard, Suzanne W; Cahill, James F

    2015-01-01

    The current unprecedented outbreak of mountain pine beetle (Dendroctonus ponderosae) in lodgepole pine (Pinus contorta) forests of western Canada has resulted in a landscape consisting of a mosaic of forest stands at different stages of mortality. Within forest stands, understory communities are the reservoir of the majority of plant species diversity and influence the composition of future forests in response to disturbance. Although changes to stand composition following beetle outbreaks are well documented, information on immediate responses of forest understory plant communities is limited. The objective of this study was to examine the effects of D. ponderosae-induced tree mortality on initial changes in diversity and productivity of understory plant communities. We established a total of 110 1-m2 plots across eleven mature lodgepole pine forests to measure changes in understory diversity and productivity as a function of tree mortality and below ground resource availability across multiple years. Overall, understory community diversity and productivity increased across the gradient of increased tree mortality. Richness of herbaceous perennials increased with tree mortality as well as soil moisture and nutrient levels. In contrast, the diversity of woody perennials did not change across the gradient of tree mortality. Understory vegetation, namely herbaceous perennials, showed an immediate response to improved growing conditions caused by increases in tree mortality. How this increased pulse in understory richness and productivity affects future forest trajectories in a novel system is unknown.

  18. A restricted parabrachial pontine region is active during non-rapid eye movement sleep.

    PubMed

    Torterolo, P; Sampogna, S; Chase, M H

    2011-09-08

    The principal site that generates both rapid eye movement (REM) sleep and wakefulness is located in the mesopontine reticular formation, whereas non-rapid eye movement (NREM) sleep is primarily dependent upon the functioning of neurons that are located in the preoptic region of the hypothalamus. In the present study, we were interested in determining whether the occurrence of NREM might also depend on the activity of mesopontine structures, as has been shown for wakefulness and REM sleep. Adult cats were maintained in one of the following states: quiet wakefulness (QW), alert wakefulness (AW), NREM, or REM sleep induced by microinjections of carbachol into the nucleus pontis oralis (REM-carbachol). Subsequently, they were euthanized and single-labeling immunohistochemical studies were undertaken to determine state-dependent patterns of neuronal activity in the brainstem based upon the expression of the protein Fos. In addition, double-labeling immunohistochemical studies were carried out to detect neurons that expressed Fos as well as choline acetyltransferase, tyrosine hydroxylase, or GABA. During NREM, only a few Fos-immunoreactive cells were present in different regions of the brainstem; however, a discrete cluster of Fos+ neurons was observed in the caudolateral parabrachial region (CLPB). The number of Fos+ neurons in the CLPB during NREM was significantly greater (67.9±10.9, P<0.0001) compared with QW (8.0±6.7), AW (5.2±4.2), or REM-carbachol (8.0±4.7). In addition, there was a positive correlation (R=0.93) between the time the animals spent in NREM and the number of Fos+ neurons in the CLPB. Fos-immunoreactive neurons in the CLPB were neither cholinergic nor catecholaminergic; however, about 50% of these neurons were GABAergic. We conclude that a group of GABAergic and unidentified neurons in the CLPB are active during NREM and likely involved in the control of this behavioral state. These data open new avenues for the study of NREM, as well as for the

  19. Rapid fecal calprotectin testing to assess for endoscopic disease activity in inflammatory bowel disease: A diagnostic cohort study

    PubMed Central

    Kwapisz, Lukasz; Mosli, Mahmoud; Chande, Nilesh; Yan, Brian; Beaton, Melanie; Micsko, Jessica; Mennill, Pauline W.; Barnett, William; Bax, Kevin; Ponich, Terry; Howard, John; Tirolese, Anthony; Lannigan, Robert; Gregor, James

    2015-01-01

    Background and Aim: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. Patients and Methods: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver–operator characteristics (ROC) curve was used to identify the ideal FC cutoff that predicts endoscopic disease activity. Correlation between FC and endoscopic disease activity, disease location, and C-reactive protein (CRP) levels were measured. Results: One hundred and twenty-six patients, of whom 52% were females, were included in the final analysis with a mean age of 44.4 ± 16.7 years. Comparing FC to endoscopic findings, the following results were calculated: A cutoff point of 100 μg/g showed Sn = 83%, Sp = 67%, PPV = 65%, and NPV = 85%; and 200 μg/g showed Sn = 66%, Sp = 82%, PPV = 73%, and NPV = 77%. Based on ROC curve, the best FC cutoff point to predict endoscopic disease activity was 140 μg/g. Using this reference, FC levels strongly correlated with colorectal, ileocolonic, and ileal disease and predicted endoscopic activity. Conclusions: FC is an accurate test when used as an initial screening tool for patients suspected of having active IBD. Given its noninvasive nature, it may prove to reduce the need for colonoscopy and be an added tool in the management of IBD. PMID:26655130

  20. Development of a universal approach to increase physical activity among adolescents: the GoActive intervention

    PubMed Central

    Corder, Kirsten; Schiff, Annie; Kesten, Joanna M; van Sluijs, Esther M F

    2015-01-01

    Objectives To develop a physical activity (PA) promotion intervention for adolescents using a process addressing gaps in the literature while considering participant engagement. We describe the initial development stages; (1) existing evidence, (2) large scale opinion gathering and (3) developmental qualitative work, aiming (A) to gain insight into how to increase PA among the whole of year 9 (13–14 years-old) by identifying elements for intervention inclusion (B) to improve participant engagement and (C) to develop and refine programme design. Methods Relevant systematic reviews and longitudinal analyses of change were examined. An intervention was developed iteratively with older adolescents (17.3±0.5 years) and teachers, using the following process: (1) focus groups with (A) adolescents (n=26) and (B) teachers (n=4); (2) individual interviews (n=5) with inactive and shy adolescents focusing on engagement and programme acceptability. Qualitative data were analysed thematically. Results Limitations of the existing literature include lack of evidence on whole population approaches, limited adolescent involvement in intervention development, and poor participant engagement. Qualitative work suggested six themes which may encourage adolescents to do more PA; choice, novelty, mentorship, competition, rewards and flexibility. Teachers discussed time pressures as a barrier to encouraging adolescent PA and suggested between-class competition as a strategy. GoActive aims to increase PA through increased peer support, self-efficacy, group cohesion, self-esteem and friendship quality, and is implemented in tutor groups using a student-led tiered-leadership system. Conclusions We have followed an evidence-based iterative approach to translate existing evidence into an adolescent PA promotion intervention. Qualitative work with adolescents and teachers supported intervention design and addressed lack of engagement with health promotion programmes within this age group

  1. Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models.

    PubMed

    Boyle, Glen M; D'Souza, Marjorie M A; Pierce, Carly J; Adams, Ryan A; Cantor, Aaron S; Johns, Jenny P; Maslovskaya, Lidia; Gordon, Victoria A; Reddell, Paul W; Parsons, Peter G

    2014-01-01

    Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-βI, -βII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer.

  2. Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models

    PubMed Central

    Pierce, Carly J.; Adams, Ryan A.; Cantor, Aaron S.; Johns, Jenny P.; Maslovskaya, Lidia; Gordon, Victoria A.; Reddell, Paul W.; Parsons, Peter G.

    2014-01-01

    Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models. EBC-46 induced oxidative burst from purified human polymorphonuclear cells, which was prevented by the Protein Kinase C inhibitor bisindolylmaleimide-1. EBC-46 activated a more specific subset of PKC isoforms (PKC-βI, -βII, -α and -γ) compared to the structurally related phorbol 12-myristate 13-acetate (PMA). Although EBC-46 showed threefold less potency for inhibiting cell growth than PMA in vitro, it was more effective for cure of tumors in vivo. No viable tumor cells were evident four hours after injection by ex vivo culture. Pharmacokinetic profiles from treated mice indicated that EBC-46 was retained preferentially within the tumor, and resulted in significantly greater local responses (erythema, oedema) following intra-lesional injection compared with injection into normal skin. The efficacy of EBC-46 was reduced by co-injection with bisindolylmaleimide-1. Loss of vascular integrity following treatment was demonstrated by an increased permeability of endothelial cell monolayers in vitro and by CD31 immunostaining of treated tumors in vivo. Our results demonstrate that a single intra-lesional injection of EBC-46 causes PKC-dependent hemorrhagic necrosis, rapid tumor cell death and ultimate cure of solid tumors in pre-clinical models of cancer. PMID:25272271

  3. Characterization of apoplast phenolics: Invitro oxidation of acetosyringone results in a rapid prolonged increase in the redox potential

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a previous study we observed that if tobacco cell suspensions were inoculated with certain bacterial strains, several hours later the redox potential of the suspensions would increase (oxidative), as much as 100 mV, and in some cases last more than an hour. To discover possible contributors to t...

  4. Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism.

    PubMed

    Ozaki, Yori; Saito, Kenji; Nakazawa, Kyoko; Konishi, Morichika; Itoh, Nobuyuki; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Kato, Hisanori; Takenaka, Asako

    2015-11-14

    Protein malnutrition promotes hepatic steatosis, decreases insulin-like growth factor (IGF)-I production and retards growth. To identify new molecules involved in such changes, we conducted DNA microarray analysis on liver samples from rats fed an isoenergetic low-protein diet for 8 h. We identified the fibroblast growth factor 21 gene (Fgf21) as one of the most strongly up-regulated genes under conditions of acute protein malnutrition (P<0·05, false-discovery rate<0·001). In addition, amino acid deprivation increased Fgf21 mRNA levels in rat liver-derived RL-34 cells (P<0·01). These results suggested that amino acid limitation directly increases Fgf21 expression. FGF21 is a polypeptide hormone that regulates glucose and lipid metabolism. FGF21 also promotes a growth hormone-resistance state and suppresses IGF-I in transgenic mice. Therefore, to determine further whether Fgf21 up-regulation causes hepatic steatosis and growth retardation after IGF-I decrease in protein malnutrition, we fed an isoenergetic low-protein diet to Fgf21-knockout (KO) mice. Fgf21-KO did not rescue growth retardation and reduced plasma IGF-I concentration in these mice. Fgf21-KO mice showed greater epididymal white adipose tissue weight and increased hepatic TAG and cholesterol levels under protein malnutrition conditions (P<0·05). Overall, the results showed that protein deprivation directly increased Fgf21 expression. However, growth retardation and decreased IGF-I were not mediated by increased FGF21 expression in protein malnutrition. Furthermore, FGF21 up-regulation rather appears to have a protective effect against obesity and hepatic steatosis in protein-malnourished animals.

  5. Rapid Detection of Thrombin and Other Protease Activity Directly in Whole Blood

    NASA Astrophysics Data System (ADS)

    Yu, Johnson Chung Sing

    Thrombin is a serine protease that plays a key role in the clotting cascade to promote hemostasis following injury to the endothelium. From a clinical diagnostic perspective, in-vivo thrombin activity is linked to various blood clotting disorders, as well as cardiovascular disease (DVT, arteriosclerosis, etc). Thus, the ability to rapidly measure protease activity directly in whole blood will provide important new diagnostics, and clinical researchers with a powerful tool to further elucidate the relationship between circulating protease levels and disease. The ultimate goal is to design novel point of care (POC) diagnostic devices that are capable of monitoring protease activities directly in whole blood and biological sample. A charge-changing substrate specific to the thrombin enzyme was engineered and its functionality was confirmed by a series of experiments. This led to the preliminary design, construction, and testing of two device platforms deemed fully functional for the electrophoretic separation and focusing of charged peptide fragments. The concept of using the existing charge-changing substrate platform for bacterial protease detection was also investigated. Certain strains of E coli are associated with severe symptoms such as abdominal cramps, bloody diarrhea, and vomiting. The OmpT protease is expressed on the outer membrane of E coli and plays a role in the cleavage of antimicrobial peptides, the degradation of recombinant heterologous proteins, and the activation of plasminogen in the host. Thus, a synthetic peptide substrate specific to the OmpT protease was designed and modeled for the purpose of detecting E coli in biological sample.

  6. Playground Designs to Increase Physical Activity Levels during School Recess: A Systematic Review

    ERIC Educational Resources Information Center

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M.

    2014-01-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A…

  7. Post-Mesozoic Rapid Increase of Seawater Mg/Ca due to Enhanced Mantle-Seawater Interaction

    PubMed Central

    Ligi, Marco; Bonatti, Enrico; Cuffaro, Marco; Brunelli, Daniele

    2013-01-01

    The seawater Mg/Ca ratio increased significantly from ~ 80 Ma to present, as suggested by studies of carbonate veins in oceanic basalts and of fluid inclusions in halite. We show here that reactions of mantle-derived peridotites with seawater along slow spreading mid-ocean ridges contributed to the post-Cretaceous Mg/Ca increase. These reactions can release to modern seawater up to 20% of the yearly Mg river input. However, no significant peridotite-seawater interaction and Mg-release to the ocean occur in fast spreading, East Pacific Rise-type ridges. The Mesozoic Pangean superocean implies a hot fast spreading ridge system. This prevented peridotite-seawater interaction and Mg release to the Mesozoic ocean, but favored hydrothermal Mg capture and Ca release by the basaltic crust, resulting in a low seawater Mg/Ca ratio. Continent dispersal and development of slow spreading ridges allowed Mg release to the ocean by peridotite-seawater reactions, contributing to the increase of the Mg/Ca ratio of post-Mesozoic seawater. PMID:24067442

  8. Post-mesozoic rapid increase of seawater Mg/Ca due to enhanced mantle-seawater interaction.

    PubMed

    Ligi, Marco; Bonatti, Enrico; Cuffaro, Marco; Brunelli, Daniele

    2013-09-25

    The seawater Mg/Ca ratio increased significantly from ~ 80 Ma to present, as suggested by studies of carbonate veins in oceanic basalts and of fluid inclusions in halite. We show here that reactions of mantle-derived peridotites with seawater along slow spreading mid-ocean ridges contributed to the post-Cretaceous Mg/Ca increase. These reactions can release to modern seawater up to 20% of the yearly Mg river input. However, no significant peridotite-seawater interaction and Mg-release to the ocean occur in fast spreading, East Pacific Rise-type ridges. The Mesozoic Pangean superocean implies a hot fast spreading ridge system. This prevented peridotite-seawater interaction and Mg release to the Mesozoic ocean, but favored hydrothermal Mg capture and Ca release by the basaltic crust, resulting in a low seawater Mg/Ca ratio. Continent dispersal and development of slow spreading ridges allowed Mg release to the ocean by peridotite-seawater reactions, contributing to the increase of the Mg/Ca ratio of post-Mesozoic seawater.

  9. Rapid and efficient assembly of transcription activator-like effector genes by USER cloning.

    PubMed

    Wang, Song; Li, Wei; Wang, Shuo; Hu, Baoyang

    2014-06-20

    Transcription activator-like effectors (TALEs) that were related to bacteria immune system have lately been employed in a promising approach of precise gene targeting. Because of the repetitive characteristics of TALEs, existing TALE assembly methods are either very complicated, time-consuming, or too tricky to be handled in common labs. Here, we reported a rapid, efficient and easy method for TALE assembly. This method takes advantage of uracil-specific excision reagent (USER), an enzyme that can cleave DNA constructs and create long, unique single-strand DNA overhangs. Upon USER treatment, the overhangs on each individual TALE repeat unit can be rejoined hierarchically to form pentamers in a ligation-independent manner. Eventually, three pentamers are assembled into a full TALE construct by Golden Gate cloning. TALE nucleases (TALENs) generated with this method exhibit high genome-editing activity in human cells such as HEK293FT cells. Using this method, we have successfully synthesized three TALEN pairs targeting endogenous Tet1 locus, and proved that all can specifically target Tet1 gene, though in various degree. Comparing to other methods of TALEN assembly, this one is much less labor intensive and fairly faster, and positive clones can be obtained at high efficiency within only two days. We thus contribute to an easier approach for effective TALENs synthesis, which may highly facilitate the wide application of TALEN technology in genome editing, especially for human cells that require precise targeting.

  10. Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes

    PubMed Central

    Fischbach, Michael A.; Lai, Jonathan R.; Roche, Eric D.; Walsh, Christopher T.; Liu, David R.

    2007-01-01

    Nonribosomal peptides (NRPs) are produced by NRP synthetase (NRPS) enzymes that function as molecular assembly lines. The modular architecture of NRPSs suggests that a domain responsible for activating a building block could be replaced with a domain from a foreign NRPS to create a chimeric assembly line that produces a new variant of a natural NRP. However, such chimeric NRPS modules are often heavily impaired, impeding efforts to create novel NRP variants by swapping domains from different modules or organisms. Here we show that impaired chimeric NRPSs can be functionally restored by directed evolution. Using rounds of mutagenesis coupled with in vivo screens for NRP production, we rapidly isolated variants of two different chimeric NRPSs with ≈10-fold improvements in enzyme activity and product yield, including one that produces new derivatives of the potent NRP/polyketide antibiotic andrimid. Because functional restoration in these examples required only modest library sizes (103 to 104 clones) and three or fewer rounds of screening, our approach may be widely applicable even for NRPSs from genetically challenging hosts. PMID:17620609

  11. A rapid and simple assay for growth hormone-binding protein activity in human plasma.

    PubMed

    Baumann, G; Shaw, M A; Amburn, K

    1988-12-01

    The newly discovered circulating growth hormone binding proteins dictate a re-evaluation of the state of GH in plasma in health and disease as the binding proteins are known to affect GH metabolism and action. We describe a rapid and simple GH-binding assay that allows determination of free and complexed plasma GH, as well as GH-binding protein activity as an index of GH-binding protein levels, with relative ease. The method is based on incubation of plasma with 125I-GH and separation of bound from free GH on small DEAE-cellulose columns; it can be used on a large scale for routine determinations. The results obtained by this method are comparable to those obtained with the previously used slow and more cumbersome gel filtration technique. Initial data obtained in normal subjects and certain disease states show that the bound fraction of plasma GH is similar in men, women and children, is unaffected by pregnancy or acute infection, but is marginally decreased in liver cirrhosis. In acromegaly, binding protein activity also appears normal when allowance is made for partial saturation of the binding proteins by the high prevailing GH levels. The technique we describe should facilitate investigations of normal and abnormal regulation of the GH binding proteins.

  12. Analytical-HZETRN Model for Rapid Assessment of Active Magnetic Radiation Shielding

    NASA Technical Reports Server (NTRS)

    Washburn, S. A.; Blattnig, S. R.; Singleterry, R. C.; Westover, S. C.

    2014-01-01

    The use of active radiation shielding designs has the potential to reduce the radiation exposure received by astronauts on deep-space missions at a significantly lower mass penalty than designs utilizing only passive shielding. Unfortunately, the determination of the radiation exposure inside these shielded environments often involves lengthy and computationally intensive Monte Carlo analysis. In order to evaluate the large trade space of design parameters associated with a magnetic radiation shield design, an analytical model was developed for the determination of flux inside a solenoid magnetic field due to the Galactic Cosmic Radiation (GCR) radiation environment. This analytical model was then coupled with NASA's radiation transport code, HZETRN, to account for the effects of passive/structural shielding mass. The resulting model can rapidly obtain results for a given configuration and can therefore be used to analyze an entire trade space of potential variables in less time than is required for even a single Monte Carlo run. Analyzing this trade space for a solenoid magnetic shield design indicates that active shield bending powers greater than 15 Tm and passive/structural shielding thicknesses greater than 40 g/cm2 have a limited impact on reducing dose equivalent values. Also, it is shown that higher magnetic field strengths are more effective than thicker magnetic fields at reducing dose equivalent.

  13. Analytical-HZETRN model for rapid assessment of active magnetic radiation shielding

    NASA Astrophysics Data System (ADS)

    Washburn, S. A.; Blattnig, S. R.; Singleterry, R. C.; Westover, S. C.

    2014-01-01

    The use of active radiation shielding designs has the potential to reduce the radiation exposure received by astronauts on deep-space missions at a significantly lower mass penalty than designs utilizing only passive shielding. Unfortunately, the determination of the radiation exposure inside these shielded environments often involves lengthy and computationally intensive Monte Carlo analysis. In order to evaluate the large trade space of design parameters associated with a magnetic radiation shield design, an analytical model was developed for the determination of flux inside a solenoid magnetic field due to the Galactic Cosmic Radiation (GCR) radiation environment. This analytical model was then coupled with NASA's radiation transport code, HZETRN, to account for the effects of passive/structural shielding mass. The resulting model can rapidly obtain results for a given configuration and can therefore be used to analyze an entire trade space of potential variables in less time than is required for even a single Monte Carlo run. Analyzing this trade space for a solenoid magnetic shield design indicates that active shield bending powers greater than ∼15 Tm and passive/structural shielding thicknesses greater than 40 g/cm2 have a limited impact on reducing dose equivalent values. Also, it is shown that higher magnetic field strengths are more effective than thicker magnetic fields at reducing dose equivalent.

  14. Rac1 Activation in Podocytes Induces Rapid Foot Process Effacement and Proteinuria

    PubMed Central

    Yu, Haiyang; Suleiman, Hani; Kim, Alfred H. J.; Miner, Jeffrey H.; Dani, Adish; Akilesh, Shreeram

    2013-01-01

    The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton. PMID:24061480

  15. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness.

    PubMed

    Chow, Ho Ming; Horovitz, Silvina G; Carr, Walter S; Picchioni, Dante; Coddington, Nate; Fukunaga, Masaki; Xu, Yisheng; Balkin, Thomas J; Duyn, Jeff H; Braun, Allen R

    2013-06-18

    Rapid eye movement (REM) sleep constitutes a distinct "third state" of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects "level of consciousness," we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.

  16. Continued Development of the Rapid Cycle Amine (RCA) System for Advanced Extravehicular Activity Systems

    NASA Technical Reports Server (NTRS)

    Papale, William; Chullen, Cinda; Campbell, Colin; Conger, Bruce; McMillin, Summer; Jeng, Frank

    2014-01-01

    Development activities related to the Rapid Cycle Amine (RCA) Carbon Dioxide (CO2) and Humidity control system have progressed to the point of integrating the RCA into an advanced Primary Life Support System (PLSS 2.0) to evaluate the interaction of the RCA among other PLSS components in a ground test environment. The RCA 2.0 assembly (integrated into PLSS 2.0) consists of a valve assembly with commercial actuator motor, a sorbent canister, and a field-programmable gate array (FPGA)-based process node controller. Continued design and development activities for RCA 3.0 have been aimed at optimizing the canister size and incorporating greater fidelity in the valve actuator motor and valve position feedback design. Further, the RCA process node controller is envisioned to incorporate a higher degree of functionality to support a distributed PLSS control architecture. This paper will describe the progression of technology readiness levels of RCA 1.0, 2.0 and 3.0 along with a review of the design and manufacturing successes and challenges for 2.0 and 3.0 units. The anticipated interfaces and interactions with the PLSS 2.0/2.5/3.0 assemblies will also be discussed.

  17. Isotropic Heating of Galaxy Cluster Cores via Rapidly Reorienting Active Galactic Nucleus Jets

    NASA Astrophysics Data System (ADS)

    Babul, Arif; Sharma, Prateek; Reynolds, Christopher S.

    2013-05-01

    Active galactic nucleus (AGN) jets carry more than sufficient energy to stave off catastrophic cooling of the intracluster medium (ICM) in the cores of cool-core clusters. However, in order to prevent catastrophic cooling, the ICM must be heated in a near-isotropic fashion and narrow bipolar jets with P jet = 1044 - 45 erg s-1, typical of radio AGNs at cluster centers, are inefficient in heating the gas in the transverse direction to the jets. We argue that due to existent conditions in cluster cores, the supermassive black holes (SMBHs) will, in addition to accreting gas via radiatively inefficient flows, experience short stochastic episodes of enhanced accretion via thin disks. In general, the orientation of these accretion disks will be misaligned with the spin axis of the black holes (BHs) and the ensuing torques will cause the BH's spin axis (and therefore the jet axis) to slew and rapidly change direction. This model not only explains recent observations showing successive generations of jet-lobes-bubbles in individual cool-core clusters that are offset from each other in the angular direction with respect to the cluster center, but also shows that AGN jets can heat the cluster core nearly isotropically on the gas cooling timescale. Our model does require that the SMBHs at the centers of cool-core clusters be spinning relatively slowly. Torques from individual misaligned disks are ineffective at tilting rapidly spinning BHs by more than a few degrees. Additionally, since SMBHs that host thin accretion disks will manifest as quasars, we predict that roughly 1-2 rich clusters within z < 0.5 should have quasars at their centers.

  18. 20 CFR 665.330 - Are the NAFTA-TAA program requirements for rapid response also required activities?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false Are the NAFTA-TAA program requirements for... TITLE I OF THE WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.330 Are the NAFTA-TAA program... activities under WIA are made available to workers who, under the NAFTA Implementation Act (Public Law...

  19. 20 CFR 665.330 - Are the NAFTA-TAA program requirements for rapid response also required activities?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false Are the NAFTA-TAA program requirements for... TITLE I OF THE WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.330 Are the NAFTA-TAA program... activities under WIA are made available to workers who, under the NAFTA Implementation Act (Public Law...

  20. 20 CFR 665.330 - Are the NAFTA-TAA program requirements for rapid response also required activities?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false Are the NAFTA-TAA program requirements for... TITLE I OF THE WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.330 Are the NAFTA-TAA program... activities under WIA are made available to workers who, under the NAFTA Implementation Act (Public Law...

  1. Rapid increase of inositol 1,4,5-trisphosphate in the HeLa cells after hypergravity exposure

    NASA Technical Reports Server (NTRS)

    Kumei, Yasuhiro; Whitson, Peggy A.; Cintron, Nitza M.; Sato, Atsushige

    1990-01-01

    The IP3 level in HeLa cells has been elevated through the application in hypergravity in a time-dependent manner. The data obtained for the hydrolytic products of PIP2, IP3, and DG are noted to modulate c-myc gene expression. It is also established that the cAMP accumulation by the IBMX in hypergravity-exposed cells was suppressed relative to the control. In light of IP3 increase and cAMP decrease results, a single GTP-binding protein may play a role in the hypergravity signal transduction of HeLa cells by stimulating PLC while inhibiting adenylate cyclase.

  2. Constitutive gp130 activation rapidly accelerates the transformation of human hepatocytes via an impaired oxidative stress response

    PubMed Central

    Herden, Johannes; Parplys, Ann Christin; Borgmann, Kerstin; Schmidt-Arras, Dirk; Lohse, Ansgar W.; Rose-John, Stefan; Wege, Henning

    2016-01-01

    Pro-inflammatory signaling pathways, especially interleukin 6 (IL-6), and reactive oxygen species (ROS) promote carcinogenesis in the liver. In order to elucidate the underlying oncogenic mechanism, we activated the IL-6 signal transducer glycoprotein 130 (gp130) via stable expression of a constitutively active gp130 construct (L-gp130) in untransformed telomerase-immortalized human fetal hepatocytes (FH-hTERT). As known from hepatocellular adenomas, forced gp130 activation alone was not sufficient to induce malignant transformation. However, additional challenge of FH-hTERT L-gp130 clones with oxidative stress resulted in 2- to 3-fold higher ROS levels and up to 6-fold more DNA-double strand breaks (DSB). Despite increased DNA damage, ROS-challenged FH-hTERT L-gp130 clones displayed an enhanced proliferation and rapidly developed colony growth capabilities in soft agar. As driving gp130-mediated oncogenic mechanism, we detected a decreased expression of antioxidant genes, in particular glutathione peroxidase 3 and apolipoprotein E, and an absence of P21 upregulation following ROS-conferred induction of DSB. In summary, an impaired oxidative stress response in hepatocytes with gp130 gain-of-function mutations, as detected in dysplastic intrahepatic nodules and hepatocellular adenomas, is one of the central oncogenic mechanisms in chronic liver inflammation. PMID:27489351

  3. Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR.

    PubMed

    Bajpai, Arun K; Park, Jeong-Hoh; Moon, Ik-Jae; Kang, Hyungu; Lee, Yun-Han; Doh, Kyung-Oh; Suh, Seong-Il; Chang, Byeong-Churl; Park, Jong-Gu

    2005-09-29

    Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.

  4. MULTIVALENT DISPLAY OF PENDANT PRO-APOPTOTIC PEPTIDES INCREASES CYTOTOXIC ACTIVITY

    PubMed Central

    Chu, David S.H.; Bocek, Michael J.; Shi, Julie; Ta, Anh; Ngambenjawong, Chayanon; Rostomily, Robert C.; Pun, Suzie H.

    2015-01-01

    Several cationic antimicrobial peptides have been investigated as potential anti-cancer drugs due to their demonstrated selective toxicity towards cancer cells relative to normal cells. For example, intracellular delivery of KLA, a pro-apoptotic peptide, results in toxicity against a variety of cancer cell lines; however, the relatively low activity and small size leads to rapid renal excretion when applied in vivo, limiting its therapeutic potential. In this work, apoptotic peptide-polymer hybrid materials were developed to increase apoptotic peptide activity via multivalent display. Multivalent peptide materials were prepared with comb-like structure by RAFT copolymerization of peptide macromonomers with N-(2-hydroxypropyl) methacrylamide (HPMA). Polymers displayed a GKRK peptide sequence for targeting p32, a protein often overexpressed on the surface of cancer cells, either fused with or as a comonomer to a KLA macromonomer. In three tested cancer cell lines, apoptotic polymers were significantly more cytotoxic than free peptides as evidenced by an order of magnitude decrease in IC50 values for the polymers compared to free peptide. The uptake efficiency and intracellular trafficking of one polymer construct was determined by radiolabeling and subcellular fractionation. Despite their more potent cytotoxic profile, polymeric KLA constructs have poor cellular uptake efficiency (<1%). A significant fraction (20%) of internalized constructs localize with intact mitochondrial fractions. In an effort to increase cellular uptake, polymer amines were converted to guanidines by reaction with O-methylisourea. Guanidinylated polymers disrupted function of isolated mitochondria more than their lysine-based analogs, but overall toxicity was decreased, likely due to inefficient mitochondrial trafficking. Thus, while multivalent KLA polymers are more potent than KLA peptides, these materials can be substantially improved by designing next generation materials with improved

  5. Colorimetry and SERS dual-mode detection of telomerase activity: combining rapid screening with high sensitivity

    NASA Astrophysics Data System (ADS)

    Zong, Shenfei; Wang, Zhuyuan; Chen, Hui; Hu, Guohua; Liu, Min; Chen, Peng; Cui, Yiping

    2014-01-01

    As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and surface enhanced Raman scattering (SERS) dual-mode telomerase activity detection method, which has several distinctive advantages. First, colorimetric functionality allows rapid preliminary discrimination of telomerase activity by the naked eye. Second, the employment of SERS technique results in greatly improved detection sensitivity. Third, the combination of colorimetry and SERS into one detection system can ensure highly efficacious and sensitive screening of numerous samples. Besides, the avoidance of polymerase chain reaction (PCR) procedures further guarantees fine reliability and simplicity. Generally, the presented method is realized by an ``elongate and capture'' procedure. To be specific, gold nanoparticles modified with Raman molecules and telomeric repeat complementary oligonucleotide are employed as the colorimetric-SERS bifunctional reporting nanotag, while magnetic nanoparticles functionalized with telomerase substrate oligonucleotide are used as the capturing substrate. Telomerase can synthesize and elongate telomeric repeats onto the capturing substrate. The elongated telomeric repeats subsequently facilitate capturing of the reporting nanotag via hybridization between telomeric repeat and its complementary strand. The captured nanotags can cause a significant difference in the color and SERS intensity of the magnetically separated sediments. Thus both the color and SERS can be used as indicators of the telomerase activity. With fast screening ability and outstanding sensitivity, we anticipate that this method would greatly promote practical application of telomerase-based early-stage cancer diagnosis.As an important biomarker and therapeutic target, telomerase has attracted considerable attention concerning its detection and monitoring. Here, we present a colorimetry and

  6. Rapid increases in permeability and porosity of bentonite-sand mixtures due to alteration by water vapor

    SciTech Connect

    Couture, R.A.

    1984-01-01

    Packed columns of canister packing material containing 25% bentonite and 75% quartz or basalt sand, were exposed to water vapor at temperatures up t 260/sup 0/C. The permeabilities of the columns were subsequently measured after complete saturation with liquid water in a pressurized system. Exposure to water vapor caused irreversible increases in permeability by factors of up to 10/sup 5/. After saturation with liquid water, the permeability was nearly independent of temperature. The increases in permeability were due to a large decrease in the ability of the bentonite to swell in water. Calculations suggest that swelling of bentonite altered at 250/sup 0/C was not sufficient to fill the pore spaces. If the pore spaces are filled, the mixture will form an effective barrier against flow, diffusion, and transport of colloids. The results suggest that if bentonite-based canister packing material is exposed even briefly to water vapor at high temperatures in a high-level nuclear waste repository, its performance will be seriously impaired. The problem is less severe if the proportion of bentonite is high and the material is highly compacted. Previous results show significant degradation of bentonite by water vapor at temperatures as low as 150/sup 0/C. This suggests that in some repositories, backfill in tunnels and drifts may also be affected. 9 references, 5 figures, 1 table.

  7. Increased large unstained cells value in varicella patients: A valuable parameter to aid rapid diagnosis of varicella infection.

    PubMed

    Shin, Dongyun; Lee, Min Seok; Kim, Do Young; Lee, Min-Geol; Kim, Dae Suk

    2015-08-01

    Varicella is a highly contagious infection caused by varicella zoster virus. Sometimes it is difficult to differentiate between other viral infections such as Kaposi's varicelliform eruption (KVE) and disseminated herpes zoster (HZ). The large unstained cells (LUC) value is a differential count parameter reported by routing hematology analysis. LUC have been studied previously, but never been reported in the context of varicella or in dermatological published work. The aim of this study was to compare the LUC values in varicella patients with that in KVE and disseminated HZ patients. Sixty-nine varicella patients, 30 KVE patients and 11 disseminated HZ patients were included in this retrospective study. All data were analyzed using SPSS version 17.0 or GraphPad Prism version 5.0. The mean percentage of LUC (%LUC) in varicella patients was higher than the upper limit of normal reference range and it was increased compared to %LUC of both KVE (P < 0.0001) and disseminated HZ (P = 0.0051) patients. %LUC of varicella patients significantly decreased with clinical improvements (P = 0.0017). %LUC was significantly increased in varicella patients and corresponded with clinical improvements. Patients with %LUC of 3.55 or more favor the diagnosis of varicella over both KVE and disseminated HZ with 71.01% sensitivity and 84.44% specificity. We suggest that %LUC can assist in making a precise diagnosis of varicella in confusing cases.

  8. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    PubMed Central

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  9. Rapid loss of factor XII and XI activity in ellagic acid-activated normal plasma: role of plasma inhibitors and implications for automated activated partial thromboplastin time recording.

    PubMed

    Joist, J H; Cowan, J F; Khan, M

    1977-12-01

    Rapid prolongation of the aPTT of normal plasma upon incubation with ellagic acid containing aPTT reagents was observed. The aPTT prolongation was not due to time-dependent changes in pH in the incubation mixture or loss of activity of the labile coagulation factors VIII and V but occurred as a result of rapid progressive inactivation of ellagic acid-activated factors XII and XI. Prolongation of the aPTT and loss of contact factor activities was not observed in plasma incubated with particulate activator reagents. This finding seemed to indicate that adsorption of factors XII and XI to larger particles during the activation process might protect these factors from inactivation by naturally occurring plasma inhibitors. Evidence is presented which supports previous findings that C1-INH, alpha1-AT, and antithrombin (in the presence of heparin) contribute to factor XIIa and XI a inactivation in ellagic acid-activated plasma and that plasma albumin may compete with factor XII for ellagic acid binding. The data indicate that ellagic acid-containing aPTT reagents have unfavorable properties which seriously limit their usefulness in the clinical laboratory, particularly in respect to recording of the aPTT with certain fully automated clot timers.

  10. Rapid mass spectrometric DNA diagnostics for assessing microbial community activity during bioremediation. 1997 annual progress report

    SciTech Connect

    Benner, W.H.; Hunter-Cevera, J.

    1997-01-01

    'The effort of the past year''s activities, which covers the first year of the project, was directed at developing DNA-based diagnostic procedures for implementation in high through-put analytical instrumentation. The diagnostic procedures under evaluation are designed to identify specific genes in soil microorganisms that code for pollutant-degrading enzymes. Current DNA-based diagnostic procedures, such as the ligase chain reaction (LCR) and the polymerase chain reaction (PCR), rely on gel electrophoresis as a way to score a diagnostic test. The authors are attempting to implement time-of-flight (TOF) mass spectrometry as a replacement for gel separations because of its speed advantage and potential for sample automation. The authors anticipate that if TOF techniques can be implemented in the procedures, then a very large number of microorganisms and soil samples can be screened for the presence of specific pollutant-degrading genes. The use of DNA-based procedures for the detection of biodegrading organisms or genes that code for pollutant-degrading enzymes constitutes a critical technology for following biochemical transformation and substantiating the impact of bioremediation. DNA-based technology has been demonstrated to be a sensitive technique for tracking micro-organism activity at the molecular level. These procedures can be tuned to identify groups of organisms, specific organisms, and activity at the molecular level. They are developing a P-monitoring strategy that relies on the combined use of DNA diagnostics with mass spectrometry as the detection scheme. The intent of this work is a two-fold evaluation of (1) the feasibility of replacing the use of gel separations for identifying polymerase chain reaction (PCR) products with a rapid and automatable form of electrospray mass spectrometry and (2) the use of matrix-assisted-laser-desorption-ionization mass spectrometry (MALDI-MS) as a tool to score oligonucleotide ligation assays (OLA).'

  11. DAAs Rapidly Reduce Inflammation but Increase Serum VEGF Level: A Rationale for Tumor Risk during Anti-HCV Treatment

    PubMed Central

    Villani, Rosanna; Facciorusso, Antonio; Bellanti, Francesco; Tamborra, Rosanna; Piscazzi, Annamaria; Landriscina, Matteo; Vendemiale, Gianluigi; Serviddio, Gaetano

    2016-01-01

    Background Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has been reported within weeks of starting treatment, but the mechanism is not known. Methods We monitored the serum level of vascular endothelial growth factor (VEGF) and changes in the pattern of circulating interleukins in 103 chronic hepatitis C patients during antiviral treatment with DAA-regimens. VEGF, epidermal growth factor (EGF), and several interleukins were assessed at baseline, during treatment, and after treatment. The biological effect of DAA-treated patient serum on human umbilical vein endothelial cell (HUVEC) proliferation was also confirmed. Results After 4 weeks of therapy, VEGF increased approximately 4-fold compared to baseline, remained elevated up to the end of treatment, and returned to the pre-treatment level after the end of therapy. In contrast, interleukin-10 and tumor necrosis factor-alpha significantly decreased during therapy, which was coincident with HCV clearance. The levels of both remained low after treatment. The addition of serum from patients collected during therapy induced HUVEC proliferation; however, this disappeared after the end of therapy. Conclusions DAA administration induces an early increase in serum VEGF and a change in the inflammatory pattern, coinciding with HCV clearance. This may alter the balance between inflammatory and anti-inflammatory processes and modify the antitumor surveillance of the host. Fortunately, such modifications return reverse to normal after the end of treatment. PMID:27997563

  12. Increased levels of soluble Fas ligand in CSF of rapidly progressive HTLV-1-associated myelopathy/tropical spastic paraparesis patients.

    PubMed

    Saito, M; Nakamura, N; Nagai, M; Shirakawa, K; Sato, H; Kawahigashi, N; Furukawa, Y; Usuku, K; Nakagawa, M; Izumo, S; Osame, M

    1999-08-03

    The interaction of Fas ligand (FasL) with Fas-bearing cells induces apoptosis and contributes to the negative regulation of peripheral T-cell responses. Membrane-bound FasL is cleaved by a matrix metalloproteinase-like enzyme and converted to a soluble form (sFasL). Recent studies suggest that such sFasL can cause systemic tissue damage. Here we report that serum and CSF levels of soluble FasL (sFasL) are markedly higher in three active phase patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). All of these patients showed higher sFasL levels in CSF than in serum. Although the HTLV-1 proviral load of patients showed no correlation with serum or with CSF sFasL, CSF sFasL levels of 14 HAM/TSP patients correlated with the anti-HTLV-1 antibody titer and neopterin concentration in CSF. These results indicate that sFasL mediated mechanisms may contribute to the inflammatory process and subsequent spinal tissue damage seen in HAM/TSP patients.

  13. Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin.

    PubMed

    Abolhoda, A; Wilson, A E; Ross, H; Danenberg, P V; Burt, M; Scotto, K W

    1999-11-01

    Overexpression of P-glycoprotein (Pgp), a multidrug transporter encoded by the MDR1 gene, is associated with chemoresistance in some human solid tumor malignancies. To date, analyses of MDR1 levels in solid tumors have examined constitutive increases in expression at relapse. In the present study, we have evaluated the acute induction of MDR1 gene expression in a solid human tumor as a function of time in response to in vivo exposure to chemotherapy. Five patients with unresectable sarcoma pulmonary metastases underwent isolated single lung perfusion with doxorubicin. Relative MDR1 gene expression was measured in metastatic tumor nodules and normal lung specimens after initiation of chemoperfusion. In four of five patients, a 3-15-fold (median, 6.8) increase in MDR1 RNA levels was detected in tumors at 50 min after administration of doxorubicin. In contrast, normal lung samples had very low levels of MDR1 RNA prior to perfusion, and no acute increases were observed after therapy. These findings demonstrate, for the first time, that MDR1 gene expression can be rapidly activated in human tumors after transient in vivo exposure to cytotoxic chemotherapy.

  14. Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity

    PubMed Central

    Serita, Tatsurou; Fukushima, Hotaka; Kida, Satoshi

    2017-01-01

    Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM. PMID:28195219

  15. Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity.

    PubMed

    Serita, Tatsurou; Fukushima, Hotaka; Kida, Satoshi

    2017-02-14

    Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM.

  16. Viral particles drive rapid differentiation of memory B cells into secondary plasma cells producing increased levels of antibodies.

    PubMed

    Zabel, Franziska; Mohanan, Deepa; Bessa, Juliana; Link, Alexander; Fettelschoss, Antonia; Saudan, Philippe; Kündig, Thomas M; Bachmann, Martin F

    2014-06-15

    Extensive studies have been undertaken to describe naive B cells differentiating into memory B cells at a cellular and molecular level. However, relatively little is known about the fate of memory B cells upon Ag re-encounter. We have previously established a system based on virus-like particles (VLPs), which allows tracking of VLP-specific B cells by flow cytometry as well as histology. Using allotype markers, it is possible to adoptively transfer memory B cells into a naive mouse and track responses of naive and memory B cells in the same mouse under physiological conditions. We have observed that VLP-specific memory B cells quickly differentiated into plasma cells that drove the early onset of a strong humoral IgG response. However, neither IgM(+) nor IgG(+) memory B cells proliferated extensively or entered germinal centers. Remarkably, plasma cells derived from memory B cells preferentially homed to the bone marrow earlier and secreted increased levels of Abs when compared with primary plasma cells derived from naive B cells. Hence, memory B cells have the unique phenotype to differentiate into highly effective secondary plasma cells.

  17. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration.

    PubMed

    Li, Yiqing; Andereggen, Lukas; Yuki, Kenya; Omura, Kumiko; Yin, Yuqin; Gilbert, Hui-Ya; Erdogan, Burcu; Asdourian, Maria S; Shrock, Christine; de Lima, Silmara; Apfel, Ulf-Peter; Zhuo, Yehong; Hershfinkel, Michal; Lippard, Stephen J; Rosenberg, Paul A; Benowitz, Larry

    2017-01-10

    Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release. Zn(2+) accumulation in amacrine cell processes involves the Zn(2+) transporter protein ZnT-3, and deletion of slc30a3, the gene encoding ZnT-3, promotes RGC survival and axon regeneration. Intravitreal injection of Zn(2+) chelators enables many RGCs to survive for months after nerve injury and regenerate axons, and enhances the prosurvival and regenerative effects of deleting the gene for phosphatase and tensin homolog (pten). Importantly, the therapeutic window for Zn(2+) chelation extends for several days after nerve injury. These results show that retinal Zn(2+) dysregulation is a major factor limiting the survival and regenerative capacity of injured RGCs, and point to Zn(2+) chelation as a strategy to promote long-term RGC protection and enhance axon regeneration.

  18. Increased hepcidin in transferrin-treated thalassemic mice correlates with increased liver BMP2 expression and decreased hepatocyte ERK activation.

    PubMed

    Chen, Huiyong; Choesang, Tenzin; Li, Huihui; Sun, Shuming; Pham, Petra; Bao, Weili; Feola, Maria; Westerman, Mark; Li, Guiyuan; Follenzi, Antonia; Blanc, Lionel; Rivella, Stefano; Fleming, Robert E; Ginzburg, Yelena Z

    2016-03-01

    Iron overload results in significant morbidity and mortality in β-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in β-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes from apo-transferrin-treated mice demonstrate decreased ERK1/2 pathway and increased serum BMP2 concentration and hepatocyte BMP2 expression. Furthermore, hepatocyte ERK1/2 phosphorylation is enhanced by neutralizing anti-BMP2/4 antibodies and suppressed in vitro in a dose-dependent manner by BMP2, resulting in converse effects on hepcidin expression, and hepatocytes treated with MEK/ERK1/2 inhibitor U0126 in combination with BMP2 exhibit an additive increase in hepcidin expression. Lastly, bone marrow erythroferrone expression is normalized in apo-transferrin treated thalassemic mice but increased in apo-transferrin injected wild-type mice. These findings suggest that increased hepcidin expression after exogenous apo-transferrin is in part independent of erythroferrone and support a model in which apo-transferrin treatment in thalassemic mice increases BMP2 expression in the liver and other organs, decreases hepatocellular ERK1/2 activation, and increases nuclear Smad to increase hepcidin expression in hepatocytes.

  19. Opsonic antibody activity against Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

    PubMed Central

    Sjöström, K; Darveau, R; Page, R; Whitney, C; Engel, D

    1992-01-01

    Actinobacillus actinomycetemcomitans has been closely associated with early-onset, severe periodontitis, and such patients often have serum immunoglobulin G (IgG) antibodies reactive with antigens of this gram-negative pathogen. We examined the functionality and potential importance of these antibodies. The opsonic activity against A. actinomycetemcomitans of sera from 30 patients with rapidly progressive periodontitis (RPP) and from 28 periodontally normal subjects was tested by using polymorphonuclear leukocyte (PMN) chemiluminescence and bactericidal assays. Peak chemiluminescence values correlated strongly with killing observed in the PMN-dependent bactericidal assay (r = 0.88; P < 0.001). Neither the mean IgG titer nor the mean peak chemiluminescence differed significantly between the two groups. However, when the relationship between chemiluminescence and titer was examined, regression analysis showed that antibodies present in low-titer normal sera were significantly more effective at opsonizing A. actinomycetemcomitans than antibodies present in low-titer RPP patient sera (P = 0.04). Thus, periodontally normal individuals may be better able than RPP patients to clear A. actinomycetemcomitans in early stages of colonization, and anti-A. actinomycetemcomitans antibodies in RPP patients may be relatively ineffective in preventing infection by this organism. PMID:1398993

  20. A rapid ceramide synthase activity using NBD-sphinganine and solid phase extraction

    PubMed Central

    Tidhar, Rotem; Sims, Kacee; Rosenfeld-Gur, Eden; Shaw, Walter; Futerman, Anthony H.

    2015-01-01

    Ceramides are synthesized by six mammalian ceramide synthases (CerSs), each of which uses fatty acyl-CoAs of different chain lengths for N-acylation of the sphingoid long-chain base. We now describe a rapid and reliable CerS assay that uses a fluorescent N-[6-[(7-nitrobenzo-2-oxa-1,3-diazol-4-yl) (NBD) sphinganine substrate followed by separation of the NBD-lipid substrate and products using solid phase extraction (SPE) C18 chromatography. SPE chromatography is a quick and reliable alternative to TLC, and moreover, there is no degradation of either NBD-sphinganine or NBD-ceramide. We have optimized the assay for use with minimal amounts of protein in a minimal volume. This assay will prove useful for the analysis of CerS activity, which is of particular importance in light of the growing involvement of CerS in cell regulation and in the pathology of human diseases. PMID:25368106

  1. Hydrodynamic Voltammetry as a Rapid and Simple Method for Evaluating Soil Enzyme Activities

    PubMed Central

    Sazawa, Kazuto; Kuramitz, Hideki

    2015-01-01

    Soil enzymes play essential roles in catalyzing reactions necessary for nutrient cycling in the biosphere. They are also sensitive indicators of ecosystem stress, therefore their evaluation is very important in assessing soil health and quality. The standard soil enzyme assay method based on spectroscopic detection is a complicated operation that requires the removal of soil particles. The purpose of this study was to develop a new soil enzyme assay based on hydrodynamic electrochemical detection using a rotating disk electrode in a microliter droplet. The activities of enzymes were determined by measuring the electrochemical oxidation of p-aminophenol (PAP), following the enzymatic conversion of substrate-conjugated PAP. The calibration curves of β-galactosidase (β-gal), β-glucosidase (β-glu) and acid phosphatase (AcP) showed good linear correlation after being spiked in soils using chronoamperometry. We also performed electrochemical detection using real soils. Hydrodynamic chronoamperometry can be used to assess the AcP in soils, with a detection time of only 90 s. Linear sweep voltammetry was used to measure the amount of PAP released from β-gal and β-glu by enzymatic reaction after 60 min. For the assessment of soil enzymes, the results of hydrodynamic voltammetry assay compared favorably to those using a standard assay procedure, but this new procedure is more user-friendly, rapid and simple. PMID:25746097

  2. Rapid and Bright Stellar-mass Binary Black Hole Mergers in Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Bartos, Imre; Kocsis, Bence; Haiman, Zoltán; Márka, Szabolcs

    2017-02-01

    The Laser Interferometer Gravitational-wave Observatory (LIGO) found direct evidence for double black hole binaries emitting gravitational waves. Galactic nuclei are expected to harbor the densest population of stellar-mass black holes. A significant fraction (∼ 30 % ) of these black holes can reside in binaries. We examine the fate of the black hole binaries in active galactic nuclei, which get trapped in the inner region of the accretion disk around the central supermassive black hole. We show that binary black holes can migrate into and then rapidly merge within the disk well within a Salpeter time. The binaries may also accrete a significant amount of gas from the disk, well above the Eddington rate. This could lead to detectable X-ray or gamma-ray emission, but would require hyper-Eddington accretion with a few percent radiative efficiency, comparable to thin disks. We discuss implications for gravitational-wave observations and black hole population studies. We estimate that Advanced LIGO may detect ∼20 such gas-induced binary mergers per year.

  3. Rapid prototyping of reflectors for vehicle lighting using laser activated remote phosphor

    NASA Astrophysics Data System (ADS)

    Lachmayer, Roland; Kloppenburg, Gerolf; Wolf, Alexander

    2015-03-01

    Bright white light sources are of significant importance for automotive front lighting systems. Today's upper class vehicles mainly use HID or LED as light source. As a further step in this development laser diode based systems offer high luminance, efficiency and allow the realization of new styling concepts and new dynamic lighting functions. These white laser diode systems can either be realized by mixing different spectral sources or by combining diodes with specific phosphors. Based on the approach of generating light using a laser and remote phosphor, lighting modules are manufactured. Four blue laser diodes (450 nm) are used to activate a phosphor coating and thus to achieve white light. A segmented paraboloid reflector generates the desired light distribution for an additional car headlamp. We use high speed milling and selective laser melting to build the reflector system for this lighting module. We compare the spectral reflection grade of these materials. Furthermore the generated modules are analyzed regarding their efficiency and light distribution. The use of Rapid Prototyping technologies allows an early validation of the chosen concept and is supposed to reduce cost and time in the product development process significantly. Therefor we discuss costs and times of the applied manufacturing technologies.

  4. LOW-MASS ACTIVE GALACTIC NUCLEI WITH RAPID X-RAY VARIABILITY

    SciTech Connect

    Ho, Luis C.; Kim, Minjin

    2016-04-10

    We present a detailed study of the optical spectroscopic properties of 12 active galactic nuclei (AGNs) with candidate low-mass black holes (BHs) selected by Kamizasa et al. through rapid X-ray variability. The high-quality, echellette Magellan spectra reveal broad Hα emission in all the sources, allowing us to estimate robust virial BH masses and Eddington ratios for this unique sample. We confirm that the sample contains low-mass BHs accreting at high rates: the median M{sub BH} = 1.2 × 10{sup 6} M{sub ⊙} and median L{sub bol}/L{sub Edd} = 0.44. The sample follows the M{sub BH}–σ{sub *} relation, within the considerable scatter typical of pseudobulges, the probable hosts of these low-mass AGNs. Various lines of evidence suggest that ongoing star formation is prevalent in these systems. We propose a new strategy to estimate star formation rates in AGNs hosted by low-mass, low-metallicity galaxies, based on modification of an existing method using the strength of [O ii] λ3727, [O iii] λ5007, and X-rays.

  5. Rapidly Alternating Transmission Mode Electron Transfer Dissociation and Collisional Activation for the Characterization of Polypeptide Ions

    PubMed Central

    Han, Hongling; Xia, Yu; Yang, Min; McLuckey, Scott A.

    2009-01-01

    Cation transmission/electron transfer reagent anion storage mode electron transfer ion/ion reactions and beam-type collisional activation of the polypeptide ions are performed in rapid succession in the high pressure collision cell (Q2) of a quadrupole/time-of-flight tandem mass spectrometer (QqTOF), where the electron transfer reagent anions are accumulated. Duty cycles for both electron transfer dissociation (ETD) and collision-induced dissociation (CID) experiments are improved relative to ion trapping approaches since there are no discrete ion storage and reaction steps for ETD experiments and no discrete ion storage step and frequency tuning for CID experiments. For this technique, moderately high resolution and mass accuracy are also obtained due to mass analysis via the TOF analyzer. This relatively simple approach has been demonstrated with a triply charged tryptic peptide, a triply charged tryptic phosphopeptide, and a triply charged tryptic N-linked glycopeptide. For the tryptic peptide, the sequence is identified with more certainty than would be available from a single method alone due to the complementary information provided by these two dissociation methods. Because of the complementary information derived from both ETD and CID dissociation methods, peptide sequence and post-translational modification (PTM) sites for the phosphopeptide are identified. This combined ETD and CID approach is particularly useful for characterizing glycopeptides because ETD generates information about both peptide sequence and locations of the glycosylation sites while CID provides information about the glycan structure. PMID:18396915

  6. Rapid, Dynamic Activation of Müller Glial Stem Cell Responses in Zebrafish

    PubMed Central

    Sifuentes, Christopher J.; Kim, Jung-Woong; Swaroop, Anand; Raymond, Pamela A.

    2016-01-01

    Purpose Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases. Methods To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute photic lesion, prior to the asymmetric division that produces retinal progenitors. Results We report a rapid, dynamic response of zebrafish Müller glia, characterized by activation of pathways related to stress, nuclear factor–κB (NF-κB) signaling, cytokine signaling, immunity, prostaglandin metabolism, circadian rhythm, and pluripotency, and an initial repression of Wnt signaling. When we compared publicly available transcriptomes of isolated mouse Müller glia from two retinal degeneration models, we found that mouse Müller glia showed evidence of oxidative stress, variable responses associated with immune regulation, and repression of pathways associated with pluripotency, development, and proliferation. Conclusions Categories of biological processes/pathways activated following photoreceptor loss in regeneration-competent zebrafish Müller glia, which distinguished them from mouse Müller glia in retinal degeneration models, included cytokine signaling (notably NF-κB), prostaglandin E2 synthesis, expression of core clock genes, and pathways/metabolic states associated with pluripotency. These regulatory mechanisms are relatively unexplored as potential mediators of stem cell properties likely to be important in Müller glial cells for successful retinal regeneration. PMID:27699411

  7. Trajectory Hunting: A Case Study of Rapid Chlorine Activation in December 1992 as Seen by UARS

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Santee, M. L.; Rodriguez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.; Livesey, N. J.

    2000-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the Atmospheric and Environmental Research, Inc. (AER) photochemical box model. As a case study, we investigate rapid chlorine activation in the Arctic lower stratosphere on December 29, 1992 associated with a polar stratospheric cloud (PSC) event. Eleven air parcels that have been sampled several times along five-day trajectories at the 465 K (approx. 46 hPa), 520 K (approx. 31 hPa), and 585 K (approx. 22 hPa) levels were investigated. For the first time, the latest versions of the Cryogenic Limb Array Etalon Spectrometer (CLAES, version 9) and Microwave Limb Sounder (MLS, version 5) data sets are analyzed, and their consistency is assessed. A detailed sensitivity study with the AER photochemical box model along these trajectories leads to the conclusion that for the December 24-29, 1992 episode: (1) the individual CLAES ClONO2 and MLS ClO measurements are self-consistent within their uncertainties; and (2) most of the time, UARS measurements of ClO, ClONO2, HNO3, and aerosol extinction at 780 cm(exp -1) agree within the range of their uncertainties with the model calculations. It appears that the HNO3 and aerosol extinction measurements for four parcels at 520 K look more supportive for the nitric acid trihydrate (NAT) scheme, However, the uncertainties in the individual UARS measurements and UK Meteorological Office temperature do not allow a definite discrimination between the NAT and supercooled ternary solution (STS) PSC schemes for this chlorine activation episode in December 1992.

  8. Trajectory Hunting: A Case Study of Rapid Chlorine Activation in December 1992 as Seen by UARS

    NASA Technical Reports Server (NTRS)

    Danilin, M. Y.; Santee, M. L.; Rodriquez, J. M.; Ko, M. K. W.; Mergenthaler, J. M.; Kumer, J. B.; Tabazadeh, A.; Livesey

    2000-01-01

    Trajectory hunting (i.e., a technique to find air parcels sampled at least twice over the course of a few days) is applied to analyze Upper Atmosphere Research Satellite (UARS) measurements in conjunction with the Atmospheric and Environmental Research, Inc. (AER) photochemical box model. As a case study, we investigate rapid chlorine activation in the Arctic lower stratosphere on December 29, 1992 associated with a polar stratospheric cloud (PSC) event. Eleven air parcels that have been sampled several times along 5-day trajectories at the 465 K (approx. 46 hPa), 520 K (approx. 31 hPa), and 585 K (approx. 22 hPa) levels were investigated. For the first time, the latest versions of the Cryogenic Limb Array Etalon Spectrometer (CLAES, version 9) and Microwave Limb Sounder (MLS, version 5) data sets are analyzed, and their consistency is assessed. A detailed sensitivity study with the AER photochemical box model along these trajectories leads to the conclusion that for the December 24-29, 1992 episode (1) the individual CLAES version 9 ClONO2 and MLS version 5 ClO measurements are self-consistent within their uncertainties; and (2) most of the time, UARS measurements of ClO, ClONO2, HNO3, and aerosol extinction at 780 cm (exp -1) agree within the range of their uncertainties with the model calculations. It appears that the HNO3 and aerosol extinction measurements for four parcels at 520 K look more supportive for the nitric acid trihydrate (NAT) scheme. However, the uncertainties in the individual UARS measurements and U.K. Meteorological Office temperature do not allow a definite discrimination between the NAT and supercooled ternary solution (STS) PSC schemes for this chlorine activation episode in December 1992.

  9. Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection

    PubMed Central

    de Medeiros, Rúbia M.; Valverde-Villegas, Jacqueline M.; Junqueira, Dennis M.; Gräf, Tiago; Lindenau, Juliana D.; de Mello, Marineide G.; Vianna, Priscila; Almeida, Sabrina E. M.; Chies, Jose Artur B.

    2016-01-01

    Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals. PMID:27214135

  10. The effect of increasing autonomy through choice on young children’s physical activity behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing autonomy by manipulating the choice of available physical activity options in a laboratory setting can increase physical activity in older children and adults. However, the effect of manipulating the number of physically active choices has yet to be examined in young children in a gymnas...

  11. Promising School-Based Strategies and Intervention Guidelines to Increase Physical Activity of Adolescents

    ERIC Educational Resources Information Center

    Pardo, Berta Murillo; Bengoechea, Enrique Garcia; Lanaspa, Eduardo Generelo; Bush, Paula L.; Casterad, Javier Zaragoza; Clemente, Jose A. Julian; Gonzalez, Luis Garcia

    2013-01-01

    This narrative review describes the available scientific evidence regarding promising school-based strategies to increase physical activity of adolescents. We conducted a literature search for studies published up to 2011, regarding adolescent physical activity intervention studies that resulted in increased physical activity (regardless of…

  12. Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse

    PubMed Central

    Apostolides, Pierre F.; Trussell, Laurence O.

    2013-01-01

    The release of neurotransmitter via the fusion of transmitter-filled, presynaptic vesicles is the primary means by which neurons relay information. However, little is known regarding the molecular mechanisms that supply neurotransmitter destined for vesicle filling, the endogenous transmitter concentrations inside presynaptic nerve terminals or the dynamics of vesicle refilling after exocytosis. We addressed these issues by recording from synaptically-coupled pairs of glycine/GABA co-releasing interneurons (cartwheel cells) of the mouse dorsal cochlear nucleus. We find that the plasma membrane transporter GlyT2 and the intracellular enzyme glutamate decarboxylase supply the majority of glycine and GABA, respectively. Pharmacological block of GlyT2 or glutamate decarboxylase led to rapid and complete rundown of transmission, whereas increasing GABA synthesis via intracellular glutamate uncaging dramatically potentiated GABA release within one minute. These effects were surprisingly independent of exocytosis, indicating that pre-filled vesicles re-equilibrated upon acute changes in cytosolic transmitter. Titration of cytosolic transmitter with postsynaptic responses indicated that endogenous, non-vesicular glycine/GABA levels in nerve terminals are 5 to 7 mM, and that vesicular transport mechanisms are not saturated under basal conditions. Thus, cytosolic transmitter levels dynamically set the strength of inhibitory synapses in a release-independent manner. PMID:23486948

  13. Molecular Basis of the Increase in Invertase Activity Elicited by Gravistimulation of Oat-Shoot Pulvini

    NASA Technical Reports Server (NTRS)

    Wu, Liu-Lai; Song, Il; Kim, Donghern; Kaufman, Peter B.

    1993-01-01

    An asymmetric (top vs. bottom) increase in invertase activity is elicited by gravistimulation in oatshoot pulvini starting within 3h after treatment. In order to analyze the regulation of invertase gene expression in this system, we examined the effect of gravistimulation on invertase mRNA induction. Total RNA and poly(A)(+)RNA, isolated from oat pulvini, and two oligonucleotide primers, corresponding to two conserved amino-acid sequences (NDPNG and WECPD) found in invertase from other species, were used for the Polymerase Chain Reaction (PCR). A partial-length cDNA (550 base pairs) was obtained and characterized. There was a 52 % deduced amino-acid sequence homology to that of carrot beta-fructosi- dase and a 48 % homology to that of tomato invertase. Northern blot analysis showed that there was an obvious transient accumulation of invertase mRNA elicited by gravistimulation of oat pulvini. The mRNA was rapidly induced to a maximum level at 1h following gravistimulation treatment and gradually decreased afterwards. The mRNA level in the bottom half of the oat pulvinus was significantly higher (five-fold) than that in the top half of the pulvinus tissue. The induction of invertase mRNA was consistent with the transient enhancement of invertase activity during the graviresponse of the pulvinus. These data indicate that the expression of the invertase gene(s) could be regulated by gravistimulation at the transcriptional and/or translational levels. Southern blot analysis showed that there were four genomic DNA fragments hybridized to the invertase cDNA. This suggests that an invertase gene family may exist in oat plants.

  14. What are the implications of rapid global warming for landslide-triggered turbidity current activity?

    NASA Astrophysics Data System (ADS)

    Clare, Michael; Peter, Talling; James, Hunt

    2014-05-01

    arithmetic mean recurrence, λ, for the full records (λ=0.007 and 0.0125 Myr). This period of inactivity is coincident with a dramatic carbon isotopic excursion (i.e. warmest part of the IETM) and heavily skews statistical analyses for both records. Dramatic global warming appears to exert a strong control on inhibiting turbidity current activity; whereas the effects of sea level change are not shown to be statistically significant. Rapid global warming is often implicated as a potential landslide trigger, due to dissociation of gas hydrates in response to elevated ocean temperatures. Other studies have suggested that intense global warming may actually be attributed to the atmospheric release of gas hydrates following catastrophic failure of large parts of a continental slope. Either way, a greater intensity of landslide and resultant turbidity current activity would be expected during the IETM; however, our findings are to the contrary. We offer some explanations in relation to potential triggers. Our work suggests that previous rapid global warming at the IETM did not trigger more frequent turbidity currents. This has direct relevance to future assessments relating to landslide-triggered tsunami hazard, and breakage of subsea cables by turbidity currents.

  15. Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency.

    PubMed

    Lee, Eun-Jeong; De Winter, Josine M; Buck, Danielle; Jasper, Jeffrey R; Malik, Fady I; Labeit, Siegfried; Ottenheijm, Coen A; Granzier, Henk

    2013-01-01

    The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT) and nebulin deficient (NEB KO) mice. Nebulin is a sarcomeric protein that when absent (NEB KO mouse) or present at low levels (nemaline myopathy (NM) patients with NEB mutations) causes muscle weakness. We studied the effect of fast skeletal troponin activation on WT muscle and tested whether it might be a therapeutic mechanism to increase muscle strength in nebulin deficient muscle. We measured tension-pCa relations with and without added CK-2066260. Maximal active tension in NEB KO tibialis cranialis fibers in the absence of CK-2066260 was ∼60% less than in WT fibers, consistent with earlier work. CK-2066260 shifted the tension-calcium relationship leftwards, with the largest relative increase (up to 8-fold) at low to intermediate calcium levels. This was a general effect that was present in both WT and NEB KO fiber bundles. At pCa levels above ∼6.0 (i.e., calcium concentrations <1 µM), CK-2066260 increased tension of NEB KO fibers to beyond that of WT fibers. Crossbridge cycling kinetics were studied by measuring k(tr) (rate constant of force redevelopment following a rapid shortening/restretch). CK-2066260 greatly increased k(tr) at submaximal activation levels in both WT and NEB KO fiber bundles. We also studied the sarcomere length (SL) dependence of the CK-2066260 effect (SL 2.1 µm and 2.6 µm) and found that in the NEB KO fibers, CK-2066260 had a larger effect on calcium sensitivity at the long SL. We conclude that fast skeletal muscle troponin activation increases force at submaximal activation in both wildtype and NEB KO fiber bundles and, importantly, that this troponin activation is a potential therapeutic mechanism for increasing force in NM and other skeletal muscle diseases with loss of muscle strength.

  16. Glucocorticoid acts on a putative G protein-coupled receptor to rapidly regulate the activity of NMDA receptors in hippocampal neurons.

    PubMed

    Zhang, Yanmin; Sheng, Hui; Qi, Jinshun; Ma, Bei; Sun, Jihu; Li, Shaofeng; Ni, Xin

    2012-04-01

    Glucocorticoids (GCs) have been demonstrated to act through both genomic and nongenomic mechanisms. The present study demonstrated that corticosterone rapidly suppressed the activity of N-methyl-D-aspartate (NMDA) receptors in cultured hippocampal neurons. The effect was maintained with corticosterone conjugated to bovine serum albumin and blocked by inhibition of G protein activity with intracellular GDP-β-S application. Corticosterone increased GTP-bound G(s) protein and cyclic AMP (cAMP) production, activated phospholipase Cβ(3) (PLC-β(3)), and induced inositol-1,4,5-triphosphate (IP(3)) production. Blocking PLC and the downstream cascades with PLC inhibitor, IP(3) receptor antagonist, Ca(2+) chelator, and protein kinase C (PKC) inhibitors prevented the actions of corticosterone. Blocking adenylate cyclase (AC) and protein kinase A (PKA) caused a decrease in NMDA-evoked currents. Application of corticosterone partly reversed the inhibition of NMDA currents caused by blockage of AC and PKA. Intracerebroventricular administration of corticosterone significantly suppressed long-term potentiation (LTP) in the CA1 region of the hippocampus within 30 min in vivo, implicating the possibly physiological significance of rapid effects of GC on NMDA receptors. Taken together, our results indicate that GCs act on a putative G protein-coupled receptor to activate multiple signaling pathways in hippocampal neurons, and the rapid suppression of NMDA activity by GCs is dependent on PLC and downstream signaling.

  17. Tetrachlorobenzoquinone induces Nrf2 activation via rapid Bach1 nuclear export/ubiquitination and JNK-P62 signaling.

    PubMed

    Su, Chuanyang; Shi, Qiong; Song, Xiufang; Fu, Juanli; Liu, Zixuan; Wang, Yawen; Wang, Yuxin; Xia, Xiaomin; Song, Erqun; Song, Yang

    2016-07-01

    Our previous studies demonstrated that tetrachlorobenzoquinone (TCBQ), an active metabolite of pentachlorophenol, has effects on the generation of reactive oxygen species (ROS) and oxidative stress in vitro and in vivo. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of electrophilic or oxidative stress that regulates the expression of antioxidant enzymes and defensive proteins. We have illustrated that TCBQ activates Nrf2 signaling by promoting the formation of the Kelch-like ECH-associated protein 1 (Keap1) cross-linking dimer and the formation of an ubiquitination switch from Nrf2 to Keap1. The activation of Nrf2 by TCBQ may serve as an adaptive response to a TCBQ-induced oxidative insult. BTB and CNC homolog 1 (Bach1) compete with Nrf2, leading to the negative regulation of the antioxidant response element (ARE). In this report, we propose that TCBQ induces the dynamic inactivation of Bach1. We observed a rapid nuclear efflux of Bach1 and an accumulation of Nrf2 in nuclei upon TCBQ treatment that precedes the binding of Nrf2 with ARE. We found that the nuclear export of Bach1 is dependent on its chromosomal region maintenance 1 (Crm1) interaction and tyrosine phosphorylation. Although TCBQ induces the ubiquitination of Bach1, TCBQ also increases the mRNA and protein levels of Bach1, returning Bach1 to normal levels. Moreover, we found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling.

  18. Production and food web efficiency decrease as fishing activity increases in a coastal ecosystem

    NASA Astrophysics Data System (ADS)

    Anh, Pham Viet; Everaert, Gert; Goethals, Peter; Vinh, Chu Tien; De Laender, Frederik

    2015-11-01

    Fishing effort in the Vietnamese coastal ecosystem has rapidly increased from the 1990s to the 2000s, with unknown consequences for local ecosystem structure and functioning. Using ecosystem models that integrate fisheries and food webs we found profound differences in the production of six functional groups, the food web efficiency, and eight functional food web indices between the 1990s (low fishing intensity) and the 2000s (high fishing intensity). The functional attributes (e.g. consumption) of high trophic levels (e.g. predators) were lower in the 2000s than in the 1990s while primary production did not vary, causing food web efficiency to decrease up to 40% with time for these groups. The opposite was found for lower trophic levels (e.g. zooplankton): the functional attributes and food web efficiency increased with time (22 and 10% for the functional attributes and food web efficiency, respectively). Total system throughput, a functional food web index, was about 10% higher in the 1990s than in the 2000s, indicating a reduction of the system size and activity with time. The network analyses further indicated that the Vietnamese coastal ecosystem in the 1990s was more developed (higher ascendancy and capacity), more stable (higher overhead) and more mature (higher ratio of ascendancy and capacity) than in the 2000s. In the 1990s the recovery time of the ecosystem was shorter than in 2000s, as indicated by a higher Finn's cycling index in the 1990s (7.8 and 6.5% in 1990s and 2000s, respectively). Overall, our results demonstrate that the Vietnamese coastal ecosystem has experienced profound changes between the 1990s and 2000s, and emphasise the need for a closer inspection of the ecological impact of fishing.

  19. A rapid, sensitive, simple plate assay for detection of microbial alginate lyase activity.

    PubMed

    Sawant, Shailesh S; Salunke, Bipinchandra K; Kim, Beom Soo

    2015-09-01

    Screening of microorganisms capable of producing alginate lyase enzyme is commonly carried out by investigating their abilities to grow on alginate-containing solid media plates and occurrence of a clearance zone after flooding the plates with agents such as 10% (w/v) cetyl pyridinium chloride (CPC), which can form complexes with alginate. Although the CPC method is good, advantageous, and routinely used, the agar in the media interferes with the action of CPC, which makes judgment about clearance zones very difficult. In addition, this method takes a minimum of 30 min to obtain the zone of hydrolysis after flooding and the hydrolyzed area is not sharply discernible. An improved plate assay is reported herein for the detection of extracellular alginate lyase production by microorganisms. In this method, alginate-containing agar plates are flooded with Gram's iodine instead of CPC. Gram's iodine forms a bluish black complex with alginate but not with hydrolyzed alginate, giving sharp, distinct zones around the alginate lyase producing microbial colonies within 2-3 min. Gram's iodine method was found to be more effective than the CPC method in terms of visualization and measurement of zone size. The alginate-lyase-activity area indicated using the Gram's iodine method was found to be larger than that indicated by the CPC method. Both methods (CPC and Gram's iodine) showed the largest alginate lyase activity area for Saccharophagus degradans (ATCC 43961) followed by Microbulbifer mangrovi (KCTC 23483), Bacillus cereus (KF801505) and Paracoccus sp. LL1 (KP288668) grown on minimal sea salt medium. The rate of growth and metabolite production in alginate-containing minimal sea salt liquid medium, followed trends similar to that of the zone activity areas for the four bacteria under study. These results suggested that the assay developed in this study of Gram's iodine could be useful to predict the potential of microorganisms to produce alginate lyase. The method also

  20. An Evaluation of Photographic Activity Schedules to Increase Independent Playground Skills in Young Children with Autism

    ERIC Educational Resources Information Center

    Akers, Jessica S.; Higbee, Thomas S.; Pollard, Joy S.; Pellegrino, Azure J.; Gerencser, Kristina R.

    2016-01-01

    We used photographic activity schedules to increase the number of play activities completed by children with autism during unstructured time on the playground. All 3 participants engaged in more playground activities during and after training, and they continued to complete activities when novel photographs were introduced.

  1. [Two cases of Lambert-Eaton syndrome with an increase of serum cholinesterase activity].

    PubMed

    Ciechanowski, K; Cebula, D

    1997-02-01

    Paraneoplastic Lambert-Eaton myasthenia syndrome is presented in two cases with small cell lung cancer. An increase of serum cholinesterase activity was explained by induced release of biologically active proteins by neoplastic tissue.

  2. A Rapid and Quantitative Flow Cytometry Method for the Analysis of Membrane Disruptive Antimicrobial Activity

    PubMed Central

    O’Brien-Simpson, Neil M.; Pantarat, Namfon; Attard, Troy J.; Walsh, Katrina A.; Reynolds, Eric C.

    2016-01-01

    We describe a microbial flow cytometry method that quantifies within 3 hours antimicrobial peptide (AMP) activity, termed Minimum Membrane Disruptive Concentration (MDC). Increasing peptide concentration positively correlates with the extent of bacterial membrane disruption and the calculated MDC is equivalent to its MBC. The activity of AMPs representing three different membranolytic modes of action could be determined for a range of Gram positive and negative bacteria, including the ESKAPE pathogens, E. coli and MRSA. By using the MDC50 concentration of the parent AMP, the method provides high-throughput, quantitative screening of AMP analogues. A unique feature of the MDC assay is that it directly measures peptide/bacteria interactions and lysed cell numbers rather than bacteria survival as with MIC and MBC assays. With the threat of multi-drug resistant bacteria, this high-throughput MDC assay has the potential to aid in the development of novel antimicrobials that target bacteria with improved efficacy. PMID:26986223

  3. Acute canine distemper encephalitis is associated with rapid neuronal loss and local immune activation.

    PubMed

    Rudd, Penny A; Bastien-Hamel, Louis-Etienne; von Messling, Veronika

    2010-04-01

    For most virus infections of the central nervous system (CNS), immune-mediated damage, the route of inoculation and death of infected cells all contribute to the pathology observed. To investigate the role of these factors in early canine distemper neuropathogenesis, we infected ferrets either intranasally or intraperitoneally with the neurovirulent canine distemper virus strain Snyder Hill. Regardless of the route of inoculation, the virus primarily targeted the olfactory bulb, brainstem, hippocampus and cerebellum, whereas only occasional foci were detected in the cortex. The infection led to widespread neuronal loss, which correlated with the clinical signs observed. Increased numbers of activated microglia, reactive gliosis and different pro-inflammatory cytokines were detected in the infected areas, suggesting that the presence and ultimate death of infected cells at early times after infection trigger strong local immune activation, despite the observed systemic immunosuppression.

  4. Rapid Activation of Phenylpropanoid Metabolism in Elicitor-Treated Hybrid Poplar (Populus trichocarpa Torr. & Gray × Populus deltoides Marsh) Suspension-Cultured Cells 1

    PubMed Central

    de Sá, Mário Moniz; Subramaniam, Rajgopal; Williams, Frank E.; Douglas, Carl J.

    1992-01-01

    Elicitor induction of phenylpropanoid metabolism was investigated in suspension-cultured cells of the fast-growing poplar hybrid (Populus trichocarpa Torr. & Gray × Populus deltoides Marsh) H11-11. Treatment of cells with polygalacturonic acid lyase or two fungal elicitors resulted in rapid and transient increases in extractable l-phenylalanine ammonia lyase and 4-coumarate:coenzyme A ligase enzyme activities. The substrate specificity of the inducible 4-coumarate:coenzyme A ligase enzyme activity appeared to differ from substrate specificity of 4-coumarate:coenzyme A ligase enzyme activity in untreated control cells. Large and transient increases in the accumulation of l-phenylalanine ammonia-lyase and 4-coumarate:coenzyme A ligase mRNAs preceded the increases in enzyme activities and were detectable by 30 minutes after the start of elicitor treatment. Chalcone synthase, cinnamyl alcohol dehydrogenase, and coniferin β-glucosidase enzyme activities were unaffected by the elicitors, but a large and transient increase in β-glucosidase activity capable of hydrolyzing 4-nitrophenyl-β-glucoside was observed. Subsequent to increases in l-phenylalanine ammonialyase and 4-coumarate:coenzyme A ligase enzyme activities, cell wall-bound thioglycolic acid-extractable compounds accumulated in elicitor-treated cultures, and these cells exhibited strong staining with phloroglucinol, suggesting the accumulation of wall-bound phenolic compounds. ImagesFigure 7Figure 9 PMID:16668702

  5. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity.

    PubMed

    Arrol, S; Mackness, M I; Durrington, P N

    2000-05-01

    There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu(2+) was increased by 157% (110-232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185-259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122-192%) (P<0.005) and 177% (101-267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115-169%) (P<0.005) and 171% (122-192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104-153%) (P<0.05) on 200 mg/day and 240% (97-360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12. 7+/-2.6 (mean+/-SEM) to 16+/-3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4+/-2.0 to 19.2+/-3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA

  6. Rapid cooling rates at an active mid-ocean ridge from zircon thermochronology

    USGS Publications Warehouse

    Schmitt, Axel K.; Perfit, Michael R.; Rubin, Kenneth H.; Stockli, Daniel F.; Smith, Matthew C.; Cotsonika, Laurie A.; Zellmer, Georg F.; Ridley, W. Ian

    2011-01-01

    Oceanic spreading ridges are Earth's most productive crust generating environment, but mechanisms and rates of crustal accretion and heat loss are debated. Existing observations on cooling rates are ambiguous regarding the prevalence of conductive vs. convective cooling of lower oceanic crust. Here, we report the discovery and dating of zircon in mid-ocean ridge dacite lavas that constrain magmatic differentiation and cooling rates at an active spreading center. Dacitic lavas erupted on the southern Cleft segment of the Juan de Fuca ridge, an intermediate-rate spreading center, near the intersection with the Blanco transform fault. Their U–Th zircon crystallization ages (29.3-4.6+4.8 ka; 1δ standard error s.e.) overlap with the (U–Th)/He zircon eruption age (32.7 ± 1.6 ka) within uncertainty. Based on similar 238U-230Th disequilibria between southern Cleft dacite glass separates and young mid-ocean ridge basalt (MORB) erupted nearby, differentiation must have occurred rapidly, within ~ 10–20 ka at most. Ti-in-zircon thermometry indicates crystallization at 850–900 °C and pressures > 70–150 MPa are calculated from H2O solubility models. These time-temperature constraints translate into a magma cooling rate of ~ 2 × 10-2 °C/a. This rate is at least one order-of-magnitude faster than those calculated for zircon-bearing plutonic rocks from slow spreading ridges. Such short intervals for differentiation and cooling can only be resolved through uranium-series (238U–230Th) decay in young lavas, and are best explained by dissipating heat convectively at high crustal permeability.

  7. Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation

    PubMed Central

    Raymond, Warren D; Eilertsen, Gro Østli

    2016-01-01

    Background von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Methods Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. Results VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). Conclusions In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE. PMID:27651919

  8. Activation of the G protein-coupled estrogen receptor, but not estrogen receptor α or β, rapidly enhances social learning.

    PubMed

    Ervin, Kelsy Sharice Jean; Mulvale, Erin; Gallagher, Nicola; Roussel, Véronique; Choleris, Elena

    2015-08-01

    Social learning is a highly adaptive process by which an animal acquires information from a conspecific. While estrogens are known to modulate learning and memory, much of this research focuses on individual learning. Estrogens have been shown to enhance social learning on a long-term time scale, likely via genomic mechanisms. Estrogens have also been shown to affect individual learning on a rapid time scale through cell-signaling cascades, rather than via genomic effects, suggesting they may also rapidly influence social learning. We therefore investigated the effects of 17β-estradiol and involvement of the estrogen receptors (ERs) using the ERα agonist propyl pyrazole triol, the ERβ agonist diarylpropionitrile, and the G protein-coupled ER 1 (GPER1) agonist G1 on the social transmission of food preferences (STFP) task, within a time scale that focused on the rapid effects of estrogens. General ER activation with 17β-estradiol resulted in a modest facilitation of social learning, with mice showing a preference up to 30min of testing. Specific activation of the GPER1 also rapidly enhanced social learning, with mice showing a socially learned preference up to 2h of testing. ERα activation instead shortened the expression of a socially learned food preference, while ERβ activation had little to no effects. Thus, rapid estrogenic modulation of social learning in the STFP may be the outcome of competing action at the three main receptors. Hence, estrogens' rapid effects on social learning likely depend on the specific ERs present in brain regions recruited during social learning.

  9. 20 CFR 665.330 - Are the NAFTA-TAA program requirements for rapid response also required activities?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Are the NAFTA-TAA program requirements for... WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.330 Are the NAFTA-TAA program requirements for... WIA are made available to workers who, under the NAFTA Implementation Act (Public Law 103-182),...

  10. 20 CFR 665.330 - Are the NAFTA-TAA program requirements for rapid response also required activities?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Are the NAFTA-TAA program requirements for... WORKFORCE INVESTMENT ACT Rapid Response Activities § 665.330 Are the NAFTA-TAA program requirements for... WIA are made available to workers who, under the NAFTA Implementation Act (Public Law 103-182),...

  11. 20 CFR 671.160 - What rapid response activities are required before a national emergency grant application is...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false What rapid r