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Sample records for involves sequential activation

  1. Dissociation of MIF-rpS3 complex and sequential NF-κB activation is involved in IR-induced metastatic conversion of NSCLC.

    PubMed

    Youn, HyeSook; Son, Beomseok; Kim, Wanyeon; Jun, Se Young; Lee, Jung Sub; Lee, Jae-Myung; Kang, ChulHee; Kim, Joon; Youn, BuHyun

    2015-11-01

    Frequent relapse and spreading of tumors during radiotherapy are principal obstacles to treatment of non-small cell lung cancer (NSCLC). In this study, we aimed to investigate how macrophage migration inhibitory factor (MIF) which is expressed at high levels in metastatic and primary lung cancer cells could regulate NSCLC metastasis in response to ionizing radiation (IR). The results indicated that MIF and ribosomal protein S3 (rpS3) were shown to be connected to inflammation, proliferation, and metastasis of NSCLC via IR-induced activation of the NF-κB pathway. Under unirradiated conditions, MIF physically established a complex with rpS3. MIF-rpS3 dissociation induced by IR activated NF-κB and made the expression of target genes of this factor transactivated in two NSCLC cell lines, A549, and NCI-H358. We also found that IR-induced dissociation of this complex led to increased secretion of pro-inflammatory cytokines and modulated the expression of epithelial-mesenchymal transition marker proteins. Finally, the effects of IR-induced dissociation of the MIF-rpS3 complex on tumor metastasis were confirmed by in vivo xenograft studies. Taken together, the present study revealed that dissociation of the MIF-rpS3 complex and subsequent activation of NF-κB is a critical post-IR exposure event that accounts for IR-induced metastatic conversion of NSCLC.

  2. Involvement of Working Memory in College Students' Sequential Pattern Learning and Performance

    ERIC Educational Resources Information Center

    Kundey, Shannon M. A.; De Los Reyes, Andres; Rowan, James D.; Lee, Bern; Delise, Justin; Molina, Sabrina; Cogdill, Lindsay

    2013-01-01

    When learning highly organized sequential patterns of information, humans and nonhuman animals learn rules regarding the hierarchical structures of these sequences. In three experiments, we explored the role of working memory in college students' sequential pattern learning and performance in a computerized task involving a sequential…

  3. Dissociating estimation from comparison and response eliminates parietal involvement in sequential numerosity perception.

    PubMed

    Cavdaroglu, Seda; Katz, Curren; Knops, André

    2015-08-01

    It has been widely debated whether the parietal cortex stores an abstract representation of numerosity that is activated for Arabic digits as well as for non-symbolic stimuli in a sensory modality independent fashion. Some studies suggest that numerical information in time-invariant (simultaneous) symbolic and non-symbolic visual stimuli is represented in the parietal cortex. In humans, whether the same representation is activated for time-variant (sequential) stimuli and for stimuli coming from different modalities has not been determined. To investigate this idea, we measured the brain activation of healthy adults performing estimation and/or comparison of sequential visual (series of dots) and auditory (series of beeps) numerosities. Our experimental design allowed us to separate numerosity estimation from comparison and response related factors. The BOLD response in the parietal cortex increased only when participants were engaged in the comparison of two consecutive numerosities that required a response. Using multivariate pattern analysis we trained a classifier to decode numerosity in various regions of interest (ROI). We failed to find any parietal ROI where the classifier could decode numerosities during the estimation phase. Rather, when participants were not engaged in comparison we were able to decode numerosity in an auditory cortex ROI for auditory stimuli and in a visual cortex ROI for visual stimuli. On the other hand, during the response period the classifier successfully decoded numerosity information in a parietal ROI for both visual and auditory numerosities. These results were further confirmed by support vector regression. In sum, our study does not support the involvement of the parietal cortex during estimation of sequential numerosity in the absence of an active task with a response requirement.

  4. Sequential activation of multiple grounding pads reduces skin heating.

    PubMed

    Schutt, D J; Haemmerich, D

    2006-01-01

    Radio frequency (RF) tumor ablation has become an accepted treatment modality for tumors not amenable to surgery. The need for larger ablation zones has required increase in RF generator power, with current generation devices delivering 200-250 W. Skin burns due to ground pad heating have become a common complication and are now a limiting factor for further increase in ablation zone and generator power. We performed ex vivo experiments with three ground pads (5 x 5 cm) placed on a tissue phantom. We applied 100 W of power for 12 min between the pads, and an RF electrode while we measured leading edge temperature below each pad, and temperature profile on the pads using temperature-sensitive LCD-paper. We compared conventional operation (i.e. simultaneous connection of all three pads) to sequential activation of the pads where each pad is only active for approximately 0.5 s. The timing during sequential activation was adjusted to keep leading edge temperature equal between the pads. Temperature rise below the leading edge for proximal, middle and distal ground pad was 10.7 +/- 1.04, 1.0 +/- 0.15 and 0.3 +/- 0.07 degrees C for conventional operation, and 4.8 +/- 0.16, 4.4 +/- 0.20 and 4.5 +/- 0.35 degrees C for sequentially activated operation. The maximum leading edge temperature rise was more than twice as high for conventional compared to switched operation (p<0.001). Sequential activation of multiple ground pads resulted in reduced maximum leading edge temperature, and allows control of each pad such that leading edge temperature of all pads is the same. This may reduce the incidence of ground pad burns by allowing each pad to reach same temperatures independent of location, and may allow higher power RF generators due to reduced skin heating.

  5. Movement of particles using sequentially activated dielectrophoretic particle trapping

    DOEpatents

    Miles, Robin R.

    2004-02-03

    Manipulation of DNA and cells/spores using dielectrophoretic (DEP) forces to perform sample preparation protocols for polymerized chain reaction (PCR) based assays for various applications. This is accomplished by movement of particles using sequentially activated dielectrophoretic particle trapping. DEP forces induce a dipole in particles, and these particles can be trapped in non-uniform fields. The particles can be trapped in the high field strength region of one set of electrodes. By switching off this field and switching on an adjacent electrodes, particles can be moved down a channel with little or no flow.

  6. Public Involvement in BOSC Activities

    EPA Pesticide Factsheets

    EPA policy and the Federal Advisory Committee Act provide for public involvement in committee activities primarily by open access to meetings and records and by providing the public an opportunity to submit comments to the committee.

  7. Promoting Active Involvement in Classrooms

    ERIC Educational Resources Information Center

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2012-01-01

    This article presents a rationale for using active involvement techniques, describes large- and small-group methods based on their documented effectiveness and applicability to K-12 classrooms, and illustrates their use. These approaches include ways of engaging students in large groups (e.g., unison responses, response cards, dry-erase boards,…

  8. The sequential encoding of competing action goals involves dynamic restructuring of motor plans in working memory.

    PubMed

    Gallivan, Jason P; Bowman, Natasha A R; Chapman, Craig S; Wolpert, Daniel M; Flanagan, J Randall

    2016-06-01

    Recent neural and behavioral findings provide support for the influential idea that in situations in which multiple action options are presented simultaneously, we prepare action plans for each competing option before deciding between and executing one of those plans. However, in natural, everyday environments, our available action options frequently change from one moment to the next, and there is often uncertainty as to whether additional options will become available before having to select a particular course of action. Here, with the use of a target-directed reaching task, we show that in this situation, the brain specifies a competing action for each new, sequentially presented potential target and that recently formed action plans can be revisited and updated so as to conform with separate, more newly developed, plans. These findings indicate that the brain forms labile motor plans for sequentially arising target options that can be flexibly restructured to accommodate new motor plans.

  9. Sequential activation of ground pads reduces skin heating during radiofrequency tumor ablation: in vivo porcine results.

    PubMed

    Schutt, David J; Swindle, M Michael; Helke, Kristi L; Bastarrika, Gorka; Schwarz, Florian; Haemmerich, Dieter

    2010-03-01

    Skin burns below ground pads during monopolar RF ablation are increasingly prevalent, thereby hindering the development of higher power RF generators capable of creating larger tumor ablation zones in combination with multiple or new applicators. Our goal was to evaluate reduction in skin temperatures via additional ground pads in an in vivo porcine model. Three ground pads placed on the animal's abdomen were activated either simultaneously or sequentially, where activation timing was adjusted to equilibrate skin temperature below each pad. Thirteen RF ablations (n = 4 simultaneous at 300 W, n = 5 sequential at 300 W, and n = 4 sequential at 375 W) were performed for 12 min via two internally cooled cluster electrodes placed in the gluteus maximus of domestic swine. Temperature rise at each pad and burn degree as determined via histology were compared. Ablation zone size was determined via T2-weighted MRI. Maximum temperature rise was significantly higher with simultaneous activation than with either of the sequential activation group (21.4 degrees C versus 8.1 degrees C or 9.6 degrees C, p < 0.01). Ablation zone diameters during simultaneous (300 W) and sequential activations (300 and 375 W) were and 6.9 +/- 0.3, 5.6 +/- 0.3, and 7.5 +/- 0.6 cm, respectively. Sequential activation of multiple ground pads results in significantly lower skin temperatures and less severe burns, as measured by histological examination.

  10. Active Thermochemical Tables: Sequential Bond Dissociation Enthalpies of Methane, Ethane, and Methanol and the Related Thermochemistry.

    PubMed

    Ruscic, Branko

    2015-07-16

    Active Thermochemical Tables (ATcT) thermochemistry for the sequential bond dissociations of methane, ethane, and methanol systems were obtained by analyzing and solving a very large thermochemical network (TN). Values for all possible C-H, C-C, C-O, and O-H bond dissociation enthalpies at 298.15 K (BDE298) and bond dissociation energies at 0 K (D0) are presented. The corresponding ATcT standard gas-phase enthalpies of formation of the resulting CHn, n = 4-0 species (methane, methyl, methylene, methylidyne, and carbon atom), C2Hn, n = 6-0 species (ethane, ethyl, ethylene, ethylidene, vinyl, ethylidyne, acetylene, vinylidene, ethynyl, and ethynylene), and COHn, n = 4-0 species (methanol, hydroxymethyl, methoxy, formaldehyde, hydroxymethylene, formyl, isoformyl, and carbon monoxide) are also presented. The ATcT thermochemistry of carbon dioxide, water, hydroxyl, and carbon, oxygen, and hydrogen atoms is also included, together with the sequential BDEs of CO2 and H2O. The provenances of the ATcT enthalpies of formation, which are quite distributed and involve a large number of relevant determinations, are analyzed by variance decomposition and discussed in terms of principal contributions. The underlying reasons for periodic appearances of remarkably low and/or unusually high BDEs, alternating along the dissociation sequences, are analyzed and quantitatively rationalized. The present ATcT results are the most accurate thermochemical values currently available for these species.

  11. An automated sequential injection spectrophotometric method for evaluation of tyramine oxidase inhibitory activity of some flavonoids.

    PubMed

    Moonrungsee, Nuntaporn; Shimamura, Tomoko; Kashiwagi, Takehiro; Jakmunee, Jaroon; Higuchi, Keiro; Ukeda, Hiroyuki

    2014-05-01

    An automated sequential injection (SI) spectrophotometric system has been developed for evaluation of tyramine oxidase (TOD) inhibitory activity. The method is based on the inhibition of TOD that catalyzes the oxidation of tyramine substrate to produce aldehyde and hydrogen peroxide (H₂O₂). The produced H₂O₂ reacts with vanillic acid and 4-aminoantipyrine (4-AA) in the presence of peroxidase (POD) to form a quinoneimine dye, the absorbance of which is measured of absorbance at wavelength of 490 nm. The decrease of the quinoneimine dye is related to an increase of TOD inhibitory activity. Under the optimum conditions: 1.0 mM tyramine, 8 U mL(-1) TOD, 1.0 mM vanillic acid, 1.0 mM 4-AA and delay time of 10 s, some flavonoid compounds were examined for the TOD inhibitory activity expressed as IC₅₀ value. It was found that flavonols (quercetin and myricetin) and flavans (epicatechin gallate (ECG) and epigallocatechin (EGC)) showed higher TOD inhibitory activity than flavones and flavanones. The results of IC₅₀ values obtained from the proposed method and a batch-wise method were not significantly different from each other. Moreover, the SI system enabled automation of the analysis, leading to more convenient, more sensitive and faster analysis than the batch-wise method. A precise timing of the system also improves precision and accuracy of the assay, especially when the measurement of absorbance at non-steady state condition is involved.

  12. Sequential analysis of sperm functional aspects involved in fertilisation: a pilot study.

    PubMed

    Abu, D A H; Franken, D R; Hoffman, B; Henkel, R

    2012-05-01

    The development of diagnostic techniques in andrology as a second level of approach to the diagnosis of male factor infertility has enthused the focus of researchers on the development of a sequential diagnostic programme for these men. Semen samples of 78 men form couples undergoing in vitro fertilisation therapy were used in the study. The semen samples were used to test sperm functional aspects known to interfere with fertilisation. These tests included semen profile, DNA integrity, apoptosis, chromatin packaging, acridin orange staining, zona binding capacity, zona-induced acrosome reaction (AR). Results were correlated with fertilisation outcome. Statistical analyses of the recorded data were carried out using a logistic regression analysis model on all sperm functional tests. A negative and significant association with the fertilisation rates was recorded for DNA damage (r = -0.56; P ≤ 0.0005). A positive significant correlation was recorded between fertilisation rates and sperm with normal DNA (r = -0.57, P ≤ 0.0004), and zona-induced AR (r = 0.33, P ≤ 0.002). Diagnostic andrology can be regarded as a mandatory part of the male factor patient's work-up schedule to assist clinicians with the most suitable therapeutic modality to follow.

  13. How active gaze informs the hand in sequential pointing movements.

    PubMed

    Wilmut, Kate; Wann, John P; Brown, Janice H

    2006-11-01

    Visual information is vital for fast and accurate hand movements. It has been demonstrated that allowing free eye movements results in greater accuracy than when the eyes maintain centrally fixed. Three explanations as to why free gaze improves accuracy are: shifting gaze to a target allows visual feedback in guiding the hand to the target (feedback loop), shifting gaze generates ocular-proprioception which can be used to update a movement (feedback-feedforward), or efference copy could be used to direct hand movements (feedforward). In this experiment we used a double-step task and manipulated the utility of ocular-proprioceptive feedback from eye to head position by removing the second target during the saccade. We confirm the advantage of free gaze for sequential movements with a double-step pointing task and document eye-hand lead times of approximately 200 ms for both initial movements and secondary movements. The observation that participants move gaze well ahead of the current hand target dismisses foveal feedback as a major contribution. We argue for a feedforward model based on eye movement efference as the major factor in enabling accurate hand movements. The results with the double-step target task also suggest the need for some buffering of efference and ocular-proprioceptive signals to cope with the situation where the eye has moved to a location ahead of the current target for the hand movement. We estimate that this buffer period may range between 120 and 200 ms without significant impact on hand movement accuracy.

  14. Dissociated sequential activity and stimulus encoding in the dorsomedial striatum during spatial working memory

    PubMed Central

    Akhlaghpour, Hessameddin; Wiskerke, Joost; Choi, Jung Yoon; Taliaferro, Joshua P; Au, Jennifer; Witten, Ilana B

    2016-01-01

    Several lines of evidence suggest that the striatum has an important role in spatial working memory. The neural dynamics in the striatum have been described in tasks with short delay periods (1–4 s), but remain largely uncharacterized for tasks with longer delay periods. We collected and analyzed single unit recordings from the dorsomedial striatum of rats performing a spatial working memory task with delays up to 10 s. We found that neurons were activated sequentially, with the sequences spanning the entire delay period. Surprisingly, this sequential activity was dissociated from stimulus encoding activity, which was present in the same neurons, but preferentially appeared towards the onset of the delay period. These observations contrast with descriptions of sequential dynamics during similar tasks in other brains areas, and clarify the contribution of the striatum to spatial working memory. DOI: http://dx.doi.org/10.7554/eLife.19507.001 PMID:27636864

  15. Active stream segregation specifically involves the left human auditory cortex.

    PubMed

    Deike, Susann; Scheich, Henning; Brechmann, André

    2010-06-14

    An important aspect of auditory scene analysis is the sequential grouping of similar sounds into one "auditory stream" while keeping competing streams separate. In the present low-noise fMRI study we presented sequences of alternating high-pitch (A) and low-pitch (B) complex harmonic tones using acoustic parameters that allow the perception of either two separate streams or one alternating stream. However, the subjects were instructed to actively and continuously segregate the A from the B stream. This was controlled by the additional instruction to listen for rare level deviants only in the low-pitch stream. Compared to the control condition in which only one non-separable stream was presented the active segregation of the A from the B stream led to a selective increase of activation in the left auditory cortex (AC). Together with a similar finding from a previous study using a different acoustic cue for streaming, namely timbre, this suggests that the left auditory cortex plays a dominant role in active sequential stream segregation. However, we found cue differences within the left AC: Whereas in the posterior areas, including the planum temporale, activation increased for both acoustic cues, the anterior areas, including Heschl's gyrus, are only involved in stream segregation based on pitch.

  16. Active Beam Shaping System and Method Using Sequential Deformable Mirrors

    NASA Technical Reports Server (NTRS)

    Norman, Colin A. (Inventor); Pueyo, Laurent A. (Inventor)

    2015-01-01

    An active optical beam shaping system includes a first deformable mirror arranged to at least partially intercept an entrance beam of light and to provide a first reflected beam of light, a second deformable mirror arranged to at least partially intercept the first reflected beam of light from the first deformable mirror and to provide a second reflected beam of light, and a signal processing and control system configured to communicate with the first and second deformable mirrors. The first deformable mirror, the second deformable mirror and the signal processing and control system together provide a large amplitude light modulation range to provide an actively shaped optical beam.

  17. Phenolic content and antioxidant activity of Hibiscus cannabinus L. seed extracts after sequential solvent extraction.

    PubMed

    Yusri, Noordin Mohd; Chan, Kim Wei; Iqbal, Shahid; Ismail, Maznah

    2012-10-25

    A sequential solvent extraction scheme was employed for the extraction of antioxidant compounds from kenaf (Hibiscus cannabinus L.) seeds. Yield of extracts varied widely among the solvents and was the highest for hexane extract (16.6% based on dry weight basis), while water extract exhibited the highest total phenolic content (18.78 mg GAE/g extract), total flavonoid content (2.49 mg RE/g extract), and antioxidant activities (p < 0.05). DPPH and hydroxyl radical scavenging, β-carotene bleaching, metal chelating activity, ferric thiocyanate and thiobarbituric acid reactive substances assays were employed to comprehensively assess the antioxidant potential of different solvent extracts prepared sequentially. Besides water, methanolic extract also exhibited high retardation towards the formation of hydroperoxides and thiobarbituric acid reactive substances in the total antioxidant activity tests (p < 0.05). As conclusion, water and methanol extracts of kenaf seed may potentially serve as new sources of antioxidants for food and nutraceutical applications.

  18. Sequential activation of Elk-1/Egr-1/GADD45α by arsenic.

    PubMed

    Shi, Qiwen; Sutariya, Vijaykumar; Bishayee, Anupam; Bhatia, Deepak

    2014-06-15

    Long-term exposure to arsenic, an environmental contaminant, leads to increased risks of cancers. In the present study, we investigated the sequential regulation of Elk-1 and Egr-1 on As3+-induced GADD45α, an effector of G2/M checkpoint. We found that As3+ transcriptionally induced both Elk-1 and Egr-1, and NF-κB binding site was necessary for As3+-induced Egr-1 promoter activity. However, specific inhibition of JNK, ERK, and Elk-1 inhibited Egr-1 induction. Furthermore, silencing of Egr-1 downregulated As3+-induced expression of GADD45α and ChIP assay confirmed the direct binding of Egr-1 to GADD45α promoter. Taken together, our data indicated that the increase of GADD45α in response to As3+ was mediated sequentially by Elk-1 and Egr-1.

  19. Formation and reverberation of sequential neural activity patterns evoked by sensory stimulation are enhanced during cortical desynchronization.

    PubMed

    Bermudez Contreras, Edgar J; Schjetnan, Andrea Gomez Palacio; Muhammad, Arif; Bartho, Peter; McNaughton, Bruce L; Kolb, Bryan; Gruber, Aaron J; Luczak, Artur

    2013-08-07

    Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.

  20. Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

    PubMed Central

    Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

    2009-01-01

    Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

  1. Physicochemical properties and antioxidant activities of polysaccharides sequentially extracted from peony seed dreg.

    PubMed

    Shi, Jun-Jun; Zhang, Jian-Guo; Sun, Yu-Han; Qu, Jie; Li, Ling; Prasad, Chandan; Wei, Zhao-Jun

    2016-10-01

    The sequential extraction of peony seed dreg polysaccharides (PSDP) with hot buffer (HBSS), chelating agent (CHSS), dilute alkaline (DASS) and concentrated alkaline (CASS) yielded four different polysaccharide fractions. Based on their absorptions at 3600-3200cm(-1) and 1200-800cm(-1), these fractions were confirmed to be polysaccharides. The properties of four PSDPs displayed some slight differences. The CASS showed the highest peak temperature and endothermic enthalpy. The emulsifying activity and emulsifying stability of four PSDPs exhibited a dose-dependent pattern; HBSS showed the highest emulsifying activity, and CHSS displayed the longest emulsifying stability. The four PSDPs also exhibited wide variations in their antioxidant activities. For example, i) CASS showed the highest DPPH radical scavenging activity, reducing power and ABTS radical scavenging activity; ii) HBSS exhibited the highest hydroxyl radical scavenging activity, and iii) CHSS displayed the higher ferrous ions chelating ability than others.

  2. Promoting Active Involvement in Today's Classrooms

    ERIC Educational Resources Information Center

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2011-01-01

    In today's diverse classrooms and age of accountability, teachers need to use efficient, research-based instructional approaches that engage all students, promote interest and variety in learning and teaching, and provide immediate and continuous informal assessment data. This article presents a rationale for using active involvement techniques,…

  3. The sequential activation of the mitotic microtubule assembly pathways favors bipolar spindle formation

    PubMed Central

    Cavazza, Tommaso; Malgaretti, Paolo; Vernos, Isabelle

    2016-01-01

    Centrosome maturation is the process by which the duplicated centrosomes recruit pericentriolar components and increase their microtubule nucleation activity before mitosis. The role of this process in cells entering mitosis has been mostly related to the separation of the duplicated centrosomes and thereby to the assembly of a bipolar spindle. However, spindles can form without centrosomes. In fact, all cells, whether they have centrosomes or not, rely on chromatin-driven microtubule assembly to form a spindle. To test whether the sequential activation of these microtubule assembly pathways, defined by centrosome maturation and nuclear envelope breakdown, plays any role in spindle assembly, we combined experiments in tissue culture cells and Xenopus laevis egg extracts with a mathematical model. We found that interfering with the sequential activation of the microtubule assembly pathways compromises bipolar spindle assembly in tissue culture cells but not in X. laevis egg extracts. Our data suggest a novel function for centrosome maturation that determines the contribution of the chromosomal microtubule assembly pathway and favors bipolar spindle formation in most animal cells in which tubulin is in limiting amounts. PMID:27489339

  4. Sequential activation of a segmented ground pad reduces skin heating during radiofrequency tumor ablation: optimization via computational models.

    PubMed

    Schutt, David J; Haemmerich, Dieter

    2008-07-01

    Radiofrequency (RF) ablation has become an accepted treatment modality for unresectable tumors. The need for larger ablation zones has resulted in increased RF generator power. Skin burns due to ground pad heating are increasingly limiting further increases in generator power, and thus, ablation zone size. We investigated a method for reducing ground pad heating in which a commercial ground pad is segmented into multiple ground electrodes, with sequential activation of ground electrode subsets. We created finite-element method computer models of a commercial ground pad (14 x 23 cm) and compared normal operation of a standard pad to sequential activation of a segmented pad (two to five separate ground electrode segments). A constant current of 1 A was applied for 12 min in all simulations. Time periods during sequential activation simulations were adjusted to keep the leading edge temperatures at each ground electrode equal. The maximum temperature using standard activation of the commercial pad was 41.7 degrees C. For sequential activation of a segmented pad, the maximum temperature ranged from 39.3 degrees C (five segments) to 40.9 degrees C (two segments). Sequential activation of a segmented ground pad resulted in lower tissue temperatures. This method may reduce the incidence of ground pad burns and enable the use of higher power generators during RF tumor ablation.

  5. Sequential Activation of a Segmented Ground Pad Reduces Skin Heating During Radiofrequency Tumor Ablation: Optimization via Computational Models

    PubMed Central

    Schutt, David J.; Haemmerich, Dieter

    2009-01-01

    Radiofrequency (RF) ablation has become an accepted treatment modality for unresectable tumors. The need for larger ablation zones has resulted in increased RF generator power. Skin burns due to ground pad heating are increasingly limiting further increases in generator power, and thus, ablation zone size. We investigated a method for reducing ground pad heating in which a commercial ground pad is segmented into multiple ground electrodes, with sequential activation of ground electrode subsets. We created finite-element method computer models of a commercial ground pad (14 × 23 cm) and compared normal operation of a standard pad to sequential activation of a segmented pad (two to five separate ground electrode segments). A constant current of 1 A was applied for 12 min in all simulations. Time periods during sequential activation simulations were adjusted to keep the leading edge temperatures at each ground electrode equal. The maximum temperature using standard activation of the commercial pad was 41.7 °C. For sequential activation of a segmented pad, the maximum temperature ranged from 39.3 °C (five segments) to 40.9 °C (two segments). Sequential activation of a segmented ground pad resulted in lower tissue temperatures. This method may reduce the incidence of ground pad burns and enable the use of higher power generators during RF tumor ablation. PMID:18595807

  6. A high accuracy sequential solver for simulation and active control of a longitudinal combustion instability

    NASA Technical Reports Server (NTRS)

    Shyy, W.; Thakur, S.; Udaykumar, H. S.

    1993-01-01

    A high accuracy convection scheme using a sequential solution technique has been developed and applied to simulate the longitudinal combustion instability and its active control. The scheme has been devised in the spirit of the Total Variation Diminishing (TVD) concept with special source term treatment. Due to the substantial heat release effect, a clear delineation of the key elements employed by the scheme, i.e., the adjustable damping factor and the source term treatment has been made. By comparing with the first-order upwind scheme previously utilized, the present results exhibit less damping and are free from spurious oscillations, offering improved quantitative accuracy while confirming the spectral analysis reported earlier. A simple feedback type of active control has been found to be capable of enhancing or attenuating the magnitude of the combustion instability.

  7. Sequential extraction study of stability of adsorbed mercury in chemically modified activated carbons.

    PubMed

    Tong, Shitang; Fan, Mingxia; Mao, Lei; Jia, Charles Q

    2011-09-01

    Activated carbons chemically modified with sulfur and bromine are known for their greater effectiveness in capturing vapor Hg from coal combustion and other industrial flue gases. The stability of captured Hg in spent activated carbons determines the final fate of Hg and is critical to devising Hg control strategy. However, it remains a subject that is largely unknown, particularly for Br-treated activated carbons. Using a six-step sequential extraction procedure, this work evaluated the leaching potential of Hg captured with four activated carbons, one lignite-derived activated carbon, and three chemically treated with Br(2), KClO(3), and SO(2). The results demonstrated clearly the positive effect of Br- and SO(2)-treatment on the stability of captured Hg. The Hg captured with brominated activated carbon was very stable and likely in the form of mercurous bromide complex. Sulfur added at high temperature with SO(2) was able to stabilize a majority of Hg by forming sulfide and possibly sulfonate chelate. The presence of sulfate however made a small fraction of captured Hg (<10%) labile under mild conditions. Treating activated carbon with KClO(3) lowered the overall stability of captured Hg. A positive dependence of Hg stability on Hg loading temperature was observed for the first time.

  8. Immunoreceptor tyrosine-based inhibitory motif (ITIM)-mediated inhibitory signaling is regulated by sequential phosphorylation mediated by distinct nonreceptor tyrosine kinases: a case study involving PECAM-1.

    PubMed

    Tourdot, Benjamin E; Brenner, Michelle K; Keough, Kathleen C; Holyst, Trudy; Newman, Peter J; Newman, Debra K

    2013-04-16

    The activation state of many blood and vascular cells is tightly controlled by a delicate balance between receptors that contain immunoreceptor tyrosine-based activation motifs (ITAMs) and those that contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Precisely how the timing of cellular activation by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood. Using platelet endothelial cell adhesion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of inhibitory signaling occurs via a novel, sequential process in which Src family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containing nonreceptor tyrosine kinases (NRTKs). NRTKs capable of mediating the second phosphorylation event include C-terminal Src kinase (Csk) and Bruton's tyrosine kinase (Btk). Btk and Csk function downstream of phosphatidylinositol 3-kinase (PI3K) activation during ITAM-dependent platelet activation. In ITAM-activated platelets that were treated with a PI3K inhibitor, PECAM-1 was phosphorylated but did not bind the tandem SH2 domain-containing tyrosine phosphatase SHP-2, indicating that it was not phosphorylated on its N-terminal ITIM. Csk bound to and phosphorylated PECAM-1 more efficiently than did Btk and required its SH2 domain to perform these functions. Additionally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphorylated. On the basis of these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for precise temporal control over the recruitment and activation of tandem SH2 domain-containing tyrosine phosphatases that dampen ITAM-dependent signals.

  9. Synthesis of a novel, sequentially active-targeted drug delivery nanoplatform for breast cancer therapy.

    PubMed

    Satsangi, Arpan; Roy, Sudipa S; Satsangi, Rajiv K; Tolcher, Anthony W; Vadlamudi, Ratna K; Goins, Beth; Ong, Joo L

    2015-08-01

    Breast cancer is the leading cause of cancer deaths among women. Paclitaxel (PTX), an important breast cancer medicine, exhibits reduced bioavailability and therapeutic index due to high hydrophobicity and indiscriminate cytotoxicity. PTX encapsulation in one-level active targeting overcomes such barriers, but enhances toxicity to normal tissues with cancer-similar expression profiles. This research attempted to overcome this challenge by increasing selectivity of cancer cell targeting while maintaining an ability to overcome traditional pharmacological barriers. Thus, a multi-core, multi-targeting construct for tumor specific delivery of PTX was fabricated with (i) an inner-core prodrug targeting the cancer-overexpressed cathepsin B through a cathepsin B-cleavable tetrapeptide that conjugates PTX to a poly(amidoamine) dendrimer, and (ii) the encapsulation of this prodrug (PGD) in an outer core of a RES-evading, folate receptor (FR)-targeting liposome. Compared to traditional FR-targeting PTX liposomes, this sequentially active-targeted dendrosome demonstrated better prodrug retention, an increased cytotoxicity to cancer cells (latter being true when FR and cathepsin B activities were both at moderate-to-high levels) and higher tumor reduction. This research may eventually evolve a product platform with reduced systemic toxicity inherent with traditional chemotherapy and localized toxicity inherent to single-target nanoplatforms, thereby allowing for better tolerance of higher therapeutic load in advanced disease states.

  10. How Cognitive Styles Affect the Learning Behaviors of Online Problem-Solving Based Discussion Activity: A Lag Sequential Analysis

    ERIC Educational Resources Information Center

    Wu, Sheng-Yi; Hou, Huei-Tse

    2015-01-01

    Cognitive styles play an important role in influencing the learning process, but to date no relevant study has been conducted using lag sequential analysis to assess knowledge construction learning patterns based on different cognitive styles in computer-supported collaborative learning activities in online collaborative discussions. This study…

  11. Bioactive bilayered dressing for compromised epidermal tissue regeneration with sequential activity of complementary agents.

    PubMed

    Reyes-Ortega, Felisa; Cifuentes, Alberto; Rodríguez, Gema; Aguilar, María Rosa; González-Gómez, Álvaro; Solis, Raul; García-Honduvilla, Natalio; Buján, Julia; García-Sanmartin, Josune; Martínez, Alfredo; Román, Julio San

    2015-09-01

    The article deals with the design, preparation, and evaluation of a new bilayered dressing for application in the healing of compromised wounds. The system is based on the sequential release of two complementary bioactive components to enhance the activation of the regeneration of dermal tissue. The internal layer is a highly hydrophilic and biodegradable film of gelatin and hyaluronic acid (HG), crosslinked with the natural compound genipin, which reacts with the amine groups of gelatin. This film is loaded with the proangiogenic, anti-inflammatory, and antibacterial peptide, proadrenomedullin N-terminal 20 peptide (PAMP), that is released slowly in the wound site. The external layer, more stable and less hydrophilic, is constituted by a biodegradable polyurethane derived from poly(caprolactone) and pluronic L61. This layer is loaded with resorbable nanoparticles of bemiparin (a fractionated low molecular weight heparin), which promotes the activation of growth factors, FGF and VEGF, and provides a good biomechanical stability and controlled permeability of the bilayered dressing. Experiments carried out in mice demonstrate the excellent angiogenic effect of the HG film in the dermal tissue. Application of the bilayered dressing in the wound healing rabbit ear model shows an improved cicatrization of the wound in both ischemic and non-ischemic defects, favoring epithelialization and reducing noticeably the contraction and the inflammation.

  12. Application of Sequential Quadratic Programming to Minimize Smart Active Flap Rotor Hub Loads

    NASA Technical Reports Server (NTRS)

    Kottapalli, Sesi; Leyland, Jane

    2014-01-01

    In an analytical study, SMART active flap rotor hub loads have been minimized using nonlinear programming constrained optimization methodology. The recently developed NLPQLP system (Schittkowski, 2010) that employs Sequential Quadratic Programming (SQP) as its core algorithm was embedded into a driver code (NLP10x10) specifically designed to minimize active flap rotor hub loads (Leyland, 2014). Three types of practical constraints on the flap deflections have been considered. To validate the current application, two other optimization methods have been used: i) the standard, linear unconstrained method, and ii) the nonlinear Generalized Reduced Gradient (GRG) method with constraints. The new software code NLP10x10 has been systematically checked out. It has been verified that NLP10x10 is functioning as desired. The following are briefly covered in this paper: relevant optimization theory; implementation of the capability of minimizing a metric of all, or a subset, of the hub loads as well as the capability of using all, or a subset, of the flap harmonics; and finally, solutions for the SMART rotor. The eventual goal is to implement NLP10x10 in a real-time wind tunnel environment.

  13. Photoluminescence Mechanism and Photocatalytic Activity of Organic-Inorganic Hybrid Materials Formed by Sequential Vapor Infiltration.

    PubMed

    Akyildiz, Halil I; Stano, Kelly L; Roberts, Adam T; Everitt, Henry O; Jur, Jesse S

    2016-05-03

    Organic-inorganic hybrid materials formed by sequential vapor infiltration (SVI) of trimethylaluminum into polyester fibers are demonstrated, and the photoluminescence of the fibers is evaluated using a combined UV-vis and photoluminescence excitation (PLE) spectroscopy approach. The optical activity of the modified fibers depends on infiltration thermal processing conditions and is attributed to the reaction mechanisms taking place at different temperatures. At low temperatures a single excitation band and dual emission bands are observed, while, at high temperatures, two distinct absorption bands and one emission band are observed, suggesting that the physical and chemical structure of the resulting hybrid material depends on the SVI temperature. Along with enhancing the photoluminescence intensity of the PET fibers, the internal quantum efficiency also increased to 5-fold from ∼4-5% to ∼24%. SVI processing also improved the photocatalytic activity of the fibers, as demonstrated by photodeposition of Ag and Au metal particles out of an aqueous metal salt solution onto fiber surfaces via UVA light exposure. Toward applications in flexible electronics, well-defined patterning of the metallic materials is achieved by using light masking and focused laser rastering approaches.

  14. Structural Evidence for a Sequential Release Mechanism for Activation of Heterotrimeric G Proteins

    SciTech Connect

    Kapoor, Neeraj; Menon, Santosh T.; Chauhan, Radha; Sachdev, Pallavi; Sakmar, Thomas P.

    2010-01-12

    Heptahelical G-protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors couple to heterotrimeric G proteins to relay extracellular signals to intracellular signaling networks, but the molecular mechanism underlying guanosine 5'-diphosphate (GDP) release by the G protein {alpha}-subunit is not well understood. Amino acid substitutions in the conserved {alpha}5 helix of Gi, which extends from the C-terminal region to the nucleotide-binding pocket, cause dramatic increases in basal (receptor-independent) GDP release rates. For example, mutant G{alpha}{sub i1}-T329A shows an 18-fold increase in basal GDP release rate and, when expressed in culture, it causes a significant decrease in forskolin-stimulated cAMP accumulation. The crystal structure of G{alpha}{sub i1}-T329A {center_dot} GDP shows substantial conformational rearrangement of the switch I region and additional striking alterations of side chains lining the catalytic pocket that disrupt the Mg{sup +2} coordination sphere and dislodge bound Mg{sup +2}. We propose a 'sequential release' mechanism whereby a transient conformational change in the {alpha}5 helix alters switch I to induce GDP release. Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8.

  15. Activated Protein C Enhances Human Keratinocyte Barrier Integrity via Sequential Activation of Epidermal Growth Factor Receptor and Tie2*

    PubMed Central

    Xue, Meilang; Chow, Shu-Oi; Dervish, Suat; Chan, Yee-Ka Agnes; Julovi, Sohel M.; Jackson, Christopher J.

    2011-01-01

    Keratinocytes play a critical role in maintaining epidermal barrier function. Activated protein C (APC), a natural anticoagulant with anti-inflammatory and endothelial barrier protective properties, significantly increased the barrier impedance of keratinocyte monolayers, measured by electric cell substrate impedance sensing and FITC-dextran flux. In response to APC, Tie2, a tyrosine kinase receptor, was rapidly activated within 30 min, and relocated to cell-cell contacts. APC also increased junction proteins zona occludens, claudin-1 and VE-cadherin. Inhibition of Tie2 by its peptide inhibitor or small interfering RNA abolished the barrier protective effect of APC. Interestingly, APC did not activate Tie2 through its major ligand, angiopoietin-1, but instead acted by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor. Furthermore, when activation of Akt, but not ERK, was inhibited, the barrier protective effect of APC on keratinocytes was abolished. Thus, APC activates Tie2, via a mechanism requiring, in sequential order, the receptors, endothelial protein C receptor, protease-activated receptor-1, and EGF receptor, which selectively enhances the PI3K/Akt signaling to enhance junctional complexes and reduce keratinocyte permeability. PMID:21173154

  16. Sequential Myosin Phosphorylation Activates Tarantula Thick Filament via a Disorder-Order Transition

    PubMed Central

    Espinoza-Fonseca, L. Michel; Alamo, Lorenzo; Pinto, Antonio; Thomas, David D.; Padrón, Raúl

    2015-01-01

    Phosphorylation of myosin regulatory light chain (RLC) N-terminal extension (NTE) activates myosin in thick filaments. RLC phosphorylation plays a primary regulatory role in smooth muscle and a secondary (modulatory) role in striated muscle, which is regulated by Ca2+ via TnC/TM on the thin filament. Tarantula striated muscle exhibits both regulatory systems: one switches on/off contraction through thin filament regulation, and another through PKC constitutively Ser35 phosphorylated swaying free heads in the thick filaments that produces quick force on twitches regulated from 0 to 50% and modulation is accomplished recruiting additional force-potentiating free and blocked heads via Ca2+4-CaM-MLCK Ser45 phosphorylation. We have used microsecond molecular dynamics (MD) simulations of tarantula RLC NTE to understand the structural basis for phosphorylation-based regulation in tarantula thick filament activation. Trajectories analysis revealed that an inter-domain salt bridges network (R39/E58,E61) facilitates formation of a stable helix-coil-helix (HCH) motif made up by helices P and A in the unphosphorylated NTE of both myosin heads. Phosphorylation of blocked head on Ser45 does not induce any substantial structural change. However, phosphorylation of free head on Ser35 disrupts this salt bridge network and induces a partial extension of helix P along RLC helix A. While not directly participating in the HCH inter-domain folding, phosphorylation of Ser35 unlocks compact structure and allows the NTE to spontaneously undergo coil-helix transitions. The modest structural change induced by subsequent Ser45 diphosphorylation monophosphorylated Ser35 free head, facilitates full helix P extension into a single structurally stable α-helix through a network of intra-domain salt bridges (pS35/R38,R39,R42). We conclude that tarantula thick filament activation is controlled by sequential Ser35-Ser45 phosphorylation via a conserved disorder-to-order transition. PMID:26038232

  17. Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation.

    PubMed

    Halangk, Walter; Krüger, Burkhard; Ruthenbürger, Manuel; Stürzebecher, Jörg; Albrecht, Elke; Lippert, Hans; Lerch, Markus M

    2002-02-01

    A premature and intracellular activation of digestive zymogens is thought to be responsible for the onset of pancreatitis. Because trypsin has a critical role in initiating the activation cascade of digestive enzymes in the gut, it has been assumed that trypsin also initiates intracellular zymogen activation in the pancreas. We have tested this hypothesis in isolated acini and lobules from rat pancreas. Intracellular trypsinogen activation was induced by supramaximal secretagogue stimulation and measured using either specific trypsin substrates or immunoreactivity of the trypsinogen activation peptide (TAP). To prevent a trypsin-induced trypsinogen activation, we used the cell-permeant, highly specific, and reversible inhibitor Nalpha-(2-naphthylsulfonyl)-3-amidinophenylalanine-carboxymethylpiperazide (S124), and to prevent cathepsin-induced trypsinogen activation, we used the cysteine protease inhibitor E-64d. Incubation of acini or lobules in the presence of S124 completely prevented the generation of trypsin activity in response to supramaximal caerulein but had no effect whatsoever on the generation of TAP. Conversely, when trypsin activity was recovered at the end of the experiment by either washout of S124 from acini or extensive dilution of lobule homogenates, it was up to 400% higher than after caerulein alone and corresponded, in molar terms, to the generation of TAP. Both trypsin activity and TAP release were inhibited in parallel by E-64d. We conclude that caerulein-induced trypsinogen activation in the pancreas is caused by an E-64d-inhibitable mechanism such as cathepsin-induced trypsinogen activation, and neither involves nor requires intracellular trypsin activity. Specific trypsin inhibition, on the other hand, prevents 80% of trypsin inactivation or autodegradation in the pancreas.

  18. Evaluation of the Therapeutic Efficacy of Sequential Therapy Involving Percutaneous Microwave Ablation in Combination with 131I-Hypericin Using the VX2 Rabbit Breast Solid Tumor Model

    PubMed Central

    Zhu, Miao; Lin, Xiao-An; Zha, Xiao-Ming; Zhou, Wen-Bin; Xia, Tian-Song; Wang, Shui

    2015-01-01

    . Sequential therapy involving PMWA+IIIH was successfully inhibiting tumor growth and prolonging survival. PMID:25799220

  19. Understanding the sequential activation of Type III and Type VI Secretion Systems in Salmonella typhimurium using Boolean modeling

    PubMed Central

    2013-01-01

    Background Three pathogenicity islands, viz. SPI-1 (Salmonella pathogenicity island 1), SPI-2 (Salmonella pathogenicity island 2) and T6SS (Type VI Secretion System), present in the genome of Salmonella typhimurium have been implicated in the virulence of the pathogen. While the regulation of SPI-1 and SPI-2 (both encoding components of the Type III Secretion System - T3SS) are well understood, T6SS regulation is comparatively less studied. Interestingly, inter-connections among the regulatory elements of these three virulence determinants have also been suggested to be essential for successful infection. However, till date, an integrated view of gene regulation involving the regulators of these three secretion systems and their cross-talk is not available. Results In the current study, relevant regulatory information available from literature have been integrated into a single Boolean network, which portrays the dynamics of T3SS (SPI-1 and SPI-2) and T6SS mediated virulence. Some additional regulatory interactions involving a two-component system response regulator YfhA have also been predicted and included in the Boolean network. These predictions are aimed at deciphering the effects of osmolarity on T6SS regulation, an aspect that has been suggested in earlier studies, but the mechanism of which was hitherto unknown. Simulation of the regulatory network was able to recreate in silico the experimentally observed sequential activation of SPI-1, SPI-2 and T6SS. Conclusions The present study integrates relevant gene regulatory data (from literature and our prediction) into a single network, representing the cross-communication between T3SS (SPI-1 and SPI-2) and T6SS. This holistic view of regulatory interactions is expected to improve the current understanding of pathogenesis of S. typhimurium. PMID:24079299

  20. Differences in Sugar Accumulation and Mobilization between Sequential and Non-Sequential Senescence Wheat Cultivars under Natural and Drought Conditions

    PubMed Central

    Shi, Huarong; Wang, Bin; Yang, Piaojuan; Li, Yibo; Miao, Fang

    2016-01-01

    Wheat leaf non-sequential senescence at the late grain-filling stage involves the early senescence of younger flag leaves compared to that observed in older second leaves. On the other hand, sequential senescence involves leaf senescence that follows an age-related pattern, in which flag leaves are the latest to undergo senescence. The characteristics of sugar metabolism in two sequential senescence cultivars and two non-sequential senescence cultivars under both natural and drought conditions were studied to elucidate the underlying mechanism of drought tolerance in two different senescence modes. The results showed that compared to sequential senescence wheat cultivars, under natural and drought conditions, non-sequential senescence wheat cultivars showed a higher leaf net photosynthetic rate, higher soluble sugar levels in leaves, leaf sheaths, and internodes, higher leaf sucrose synthase (SS) and sucrose phosphate synthase (SPS) activity, and higher grain SS activity, thereby suggesting that non-sequential senescence wheat cultivars had stronger source activity. Spike weight, grain weight per spike, and 100-grain weight of non-sequential senescence cultivars at maturity were significantly higher than those of sequential senescence cultivars under both natural and drought conditions. These findings indicate that the higher rate of accumulation and the higher mobilization of soluble sugar in the leaves, leaf sheaths and internodes of non-sequential senescence cultivars improve grain weight and drought tolerance. At the late grain-filling stage, drought conditions adversely affected leaf chlorophyll content, net photosynthetic rate, soluble sugar and sucrose content, SS and SPS activity, gain SS activity, and weight. This study showed that higher rates of soluble sugar accumulation in the source was one of the reasons of triggering leaf non-sequential senescence, and higher rates of soluble sugar mobilization during leaf non-sequential senescence promoted high and

  1. Relationship of Power and Involvement to Working Alliance: A Multiple-Case Sequential Analysis of Brief Therapy.

    ERIC Educational Resources Information Center

    Reandeau, Sharon Gardner; Wampold, Bruce E.

    1991-01-01

    Examined within-session interactional behavior in four brief-therapy cases, two characterized by high alliance and two by low alliance. Coded message units along dimensions of power and involvement. In all cases, there was general pattern of high power for therapists and low power for clients. High-alliance clients evidenced larger proportions of…

  2. Activation of Two Sequential H-transfers in the Thymidylate Synthase Catalyzed Reaction

    PubMed Central

    Islam, Zahidul; Strutzenberg, Timothy S.; Ghosh, Ananda K.; Kohen, Amnon

    2015-01-01

    Thymidylate synthase (TSase) catalyzes the de novo biosynthesis of thymidylate, a precursor for DNA, and is thus an important target for chemotherapeutics and antibiotics. Two sequential C-H bond cleavages catalyzed by TSase are of particular interest: a reversible proton abstraction from the 2′-deoxy-uridylate substrate, followed by an irreversible hydride transfer forming the thymidylate product. QM/MM calculations of the former predicted a mechanism where the abstraction of the proton leads to formation of a novel nucleotide-folate intermediate that is not covalently bound to the enzyme (Wang, Z.; Ferrer, S.; Moliner, V.; Kohen, A. Biochemistry 2013, 52, 2348–2358). Existence of such intermediate would hold promise as a target for a new class of drugs. Calculations of the subsequent hydride transfer predicted a concerted H-transfer and elimination of the enzymatic cysteine (Kanaan, N.; Ferrer, S.; Marti, S.; Garcia-Viloca, M.; Kohen, A.; Moliner, V. J. Am. Chem. Soc. 2011, 133, 6692–6702). A key to both C-H activations is a highly conserved arginine (R166) that stabilizes the transition state of both H-transfers. Here we test these predictions by studying the R166 to lysine mutant of E. coli TSase (R166K) using intrinsic kinetic isotope effects (KIEs) and their temperature dependence to assess effects of the mutation on both chemical steps. The findings confirmed the predictions made by the QM/MM calculations, implicate R166 as an integral component of both reaction coordinates, and thus provide critical support to the nucleotide-folate intermediate as a new target for rational drug design. PMID:26576323

  3. Use of solid phase extraction for the sequential injection determination of alkaline phosphatase activity in dynamic water systems.

    PubMed

    Santos, Inês C; Mesquita, Raquel B R; Bordalo, Adriano A; Rangel, António O S S

    2012-08-30

    In this work, a solid phase extraction sequential injection methodology for the determination of alkaline phosphatase activity in dynamic water systems was developed. The determination of the enzymatic activity was based on the spectrophotometric detection of a coloured product, p-nitrophenol, at 405 nm. The p-nitrophenol is the product of the catalytic decomposition of p-nitrophenyl phosphate, a non-coloured substrate. Considering the low levels expected in natural waters and exploiting the fact of alkaline phosphatase being a metalloprotein, the enzyme was pre-concentrated in-line using a NTA Superflow resin charged with Zn(2+) ions. The developed sequential injection method enabled a quantification range of 0.044-0.441 unit mL(-1) of enzyme activity with a detection limit of 0.0082 unit mL(-1) enzyme activity (1.9 μmol L(-1) of pNP) and a determination rate of 17 h(-1). Recovery tests confirmed the accuracy of the developed sequential injection method and it was effectively applied to different natural waters and to plant root extracts.

  4. A process for the purification of organochlorine contaminated activated carbon: Sequential solvent purging and reductive dechlorination.

    PubMed

    Lee, Matthew; Cord-Ruwisch, Ralf; Manefield, Mike

    2010-03-01

    A system for the purification of organochlorine contaminated activated carbon is described. The system involves a continuous flow of aqueous ethanol to purge organochlorines from activated carbon. The organochlorine laden solvent is simultaneously treated with zero valent zinc as the bulk electron source, water as the proton source and the electron shuttle cyanocobalamin as a catalyst for reductive dechlorination. The system was characterised by performing batch reactions and extractions before being applied in a continuous flow system. In particular the ratio of water to ethanol in the system needed to be optimised. Water is needed for the reductive dechlorination reaction whilst it is not conducive to the extraction process. An 80% ethanolic solution was found to give optimal reductive dechlorination rates without compromising extraction of organochlorines from activated carbon. Of three electron shuttles evaluated cyanocobalamin was discovered to be the most relevant to the system with respect to reductive dechlorination rates and its ability to avoid absorption to activated carbon.

  5. DESIGN CONSIDERATION INVOLVING ACTIVE SEDIMENT CAPS (PRESENTATION)

    EPA Science Inventory

    When contaminated sediments pose unacceptable risks to human health and the environment, management activities such as removal, treatment, or isolation of contaminated sediments may be required. Various capping designs are being considered for isolating contaminated sediment are...

  6. DESIGN CONSIDERATION INVOLVING ACTIVE SEDIMENT CAPS

    EPA Science Inventory

    When contaminated sediments pose unacceptable risks to human health and the environment, management activities such as removal, treatment, or isolation of contaminated sediments may be required. Various capping designs are being considered for isolating contaminated sediment are...

  7. Comprehensive investigation of sequential plasma activated Si/Si bonded interfaces for nano-integration on the wafer scale.

    PubMed

    Kibria, M G; Zhang, F; Lee, T H; Kim, M J; Howlader, M M R

    2010-04-02

    The sequentially plasma activated bonding of silicon wafers has been investigated to facilitate the development of chemical free, room temperature and spontaneous bonding required for nanostructure integration on the wafer scale. The contact angle of the surface and the electrical and nanostructural behavior of the interface have been studied. The contact angle measurements show that the sequentially plasma (reactive ion etching plasma followed by microwave radicals) treated surfaces offer highly reactive and hydrophilic surfaces. These highly reactive surfaces allow spontaneous integration at the nanometer scale without any chemicals, external pressure or heating. Electrical characteristics show that the current transportation across the nanobonded interface is dependent on the plasma parameters. High resolution transmission electron microscopy results confirm nanometer scale bonding which is needed for the integration of nanostructures. The findings can be applied in spontaneous integration of nanostructures such as nanowires/nanotubes/quantum dots on the wafer scale.

  8. Measuring psychological engagement in youth activity involvement.

    PubMed

    Ramey, Heather L; Rose-Krasnor, Linda; Busseri, Michael A; Gadbois, Shannon; Bowker, Anne; Findlay, Leanne

    2015-12-01

    Although psychological engagement (e.g., enjoyment, concentration) may be critical in fostering positive outcomes of youth activity participation, too few studies have been conducted to establish its role in development. Furthermore, an established measurement tool is lacking. In the current study, we evaluated a brief engagement measure with two Canadian samples of youth (Sample 1, N = 290, mean age = 16.9 years, 62% female; Sample 2, N = 1827, mean age = 13.1 years, 54% female). We conducted a confirmatory factor analysis with structural equation modeling to examine the hypothesized structure of the model. We also assessed the measure's validity by testing relations between engagement and both perceived outcomes and positive features of activity settings. Psychological engagement was best captured by three latent cognitive, affective, and relational/spiritual factors and a second-order latent factor. Also, as anticipated, psychological engagement was associated with features of the activity setting and perceived impact.

  9. Sequential expression, activity and nuclear localization of prolyl oligopeptidase protein in the developing rat brain.

    PubMed

    Hannula, Mirva J; Männistö, Pekka T; Myöhänen, Timo T

    2011-01-01

    Prolyl oligopeptidase (POP) is a serine protease that hydrolyzes peptides shorter than 30-mer. Some evidence has recently been obtained that POP can generate protein-protein interactions and therefore participate in various physiological and pathological events. Several studies have reported that POP may be involved in neurogenesis since its activity increases during development and can be found in the nucleus of proliferating tissues. In cell cultures, POP has been shown to be localized in the nucleus, but only early in the development, since during maturation it is moved to the cytosol. We have now studied for the first time the expression of POP protein, its enzymatic activity and nuclear localization in vivo in the developing rat brain. We observed that enzymatic activity of POP is highest on embryonic day 18 while the protein amounts reach their peak at birth. Furthermore, POP is located in the nucleus only early in the development but is transferred to the cytosol already before parturition. Our in vivo results confirm the previous cell culture results supporting the role of POP in neurogenesis. A discordance of antenatal protein amounts and enzymatic activities is suggesting a tight regulation of POP activity and possibly even a nonhydrolytic role at that stage.

  10. Monitoring Lipase/Esterase Activity by Stopped Flow in a Sequential Injection Analysis System Using p-Nitrophenyl Butyrate

    PubMed Central

    Pliego, Jorge; Mateos, Juan Carlos; Rodriguez, Jorge; Valero, Francisco; Baeza, Mireia; Femat, Ricardo; Camacho, Rosa; Sandoval, Georgina; Herrera-López, Enrique J.

    2015-01-01

    Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05–1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed. PMID:25633600

  11. Monitoring lipase/esterase activity by stopped flow in a sequential injection analysis system using p-nitrophenyl butyrate.

    PubMed

    Pliego, Jorge; Mateos, Juan Carlos; Rodriguez, Jorge; Valero, Francisco; Baeza, Mireia; Femat, Ricardo; Camacho, Rosa; Sandoval, Georgina; Herrera-López, Enrique J

    2015-01-27

    Lipases and esterases are biocatalysts used at the laboratory and industrial level. To obtain the maximum yield in a bioprocess, it is important to measure key variables, such as enzymatic activity. The conventional method for monitoring hydrolytic activity is to take out a sample from the bioreactor to be analyzed off-line at the laboratory. The disadvantage of this approach is the long time required to recover the information from the process, hindering the possibility to develop control systems. New strategies to monitor lipase/esterase activity are necessary. In this context and in the first approach, we proposed a lab-made sequential injection analysis system to analyze off-line samples from shake flasks. Lipase/esterase activity was determined using p-nitrophenyl butyrate as the substrate. The sequential injection analysis allowed us to measure the hydrolytic activity from a sample without dilution in a linear range from 0.05-1.60 U/mL, with the capability to reach sample dilutions up to 1000 times, a sampling frequency of five samples/h, with a kinetic reaction of 5 min and a relative standard deviation of 8.75%. The results are promising to monitor lipase/esterase activity in real time, in which optimization and control strategies can be designed.

  12. Colocalization and Sequential Enzyme Activity in Aqueous Biphasic Systems: Experiments and Modeling

    PubMed Central

    Davis, Bradley W.; Aumiller, William M.; Hashemian, Negar; An, Songon; Armaou, Antonios; Keating, Christine D.

    2015-01-01

    Subcellular compartmentalization of biomolecules and their reactions is common in biology and provides a general strategy for improving and/or controlling kinetics in metabolic pathways that contain multiple sequential enzymes. Enzymes can be colocalized in multiprotein complexes, on scaffolds or inside subcellular organelles. Liquid organelles formed by intracellular phase coexistence could provide an additional means of sequential enzyme colocalization. Here we use experiment and computation to explore the kinetic consequences of sequential enzyme compartmentalization into model liquid organelles in a crowded polymer solution. Two proteins of the de novo purine biosynthesis pathway, ASL (adenylosuccinate lyase, Step 8) and ATIC (5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase, Steps 9 and 10), were studied in a polyethylene glycol/dextran aqueous two-phase system. Dextran-rich phase droplets served as model liquid compartments for enzyme colocalization. In this system, which lacks any specific binding interactions between the phase-forming polymers and the enzymes, we did not observe significant rate enhancements from colocalization for the overall reaction under our experimental conditions. The experimental results were used to adapt a mathematical model to quantitatively describe the kinetics. The mathematical model was then used to explore additional, experimentally inaccessible conditions to predict when increased local concentrations of enzymes and substrates can (or cannot) be expected to yield increased rates of product formation. Our findings indicate that colocalization within these simplified model liquid organelles can lead to enhanced metabolic rates under some conditions, but that very strong partitioning into the phase that serves as the compartment is necessary. In vivo, this could be provided by specific binding affinities between components of the liquid compartment and the molecules to be

  13. Exploring Extension Involvement in Farm to School Program Activities

    ERIC Educational Resources Information Center

    Benson, Matthew C.

    2014-01-01

    The study reported here examined Extension professionals' involvement in farm-to-school program activities. Results of an online survey distributed to eight state Extension systems indicate that on average, Extension professionals are involved with one farm to school program activity, with most supporting school or community garden programs.…

  14. Involvement in Extracurricular Activities and Adjustment to College.

    ERIC Educational Resources Information Center

    Woo, Tae O.; Bilynsky, Julie

    Past research has supported the idea that involvement in extracurricular activities has a positive impact on students' evaluation of their college lives. This study investigated whether involvement, as measured by time commitment to campus activities, had a differential impact on the students' adjustment to various aspects of college life,…

  15. Multimodal sensory integration during sequential eating--linking chewing activity, aroma release, and aroma perception over time.

    PubMed

    Leclercq, Ségolène; Blancher, Guillaume

    2012-10-01

    The respective effects of chewing activity, aroma release from a gelled candy, and aroma perception were investigated. Specifically, the study aimed at 1) comparing an imposed chewing and swallowing pattern (IP) and free protocol (FP) on panelists for in vivo measurements, 2) investigating carryover effects in sequential eating, and 3) studying the link between instrumental data and their perception counterpart. Chewing activity, in-nose aroma concentration, and aroma perception over time were measured by electromyography, proton transfer reaction-mass spectrometry, and time intensity, respectively. Model gel candies were flavored at 2 intensity levels (low-L and high-H). The panelists evaluated 3 sequences (H then H, H then L, and L then H) in duplicates with both IP and FP. They scored aroma intensity over time while their in-nose aroma concentrations and their chewing activity were measured. Overall, only limited advantages were found in imposing a chewing and swallowing pattern for instrumental and sensory data. In addition, the study highlighted the role of brain integration on perceived intensity and dynamics of perception, in the framework of sequential eating without rinsing. Because of the presence of adaptation phenomena, contrast effect, and potential taste and texture cross-modal interaction with aroma perception, it was concluded that dynamic in-nose concentration data provide only one part of the perception picture and therefore cannot be used alone in prediction models.

  16. Enzyme:nanoparticle bioconjugates with two sequential enzymes: stoichiometry and activity of malate dehydrogenase and citrate synthase on Au nanoparticles.

    PubMed

    Keighron, Jacqueline D; Keating, Christine D

    2010-12-21

    We report the synthesis and characterization of bioconjugates in which the enzymes malate dehydrogenase (MDH) and/or citrate synthase (CS) were adsorbed to 30 nm diameter Au nanoparticles. Enzyme:Au stoichiometry and kinetic parameters (specific activity, k(cat), K(M), and activity per particle) were determined for MDH:Au, CS:Au, and three types of dual-activity MDH/CS:Au bioconjugates. For single-activity bioconjugates (MDH:Au and CS:Au), the number of enzyme molecules adsorbed per particle was dependent upon the enzyme concentration in solution, with multilayers forming at high enzyme:Au solution ratios. The specific activity of adsorbed enzyme increased with increasing number adsorbed per particle for CS:Au, but was less sensitive to stoichiometry for MDH:Au. Dual activity bioconjugates were prepared in three ways: (1) by adsorption of MDH followed by CS, (2) by adsorption of CS followed by MDH, and (3) by coadsorption of both enzymes from the same solution. The resulting bioconjugates differed substantially in the number of enzyme molecules adsorbed per particle, the specific activity of the adsorbed enzymes, and also the enzymatic activity per particle. Bioconjugates formed by adding CS to the Au nanoparticles before MDH was added exhibited higher specific activities for both enzymes than those formed by adding the enzymes in the reverse order. These bioconjugates also had 3-fold higher per-particle sequential activity for conversion of malate to citrate, despite substantially fewer copies of both enzymes present.

  17. Sequential expression of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor in rat hippocampal neurons after fluid percussion injury

    PubMed Central

    Li, Zhiqiang; Shu, Qingming; Li, Lingzhi; Ge, Maolin; Zhang, Yongliang

    2014-01-01

    Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott's method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury. PMID:25206921

  18. A Bayesian active learning strategy for sequential experimental design in systems biology.

    PubMed

    Pauwels, Edouard; Lajaunie, Christian; Vert, Jean-Philippe

    2014-09-26

    BackgroundDynamical models used in systems biology involve unknown kinetic parameters. Setting these parameters is a bottleneck in many modeling projects. This motivates the estimation of these parameters from empirical data. However, this estimation problem has its own difficulties, the most important one being strong ill-conditionedness. In this context, optimizing experiments to be conducted in order to better estimate a system¿s parameters provides a promising direction to alleviate the difficulty of the task.ResultsBorrowing ideas from Bayesian experimental design and active learning, we propose a new strategy for optimal experimental design in the context of kinetic parameter estimation in systems biology. We describe algorithmic choices that allow to implement this method in a computationally tractable way and make it fully automatic. Based on simulation, we show that it outperforms alternative baseline strategies, and demonstrate the benefit to consider multiple posterior modes of the likelihood landscape, as opposed to traditional schemes based on local and Gaussian approximations.ConclusionThis analysis demonstrates that our new, fully automatic Bayesian optimal experimental design strategy has the potential to support the design of experiments for kinetic parameter estimation in systems biology.

  19. Evaluation of antimicrobial activities of sequential spray applications of decontamination treatments on chicken carcasses.

    PubMed

    Benli, Hakan; Sanchez-Plata, Marcos X; Ilhak, Osman Irfan; Núñez De González, Maryuri T; Keeton, Jimmy T

    2015-03-01

    The objective of this study was to evaluate the effects of sequential applications of ɛ-polylysine (EPL) or lauramide arginine ethyl ester (LAE) sprays followed by an acidic calcium sulfate (ACS) spray on inoculated chicken carcasses to reduce Salmonella (Salmonella enterica serovars including Salmonella typhimurium and Salmonella enteritidis) contamination during 6 days of storage (4.4°C). Secondly, reductions of the resident microflora were studied on uninoculated chicken carcasses following the sequential application of the treatments, chilling and 10 days of storage at 4.4°C. The treatment of Salmonella inoculated carcasses with 300 mg/L EPL followed by 30% ACS (EPL300-ACS30) sprays reduced Salmonella counts initially by 1.5 log cfu/mL and then by 1.2 log cfu/mL (p<0.05) following 6 days of storage at 4.4°C. Likewise, 200 mg/L LAE followed by 30% ACS (LAE200-ACS30) treatment reduced initial Salmonella counts on poultry carcasses by 1.8, 1.4 and 1.8 log cfu/mL (p<0.05), respectively, after 0, 3, and 6 days storage. Immediately after the treatments, EPL300-ACS30 and LAE200-ACS30 both reduced Escherichia coli counts significantly by 2.6 and 2.9 log cfu/mL, respectively. EPL300-ACS30 and LAE200-ASC30 were effective in lowering psychrotroph counts by 1 log cfu/mL on day 10 when compared to the control and distilled water treatments. This study demonstrated that EPL300-ACS30 and LAE200-ACS30 were effective in reducing Salmonella on inoculated chicken carcasses both after treatment and during the storage at 4.4°C for up to 6 days. In addition, reductions in psychrotroph counts indicated that these treatments might have the potential to increase the shelf-life of poultry carcasses.

  20. Curved Ferroelectric Liquid Crystal Matrix Displays Driven by Field-Sequential-Color and Active-Matrix Techniques

    NASA Astrophysics Data System (ADS)

    Fujikake, Hideo; Sato, Hiroto; Murashige, Takeshi; Fujisaki, Yoshihide; Kurita, Taiichiro; Furukawa, Tadahiro; Sato, Fumio

    This paper describes a curved field-sequential-color matrix display using fast-response ferroelectric liquid crystal. Black matrix and transparent electrode patterns were formed on a thin plastic substrate by a transfer method from a glass substrate. While a composite film of liquid crystal and micro-polymers of walls and fibers was formed between the flexible substrates by printing, laminating and curing processes of a solution of monomers and liquid crystal, the mechanical stability was enhanced by use of multi-functional monomers to form large display panels. The image pixels of the matrix panel were driven by an active matrix scheme using an external switch transistor array at a frequency of 180 Hz for intermittent three-primary-color backlight illumination. The flexible A4-paper-sized color display with 24 × 16 pixels and 60 Hz field frequency was demonstrated by illuminating it with sequential three-primary-color lights from light-emitting diodes of the backlight. Our display system is useful in various information displays because of its freedom of setting and location.

  1. Basic Business and Economics: Varied Activities Encourage Active Student Involvement.

    ERIC Educational Resources Information Center

    Baker, Robert Lee, Jr.

    1978-01-01

    Describes a variety of activities for the basic business classroom, such as having guest speakers, question-and-answer sessions, simulations, role playing, debates, small group work, field trips, games, and individualized instruction. Includes a report of business teachers' knowledge of and attitudes toward these activities. (MF)

  2. Inhibition of retinoic acid-induced activation of 3' human HOXB genes by antisense oligonucleotides affects sequential activation of genes located upstream in the four HOX clusters.

    PubMed Central

    Faiella, A; Zappavigna, V; Mavilio, F; Boncinelli, E

    1994-01-01

    Most homeobox genes belonging to the Hox family are sequentially activated in embryonal carcinoma cells upon treatment with retinoic acid. Genes located at the 3' end of each one of the four Hox clusters are activated first, whereas upstream Hox genes are activated progressively later. This activation has been extensively studied for human HOX genes in the NT2/D1 cell line and shown to take place at the transcriptional level. To understand the molecular mechanisms of sequential HOX gene activation in these cells, we tried to modulate the expression of 3' HOX genes through the use of antisense oligonucleotides added to the culture medium. We chose the HOXB locus. A 5- to 15-fold reduction of the expression of HOXB1 and HOXB3 was sufficient to produce a significant inhibition of the activation of the upstream HOXB genes, as well as of their paralogs in the HOXA, HOXC, and HOXD clusters. Conversely, no effect was detectable on downstream HOX genes. The extent of this inhibition increased for progressively more-5' genes. The stability of the corresponding mRNAs appeared to be unaffected, supporting the idea that the observed effect might be mediated at the transcriptional level. These data suggest a cascade model of progressive activation of Hox genes, with a 3'-to-5' polarity. Images PMID:7911240

  3. Class A scavenger receptor-mediated cell adhesion requires the sequential activation of Lyn and PI3-kinase.

    PubMed

    Nikolic, Dejan M; Cholewa, Jill; Gass, Cecelia; Gong, Ming C; Post, Steven R

    2007-04-01

    Class A scavenger receptors (SR-A) participate in multiple macrophage functions including macrophage adhesion to modified proteins. SR-A-mediated adhesion may therefore contribute to chronic inflammation by promoting macrophage accumulation at sites of protein modification. The mechanisms that couple SR-A binding to modified proteins with increased cell adhesion have not been defined. In this study, SR-A expressing HEK cells and SR-A+/+ or SR-A-/- macrophages were used to delineate the signaling pathways required for SR-A-mediated adhesion to modified protein. Inhibiting G(i/o) activation, which decreases initial SR-A-mediated cell attachment, did not prevent the subsequent spreading of attached cells. In contrast, inhibition of Src kinases or PI3-kinase abolished SR-A-dependent cell spreading without affecting SR-A-mediated cell attachment. Consistent with these results, the Src kinase Lyn and PI3-kinase were sequentially activated during SR-A-mediated cell spreading. Furthermore, activation of both Lyn and PI3-kinase was required for enhancing paxillin phosphorylation. Activation of a Src kinase-PI3-kinase-Akt pathway was also observed in cells expressing a truncated SR-A protein that does not internalize indicating that SR-A-mediated activation of intracellular signaling cascades following adhesion to MDA-BSA is independent of receptor internalization. Thus SR-A binding to modified protein activates signaling cascades that have distinct roles in regulating initial cell attachment and subsequent cell spreading.

  4. Empirical Evidence or Intuition? An Activity Involving the Scientific Method

    ERIC Educational Resources Information Center

    Overway, Ken

    2007-01-01

    Students need to have basic understanding of scientific method during their introductory science classes and for this purpose an activity was devised which involved a game based on famous Monty Hall game problem. This particular activity allowed students to banish or confirm their intuition based on empirical evidence.

  5. A cascading activity-based probe sequentially targets E1–E2–E3 ubiquitin enzymes

    PubMed Central

    Mulder, Monique P.C.; Witting, Katharina; Berlin, Ilana; Pruneda, Jonathan N.; Wu, Kuen-Phon; Chang, Jer-Gung; Merkx, Remco; Bialas, Johanna; Groettrup, Marcus; Vertegaal, Alfred C.O.; Schulman, Brenda A.; Komander, David; Neefjes, Jacques; Oualid, Farid El; Ovaa, Huib

    2016-01-01

    Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers, orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a staggering breadth of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Akin to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe ‘hops’ and ‘traps’ catalytically active ubiquitin-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activities in living cells, presents novel and versatile tools to interrogate the Ub/Ubl cascades. PMID:27182664

  6. Microbial respiration activities correlated to sequentially separated, particulate and water-soluble organic matter fractions from arable and forest topsoils

    NASA Astrophysics Data System (ADS)

    Kaiser, M.; Wirth, S.; Ellerbrock, R.; Sommer, M.

    2009-12-01

    Michael Kaiser1, Stephan Wirth2, Ruth H. Ellerbrock3, Michael Sommer3,4 1University of California Merced, Natural Science, 4225 N. Hospital Rd., Atwater, CA 95301 2,3 Leibniz-Center for Agricultural Research (ZALF) e. V. 2 Institute of Landscape Matter Dynamics 3 Institute of Soil Landscape Research Eberswalder Str. 84, D-15374 Muencheberg, Germany 4University of Potsdam, Institute of Geoecology, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany Microbial respiration activities correlated to sequentially separated, particulate and water-soluble organic matter fractions from arable and forest topsoils Microbial decomposition of soil organic matter (SOM) accounts for roughly half of CO2 evolution from vegetated soil surfaces and plays a crucial role in the ability of soil to mitigate the greenhouse effect. The separation and identification of labile (i.e., easily decomposable) organic matter (OM) fractions from bulk SOM is of particular importance for a mechanistic understanding of microbial decomposition processes and for predicting the response of SOM to changes in land use, management, and climate. This work aimed to reveal differences in the relevance of particulate as well as water-soluble organic matter (OM) fractions from topsoils to the easily biodegradable soil organic matter (SOM). We selected eight paired sites with quite different soil types (Udorthent, Paleudalf, Glossudalf, Aquept, Hapludalf, Aquert, Udert, Haplorthod) and soil properties (e.g., clay content: 28 to 564 g kg-1). For each of these sites, we took samples from adjacent arable and forest topsoils. Physically uncomplexed, macro-, and micro-aggregate-occluded organic particle, as well as water-soluble OM fractions were sequentially separated by a combination of electrostatic attraction, ultrasonic treatment, density separation, sieving, and water extraction. The easily biodegradable SOM of the topsoil samples was determined by measuring microbial respiration during a short-term incubation

  7. Associations between Children's Physical Activities, Sedentary Behaviours and Family Structure: A Sequential Mixed Methods Approach

    ERIC Educational Resources Information Center

    Quarmby, T.; Dagkas, S.; Bridge, M.

    2011-01-01

    This mixed method paper explored the effect of family structure on children's physical activities and sedentary pursuits. It furthers the limited understanding of how family structure impacts on children's time in, and reasons behind engaging in, certain physical activities. Children from three inner city comprehensive schools in the Midlands,…

  8. Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.

    PubMed

    Moghaddam, Ghazaal; Ebrahimi, Soltan Ahmad; Rahbar-Roshandel, Nahid; Foroumadi, Alireza

    2012-07-01

    Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation.

  9. Degradation of paracetamol by catalytic wet air oxidation and sequential adsorption - Catalytic wet air oxidation on activated carbons.

    PubMed

    Quesada-Peñate, I; Julcour-Lebigue, C; Jáuregui-Haza, U J; Wilhelm, A M; Delmas, H

    2012-06-30

    The concern about the fate of pharmaceutical products has raised owing to the increasing contamination of rivers, lakes and groundwater. The aim of this paper is to evaluate two different processes for paracetamol removal. The catalytic wet air oxidation (CWAO) of paracetamol on activated carbon was investigated both as a water treatment technique using an autoclave reactor and as a regenerative treatment of the carbon after adsorption in a sequential fixed bed process. Three activated carbons (ACs) from different source materials were used as catalysts: two microporous basic ACs (S23 and C1) and a meso- and micro-porous acidic one (L27). During the first CWAO experiment the adsorption capacity and catalytic performance of fresh S23 and C1 were higher than those of fresh L27 despite its higher surface area. This situation changed after AC reuse, as finally L27 gave the best results after five CWAO cycles. Respirometry tests with activated sludge revealed that in the studied conditions the use of CWAO enhanced the aerobic biodegradability of the effluent. In the ADOX process L27 also showed better oxidation performances and regeneration efficiency. This different ageing was examined through AC physico-chemical properties.

  10. Bringing Person-Centeredness and Active Involvement into Reality

    ERIC Educational Resources Information Center

    Torenholt, Rikke; Engelund, Gitte; Willaing, Ingrid

    2015-01-01

    Purpose: The purpose of this paper is to examine the use and applicability of cultural probes--an explorative participatory method to gain insights into a person's life and thoughts--to achieve person-centeredness and active involvement in self-management education for people with chronic illness. Design/methodology/approach: An education toolkit…

  11. Identifying Associations between Student Achievement and Parental Involvement Activities

    ERIC Educational Resources Information Center

    Waddle, Ann R.

    2011-01-01

    The revision and renewal of the Elementary and Secondary Education Act of 1965 will likely expand its parental involvement component to engage educators, parents, and community partners in supporting public education for children. This revisions call for best practices, but current literature fails to identify specific activities associated…

  12. Moon Watch: A Parental-Involvement Homework Activity.

    ERIC Educational Resources Information Center

    Rillero, Peter; Gonzalez-Jensen, Margarita; Moy, Tracy

    2000-01-01

    Presents the goals, philosophy, and methods of the SPLASH (Student-Parent Laboratories Achieving Science at Home) program. Describes an at-home, parental-involvement activity called Moon Watch in which students and their parents observe how the phases of the moon and the moon's position in the sky change over a two-week period. (WRM)

  13. Three sequential brain activations encode mental transformations of upright and inverted human bodies: a high resolution evoked potential study.

    PubMed

    Tadi, T; Overney, L S; Blanke, O

    2009-04-10

    Human bodies provide a particularly rich source of visual information. Whereas most previous studies have focused on the neural mechanisms during the perception and recognition of human bodies, the aim of the present study was to investigate the time course and location of brain activation during mental imagery of human bodies. When participants were asked to imagine themselves in the position of a visually presented human body as seen from many different angles and at two orientations (upright or inverted), their reaction times were faster for upright as compared to inverted bodies and correlated differently with the tested angles. These behavioral effects were also reflected in brain activation patterns, but only during the time period from 220 to 490 ms after stimulus onset. Evoked potential mapping and electrical neuroimaging revealed three distinct and sequential steps of processing related to mental body transformation: (1) an early activation in temporo-occipital and temporo-parietal cortex (220-360 ms) that does not distinguish between upright and inverted bodies, but closely reflects the effort of mental transformation, followed (2) by an activation in temporo-occipital and medial parieto-occipital cortex (350-460 ms) that encodes mental transformation for upright bodies, and (3) a later activation in temporo-occipital and prefrontal cortex (390-490 ms) that encodes mental transformation for inverted bodies. These data suggest that the mental transformation of human bodies is not a single process but a sequence of temporally distinct processing steps, where each step reflects a distinct aspect of the transformation process that consists of activations in a network of posterior brain areas including extrastriate cortex, temporo-parietal cortex, and medial parieto-occipital cortex, as well as an anterior brain region in prefrontal cortex.

  14. Effect of anaerobic digestion on sequential pyrolysis kinetics of organic solid wastes using thermogravimetric analysis and distributed activation energy model.

    PubMed

    Li, Xiaowei; Mei, Qingqing; Dai, Xiaohu; Ding, Guoji

    2017-03-01

    Thermogravimetric analysis, Gaussian-fit-peak model (GFPM), and distributed activation energy model (DAEM) were firstly used to explore the effect of anaerobic digestion on sequential pyrolysis kinetic of four organic solid wastes (OSW). Results showed that the OSW weight loss mainly occurred in the second pyrolysis stage relating to organic matter decomposition. Compared with raw substrate, the weight loss of corresponding digestate was lower in the range of 180-550°C, but was higher in 550-900°C. GFPM analysis revealed that organic components volatized at peak temperatures of 188-263, 373-401 and 420-462°C had a faster degradation rate than those at 274-327°C during anaerobic digestion. DAEM analysis showed that anaerobic digestion had discrepant effects on activation energy for four OSW pyrolysis, possibly because of their different organic composition. It requires further investigation for the special organic matter, i.e., protein-like and carbohydrate-like groups, to confirm the assumption.

  15. Sequential injection system for phospholipase A2 activity evaluation: studies on liposomes using an environment-sensitive fluorescent probe.

    PubMed

    Araujo, André R T S; Gaspar, Diana; Lúcio, Marlene; Reis, Salette; Saraiva, M Lúcia M F S; Lima, José L F C

    2009-09-15

    This work reports the development of an automatic methodology based on the use of 1-anilinonaphthalene-8-sulfonate (ANS) as an interfacial fluorescent probe for detecting the hydrophobic environment shift around the probe, caused by the hydrolytic action of PLA(2) on the liposomes. The implementation of this reaction in a sequential injection analysis (SIA) system along with the use of the mixing chambers permitted the evaluation of PLA(2) activity and assessment of the inhibitory effect of the non-steroidal anti-inflammatory drugs (NSAIDs) on PLA(2) activity. Several studies were performed with the aim of establishing the appropriate flow system configuration: the liposome substrate; PLA(2) and ANS optimum concentrations and incubation times before and after the enzyme addition. Based on these studies, the optimum reaction conditions were selected. It was shown that PLA(2) is effectively inhibited by the NSAIDs tested (meloxicam, tolmetin and ibuprofen) and by the alpha-lipoic acid, used as a positive control. Results obtained from the flow system are in agreement with those provided by the comparison batch procedures. The proposed methodology is in fact more efficient and rapid than the comparison batch experiments, enabling the exact timing of fluidic manipulations and precise control of the reaction conditions.

  16. Sequential rooting media and rooting capacity of Sequoiadendron giganteum in vitro. Peroxidase activity as a marker.

    PubMed

    Berthon, J Y; Boyer, N; Gaspar, T

    1987-10-01

    The rooting capacities of tips of seedling, juvenile and mature shoots of Sequoiadendron giganteum were compared on different rooting media (inductive and expressive media) after passage on an elongating medium. None of the cuttings rooted when continuously kept on medium containing the auxin NAA and vitamin D2. Peroxidase activity of all those cuttings on NAA+D2 first increased during the 7-9 first days and decreased in the days after. Rooting was obtained by transfer of the cuttings after periods longer than 7-9 days from the NAA+D2 inductive medium to a basal medium supplemented or not with rutin (expressive medium). The rooting capacity was emphasized by rutin treatment and was in correlation with the peroxidase peak reached on the NAA+D2 medium. Seedlings, characterised by the highest peroxidase activity, were most performing in rooting.

  17. Effects of lecithinized SOD on sequential change in SOD activity after cerebral contusion in rats.

    PubMed

    Yunoki, M; Kawauchi, M; Ukita, N; Noguchi, Y; Nishio, S; Ono, Y; Asari, S; Ohmoto, T; Asanuma, M; Ogawa, N

    1998-01-01

    To analyze the effect of lecithinized superoxide dismutase (SOD) on superoxide accumulation after traumatic brain injury (TBI) in rats, we studied the SOD activity by NBT-reducing method and the expression of Cu,Zn-SOD mRNA by Northern blot analysis. As determined by the specific gravity method, the administration of lecithinized SOD decreased brain edema in the periphery of the lesion at 6 hr after contusion. SOD activity, without lecithinized SOD administration, increased at the peripheral portion at 30 min after contusion, but decreased to normal level at 6 hr after TBI. By administration of lecithinized SOD, the increase of SOD activity was preserved until 6 hr after TBI. The expression of Cu,Zn-SOD mRNA increased in the core lesion, peripheral portion, and contralateral hemisphere until 6 hr after TBI, then was suppressed in all three areas by lecithinized SOD. These results support the hypothesis that superoxide anions may play an important role in the development of brain edema after TBI, and that leciyhinized SOD appears to prevent brain edema through a protective effect against superoxide anions.

  18. Sequential and Opposing Activities of Wnt and BMP Coordinate Zebrafish Bone Regeneration

    PubMed Central

    Stewart, Scott; Gomez, Alan W.; Armstrong, Benjamin E.; Henner, Astra; Stankunas, Kryn

    2014-01-01

    SUMMARY Zebrafish fully regenerate lost bone, including after fin amputation, through a process mediated by dedifferentiated, lineage-restricted osteoblasts. Mechanisms controlling the osteoblast regenerative program from its initiation through reossification are poorly understood. We show that fin amputation induces a Wnt/β-catenin-dependent epithelial to mesenchymal transformation (EMT) of osteoblasts in order to generate proliferative Runx2+ preosteoblasts. Localized Wnt/β-catenin signaling maintains this progenitor population toward the distal tip of the regenerative blastema. As they become proximally displaced, preosteoblasts upregulate sp7 and subsequently mature into re-epithelialized Runx2−/sp7+ osteoblasts that extend preexisting bone. Auto-crine bone morphogenetic protein (BMP) signaling promotes osteoblast differentiation by activating sp7 expression and counters Wnt by inducing Dickkopf-related Wnt antagonists. As such, opposing activities of Wnt and BMP coordinate the simultaneous demand for growth and differentiation during bone regeneration. This hierarchical signaling network model provides a conceptual framework for understanding innate bone repair and regeneration mechanisms and rationally designing regenerative therapeutics. PMID:24485659

  19. Transdifferentiation. Sequential histone-modifying activities determine the robustness of transdifferentiation.

    PubMed

    Zuryn, Steven; Ahier, Arnaud; Portoso, Manuela; White, Esther Redhouse; Morin, Marie-Charlotte; Margueron, Raphaël; Jarriault, Sophie

    2014-08-15

    Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.

  20. Characterization of cytochrome P450 isoforms involved in sequential two-step bioactivation of diclofenac to reactive p-benzoquinone imines.

    PubMed

    den Braver, Michiel W; den Braver-Sewradj, Shalenie P; Vermeulen, Nico P E; Commandeur, Jan N M

    2016-06-24

    Idiosyncratic drug-induced lever injury (IDILI) is a rare but severe side effect of diclofenac (DF). Several mechanisms have been proposed as cause of DF-induced toxicity including the formation of protein-reactive diclofenac-1',4'-quinone imine (DF-1',4'-QI) and diclofenac-2,5-quinone imine (DF-2,5-QI). Formation of these p-benzoquinone imines result from two-step oxidative metabolism involving aromatic hydroxylation to 4'-hydroxydiclofenac and 5-hydroxydiclofenac followed by dehydrogenation to DF-1',4'-QI and DF-2,5-QI, respectively. Although the contribution of individual cytochrome P450s (CYPs) in aromatic hydroxylation of DF is well studied, the enzymes involved in the dehydrogenation reactions have been poorly characterized. The results of the present study show that both formation of 4'-hydroxydiclofenac and it subsequent bioactivation to DF-1',4'-QI is selectively catalyzed by CYP2C9. However, the two-step bioactivation to DF-2,5-QI appears to be catalyzed with highest activity by two different CYPs: 5-hydroxylation of DF is predominantly catalyzed by CYP3A4, whereas its subsequent bioactivation to DF-2,5-QI is catalyzed with 14-fold higher intrinsic clearance by CYP2C9. The fact that both CYPs involved in two-step bioactivation of DF show large interindividual variability may play a role in different susceptibility of patients to DF-induced IDILI. Furthermore, expression levels of these enzymes and protective enzymes might be important factors determining sensitivity of in vitro models for hepatotoxicity.

  1. Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network.

    PubMed

    de Crozé, Noémie; Maczkowiak, Frédérique; Monsoro-Burq, Anne H

    2011-01-04

    The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC emergence; however, the role of AP2 factors at the NB remains unclear. We show here that AP2a initiates NB patterning and is sufficient to elicit a NB-like pattern in neuralized ectoderm. In contrast, the other early regulators do not participate in ap2a initiation at the NB, but cooperate to further establish a robust NB pattern. The NC regulatory network uses a multistep cascade of secreted inducers and transcription factors, first at the NB and then within the NC progenitors. Here we report that AP2a acts at two distinct steps of this cascade. As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB and activate pax3; as a NC specifier, AP2a regulates further NC development independent of and downstream of NB patterning. Our findings reconcile conflicting observations from various vertebrate organisms. AP2a provides a paradigm for the reiterated use of multifunctional molecules, thereby facilitating emergence of the NC in vertebrates.

  2. Sequential activation and distinct functions for distal and proximal modules within the IgH 3′ regulatory region

    PubMed Central

    Garot, Armand; Marquet, Marie; Saintamand, Alexis; Bender, Sébastien; Le Noir, Sandrine; Rouaud, Pauline; Carrion, Claire; Oruc, Zéliha; Bébin, Anne-Gaëlle; Moreau, Jeanne; Lebrigand, Kevin; Denizot, Yves; Alt, Frederick W.; Cogné, Michel; Pinaud, Eric

    2016-01-01

    As a master regulator of functional Ig heavy chain (IgH) expression, the IgH 3′ regulatory region (3′RR) controls multiple transcription events at various stages of B-cell ontogeny, from newly formed B cells until the ultimate plasma cell stage. The IgH 3′RR plays a pivotal role in early B-cell receptor expression, germ-line transcription preceding class switch recombination, interactions between targeted switch (S) regions, variable region transcription before somatic hypermutation, and antibody heavy chain production, but the functional ranking of its different elements is still inaccurate, especially that of its evolutionarily conserved quasi-palindromic structure. By comparing relevant previous knockout (KO) mouse models (3′RR KO and hs3b-4 KO) to a novel mutant devoid of the 3′RR quasi-palindromic region (3′PAL KO), we pinpointed common features and differences that specify two distinct regulatory entities acting sequentially during B-cell ontogeny. Independently of exogenous antigens, the 3′RR distal part, including hs4, fine-tuned B-cell receptor expression in newly formed and naïve B-cell subsets. At mature stages, the 3′RR portion including the quasi-palindrome dictated antigen-dependent locus remodeling (global somatic hypermutation and class switch recombination to major isotypes) in activated B cells and antibody production in plasma cells. PMID:26831080

  3. Sequential signaling cascade of IL-6 and PGC-1α is involved in high glucose-induced podocyte loss and growth arrest

    SciTech Connect

    Kim, Dong Il; Park, Soo Hyun

    2013-06-14

    Highlights: •The pathophysiological role of IL-6 in high glucose-induced podocyte loss. •The novel role of PGC-1α in the development of diabetic nephropathy. •Signaling of IL-6 and PGC-1α in high glucose-induced dysfunction of podocyte. -- Abstract: Podocyte loss, which is mediated by podocyte apoptosis, is implicated in the onset of diabetic nephropathy. In this study, we investigated the involvement of interleukin (IL)-6 in high glucose-induced apoptosis of rat podocytes. We also examined the pathophysiological role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in this system. High glucose treatment induced not only podocyte apoptosis but also podocyte growth arrest. High glucose treatment also increased IL-6 secretion and activated IL-6 signaling. The high glucose-induced podocyte apoptosis was blocked by IL-6 neutralizing antibody. IL-6 treatment or overexpression induced podocyte apoptosis and growth arrest, and IL-6 siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Furthermore, high glucose or IL-6 treatment increased PGC-1α expression, and PGC-1α overexpression also induced podocyte apoptosis and growth arrest. PGC-1α siRNA transfection blocked high glucose-induced podocyte apoptosis and growth arrest. Collectively, these findings showed that high glucose promoted apoptosis and cell growth arrest in podocytes via IL-6 signaling. In addition, PGC-1α is involved in podocyte apoptosis and cell growth arrest. Therefore, blocking IL-6 and its downstream mediators such as IL6Rα, gp130 and PGC-1α may attenuate the progression of diabetic nephropathy.

  4. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae.

    PubMed

    Donohoe, Bryon S; Kang, Byung-Ho; Gerl, Mathias J; Gergely, Zachary R; McMichael, Colleen M; Bednarek, Sebastian Y; Staehelin, L Andrew

    2013-05-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (i) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3-5 COPII vesicles in contact with a C2 cis cisterna. (ii) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (iii) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (iv) C2-Cn cis cisternae grow through COPII vesicle fusion. (v) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (vi) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (vii) In plants, ∼90% of native α-mannosidase I localizes to medial Golgi cisternae. (viii) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells.

  5. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae

    PubMed Central

    Donohoe, Bryon S.; Kang, Byung-Ho; Gerl, Mathias J.; Gergely, Zachary R.; McMichael, Colleen M.; Bednarek, Sebastian Y.; Staehelin, L. Andrew

    2013-01-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus Flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (1) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3–5 COPII vesicles in contact with a C2 cis cisterna. (2) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (3) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (4) C2-Cn cis cisternae grow through COPII vesicle fusion. (5) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (6) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (7) In plants, ~90% of native α-mannosidase I localizes to medial Golgi cisternae. (8) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells. PMID:23369235

  6. Sequential first-pass metabolism of nortilidine: the active metabolite of the synthetic opioid drug tilidine.

    PubMed

    Hajda, Jacek Piotr; Jähnchen, Eberhard; Oie, Svein; Trenk, Dietmar

    2002-11-01

    The disposition of nortildine, the active metabolite of the synthetic opioid drug tilidine, was investigated in healthy volunteers in a randomized, single-dose, three-way crossover design. Three different treatments were administered: tilidine 50 mg intravenously, tilidine 50 mg orally, and nortilidine 10 mg intravenously. The plasma concentrations of tilidine, nortilidine, and bisnortilidine were determined and subjected to pharmacokinetic analysis using noncompartmental methods. The systemic bioavailability of tilidine was low (7.6% +/- 5.3%) due to a pronounced first-pass metabolism. The areas under the plasma concentration versus time curves (A UC) of nortilidine were similar following either oral or intravenous administration of tilidine 50 mg (375 +/- 184 vs. 364 +/- 124 ng.h.ml(-1)). AUC of nortilidine was 229 +/- 42 ng.h.ml(-1) after IV infusion of nortilidine 10 mg and thus much greater than after IV tilidine corrected for differences in dose. Nortilidine had a much lower volume of distribution (275 +/- 79 vs. 1326 +/- 477 L) and a somewhat lower clearance (749 +/- 119 vs. 1198 +/- 228 ml/min) than tilidine. About two-thirds of the dose of tilidine was metabolized to nortilidine, although only half of the latter fraction was available in the peripheral circulation. Nortilidine was subsequently metabolized to bisnortilidine. The mean ratio of the AUC of bisnortilidine to nortilidine was 0.65 +/- 0.14 following IV administration of nortilidine but 1.69 +/- 0.38 and 1.40 +/- 0.27 following oral and intravenous administration of tilidine, respectively. The shapes of the plasma concentration-time curves of the metabolites and parent drug declined in parallel, indicating that the disposition of the metabolites is formation rate limited. Thus, although two-thirds of the dose of tilidine is metabolized to nortilidine, only one-third of the dose is available systemically as nortilidine for interaction with the opiate receptors after both intravenous and oral dosing

  7. Modern Sequential Analysis and Its Applications to Computerized Adaptive Testing

    ERIC Educational Resources Information Center

    Bartroff, Jay; Finkelman, Matthew; Lai, Tze Leung

    2008-01-01

    After a brief review of recent advances in sequential analysis involving sequential generalized likelihood ratio tests, we discuss their use in psychometric testing and extend the asymptotic optimality theory of these sequential tests to the case of sequentially generated experiments, of particular interest in computerized adaptive testing. We…

  8. Sequential modeling of fecal coliform removals in a full-scale activated-sludge wastewater treatment plant using an evolutionary process model induction system.

    PubMed

    Suh, Chang-Won; Lee, Joong-Won; Hong, Yoon-Seok Timothy; Shin, Hang-Sik

    2009-01-01

    We propose an evolutionary process model induction system that is based on the grammar-based genetic programming to automatically discover multivariate dynamic inference models that are able to predict fecal coliform bacteria removals using common process variables instead of directly measuring fecal coliform bacteria concentration in a full-scale municipal activated-sludge wastewater treatment plant. A sequential modeling paradigm is also proposed to derive multivariate dynamic models of fecal coliform removals in the evolutionary process model induction system. It is composed of two parts, the process estimator and the process predictor. The process estimator acts as an intelligent software sensor to achieve a good estimation of fecal coliform bacteria concentration in the influent. Then the process predictor yields sequential prediction of the effluent fecal coliform bacteria concentration based on the estimated fecal coliform bacteria concentration in the influent from the process estimator with other process variables. The results show that the evolutionary process model induction system with a sequential modeling paradigm has successfully evolved multivariate dynamic models of fecal coliform removals in the form of explicit mathematical formulas with high levels of accuracy and good generalization. The evolutionary process model induction system with sequential modeling paradigm proposed here provides a good alternative to develop cost-effective dynamic process models for a full-scale wastewater treatment plant and is readily applicable to a variety of other complex treatment processes.

  9. Estrogen Signaling via a Linear Pathway Involving Insulin-Like Growth Factor I Receptor, Matrix Metalloproteinases, and Epidermal Growth Factor Receptor to Activate Mitogen-Activated Protein Kinase in MCF-7 Breast Cancer Cells

    PubMed Central

    Song, Robert X.-D.; Zhang, Zhenguo; Chen, Yucai; Bao, Yongde; Santen, Richard J.

    2009-01-01

    We present an integrated model of an extranuclear, estrogen receptor-α (ERα)-mediated, rapid MAPK activation pathway in breast cancer cells. In noncancer cells, IGF-I initiates a linear process involving activation of the IGF-I receptor (IGF-IR) and matrix metalloproteinases (MMP), release of heparin-binding epidermal growth factor (HB-EGF), and activation of EGF receptor (EGFR)-dependent MAPK. 17β-Estradiol (E2) rapidly activates IGF-IR in breast cancer cells. We hypothesize that E2 induces a similar linear pathway involving IGF-IR, MMP, HB-EGF, EGFR, and MAPK. Using MCF-7 breast cancer cells, we for the first time demonstrated that a sequential activation of IGF-IR, MMP, and EGFR existed in E2 and IGF-I actions, which was supported by evidence that the selective inhibitors of IGF-IR and MMP or knockdown of IGF-IR all inhibited E2- or IGF-I-induced EGFR phosphorylation. Using the inhibitors and small inhibitoryRNA strategies,we also demonstrated that the same sequential activation of the receptors occurred in E2-, IGF-I-, but not EGF-induced MAPK phosphorylation. Additionally, a HB-EGF neutralizing antibody significantly blocked E2-induced MAPK activation, further supporting our hypothesis. The biological effects of sequential activation of IGF-IR and EGFR on E2 stimulation of cell proliferation were also investigated. Knockdown or blockade of IGF-IR significantly inhibited E2- or IGF-I-stimulated but not EGF-induced cell growth. Knockdown or blockade of EGFR abrogated cell growth induced by E2, IGF-I, and EGF, indicating that EGFR is a downstream molecule of IGF-IR in E2 and IGF-I action. Together, our data support the novel view that E2 can activate a linear pathway involving the sequential activation of IGF-IR, MMP, HB-EGF, EGFR, and MAPK. PMID:17525128

  10. Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation

    PubMed Central

    Xia, Yang; Buja, L. Maximilian; Scarpulla, Richard C.; McMillin, Jeanie B.

    1997-01-01

    Electrical stimulation of neonatal cardiac myocytes produces hypertrophy and cellular maturation with increased mitochondrial content and activity. To investigate the patterns of gene expression associated with these processes, cardiac myocytes were stimulated for varying times up to 72 hr in serum-free culture. The mRNA contents for genes associated with transcriptional activation [c-fos, c-jun, JunB, nuclear respiratory factor 1 (NRF-1)], mitochondrial proliferation [cytochrome c (Cyt c), cytochrome oxidase], and mitochondrial differentiation [carnitine palmitoyltransferase I (CPT-I) isoforms] were measured. The results establish a temporal pattern of mRNA induction beginning with c-fos (0.25–3 hr) and followed sequentially by c-jun (0.5–3 hr), JunB (0.5–6 hr), NRF-1 (1–12 hr), Cyt c (12–72 hr), and muscle-specific CPT-I (48–72 hr). Induction of the latter was accompanied by a marked decrease in the liver-specific CPT-I mRNA, thus supporting the developmental fidelity of this pattern of gene regulation. Consistent with a transcriptional mechanism, electrical stimulation increased c-fos, β-myosin heavy chain, and Cyt c promoter activities. These increases coincided with a rise in their respective endogenous gene transcripts. NRF-1, cAMP response element, and Sp-1 site mutations within the Cyt c promoter reduced luciferase expression in both stimulated and nonstimulated myocytes. Mutations in the NRF-1 and CRE sites inhibited the induction by electrical stimulation (5-fold and 2-fold, respectively) whereas mutation of the Sp-1 site maintained or increased the fold induction. This finding is consistent with the appearance of NRF-1 and fos/jun mRNAs prior to that of Cyt c and suggests that induction of these transcription factors is a prerequisite for the transcriptional activation of Cyt c expression. These results support a regulatory role for NRF-1 and possibly AP-1 in the initiation of mitochondrial proliferation. PMID:9326621

  11. Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

    PubMed

    Mahoney, J Matthew; Titiz, Ali S; Hernan, Amanda E; Scott, Rod C

    2016-01-01

    Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation.

  12. Involvement of novel autophosphorylation sites in ATM activation.

    PubMed

    Kozlov, Sergei V; Graham, Mark E; Peng, Cheng; Chen, Philip; Robinson, Phillip J; Lavin, Martin F

    2006-08-09

    ATM kinase plays a central role in signaling DNA double-strand breaks to cell cycle checkpoints and to the DNA repair machinery. Although the exact mechanism of ATM activation remains unknown, efficient activation requires the Mre11 complex, autophosphorylation on S1981 and the involvement of protein phosphatases and acetylases. We report here the identification of several additional phosphorylation sites on ATM in response to DNA damage, including autophosphorylation on pS367 and pS1893. ATM autophosphorylates all these sites in vitro in response to DNA damage. Antibodies against phosphoserine 1893 revealed rapid and persistent phosphorylation at this site after in vivo activation of ATM kinase by ionizing radiation, paralleling that observed for S1981 phosphorylation. Phosphorylation was dependent on functional ATM and on the Mre11 complex. All three autophosphorylation sites are physiologically important parts of the DNA damage response, as phosphorylation site mutants (S367A, S1893A and S1981A) were each defective in ATM signaling in vivo and each failed to correct radiosensitivity, genome instability and cell cycle checkpoint defects in ataxia-telangiectasia cells. We conclude that there are at least three functionally important radiation-induced autophosphorylation events in ATM.

  13. Pontine respiratory activity involved in inspiratory/expiratory phase transition

    PubMed Central

    Mörschel, Michael; Dutschmann, Mathias

    2009-01-01

    Control of the timing of the inspiratory/expiratory (IE) phase transition is a hallmark of respiratory pattern formation. In principle, sensory feedback from pulmonary stretch receptors (Breuer–Hering reflex, BHR) is seen as the major controller for the IE phase transition, while pontine-based control of IE phase transition by both the pontine Kölliker–Fuse nucleus (KF) and parabrachial complex is seen as a secondary or backup mechanism. However, previous studies have shown that the BHR can habituate in vivo. Thus, habituation reduces sensory feedback, so the role of the pons, and specifically the KF, for IE phase transition may increase dramatically. Pontine-mediated control of the IE phase transition is not completely understood. In the present review, we discuss existing models for ponto-medullary interaction that may be involved in the control of inspiratory duration and IE transition. We also present intracellular recordings of pontine respiratory units derived from an in situ intra-arterially perfused brainstem preparation of rats. With the absence of lung inflation, this preparation generates a normal respiratory pattern and many of the recorded pontine units demonstrated phasic respiratory-related activity. The analysis of changes in membrane potentials of pontine respiratory neurons has allowed us to propose a number of pontine-medullary interactions not considered before. The involvement of these putative interactions in pontine-mediated control of IE phase transitions is discussed. PMID:19651653

  14. School Involvement Leave: Providing Leave for Parental Involvement in School Activities. Policy Briefing Series. Issue 18

    ERIC Educational Resources Information Center

    Curlew, Mary; Weber, Julie

    2009-01-01

    One of the most important factors in school performance is parental involvement. However, many parents do not have the flexibility in their work schedules or the leave policies necessary to attend school functions. As a result, legislators are creating policies to address this issue. School involvement leave policies provide parents with…

  15. Potential Dengue Virus-Triggered Apoptotic Pathway in Human Neuroblastoma Cells: Arachidonic Acid, Superoxide Anion, and NF-κB Are Sequentially Involved

    PubMed Central

    Jan, Jia-Tsrong; Chen, Bor-Horng; Ma, Shiou-Hwa; Liu, Chiu-I; Tsai, Hui-Ping; Wu, Han-Chung; Jiang, Shian-Yuan; Yang, Kuen-Der; Shaio, Men-Fang

    2000-01-01

    Direct in vivo evidence for the susceptibility of human neuronal cells to dengue virus has not been reported. In this study, we demonstrated that type 2 dengue (DEN-2) virus infection induced extensive apoptosis in the human neuroblastoma cell line SK-N-SH. Phospholipase A2 (PLA2) was activated by DEN-2 infection, which led to the generation of arachidonic acid (AA). Inhibition of PLA2 activity by the PLA2 inhibitors, AACOCF3 and ONO-RS-082, diminished DEN-2 virus-induced apoptosis. In contrast, the cyclooxygenase inhibitors aspirin and indomethacin, thought to increase AA accumulation by blocking AA catabolism, enhanced apoptosis. Exogenous AA induced apoptosis in a dose-dependent manner. Superoxide anion, which is thought to be generated through the AA-activated NADPH oxidase, was increased after infection. Pretreatment with superoxide dismutase (SOD) protected cells against DEN-2 virus-induced apoptosis. Furthermore, generation of superoxide anion was blocked by AACOCF3. In addition, the transcription factors, NF-κB and c-Jun, were found to be activated after DEN-2 virus infection. However, pretreatment of cells with oligodeoxynucleotides containing NF-κB, but not c-Jun, binding sites (transcription factor decoy) strongly prevented dengue virus-induced apoptosis. The finding that AACOCF3 and SOD significantly block activation of NF-κB suggests that this activation is derived from the AA-superoxide anion pathway. Our results indicate that DEN-2 virus infection of human neuroblastoma cells triggers an apoptotic pathway through PLA2 activation to superoxide anion generation and subsequently to NF-κB activation. This apoptotic effect can be either directly derived from the action of AA and superoxide anion on mitochondria or indirectly derived from the products of apoptosis-related genes activated by NF-κB. PMID:10954569

  16. Head Start Parent Involvement Activities: Measuring the Effect of School Based Parent Involvement Activities on Parent Efficacy in Early Childhood Learning

    ERIC Educational Resources Information Center

    Quadri, Khadijat O.

    2012-01-01

    Purpose: The purpose of this position paper was to examine the impact of school based parent involvement activities on parent efficacy. Methodology: The paper explores research studies into school based activities on long term parent efficacy. Conclusions: Most schools are involving parents in school-based activities in a variety of ways but the…

  17. Mechanistic insights on iodine(III) promoted metal-free dual C-H activation involved in the formation of a spirocyclic bis-oxindole.

    PubMed

    Sreenithya, A; Sunoj, Raghavan B

    2014-12-05

    The mechanism of a metal-free, phenyliodine(III) bis(trifluoroacetate) promoted, dual aryl C-H activation of an anilide to a spirocyclic bis-oxindole is examined using density functional theory (M06-2X). The most preferred pathway proceeds through the involvement of a novel iodonium ion intermediate and a pivotal trifluoroacetate counterion. The two sequential aryl C-H activations, assisted by trifluoroacetate as well as the superior leaving group ability of PhI, facilitate the formation of spirocyclic bis-oxindole.

  18. Consumer involvement in research projects: the activities of research funders.

    PubMed

    O'Donnell, Máire; Entwistle, Vikki

    2004-08-01

    This paper reports findings from a postal questionnaire survey and in-depth interviews with UK funders of health-related research that explored whether, why and how they promote consumer involvement in research projects. Many UK funders of health-related research are adopting a policy of promoting consumer involvement in research projects. Telephone interviews revealed they have several reasons for doing so, and that they vary in the ways they encourage and support researchers to involve consumers. For some, descriptions of consumer involvement in a research proposal are important for project funding decisions. They recognized a need for flexibility when assessing consumer involvement in different contexts. We suggest that funders should continue to work to clarify what they consider to be the parameters of acceptability in terms of consumer involvement and ensure that 'flexible' criteria are fairly applied. Researchers should be aware of particular funders' views when applying for project funding.

  19. Transfer-printing of active layers to achieve high quality interfaces in sequentially deposited multilayer inverted polymer solar cells fabricated in air

    PubMed Central

    Vohra, Varun; Anzai, Takuya; Inaba, Shusei; Porzio, William; Barba, Luisa

    2016-01-01

    Abstract Polymer solar cells (PSCs) are greatly influenced by both the vertical concentration gradient in the active layer and the quality of the various interfaces. To achieve vertical concentration gradients in inverted PSCs, a sequential deposition approach is necessary. However, a direct approach to sequential deposition by spin-coating results in partial dissolution of the underlying layers which decreases the control over the process and results in not well-defined interfaces. Here, we demonstrate that by using a transfer-printing process based on polydimethylsiloxane (PDMS) stamps we can obtain increased control over the thickness of the various layers while at the same time increasing the quality of the interfaces and the overall concentration gradient within the active layer of PSCs prepared in air. To optimize the process and understand the influence of various interlayers, our approach is based on surface free energy, spreading parameters and work of adhesion calculations. The key parameter presented here is the insertion of high quality hole transporting and electron transporting layers, respectively above and underneath the active layer of the inverted structure PSC which not only facilitates the transfer process but also induces the adequate vertical concentration gradient in the device to facilitate charge extraction. The resulting non-encapsulated devices (active layer prepared in air) demonstrate over 40% increase in power conversion efficiency with respect to the reference spin-coated inverted PSCs. PMID:27877901

  20. Stacked Sequential Learning

    DTIC Science & Technology

    2005-07-01

    a constant factor of K + 2. (To see this, note sequential stacking requires training K+2 classifiers: the classifiers f1, . . . , fK used in cross...on the non- sequential learners (ME and VP) but improves per- formance of the sequential learners (CRFs and VPH - MMs) less consistently. This pattern

  1. Organized Activity Involvement among Rural Youth: Gender Differences in Associations between Activity Type and Developmental Outcomes

    ERIC Educational Resources Information Center

    Ferris, Kaitlyn A.; Oosterhoff, Benjamin; Metzger, Aaron

    2013-01-01

    The current study examined associations between organized activity involvement, academic achievement, and problem behavior in a sample of youth from a non-agricultural based rural community (M[subscript age] = 15.26, Age range = 11-19 years, N = 456). Analyses examined whether associations varied as a function of adolescent gender and age.…

  2. Decoding sequential finger movements from preparatory activity in higher-order motor regions: a functional magnetic resonance imaging multi-voxel pattern analysis.

    PubMed

    Nambu, Isao; Hagura, Nobuhiro; Hirose, Satoshi; Wada, Yasuhiro; Kawato, Mitsuo; Naito, Eiichi

    2015-11-01

    Performing a complex sequential finger movement requires the temporally well-ordered organization of individual finger movements. Previous behavioural studies have suggested that the brain prepares a whole sequence of movements as a single set, rather than the movements of individual fingers. However, direct neuroimaging support for this hypothesis is lacking and, assuming it to be true, it remains unclear which brain regions represent the information of a prepared sequence. Here, we measured brain activity with functional magnetic resonance imaging while 14 right-handed healthy participants performed two types of well-learned sequential finger movements with their right hands. Using multi-voxel pattern analysis, we examined whether the types of the forthcoming sequence could be predicted from the preparatory activities of nine regions of interest, which included the motor, somatosensory and posterior parietal regions in each hemisphere, bilateral visual cortices, cerebellum and basal ganglia. We found that, during preparation, the activity of the contralateral motor regions could predict which of the two sequences would be executed. Further detailed analysis revealed that the contralateral dorsal premotor cortex and supplementary motor area were the key areas that contributed to the prediction consistently across participants. These contrasted with results from execution-related brain activity where a performed sequence was successfully predicted from the activities in the broad cortical sensory-motor network, including the bilateral motor, parietal and ipsilateral somatosensory cortices. Our study supports the hypothesis that temporary well-organized sequences of movements are represented as a set in the brain, and that preparatory activity in higher-order motor regions represents information about upcoming motor actions.

  3. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... activities involving human subjects. 3452.224-71 Section 3452.224-71 Federal Acquisition Regulations System... Text of Provisions and Clauses 3452.224-71 Notice about research activities involving human subjects... contract will include, or is likely to include, research activities involving human subjects covered...

  4. Colorado court involvement in chemical spill clean-up activities.

    PubMed Central

    Rice, D

    1981-01-01

    Judicial involvement was utilized to force the owners of a pesticide formulation plant to decontaminate property that had been covered with toxic pesticides having the potential to contaminate both surface and groundwater supplies in the East Denver metropolitan area. This case represented the first use of the Colorado state court system in dealing with a hazardous waste "spill." In this case, judicial intervention was unsatisfactory because of the delays involved. Other courses of action will be considered in future cases of a similar nature. PMID:7270771

  5. Colorado court involvement in chemical spill clean-up activities.

    PubMed

    Rice, D

    1981-09-01

    Judicial involvement was utilized to force the owners of a pesticide formulation plant to decontaminate property that had been covered with toxic pesticides having the potential to contaminate both surface and groundwater supplies in the East Denver metropolitan area. This case represented the first use of the Colorado state court system in dealing with a hazardous waste "spill." In this case, judicial intervention was unsatisfactory because of the delays involved. Other courses of action will be considered in future cases of a similar nature.

  6. Involvement of the plasminogen activation system in cow endometritis.

    PubMed

    Moraitis, S; Taitzoglou, I A; Tsantarliotou, M P; Boscos, C M; Kaldrimidou, E; Saratsis, Ph

    2004-01-15

    The objectives of this study were to investigate the: (a) presence and activity of components of the "plasminogen activators/plasmin" system in dairy cows with or without endometritis; (b) variations in enzyme activity according to the degree of endometritis; and (c) associations between these enzymes and changes in endometrial histology after intrauterine antibiotic treatment. Endometrial biopsies were collected from anestrus (no palpable ovarian structures and milk progesterone <1 ng/ml) Holstein cows, 30-40 days postpartum. On the basis of a vaginoscopic examination, rectal palpation of the cervix and uterus, and endometrial histology, there were 92 cows with endometritis and 20 cows without endometritis. After biopsy collection, each cow was given an intrauterine infusion of 1.5x10(6) IU of procaine penicillin G. In cows with endometritis, genital tract examinations and biopsies were repeated 2 weeks later. Both plasminogen activators (PAs), tissue type (t-PA) and urokinase (u-PA), were immunologically identified in all uterine biopsies. Plasminogen activator activity (PAA) increased, whereas plasminogen activator inhibition (PAI) and plasmin inhibition (PI) decreased in proportion to the degree of inflammation. Two weeks after intrauterine treatment, PAA had decreased significantly in all cows that had reduced severity of endometrial inflammation and had increased significantly in all cows with increased severity of inflammation. The change in the degree of inflammation depended upon plasminogen activator activity; cows with higher PAA were more likely to improve. In conclusion, there was evidence for a role of the plasminogen activation proteolytic system in bovine endometritis.

  7. Peroxisome Proliferator-activated Receptor γ Regulates Genes Involved in Insulin/Insulin-like Growth Factor Signaling and Lipid Metabolism during Adipogenesis through Functionally Distinct Enhancer Classes*

    PubMed Central

    Oger, Frédérik; Dubois-Chevalier, Julie; Gheeraert, Céline; Avner, Stéphane; Durand, Emmanuelle; Froguel, Philippe; Salbert, Gilles; Staels, Bart; Lefebvre, Philippe; Eeckhoute, Jérôme

    2014-01-01

    The nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ is a transcription factor whose expression is induced during adipogenesis and that is required for the acquisition and control of mature adipocyte functions. Indeed, PPARγ induces the expression of genes involved in lipid synthesis and storage through enhancers activated during adipocyte differentiation. Here, we show that PPARγ also binds to enhancers already active in preadipocytes as evidenced by an active chromatin state including lower DNA methylation levels despite higher CpG content. These constitutive enhancers are linked to genes involved in the insulin/insulin-like growth factor signaling pathway that are transcriptionally induced during adipogenesis but to a lower extent than lipid metabolism genes, because of stronger basal expression levels in preadipocytes. This is consistent with the sequential involvement of hormonal sensitivity and lipid handling during adipocyte maturation and correlates with the chromatin structure dynamics at constitutive and activated enhancers. Interestingly, constitutive enhancers are evolutionary conserved and can be activated in other tissues, in contrast to enhancers controlling lipid handling genes whose activation is more restricted to adipocytes. Thus, PPARγ utilizes both broadly active and cell type-specific enhancers to modulate the dynamic range of activation of genes involved in the adipogenic process. PMID:24288131

  8. Effects of Sequential Applications of Bassa 50EC (Fenobucarb) and Vitashield 40EC (Chlorpyrifos ethyl) on Acetylcholinesterase Activity in Climbing Perch (Anabas testudineus) Cultured in Rice Fields in the Mekong Delta, Vietnam.

    PubMed

    Tam, Nguyen Thanh; Berg, Håkan; Laureus, Jenny; Cong, Nguyen Van; Tedengren, Michael

    2016-07-01

    This study assesses the effects of sequential applications of the insecticides Bassa 50EC (fenobucarb-F) and Vitashield 40EC (chlorpyrifos ethyl-CPF), sprayed at concentrations used by rice farmers in the Mekong Delta, on the brain acetylcholinesterase (AChE) in climbing perch fingerlings. After spraying the pesticides on the rice fields, the water concentrations of both insecticides decreased below the detection levels within 3 days. The sequential applications caused significant inhibition on the brain AChE activity in the exposed fish. The inhibition by F was quicker, but less prolonged, than for CPF. The inhibition levels caused by the sequential applications were lower than those caused by only CPF and by a mixture of CPF and F. The results indicate that sequential applications of pesticides could have a negative impact on aquatic organisms and fish yields, with implication for the aquatic biodiversity, local people's livelihood and the aquaculture industry in the Mekong Delta.

  9. Radiation protection in radiologic technology: Apathy versus active involvement

    SciTech Connect

    Franz, K.H.

    1982-11-01

    The lack of active participation in radiation protection is a serious problem in Radiologic Technology today. Underlying the problem is professional apathy. An overview of the historical changes, as well as various recent developments in radiology, accentuate the importance of necessary changes in technologists' attitudes and activities. 22 references.

  10. 101 Activities for Building More Effective School-Community Involvement.

    ERIC Educational Resources Information Center

    Rich, Dorothy; Mattox, Beverly

    This booklet contains a collection of more than 100 activities designed to promote school-home and school-community relations. Activities are organized into seven categories: (1) communicating word from home to school, (2) people to people, (3) educational events, (4) volunteers--hands on in the classroom, (5) utilizing community resources, (6)…

  11. Extracurricular Activity Involvement and Adolescent Self-Esteem

    ERIC Educational Resources Information Center

    Kort-Butler, Lisa A.

    2012-01-01

    Structured extracurricular activity participation has been linked to self-esteem and other indicators of positive youth development. This article describes the theoretical basis for this relationship, centering on extracurricular activities as a location for identity development. A summary of the empirical evidence points to the importance of…

  12. Sequential document visualization.

    PubMed

    Mao, Yi; Dillon, Joshua; Lebanon, Guy

    2007-01-01

    Documents and other categorical valued time series are often characterized by the frequencies of short range sequential patterns such as n-grams. This representation converts sequential data of varying lengths to high dimensional histogram vectors which are easily modeled by standard statistical models. Unfortunately, the histogram representation ignores most of the medium and long range sequential dependencies making it unsuitable for visualizing sequential data. We present a novel framework for sequential visualization of discrete categorical time series based on the idea of local statistical modeling. The framework embeds categorical time series as smooth curves in the multinomial simplex summarizing the progression of sequential trends. We discuss several visualization techniques based on the above framework and demonstrate their usefulness for document visualization.

  13. Sequential Medical Trials Involving Paired Data.

    DTIC Science & Technology

    1979-05-22

    2.3.2 ) and (2.3.3). If at any time ~~~ = 1 — $ ( IZ I ) stop taking observations and for the remaining N-2t units of time use * the treatment in...stopping times are restricted to those for which t takes on the values t = (a~~ + no 2 ) ~~~~~ + Na 2/2) . When N is large the successive differences...John Petkau Department of Mathematics University of British Columbia SUMMARY A continuous time version of Anscombe ’ s formulation of the problem of

  14. Baking together-the coordination of actions in activities involving people with dementia.

    PubMed

    Majlesi, Ali Reza; Ekström, Anna

    2016-08-01

    This study explores interaction and collaboration between people with dementia and their spouses in relation to the performance of household chores with the focus on instruction as an interactional context to engage the person with dementia in collaboration to accomplish joint activities. Dementia is generally associated with pathological changes in people's cognitive functions such as diminishing memory functions, communicative abilities and also diminishing abilities to take initiative as well as to plan and execute tasks. Using video recordings of everyday naturally occurring activities, we analyze the sequential organization of actions (see Schegloff, 2007) oriented toward the accomplishment of a joint multi-task activity of baking. The analysis shows the specific ways of collaboration through instructional activities in which the person with dementia exhibits his competence and skills in accomplishing the given tasks through negotiating the instructions with his partner and carrying out instructed actions. Although the driving force of the collaboration seems to be a series of directive sequences only initiated by the partner throughout the baking activity, our analyses highlight how the person with dementia can actively use the material environment-including collaborating partners-to compensate for challenges and difficulties encountered in achieving everyday tasks. The sequential organization of instructions and instructed actions are in this sense argued to provide an interactional environment wherein the person with dementia can make contributions to the joint activity in an efficient way. While a collaborator has been described as necessary for a person with dementia to be able to partake in activities, this study shows that people with dementia are not only guided by their collaborators in joint activities but they can also actively use their collaborators in intricate compensatory ways.

  15. Artificial masculinization in tilapia involves androgen receptor activation.

    PubMed

    Golan, Matan; Levavi-Sivan, Berta

    2014-10-01

    Estrogens have a pivotal role in natural female sexual differentiation of tilapia while lack of steroids results in testicular development. Despite the fact that androgens do not participate in natural sex differentiation, synthetic androgens, mainly 17-α-methyltestosterone (MT) are effective in the production of all-male fish in aquaculture. The sex inversion potency of synthetic androgens may arise from their androgenic activity or else as inhibitors of aromatase activity. The current study is an attempt to differentiate between the two alleged activities in order to evaluate their contribution to the sex inversion process and aid the search for novel sex inversion agents. In the present study, MT inhibited aromatase activity, when applied in vitro as did the non-aromatizable androgen dihydrotestosterone (DHT). In comparison, exposure to fadrozole, a specific aromatase inhibitor, was considerably more effective. Androgenic activity of MT was evaluated by exposure of Sciaenochromis fryeri fry to the substance and testing for the appearance of blue color. Flutamide, an androgen antagonist, administered concomitantly with MT, reduced the appearance of the blue color and the sex inversion potency of MT in a dose-dependent manner. In tilapia, administration of MT, fadrozole or DHT resulted in efficient sex inversion while flutamide reduced the sex inversion potency of all three compounds. In the case of MT and DHT the decrease in sex inversion efficiency caused by flutamide is most likely due to the direct blocking of the androgen binding to its cognate receptor. The negative effect of flutamide on the efficiency of the fadrozole treatment may indicate that the masculinizing activity of fadrozole may be attributed to excess, un-aromatized, androgens accumulated in the differentiating gonad. The present study shows that when androgen receptors are blocked, there is a reduction in the efficiency of sex inversion treatments. Our results suggest that in contrast to

  16. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011)...

  17. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011)...

  18. 45 CFR 1177.4 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Claims involving criminal activity or misconduct. 1177.4 Section 1177.4 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL... Claims involving criminal activity or misconduct. (a) A debtor whose indebtedness involves...

  19. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... involving human subjects. 3452.224-72 Section 3452.224-72 Federal Acquisition Regulations System DEPARTMENT... Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As prescribed... human subjects covered under 34 CFR part 97: Research Activities Involving Human Subjects (MAR 2011)...

  20. Social Work with Religious Volunteers: Activating and Sustaining Community Involvement

    ERIC Educational Resources Information Center

    Garland, Diana R.; Myers, Dennis M.; Wolfer, Terry A.

    2008-01-01

    Social workers in diverse community practice settings recruit and work with volunteers from religious congregations. This article reports findings from two surveys: 7,405 congregants in 35 Protestant congregations, including 2,570 who were actively volunteering, and a follow-up survey of 946 volunteers. It compares characteristics of congregation…

  1. Transportation as a "Related Service": Issues that Involve Transition Activities.

    ERIC Educational Resources Information Center

    Missouri Univ., Columbia. Missouri LINC.

    The paper discusses transportation as a related service for students with disabilities expecially as related to school-to-work transition activities. First, the legislative and legal basis for providing transportation services is discussed in the form of answers to frequently asked questions: why provide transportation? what is the basis for…

  2. Involvement of hypothalamic AMP-activated protein kinase in leptin-induced sympathetic nerve activation.

    PubMed

    Tanida, Mamoru; Yamamoto, Naoki; Shibamoto, Toshishige; Rahmouni, Kamal

    2013-01-01

    In mammals, leptin released from the white adipose tissue acts on the central nervous system to control feeding behavior, cardiovascular function, and energy metabolism. Central leptin activates sympathetic nerves that innervate the kidney, adipose tissue, and some abdominal organs in rats. AMP-activated protein kinase (AMPK) is essential in the intracellular signaling pathway involving the activation of leptin receptors (ObRb). We investigated the potential of AMPKα2 in the sympathetic effects of leptin using in vivo siRNA injection to knockdown AMPKα2 in rats, to produce reduced hypothalamic AMPKα2 expression. Leptin effects on body weight, food intake, and blood FFA levels were eliminated in AMPKα2 siRNA-treated rats. Leptin-evoked enhancements of the sympathetic nerve outflows to the kidney, brown and white adipose tissues were attenuated in AMPKα2 siRNA-treated rats. To check whether AMPKα2 was specific to sympathetic changes induced by leptin, we examined the effects of injecting MT-II, a melanocortin-3 and -4 receptor agonist, on the sympathetic nerve outflows to the kidney and adipose tissue. MT-II-induced sympatho-excitation in the kidney was unchanged in AMPKα2 siRNA-treated rats. However, responses of neural activities involving adipose tissue to MT-II were attenuated in AMPKα2 siRNA-treated rats. These results suggest that hypothalamic AMPKα2 is involved not only in appetite and body weight regulation but also in the regulation of sympathetic nerve discharges to the kidney and adipose tissue. Thus, AMPK might function not only as an energy sensor, but as a key molecule in the cardiovascular, thermogenic, and lipolytic effects of leptin through the sympathetic nervous system.

  3. Tumor suppressor genes are larger than apoptosis-effector genes and have more regions of active chromatin: Connection to a stochastic paradigm for sequential gene expression programs.

    PubMed

    Garcia, Marlene; Mauro, James A; Ramsamooj, Michael; Blanck, George

    2015-08-03

    Apoptosis- and proliferation-effector genes are substantially regulated by the same transactivators, with E2F-1 and Oct-1 being notable examples. The larger proliferation-effector genes have more binding sites for the transactivators that regulate both sets of genes, and proliferation-effector genes have more regions of active chromatin, i.e, DNase I hypersensitive and histone 3, lysine-4 trimethylation sites. Thus, the size differences between the 2 classes of genes suggest a transcriptional regulation paradigm whereby the accumulation of transcription factors that regulate both sets of genes, merely as an aspect of stochastic behavior, accumulate first on the larger proliferation-effector gene "traps," and then accumulate on the apoptosis effector genes, thereby effecting sequential activation of the 2 different gene sets. As IRF-1 and p53 levels increase, tumor suppressor proteins are first activated, followed by the activation of apoptosis-effector genes, for example during S-phase pausing for DNA repair. Tumor suppressor genes are larger than apoptosis-effector genes and have more IRF-1 and p53 binding sites, thereby likewise suggesting a paradigm for transcription sequencing based on stochastic interactions of transcription factors with different gene classes. In this report, using the ENCODE database, we determined that tumor suppressor genes have a greater number of open chromatin regions and histone 3 lysine-4 trimethylation sites, consistent with the idea that a larger gene size can facilitate earlier transcriptional activation via the inclusion of more transactivator binding sites.

  4. Hemolysis-induced lethality involves inflammasome activation by heme

    PubMed Central

    Dutra, Fabianno F.; Alves, Letícia S.; Rodrigues, Danielle; Fernandez, Patricia L.; de Oliveira, Rosane B.; Golenbock, Douglas T.; Zamboni, Dario S.; Bozza, Marcelo T.

    2014-01-01

    The increase of extracellular heme is a hallmark of hemolysis or extensive cell damage. Heme has prooxidant, cytotoxic, and inflammatory effects, playing a central role in the pathogenesis of malaria, sepsis, and sickle cell disease. However, the mechanisms by which heme is sensed by innate immune cells contributing to these diseases are not fully characterized. We found that heme, but not porphyrins without iron, activated LPS-primed macrophages promoting the processing of IL-1β dependent on nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3). The activation of NLRP3 by heme required spleen tyrosine kinase, NADPH oxidase-2, mitochondrial reactive oxygen species, and K+ efflux, whereas it was independent of heme internalization, lysosomal damage, ATP release, the purinergic receptor P2X7, and cell death. Importantly, our results indicated the participation of macrophages, NLRP3 inflammasome components, and IL-1R in the lethality caused by sterile hemolysis. Thus, understanding the molecular pathways affected by heme in innate immune cells might prove useful to identify new therapeutic targets for diseases that have heme release. PMID:25225402

  5. Organized activity involvement, depressive symptoms, and social adjustment in adolescents: ethnicity and socioeconomic status as moderators.

    PubMed

    Randall, Edin T; Bohnert, Amy M

    2009-10-01

    The current cross-sectional study investigated the links between various dimensions of organized activity involvement and depressive symptoms, loneliness, and peer victimization in an ethnically and economically diverse sample of adolescents (N = 152; 58% female). Results indicate that adolescents who were involved in organized activities for more years also reported lower levels of loneliness. There was evidence of diminishing returns when adolescents were very highly involved in organized activities; those who were either under- or over-involved reported the highest levels of depressive symptoms. Conversely, findings indicate that adolescents who participated in a narrow or wide range of activity contexts reported the lowest levels of depressive symptoms. In addition, results suggested that the relation between organized activity involvement and adjustment differs among adolescents from diverse ethnic and socioeconomic backgrounds. Findings from the current study also underscore the importance of considering multiple indices of activity involvement when assessing its association with adjustment.

  6. Laboratory activities involving transmissible spongiform encephalopathy causing agents

    PubMed Central

    Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

    2013-01-01

    Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

  7. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

    PubMed

    Cervellati, Carlo; Sticozzi, Claudia; Romani, Arianna; Belmonte, Giuseppe; De Rasmo, Domenico; Signorile, Anna; Cervellati, Franco; Milanese, Chiara; Mastroberardino, Pier Giorgio; Pecorelli, Alessandra; Savelli, Vinno; Forman, Henry J; Hayek, Joussef; Valacchi, Giuseppe

    2015-10-01

    A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment.

  8. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    PubMed Central

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  9. Longitudinal Modeling of Adolescents' Activity Involvement, Problem Peer Associations, and Youth Smoking

    PubMed Central

    Metzger, Aaron; Dawes, Nickki; Mermelstein, Robin; Wakschlag, Lauren

    2010-01-01

    Longitudinal associations among different types of organized activity involvement, problem peer associations, and cigarette smoking were examined in a sample of 1,040 adolescents (mean age = 15.62 at baseline, 16.89 at 15-month assessment, 17.59 at 24 months) enriched for smoking experimentation (83% had tried smoking). A structural equation model tested longitudinal paths between three categories of involvement (team sports, school clubs and activities, and religious activities, measured at baseline and 15 months), problem peer associations (baseline and 15 months), and cigarette smoking behavior (baseline and 24 months). Multi-group analyses indicated pathways differed by type of activity and adolescent gender. Boys’ baseline team sports and religious involvement predicted lower levels of smoking at 24 months via continued activity involvement at 15 months. Girls’ involvement in school clubs and activities and religious activities indirectly predicted lower levels of smoking at 24 months via reduced exposure to problem peers at 15 months. PMID:21603061

  10. Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy.

    PubMed

    Musa, Faisal; Baidas, Said

    2015-01-01

    We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse.

  11. Dynamics of Sequential Decision Making

    NASA Astrophysics Data System (ADS)

    Rabinovich, Mikhail I.; Huerta, Ramón; Afraimovich, Valentin

    2006-11-01

    We suggest a new paradigm for intelligent decision-making suitable for dynamical sequential activity of animals or artificial autonomous devices that depends on the characteristics of the internal and external world. To do it we introduce a new class of dynamical models that are described by ordinary differential equations with a finite number of possibilities at the decision points, and also include rules solving this uncertainty. Our approach is based on the competition between possible cognitive states using their stable transient dynamics. The model controls the order of choosing successive steps of a sequential activity according to the environment and decision-making criteria. Two strategies (high-risk and risk-aversion conditions) that move the system out of an erratic environment are analyzed.

  12. Predicting involvement in prison gang activity: street gang membership, social and psychological factors.

    PubMed

    Wood, Jane L; Alleyne, Emma; Mozova, Katarina; James, Mark

    2014-06-01

    The aim of this study was to examine whether street gang membership, psychological factors, and social factors such as preprison experiences could predict young offenders' involvement in prison gang activity. Data were collected via individual interviews with 188 young offenders held in a Young Offenders Institution in the United Kingdom. Results showed that psychological factors such as the value individuals attached to social status, a social dominance orientation, and antiauthority attitudes were important in predicting young offenders' involvement in prison gang activity. Further important predictors included preimprisonment events such as levels of threat, levels of individual delinquency, and levels of involvement in group crime. Longer current sentences also predicted involvement in prison gang activity. However, street gang membership was not an important predictor of involvement in prison gang activity. These findings have implications for identifying prisoners involved in prison gang activity and for considering the role of psychological factors and group processes in gang research.

  13. One-pot sequential synthesis of magnetically separable Fe3O4/AgCl photocatalysts with enhanced activity and stability

    NASA Astrophysics Data System (ADS)

    Liu, Zening; Liu, Yongcheng; Cai, Mujin; Xu, Piaopiao; Ma, Zonghua; Yuan, Hong

    2017-03-01

    Magnetically separable Fe3O4/AgCl photocatalysts were prepared by a one-pot sequential method. A series of techniques proved the hybrid structure of Fe3O4/AgCl composites. Fe3O4/AgCl composites had a much higher photocatalytic activity toward Rhodamine B (RhB) degradation than pure AgCl under the simulated solar light irradiation. The existence of metal Ag resulted in high photocatalytic activity of Fe3O4/AgCl, which was related with the amount of metallic Ag. The scavenging experiments showed that the degradation reaction most probably was initiated by the photoinduced single-electron transfer, and the generation of superoxide anion (O 2 -· ) played a significant role. The composite photocatalysts could be recycled by applying an external magnetic field, and the reused composites maintained their original photocatalytic activity. Fe3O4/AgCl composites were highly efficient, magnetically separable, and recoverable. This proves their potential applications in the photodegradation of organic pollutants.

  14. 16 CFR 1031.5 - Criteria for Commission involvement in voluntary standards activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ACTIVITIES General Policies § 1031.5 Criteria for Commission involvement in voluntary standards activities... share of product production. (g) Provisions in the standard for marking products conforming to...

  15. 75 FR 69630 - Impact of Implementation of the Chemical Weapons Convention on Commercial Activities Involving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ...-0543-02] Impact of Implementation of the Chemical Weapons Convention on Commercial Activities Involving... Chemical Weapons Convention (CWC), through the Chemical Weapons Convention Implementation Act (CWCIA) and the Chemical Weapons Convention Regulations (CWCR), has had on commercial activities...

  16. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Claims involving criminal activity or misconduct. 1215.24 Section 1215.24 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct....

  17. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Claims involving criminal activity or misconduct. 1215.24 Section 1215.24 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct....

  18. Breadth and Intensity of Youth Activity Involvement as Contexts for Positive Development

    ERIC Educational Resources Information Center

    Rose-Krasnor, Linda; Busseri, Michael A.; Willoughby, Teena; Chalmers, Heather

    2006-01-01

    Research has linked youth activity involvement to positive development. However, past studies have confounded at least two separable dimensions of involvement: breadth (number of activities) and intensity (participation frequency). Theory and the limited available evidence suggest that these dimensions may make independent contributions to…

  19. Ego Strength Development of Adolescents Involved in Adult-Sponsored Structured Activities.

    ERIC Educational Resources Information Center

    Markstrom, Carol A.; Li, Xaioming; Blackshire, Shana L.; Wilfong, Juanita J.

    2005-01-01

    A psychosocial conception of ego strengths is presented in relation to adolescent involvement in adult-sponsored structured youth activities. Five-hundred and seventeen high school students completed measures on their involvement in structured activities and on 8 ego strengths. Gender, age, and SES were controlled in a MANCOVA procedure and it was…

  20. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... about the regulations for the protection of human subjects and related policies and guidelines... activities involving human subjects. 3452.224-71 Section 3452.224-71 Federal Acquisition Regulations System... Text of Provisions and Clauses 3452.224-71 Notice about research activities involving human...

  1. 5 CFR 1215.24 - Claims involving criminal activity or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Claims involving criminal activity or misconduct. 1215.24 Section 1215.24 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION AND PROCEDURES DEBT MANAGEMENT Claims Collection § 1215.24 Claims involving criminal activity or misconduct....

  2. Breadth and Intensity: Salient, Separable, and Developmentally Significant Dimensions of Structured Youth Activity Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2009-01-01

    In recent years, an impressive volume of evidence has accumulated demonstrating that youth involvement in structured, organized activities (e.g. school sports, community clubs) may facilitate positive youth development. We present a theory-based framework for studying structured activity involvement (SAI) as a context for positive youth…

  3. Adaptive sequential controller

    DOEpatents

    El-Sharkawi, Mohamed A.; Xing, Jian; Butler, Nicholas G.; Rodriguez, Alonso

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  4. In Vitro Screening for β-Hydroxy-β-methylglutaryl-CoA Reductase Inhibitory and Antioxidant Activity of Sequentially Extracted Fractions of Ficus palmata Forsk

    PubMed Central

    Iqbal, Danish; Khan, M. Salman; Khan, Amir; Khan, Mohd. Sajid; Srivastava, Ashwani K.; Bagga, Paramdeep

    2014-01-01

    Hypercholesterolemia-induced oxidative stress has been strongly implicated in the pathogenesis of atherosclerosis, which is one of the major causes of mortality worldwide. The current work, for the first time, accounts the antioxidant, genoprotective, antilipoperoxidative, and HMG-CoA reductase (EC 1.1.1.34) inhibitory properties of traditional medicinal plant, Ficus palmata Forsk. Our result showed that among sequentially extracted fractions of Ficus palmata Forsk, FPBA (F. palmata bark aqueous extract) and FPLM (F. palmata leaves methanolic extract) extracts have higher phenolic content and also exhibited significantly more radical scavenging (DPPH and Superoxide) and antioxidant (FRAP) capacity. Moreover, FPBA extract also exhibited significantly higher inhibition of lipid peroxidation assay. Additionally, results showed almost complete and partial protection of oxidatively damaged DNA by these plant extracts when compared to mannitol. Furthermore, our results showed that FPBA extract (IC50 = 9.1 ± 0.61 µg/mL) exhibited noteworthy inhibition of HMG-CoA reductase activity as compared to other extracts, which might suggest its role as cardioprotective agent. In conclusion, results showed that FPBA extract not only possess significant antioxidant and genoprotective property but also is able to attenuate the enzymatic activity of HMG-CoA reductase, which might suggest its role in combating various oxidative stress-related diseases, including atherosclerosis. PMID:24883325

  5. Fission yeast APC/C activators Slp1 and Fzr1 sequentially trigger two consecutive nuclear divisions during meiosis.

    PubMed

    Chikashige, Yuji; Yamane, Miho; Okamasa, Kasumi; Osakada, Hiroko; Tsutsumi, Chihiro; Nagahama, Yuki; Fukuta, Noriko; Haraguchi, Tokuko; Hiraoka, Yasushi

    2017-02-28

    In meiosis, two rounds of nuclear division occur consecutively without DNA replication between the divisions. We isolated a fission yeast mutant in which the nucleus divides only once to generate two spores, as opposed to four, in meiosis. In this mutant, we found that the initiation codon of the slp1(+) gene is converted to ATA, producing a reduced amount of Slp1. As a member of the Fizzy family of APC/C activators, Slp1 is essential for vegetative growth; however, the mutant allele shows a phenotype only in meiosis. Slp1 insufficiency delays degradation of maturation-promoting factor (MPF) at the first meiotic division, and another APC/C activator, Fzr1, which acts late in meiosis, terminates meiosis immediately after the delayed first division to produce two viable spores. This article is protected by copyright. All rights reserved.

  6. Sequential protein NMR assignments in the liquid state via sequential data acquisition

    NASA Astrophysics Data System (ADS)

    Wiedemann, Christoph; Bellstedt, Peter; Kirschstein, Anika; Häfner, Sabine; Herbst, Christian; Görlach, Matthias; Ramachandran, Ramadurai

    2014-02-01

    Two different NMR pulse schemes involving sequential 1H data acquisition are presented for achieving protein backbone sequential resonance assignments: (i) acquisition of 3D {HCCNH and HNCACONH} and (ii) collection of 3D {HNCOCANH and HNCACONH} chemical shift correlation spectra using uniformly 13C,15N labelled proteins. The sequential acquisition of these spectra reduces the overall experimental time by a factor of ≈2 as compared to individual acquisitions. The suitability of this approach is experimentally demonstrated for the C-terminal winged helix (WH) domain of the minichromosome maintenance (MCM) complex of Sulfolobus solfataricus.

  7. Sequential analysis of myofibroblast differentiation and transforming growth factor-β1/Smad pathway activation in murine pulmonary fibrosis.

    PubMed

    Usuki, Jiro; Matsuda, Kuniko; Azuma, Arata; Kudoh, Shoji; Gemma, Akihiko

    2012-01-01

    Myofibroblasts play a critical role in tissue fibrosis. However, the intracellular signaling pathways in myofibroblast differentiation are poorly understood. Here, we studied the relationship between transforming growth factor-β (TGF-β)/Smad pathway activation and myofibroblast differentiation in both in vivo and in vitro experiments. In murine bleomycin-induced pulmonary fibrosis, nuclear localization of phosphorylated Smad2/3 (p-Smad2/3) was observed in pulmonary fibrotic lesions 7 days after bleomycin injection, whereas α-smooth muscle actin (ASMA)-positive myofibroblasts appeared in the lesions at 14 days, when the cytoplasmic localization of p-Smad2/3 was observed. We also compared the effects of TGF-β1 on myofibroblast differentiation and on type I collagen expression in a murine lung fibroblast cell line (MLg2908). TGF-β1 induced rapid expression of p-Smad2/3 in nuclei, after which ASMA organization in the cytoplasm of fibroblasts was observed. However, TGF-β1 produced no effect on the quantity of ASMA, either in mRNA levels or protein levels, even after the phosphorylation of Smad2/3. In contrast, TGF-β1 upregulated the expression of type I collagen mRNA. These findings suggest that in pulmonary fibrosis the molecular mechanism of myofibroblast differentiation is complex and that the difference between ASMA expression and type I collagen expression is mediated by the TGF-β/Smad pathway.

  8. Sequential truncation of the lactose permease over a three-amino acid sequence near the carboxyl terminus leads to progressive loss of activity and stability

    SciTech Connect

    McKenna, E.; Hardy, D.; Pastore, J.C.; Kaback, H.R. )

    1991-04-15

    Previous experiments are consistent with the notion that residues 396-401 (...SVFTLS...) at the carboxyl terminus of the last putative transmembrane helix of the lactose (lac) permease of Escherichia coli are important for protection against proteolytic degradation and suggest that this region of the permease may be necessary for proper folding. Stop codons (TAA) have now been substituted sequentially for amino acid codons 396-401 in the lacY gene, and the termination mutants were expressed from the plasmid pT7-5. With respect to transport, permease truncated at residue 396-or 397 is completely defective, while molecules truncated at residues 398, 399, 400, and 401, respectively, exhibit 15-25%, 30-40%, 40-45%, and 70-100% of wild-type activity. As judged by pulse-chase experiments with ({sup 35}S)methionine, wild-type permease or permease truncated at residue 401 is stable, while permease molecules truncated at position 400, 399, 398, 397, or 396 are degraded at increasingly rapid rates. The findings indicate that either the last turn of putative helix XII or the region immediately distal to helix XII is important for proper folding and protection against proteolytic degradation.

  9. Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan.

    PubMed Central

    Rankin, J A; Sylvester, I; Smith, S; Yoshimura, T; Leonard, E J

    1990-01-01

    The capacity of lipopolysaccharide (LPS), zymosan, and calcium ionophore A23187 to induce neutrophil chemotactic activity (NCA), leukotriene B4 (LTB4), and neutrophil attractant/activation protein (NAP-1) release from human alveolar macrophages (AM) retrieved from normal nonsmokers was evaluated. LPS induced a dose-dependent release of LTB4 that began by 1 h, 4.0 +/- 3.2 ng/10(6) viable AM; peaked at 3 h, 24.7 +/- 13.5 ng/10(6) viable AM; and decreased by 24 h, 1.2 +/- 1.0 ng/10(6) viable AM (n = 8). Quantities of LTB4 in cell-free supernatants of AM stimulated with LPS were determined by reverse-phase high-performance liquid chromatography and corresponded well with results obtained by radioimmunoassay. By contrast, NAP-1 release began approximately 3-5 h after stimulation of AM with LPS, 197 +/- 192 ng/ml, and peaked at 24 h, 790 +/- 124 ng/ml. Release of NAP-1 was stimulus specific because A23187 evoked the release of LTB4 but not NAP-1, whereas LPS and zymosan induced the release of both LTB4 and NAP-1. The appearance of neutrophil chemotactic activity in supernatants of AM challenged with LPS for 3 h could be explained completely by the quantities of LTB4 present. After stimulation with LPS or zymosan for 24 h, AM had metabolized almost all generated LTB4. Preincubation of AM with nordihydroguiaretic acid (10(-4) M) completely abolished the appearance of NCA, LTB4, and NAP-1 in supernatants of AM challenged with LPS. Therefore, LPS and zymosan particles were potent stimuli of the sequential release of LTB4 and NAP-1 from AM. PMID:2173722

  10. Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats.

    PubMed

    Kim, Yang Gyun; Lee, Sang Ho; Kim, Se-Yun; Lee, Arah; Moon, Ju Young; Jeong, Kyung-Hwan; Lee, Tae Won; Lim, Sung Jig; Sohn, Il Suk; Ihm, Chun-Gyoo

    2016-07-01

    The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.

  11. Sequential inductive learning

    SciTech Connect

    Gratch, J.

    1996-12-31

    This article advocates a new model for inductive learning. Called sequential induction, it helps bridge classical fixed-sample learning techniques (which are efficient but difficult to formally characterize), and worst-case approaches (which provide strong statistical guarantees but are too inefficient for practical use). Learning proceeds as a sequence of decisions which are informed by training data. By analyzing induction at the level of these decisions, and by utilizing the only enough data to make each decision, sequential induction provides statistical guarantees but with substantially less data than worst-case methods require. The sequential inductive model is also useful as a method for determining a sufficient sample size for inductive learning and as such, is relevant to learning problems where the preponderance of data or the cost of gathering data precludes the use of traditional methods.

  12. Sequential elution process

    DOEpatents

    Kingsley, I.S.

    1987-01-06

    A process and apparatus are disclosed for the separation of complex mixtures of carbonaceous material by sequential elution with successively stronger solvents. In the process, a column containing glass beads is maintained in a fluidized state by a rapidly flowing stream of a weak solvent, and the sample is injected into this flowing stream such that a portion of the sample is dissolved therein and the remainder of the sample is precipitated therein and collected as a uniform deposit on the glass beads. Successively stronger solvents are then passed through the column to sequentially elute less soluble materials. 1 fig.

  13. Optimisation of beryllium-7 gamma analysis following BCR sequential extraction.

    PubMed

    Taylor, A; Blake, W H; Keith-Roach, M J

    2012-03-30

    The application of cosmogenic (7)Be as a sediment tracer at the catchment-scale requires an understanding of its geochemical associations in soil to underpin the assumption of irreversible adsorption. Sequential extractions offer a readily accessible means of determining the associations of (7)Be with operationally defined soil phases. However, the subdivision of the low activity concentrations of fallout (7)Be in soils into geochemical fractions can introduce high gamma counting uncertainties. Extending analysis time significantly is not always an option for batches of samples, owing to the on-going decay of (7)Be (t(1/2)=53.3 days). Here, three different methods of preparing and quantifying (7)Be extracted using the optimised BCR three-step scheme have been evaluated and compared with a focus on reducing analytical uncertainties. The optimal method involved carrying out the BCR extraction in triplicate, sub-sampling each set of triplicates for stable Be analysis before combining each set and coprecipitating the (7)Be with metal oxyhydroxides to produce a thin source for gamma analysis. This method was applied to BCR extractions of natural (7)Be in four agricultural soils. The approach gave good counting statistics from a 24 h analysis period (~10% (2σ) where extract activity >40% of total activity) and generated statistically useful sequential extraction profiles. Total recoveries of (7)Be fell between 84 and 112%. The stable Be data demonstrated that the extraction procedure had a high reproducibility (<1% RSD), thus gamma counting uncertainties dominated the overall uncertainty. In addition, extractions of soil equilibrated with stable Be at a concentration below the Cation Exchange Capacity (CEC) of the soil demonstrated that doubling the soil:solution ratio to enhance the mass of soil used in a sequential extraction scheme affects the apparent distribution of approximately 10% of the total Be. At high concentration, stable Be was found to be a poor proxy for

  14. Health benefits of serious involvement in leisure activities among older Korean adults.

    PubMed

    Kim, Junhyoung; Yamada, Naoko; Heo, Jinmoo; Han, Areum

    2014-01-01

    The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging.

  15. Health benefits of serious involvement in leisure activities among older Korean adults

    PubMed Central

    Kim, Junhyoung; Yamada, Naoko; Heo, Jinmoo; Han, Areum

    2014-01-01

    The existing literature suggests that serious engagement in leisure activities leads to happiness, life satisfaction, and successful aging among older adults. This qualitative study was used to examine the benefits of serious involvement in leisure activities among older Korean adults who were members of a sports club. Using an analytic data analysis, we identified three main themes associated with the benefits of serious engagement in leisure activities: 1) the experience of psychological benefits, 2) the creation of social support, and 3) the enhancement of physical health. These themes indicate that, through serious involvement in certain physical activities, participants gain various health benefits, which may contribute to successful aging. PMID:25059979

  16. Behavioural and neurophysiological disruption of corticobulbar motor systems and their effects on sequential pharyngeal swallowing.

    PubMed

    Al-Toubi, Aamir; Daniels, Stephanie K; Huckabee, Maggie-Lee; Corey, David M; Doeltgen, Sebastian H

    2016-10-15

    Primary motor networks are known to be involved in the control of voluntary oral movements as well as the modulation of pharyngeal movements during experimentally controlled single swallows performed on command. The role of these networks in the more typical task of sequential swallowing remains unexplored. This study evaluated the hypothesis that experimental disruption of motor cortical activation would reduce the rate and regularity of repeatedly performed volitional or volitionally initiated motor tasks controlled by corticospinal (finger tapping) and corticobulbar (eyebrow movement, jaw opening, volitional sequential swallowing) motor systems, but would not influence a more reflexive corticobulbar task (reflexive sequential swallowing to pharyngeal water infusion). This premise was investigated in 24 healthy participants using two techniques: a dual task paradigm and a transcranial magnetic stimulation paradigm. Disruption effects were quantified by changes in rate and regularity of performance for each tested motor task. In summary, volitional motor tasks controlled by corticospinal motor networks (finger tapping) are more susceptible to behavioural and neurophysiological disruption than tasks controlled by cortiobulbar motor networks containing a reflexive component (both volitional and experimentally initiated consecutive swallowing). Purely volitional motor tasks controlled by the corticobulbar motor system (eyebrow raising or jaw opening) were affected in similar ways as the volitional corticospinal motor tasks. In summary, tasks involving sequential pharyngeal swallowing - whether volitionally or experimentally initiated - are largely robust against disruption of primary cortical motor networks, supporting a key role of medullary CPGs in the motor control of sequential pharyngeal swallowing.

  17. Sequential Dependencies in Driving

    ERIC Educational Resources Information Center

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  18. Sequential Reliability Tests.

    ERIC Educational Resources Information Center

    Eiting, Mindert H.

    1991-01-01

    A method is proposed for sequential evaluation of reliability of psychometric instruments. Sample size is unfixed; a test statistic is computed after each person is sampled and a decision is made in each stage of the sampling process. Results from a series of Monte-Carlo experiments establish the method's efficiency. (SLD)

  19. Sequential memory: Binding dynamics

    NASA Astrophysics Data System (ADS)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  20. Sequential Dependencies in Categorical Judgments of Radiographic Images

    ERIC Educational Resources Information Center

    Beckstead, Jason W.; Boutis, Kathy; Pecaric, Martin; Pusic, Martin V.

    2017-01-01

    Sequential context effects, the psychological interactions occurring between the events of successive trials when a sequence of similar stimuli are judged, have interested psychologists for decades. It has been well established that individuals exhibit sequential context effects in psychophysical experiments involving unidimensional stimuli.…

  1. A Bayesian Theory of Sequential Causal Learning and Abstract Transfer

    ERIC Educational Resources Information Center

    Lu, Hongjing; Rojas, Randall R.; Beckers, Tom; Yuille, Alan L.

    2016-01-01

    Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about…

  2. Getting Involved: Exploring Latino GBT Volunteerism and Activism in AIDS and LGBT Organizations

    PubMed Central

    Ramirez-Valles, Jesus; Kuhns, Lisa M.; Vázquez, Raquel; Benjamin, Gregory D.

    2014-01-01

    The purpose of this paper is to investigate the community involvement (e.g., volunteerism, activism) of Latino gay and bisexual men and transgender persons (GBT) in two areas: AIDS/GLBT and other general causes. Drawing from volunteering and identity theories, we explore: Who is likely to get involved? What factors affect variation in the levels of involvement? Where do Latino GBT participate and what do they do? Data come from a cross-sectional sample (N=643) of Latino GBT in Chicago and San Francisco. We find high levels of involvement, but primarily focused on AIDS/GLBT. Involvement appears to be driven by income, early involvement, role modeling, and childhood stigmatization of gender nonconformity. PMID:26451081

  3. Arf nucleotide binding site opener [ARNO] promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion in INS 832/13 β-cells and rat islets

    PubMed Central

    Jayaram, Bhavaani; Syed, Ismail; Kyathanahalli, Chandrashekara N.; Rhodes, Christopher J.; Kowluru, Anjaneyulu

    2011-01-01

    Glucose-stimulated insulin secretion [GSIS] involves interplay between small G-proteins and their regulatory factors. Herein, we tested the hypothesis that Arf nucleotide binding site opener [ARNO], a guanine nucleotide exchange factor [GEF] for the small G-protein Arf6, mediates the functional activation of Arf6, and that ARNO/Arf6 signaling axis, in turn, controls the activation of Cdc42 and Rac1, which have been implicated in GSIS. Molecular biological [i.e., expression of inactive mutants or siRNA] and pharmacological approaches were employed to assess the roles for ARNO/Arf6 signaling pathway in insulin secretion in normal rat islets and INS 832/13 cells. Degrees of activation of Arf6 and Cdc42/Rac1 were quantitated by GST-GGA3 and PAK-1 kinase pull-down assays, respectively. ARNO is expressed in INS 832/13 cells, rat islets and human islets. Expression of inactive mutants of Arf6 [Arf6-T27N] or ARNO [ARNO-E156K] or siRNA-ARNO markedly reduced GSIS in isolated β-cells. secinH3, a selective inhibitor of ARNO/Arf6 signaling axis, also inhibited GSIS in INS 832/13 cells and rat islets. Stimulatory concentrations of glucose promoted Arf6 activation, which was inhibited by secinH3 or siRNA-ARNO, suggesting that ARNO/Arf6 signaling cascade is necessary for GSIS. secinH3 or siRNA-ARNO also inhibited glucose-induced activation of Cdc42 and Rac1 suggesting that ARNO/Arf6 might be upstream to Cdc42 and Rac1 activation steps, which are necessary for GSIS. Lastly, co-immunoprecipitation and confocal microscopic studies suggested increased association between Arf6 and ARNO in glucose-stimulated β-cells. These findings provide the first evidence to implicate ARNO in the sequential activation of Arf6, Cdc42 and Rac1 culminating in GSIS. PMID:21276423

  4. A Study of Lipscomb University Students' Internet Use and Involvement in Extracurricular Activities

    ERIC Educational Resources Information Center

    Smith, Samuel Aarron

    2010-01-01

    The purpose of this study was to analyze Lipscomb University students' Internet use and involvement in extracurricular activities. A survey of students at Lipscomb University was conducted. As confirmed by the data the research was able to determine that the type of extracurricular activity a student participates in most often is related to the…

  5. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  6. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  7. Middle-Class Parental Involvement in the Summer Activities of Four Elementary Students: A Qualitative Study

    ERIC Educational Resources Information Center

    Ballard, Iva B.; Chappell, Manya; Johnson, Susan; Ngassam, Marlise DePaul

    2013-01-01

    In this study, we explore middle-class parental involvement in summer activities of four elementary students. Many researchers discuss summer programs initiated by institutions, but fail to explain how parents' availability, experiences, and related criteria affect student summer activities. From our interviews, observations, and artifacts, we…

  8. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  9. 40 CFR 13.5 - Claims involving criminal activities or misconduct.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... misconduct. 13.5 Section 13.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL CLAIMS COLLECTION STANDARDS General § 13.5 Claims involving criminal activities or misconduct. (a) The Administrator will refer cases of suspected criminal activity or misconduct to the EPA Office of Inspector...

  10. Understanding Threshold Effects of Organized Activity Involvement in Adolescents: Sex and Family Income as Moderators

    ERIC Educational Resources Information Center

    Randall, Edin T.; Bohnert, Amy M.

    2012-01-01

    The current study examined the curvilinear links between involvement in organized activities (OA) and sport activities specifically and various indicators of psychological and social development. Participants included 150 9th and 10th graders (57% females) from an urban, selective-enrollment high school. Eligibility for admission is based on city…

  11. 48 CFR 3452.224-72 - Research activities involving human subjects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Research activities... OF EDUCATION ACQUISITION REGULATION CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 3452.224-72 Research activities involving human subjects. As...

  12. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  13. Fibroblasts, glial, and neuronal cells are involved in extravascular prothrombin activation.

    PubMed

    Yamazaki, Y; Shikamoto, Y; Fukudome, K; Kimoto, M; Morita, T

    1999-10-01

    A membrane-associated prothrombin activator (MAPA) was found on various cultured cells derived from non-hematopoietic cells [Sekiya, F. et al. (1994) J. Biol. Chem. 269, 32441-32445]. In this study, we investigated the enzymatic properties of this enzyme using protease inhibitors. While the metalloproteinase inhibitor, o-phenanthroline, had no effect, some Kunitz type serine protease inhibitors attenuated MAPA activity. Recombinant tissue factor pathway inhibitor (rTFPI) also markedly reduced the activity (IC(50), 1. 3+/-0.6 x 10(-10) M). MAPA activity is, therefore, most likely to be due to factor Xa. We evaluated the effect of exogenous factor Xa on MAPA activity. Factor Xa-dependent prothrombin activation was observed on fibroblast cells (apparent K(d), 1.47+/-0.72 nM). Activation was also observed on glial and neuronal cells, which expressed MAPA activity. These results imply that membrane-bound factor Xa results in MAPA activity on these cells. Therefore, we considered the involvement of factor Va, a component of prothrombinase, in this activity. We examined whether or not the prothrombinase complex is assembled on these cells. Prothrombin was activated in a manner dependent on both exogenous factor Xa and factor Va (apparent K(d) of 0.51-1.81 nM for factor Va). These results indicate that the prothrombinase complex forms specifically on various extravascular cells. Although the prothrombinase complex can be assembled on monocytes and lymphocytes, it is not known why these cells can activate prothrombin specifically. These cells which have the capacity for prothrombin activator activity could also activate factor X; i.e. cells with factor X activation activity were able to convert prothrombin. These observations suggest that thrombin was generated via two procoagulant activities; factor X activation and subsequent prothrombinase complex formation on the surface of these cells. This mechanism may explain the various pathological states involving or resulting

  14. Sequential measurements of conjugate observables

    NASA Astrophysics Data System (ADS)

    Carmeli, Claudio; Heinosaari, Teiko; Toigo, Alessandro

    2011-07-01

    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  15. Activities involving aeronautical, space science, and technology support for minority institutions

    NASA Technical Reports Server (NTRS)

    1993-01-01

    The Final Report addressed the activities with which the Interracial Council for Business Opportunity (ICBO) was involved over the past 12 months. ICBO was involved in the design and development of a CARES Student Tracking System Software (CARES). Cares is intended to provide an effective means of maintaining relevant current and historical information on NASA-funded students through a range of educational program initiatives. ICBP was extensively involved in the formation of a minority university consortium amd implementation of collaborative research activities by the consortium as part of NASA's Mission to Planet Earth/Earth Observing System. ICBO was involved in the formation of an HBCU/MI Consortium to facilitate technology transfer efforts to the small and minority business community in their respective regions.

  16. Sequential cloning of chromosomes

    SciTech Connect

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  17. Sequential cloning of chromosomes

    DOEpatents

    Lacks, Sanford A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  18. Sequential cloning of chromosomes

    DOEpatents

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  19. Individual differences in dispositional mindfulness and brain activity involved in reappraisal of emotion

    PubMed Central

    Ormel, Johan; Aleman, André

    2010-01-01

    The regulation of negative emotion through reappraisal has been shown to induce increased prefrontal activity and decreased amygdala activity. Individual differences in dispositional mindfulness reflect differences in typical recognition, detachment and regulation of current experience, thought to also operate as top–down control mechanism. We sought to investigate whether such individual differences would be associated with brain activity elicited during reappraisal of negative emotion. Eighteen healthy participants completed a functional magnetic resonance imaging task that involved attending to or reappraising negative stimuli, and provided emotion experience ratings after each trial. Dispositional mindfulness was assessed with a self-report questionnaire. Reappraisal induced activity in a brain network involving predominantly dorsal portions of the prefrontal cortex, replicating previous studies. A voxelwise regression analysis showed that individual differences in the tendency to be mindful predicted activity in neural regions underlying reappraisal, with dorsomedial prefrontal cortex activation increasing with more mindfulness traits. Notably, this prefrontal activation was inversely correlated with the amygdala response to negative scenes, further supporting its role in down-regulating emotion-generation regions. These findings suggest that individual differences in dispositional mindfulness, which reflect the tendency to recognize and regulate current states, may modulate activity in neural systems involved in the effective cognitive control of negative emotion. PMID:20147457

  20. Health-Related Quality of Life, Self-Efficacy and Enjoyment Keep the Socially Vulnerable Physically Active in Community-Based Physical Activity Programs: A Sequential Cohort Study

    PubMed Central

    Herens, Marion; Bakker, Evert Jan; van Ophem, Johan; Wagemakers, Annemarie; Koelen, Maria

    2016-01-01

    Physical inactivity is most commonly found in socially vulnerable groups. Dutch policies target these groups through community-based health-enhancing physical activity (CBHEPA) programs. As robust evidence on the effectiveness of this approach is limited, this study investigated whether CBHEPA programs contribute to an increase in and the maintenance of physical activity in socially vulnerable groups. In four successive cohorts, starting at a six-month interval, 268 participants from 19 groups were monitored for twelve months in seven CBHEPA programs. Data collection was based on repeated questionnaires. Socio-economic indicators, program participation and coping ability were measured at baseline. Physical activity, health-related quality of life and on-going program participation were measured three times. Self-efficacy and enjoyment were measured at baseline and at twelve months. Statistical analyses were based on a quasi-RCT design (independent t-tests), a comparison of participants and dropouts (Mann-Whitney test), and multilevel modelling to assess change in individual physical activity, including group level characteristics. Participants of CBHEPA programs are socially vulnerable in terms of low education (48.6%), low income (52.4%), non-Dutch origin (64.6%) and health-related quality of life outcomes. Physical activity levels were not below the Dutch average. No increase in physical activity levels over time was observed. The multilevel models showed significant positive associations between health-related quality of life, self-efficacy and enjoyment, and leisure-time physical activity over time. Short CBHEPA programs (10–13 weeks) with multiple trainers and gender-homogeneous groups were associated with lower physical activity levels over time. At twelve months, dropouts' leisure-time physical activity levels were significantly lower compared to continuing participants, as were health-related quality of life, self-efficacy and enjoyment outcomes. BMI and

  1. Factors Involved in Iranian Women Heads of Household's Health Promotion Activities: A Grounded Theory Study.

    PubMed

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh

    2013-01-01

    We aimed to explore and describe the factors involved in Iranian women heads of household's health promotion activities. Grounded theory was used as the method. Sixteen women heads of household were recruited. Data were generated by semi structured interviews. Our findings indicated that remainder of resources (money, time and energy) alongside perceived severity of health risk were two main factors whereas women's personal and socio-economic characteristics were two contextual factors involved in these women's health promotion activities. To help these women improve their health status, we recommended that the government, non-governmental organizations and health care professionals provide them with required resources and increase their knowledge by holding training sessions.

  2. Transferrin Binding to Peripheral Blood Lymphocytes Activated by Phytohemagglutinin Involves a Specific Receptor

    PubMed Central

    Galbraith, Robert M.; Werner, Phillip; Arnaud, Philippe; Galbraith, Gillian M. P.

    1980-01-01

    Immunohistological studies have indicated that membrane sites binding transferrin are present upon activated human peripheral blood lymphocytes. In this study, we have investigated transferrin uptake in human lymphocytes exposed to phytohemagglutinin (PHA), by quantitative radiobinding and immunofluorescence in parallel. In stimulated lymphocytes, binding was maximal after a 30-min incubation, being greatest at 37°C, and greater at 22°C than at 4°C. Although some shedding and endocytosis of transferrin occurred at 22° and 37°C, these factors, and resulting synthesis of new sites, did not affect measurement of binding which was found to be saturable, reversible, and specific for transferrin (Ka 0.5-2.5 × 108 M−1). Binding was greater after a 48-h exposure to PHA than after 24 h, and was maximal at 66 h. Sequential Scatchard analysis revealed no significant elevation in affinity of interaction. However, although the total number of receptors increased, the proportion of cells in which binding of ligand was detected immunohistologically increased in parallel, and after appropriate correction, the cellular density of receptors remained relatively constant throughout (60,000-80,000 sites/cell). Increments in binding during the culture period were thus due predominantly to expansion of a population of cells bearing receptors. Similar differences in binding were apparent upon comparison of cells cultured in different doses of PHA, and in unstimulated cells binding was negligible. Transferrin receptors appear, therefore, to be readily detectable only upon lymphocytes that have been activated. Images PMID:6253523

  3. Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors.

    PubMed

    Hijazi, Mohamad Ali; El-Mallah, Ahmed; Aboul-Ela, Maha; Ellakany, Abdalla

    2017-01-01

    Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.

  4. Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception.

    PubMed

    Turner, Clare E; Byblow, Winston D; Stinear, Cathy M; Gant, Nicholas

    2014-09-01

    The presence of carbohydrate in the human mouth has been associated with the facilitation of motor output and improvements in physical performance. Oral receptors have been identified as a potential mode of afferent transduction for this novel form of nutrient signalling that is distinct from taste. In the current study oral exposure to carbohydrate was combined with a motor task in a neuroimaging environment to identify areas of the brain involved in this phenomenon. A mouth-rinsing protocol was conducted whilst carbohydrate (CHO) and taste-matched placebo (PLA) solutions were delivered and recovered from the mouths of 10 healthy volunteers within a double-blind, counterbalanced design. This protocol eliminates post-oral factors and controls for the perceptual qualities of solutions. Functional magnetic resonance imaging of the brain was used to identify cortical areas responsive to oral carbohydrate during rest and activity phases of a hand-grip motor task. Mean blood-oxygen-level dependent signal change experienced in the contralateral primary sensorimotor cortex was larger for CHO compared with PLA during the motor task when contrasted with a control condition. Areas of activation associated with CHO exclusively were observed over the primary taste cortex and regions involved in visual perception. Regions in the limbic system associated with reward were also significantly more active with CHO. This is the first demonstration that oral carbohydrate signalling can increase activation within the primary sensorimotor cortex during physical activity and enhance activation of neural networks involved in sensory perception.

  5. Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors

    PubMed Central

    El-Mallah, Ahmed; Aboul-Ela, Maha; Ellakany, Abdalla

    2017-01-01

    Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome. PMID:28280516

  6. Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

    SciTech Connect

    Neff, Michael M.

    2011-06-23

    This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

  7. An Active Self-Determination Technique: Involving Students in Effective Career Planning.

    ERIC Educational Resources Information Center

    Denison, Grace L.

    This paper discusses creating story boards to help students with disabilities to develop effective career plans. It describes storyboarding as a technique for project planning which requires active involvement of both hemispheres of the brain. A group of 6-8 people, including students, teachers, counselors, and vocational rehabilitation…

  8. Emotional Creativity and Real-Life Involvement in Different Types of Creative Leisure Activities

    ERIC Educational Resources Information Center

    Trnka, Radek; Zahradnik, Martin; Kuška, Martin

    2016-01-01

    The role of emotional creativity in practicing creative leisure activities and in the preference of college majors remains unknown. This study aims to explore how emotional creativity measured by the Emotional Creativity Inventory (ECI; Averill, 1999) is interrelated with the real-life involvement in different types of specific creative leisure…

  9. Regrouping: organized activity involvement and social adjustment across the transition to high school.

    PubMed

    Bohnert, Amy M; Aikins, Julie Wargo; Arola, Nicole T

    2013-01-01

    Although organized activities (OAs) have been established as important contexts of development, limited work has examined the role of OAs across the high school transition in buffering adolescents' social adjustment by providing opportunities for visibility and peer affiliation. The transition to high school is characterized by numerous changes and OAs may provide an important setting for establishing and maintaining peer relationships during this tumultuous time. This study included 151 8th grade U.S. students (58% male) who were assessed across the transition to high school (spring of 8th and 9th grade). Continuous involvement in academic activities across the transition and becoming involved (i.e., initiation) in community/service activities following the transition was associated with fewer depressive symptoms in the spring of 9th grade. Continuous involvement in sports and initiation of academic activities was associated with having more friendships. In addition, links between OAs and loneliness were only evident among females. There appear to be significant social benefits for OA involvement.

  10. Beyond the Classroom: Involving Students with Disabilities in Extracurricular Activities at Levy Middle School.

    ERIC Educational Resources Information Center

    Walker, Pam; And Others

    Six students in a special education classroom at Levy Middle School (Syracuse, New York) became involved in a variety of after-school activities with nondisabled students. The students participated in the school computer club, cross-country skiing, volleyball, stage crew, intramural basketball, the Spanish Club, and after-school programs at two…

  11. An Emergent Language Program Framework: Actively Involving Learners in Needs Analysis.

    ERIC Educational Resources Information Center

    Savage, William; Storer, Graeme

    1992-01-01

    Relates the experience of the staff of an aquaculture outreach program in Northeast Thailand in implementing an English for special purposes program. By actively involving learners in both the needs analysis and program design, teachers were able to adapt the program content to the requirements of the students. (15 references) (JL)

  12. Longitudinal Modeling of Adolescents' Activity Involvement, Problem Peer Associations, and Youth Smoking

    ERIC Educational Resources Information Center

    Metzger, Aaron; Dawes, Nickki; Mermelstein, Robin; Wakschlag, Lauren

    2011-01-01

    Longitudinal associations among different types of organized activity involvement, problem peer associations, and cigarette smoking were examined in a sample of 1040 adolescents (mean age = 15.62 at baseline, 16.89 at 15-month assessment, 17.59 at 24 months) enriched for smoking experimentation (83% had tried smoking). A structural equation model…

  13. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Restrictions on activities involving Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL...

  14. Involving Your Child or Teen with ASD in Integrated Community Activities

    ERIC Educational Resources Information Center

    McKee, Rebecca

    2011-01-01

    Participating in outside activities and community-based endeavors can be tricky for people with special needs, like Autism Spectrum Disorder (ASD). Families meet more than a few obstacles attempting to integrate their children or teens who have special needs like ASD. Most typical children are highly involved in sports, clubs and camps. If a…

  15. Reliable VLSI sequential controllers

    NASA Technical Reports Server (NTRS)

    Whitaker, S.; Maki, G.; Shamanna, M.

    1990-01-01

    A VLSI architecture for synchronous sequential controllers is presented that has attractive qualities for producing reliable circuits. In these circuits, one hardware implementation can realize any flow table with a maximum of 2(exp n) internal states and m inputs. Also all design equations are identical. A real time fault detection means is presented along with a strategy for verifying the correctness of the checking hardware. This self check feature can be employed with no increase in hardware. The architecture can be modified to achieve fail safe designs. With no increase in hardware, an adaptable circuit can be realized that allows replacement of faulty transitions with fault free transitions.

  16. Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation

    PubMed Central

    Cuadrado, I; Fernández-Velasco, M; Boscá, L; de las Heras, B

    2011-01-01

    Several labdane diterpenes exert anti-inflammatory and cytoprotective actions; therefore, we have investigated whether these molecules protect cardiomyocytes in an anoxia/reperfusion (A/R) model, establishing the molecular mechanisms involved in the process. The cardioprotective activity of three diterpenes (T1, T2 and T3) was studied in the H9c2 cell line and in isolated rat cardiomyocyte subjected to A/R injury. In both cases, treatment with diterpenes T1 and T2 protected from A/R-induced apoptosis, as deduced by a decrease in the percentage of apoptotic and caspase-3 active positive cells, a decrease in the Bcl-2/Bax ratio and an increase in the expression of antiapoptotic proteins. Analysis of cell survival signaling pathways showed that diterpenes T1 and T2 added after A/R increased phospho-AKT and phospho-ERK 1/2 levels. These cardioprotective effects were lost when AKT activity was pharmacologically inhibited. Moreover, the labdane-induced cardioprotection involves activation of AMPK, suggesting a role for energy homeostasis in their mechanism of action. Labdane diterpenes (T1 and T2) also exerted cardioprotective effects against A/R-induced injury in isolated cardiomyocytes and the mechanisms involved activation of specific survival signals (PI3K/AKT pathways, ERK1/2 and AMPK) and inhibition of apoptosis. PMID:22071634

  17. Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population.

    PubMed

    Morrison, Jamie I; Lööf, Sara; He, Pingping; Simon, András

    2006-01-30

    In contrast to mammals, salamanders can regenerate complex structures after injury, including entire limbs. A central question is whether the generation of progenitor cells during limb regeneration and mammalian tissue repair occur via separate or overlapping mechanisms. Limb regeneration depends on the formation of a blastema, from which the new appendage develops. Dedifferentiation of stump tissues, such as skeletal muscle, precedes blastema formation, but it was not known whether dedifferentiation involves stem cell activation. We describe a multipotent Pax7+ satellite cell population located within the skeletal muscle of the salamander limb. We demonstrate that skeletal muscle dedifferentiation involves satellite cell activation and that these cells can contribute to new limb tissues. Activation of salamander satellite cells occurs in an analogous manner to how the mammalian myofiber mobilizes stem cells during skeletal muscle tissue repair. Thus, limb regeneration and mammalian tissue repair share common cellular and molecular programs. Our findings also identify satellite cells as potential targets in promoting mammalian blastema formation.

  18. Involvement of surface cysteines in activity and multimer formation of thimet oligopeptidase.

    PubMed

    Sigman, J A; Sharky, M L; Walsh, S T; Pabon, A; Glucksman, M J; Wolfson, A J

    2003-08-01

    Thimet oligopeptidase is a metalloenzyme involved in regulating neuropeptide processing. Three cysteine residues (246, 248, 253) are known to be involved in thiol activation of the enzyme. In contrast to the wild-type enzyme, the triple mutant (C246S/C248S/C253S) displays increased activity in the absence of dithiothreitol. Dimers, purportedly formed through cysteines 246, 248 and 253, have been thought to be inactive. However, analysis of the triple mutant by native gel electrophoresis reveals the existence of dimers and multimers, implying that oligomer formation is mediated by other cysteines, probably on the surface, and that some of these forms are enzymatically active. Isolation and characterization of iodoacetate-modified monomers and dimers of the triple mutant revealed that, indeed, certain dimeric forms of the enzyme are still fully active, whereas others show reduced activity. Cysteine residues potentially involved in dimerization were identified by modeling of thimet oliogopeptidase to its homolog, neurolysin. Five mutants were constructed; all contained the triple mutation C246S/C248S/C253S and additional substitutions. Substitutions at C46 or C682 and C687 prevented multimer formation and inhibited dimer formation. The C46S mutant had enzymatic activity comparable to the parent triple mutant, whereas that of C682S/C687S was reduced. Thus, the location of intermolecular disulfide bonds, rather than their existence per se, is relevant to activity. Dimerization close to the N-terminus is detrimental to activity, whereas dimerization near the C-terminus has little effect. Altering disulfide bond formation is a potential regulatory factor in the cell owing to the varying oxidation states in subcellular compartments and the different compartmental locations and functions of the enzyme.

  19. Embedding a Recovery Orientation into Neuroscience Research: Involving People with a Lived Experience in Research Activity.

    PubMed

    Stratford, Anthony; Brophy, Lisa; Castle, David; Harvey, Carol; Robertson, Joanne; Corlett, Philip; Davidson, Larry; Everall, Ian

    2016-03-01

    This paper highlights the importance and value of involving people with a lived experience of mental ill health and recovery in neuroscience research activity. In this era of recovery oriented service delivery, involving people with the lived experience of mental illness in neuroscience research extends beyond their participation as "subjects". The recovery paradigm reconceptualises people with the lived experience of mental ill health as experts by experience. To support this contribution, local policies and procedures, recovery-oriented training for neuroscience researchers, and dialogue about the practical applications of neuroscience research, are required.

  20. Personal Involvement with Learning Disability Children: Activities Groups Can Do for Personal Involvement with Learning Disability Children thru Movement Education.

    ERIC Educational Resources Information Center

    Smith, Elizabeth I.

    Described are perceptual motor activities in the areas of coordination, agility, strength, balance, and endurance for use with learning disabled children. Provided are a rationale for movement education and definitions of 10 terms such as laterality and endurance. A sequence of activities is provided for the following skills: ball bouncing, rope…

  1. Difficulty with daily activities involving the lower extremities in people with systemic sclerosis.

    PubMed

    Poole, Janet L; Brandenstein, Jane

    2016-02-01

    The purpose of this study was to examine the extent of lower extremity impairments in motion and strength in people with systemic sclerosis and the relationships of the impairments to limitations in activities of daily living primarily involving the lower extremities. Participants were 69 persons with SSc who received evaluations of lower extremity joint motion (Keitel function test), strength (timed-stands test), and basic mobility (timed up and go test) and completed a demographic questionnaire regarding symptoms in the lower extremities. Activity limitations were measured by the Rheumatoid and Arthritis Outcome Score (RAOS) which examines functional ability, pain, and quality of life. The participants had difficulty with items requiring external rotation of the hips and lower extremity strength. There were moderate correlations between the impairment measures of joint motion, strength, mobility, and activity limitations. Fair correlations were found between the skin scores and the RAOS sections except for pain. The results of this study show that lower extremity involvement is present in persons with SSc. The findings, regarding strength, mobility, and joint motion are related to the ability to perform everyday activities involving the lower extremities, suggest that these areas should be targeted for intervention in persons with SSc.

  2. Colon emptying induced by sequential electrical stimulation in rats.

    PubMed

    Sevcencu, Cristian; Rijkhoff, Nico J M; Sinkjaer, Thomas

    2005-12-01

    Electrical stimulation could be used to induce colon emptying. The present experiments were performed to establish a stimulation pattern to optimize the stimulation parameters and to test neural involvement in propulsion induced by electrical stimulation. Colon segments were sequentially stimulated using rectangular pulses. The resulting propulsive activity displaced intraluminal content in consecutive propulsion steps. The propulsion steps differed in displacement latency, distance, and velocity along the stimulated colon. Increasing the pulse duration or amplitude resulted in a decrease of the latency. Increasing the stimulation amplitude doubled the displacement distance. The frequencies tested in the present study did not affect propulsion. Inhibition of cholinergic and nitrergic pathways inhibited propulsion. Electrical stimulation can induce colonic propulsion. Motor differences are present along the descending colon. The most suitable combination of pulse parameters regarding colon stimulation is 0.3 ms, 5 mA, 10 Hz. Neural circuits are involved in propulsion when using these values.

  3. Understanding affluent adolescent adjustment: The interplay of parental perfectionism, perceived parental pressure, and organized activity involvement.

    PubMed

    Randall, Edin T; Bohnert, Amy M; Travers, Lea V

    2015-06-01

    This cross-sectional study examined relations between affluent adolescent adjustment and culturally salient factors within parent-child relationship and extracurricular domain. Bootstrapping techniques evaluated mediated effects among parental perfectionism, perceived parental pressure, intensity of organized activity (OA) involvement, and adolescent adjustment (i.e., depressive and anxiety symptoms, life satisfaction) within a sample of 10th graders and their parents (n = 88 parent-child pairs) from four high schools in affluent communities. Findings indicated that adolescents with more perfectionistic parents perceived more parental pressure and experienced poorer adjustment. Results also demonstrated that affluent adolescents who perceived more parental pressure were more intensely involved in OAs, but that higher OA intensity was linked to better adjustment. Findings highlight the importance of considering parental perfectionism when understanding adolescent behaviors and psychological outcomes, confirm the negative direct effects of parental pressure on adjustment, and corroborate prior research dispelling that highly intense OA involvement is linked to adolescent maladjustment.

  4. Involvement of plasmin-mediated extracellular activation of progalanin in angiogenesis.

    PubMed

    Yamamoto, Hiroyuki; Okada, Rina; Iguchi, Kazuaki; Ohno, Satoshi; Yokogawa, Takashi; Nishikawa, Kazuya; Unno, Keiko; Hoshino, Minoru; Takeda, Atsushi

    2013-01-18

    Progalanin is released from the small cell lung carcinoma line SBC-3A and converted to its active form by plasmin. To elucidate the role of progalanin activation in the extracellular compartment, matrix metalloproteinase (MMP) activity was studied in SBC-3A cells treated with progalanin siRNA, and angiogenesis was measured in tumor tissue originating from SBC-3A cell transplantation into mice. Progalanin siRNA caused downregulation of progalanin expression for approximately 8 days. MMP activity and angiogenesis were reduced in tumors induced by transplantation of progalanin siRNA-treated SBC-3A cells. In contrast, MMP-9 and MMP-2 activity and angiogenesis increased in tumors originating from progalanin siRNA-treated SBC-3A cells in the presence of galanin and progalanin. Furthermore, injection of tranexamic acid, a plasmin inhibitor, more markedly reduced MMP-9 and MMP-2 activity and angiogenesis in tumors originating from progalanin siRNA-treated SBC-3A cells and in tumor tissue originating from progalanin siRNA-treated SBC-3A cells in the presence of progalanin. The reduction of MMP-9 and MMP-2 activity with tranexamic acid was restored by galanin, but not by progalanin. Moreover, tranexamic acid reduced angiogenesis in control siRNA-treated SBC-3A cells. These results suggest that the activation of progalanin by plasmin in the extracellular compartment was involved in MMP-9 and MMP-2 activation and in angiogenesis in tumor tissue.

  5. Generalized random sequential adsorption

    NASA Astrophysics Data System (ADS)

    Tarjus, G.; Schaaf, P.; Talbot, J.

    1990-12-01

    Adsorption of hard spherical particles onto a flat uniform surface is analyzed by using generalized random sequential adsorption (RSA) models. These models are defined by releasing the condition of immobility present in the usual RSA rules to allow for desorption or surface diffusion. Contrary to the simple RSA case, generalized RSA processes are no longer irreversible and the system formed by the adsorbed particles on the surface may reach an equilibrium state. We show by using a distribution function approach that the kinetics of such processes can be described by means of an exact infinite hierarchy of equations reminiscent of the Kirkwood-Salsburg hierarchy for systems at equilibrium. We illustrate the way in which the systems produced by adsorption/desorption and by adsorption/diffusion evolve between the two limits represented by ``simple RSA'' and ``equilibrium'' by considering approximate solutions in terms of truncated density expansions.

  6. Involving postgraduate's students in undergraduate small group teaching promotes active learning in both

    PubMed Central

    Kalra, Ruchi; Modi, Jyoti Nath; Vyas, Rashmi

    2015-01-01

    Background: Lecture is a common traditional method for teaching, but it may not stimulate higher order thinking and students may also be hesitant to express and interact. The postgraduate (PG) students are less involved with undergraduate (UG) teaching. Team based small group active learning method can contribute to better learning experience. Aim: To-promote active learning skills among the UG students using small group teaching methods involving PG students as facilitators to impart hands-on supervised training in teaching and managerial skills. Methodology: After Institutional approval under faculty supervision 92 UGs and 8 PGs participated in 6 small group sessions utilizing the jigsaw technique. Feedback was collected from both. Observations: Undergraduate Feedback (Percentage of Students Agreed): Learning in small groups was a good experience as it helped in better understanding of the subject (72%), students explored multiple reading resources (79%), they were actively involved in self-learning (88%), students reported initial apprehension of performance (71%), identified their learning gaps (86%), team enhanced their learning process (71%), informal learning in place of lecture was a welcome change (86%), it improved their communication skills (82%), small group learning can be useful for future self-learning (75%). Postgraduate Feedback: Majority performed facilitation for first time, perceived their performance as good (75%), it was helpful in self-learning (100%), felt confident of managing students in small groups (100%), as facilitator they improved their teaching skills, found it more useful and better identified own learning gaps (87.5%). Conclusions: Learning in small groups adopting team based approach involving both UGs and PGs promoted active learning in both and enhanced the teaching skills of the PGs. PMID:26380201

  7. Enhanced detection of lipid transfer inhibitor protein activity by an assay involving only low density lipoprotein.

    PubMed

    Morton, R E; Greene, D J

    1994-11-01

    Lipid transfer inhibitor protein (LTIP) activity has been typically quantitated by its ability to suppress lipid transfer protein-mediated lipid movement between low density lipoprotein (LDL) and high density lipoprotein (HDL). In an attempt to establish an LTIP activity assay that is more sensitive, we have exploited the reported preference of the inhibitor protein to interact with LDL. A lipid transfer assay was established that involves LDL as both the donor and the acceptor; LDL in one of these two pools was biotinylated to facilitate its removal with immobilized avidin. Compared to the standard LDL to HDL assay, LTIP inhibited lipid transfer from radiolabeled LDL to biotin-LDL 7-fold more. In the absence of LTIP, lipid transfer activity was the same in both assays. An added benefit of this assay was the near linearity (up to 85%) of the inhibitory response, in contrast to the highly curvilinear response of LTIP in LDL to HDL transfer assays. The high sensitivity of the LDL to biotin-LDL transfer assay in measuring LTIP activity could not be duplicated by other transfer assays including assays containing only HDL (HDL to biotin-HDL), assays between liposomes and LDL, or assays between LDL and HDL where the concentration of lipoproteins was reduced 10-fold. Thus, LTIP activity is most effectively measured in homologous lipid transfer assays involving only LDL (and its biotin derivative). This increased sensitivity to LTIP suggests that the inhibitor binds more avidly to the LDL surface than does lipid transfer protein.

  8. Sequential treatment strategy for malignant pleural effusion in non-small cell lung cancer with the activated epithelial grow factor receptor mutation.

    PubMed

    Lin, Jian-Bo; Lai, Fan-Cai; Li, Xu; Tu, Yuan-Rong; Lin, Min; Qiu, Min-Lian; Luo, Rong-Gang; Liu, Bo; Lin, Jing-Wei

    2017-02-01

    With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250 mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations.

  9. HTLV-1 Tax-mediated TAK1 activation involves TAB2 adapter protein

    SciTech Connect

    Yu Qingsheng; Minoda, Yasumasa; Yoshida, Ryoko; Yoshida, Hideyuki; Iha, Hidekatsu; Kobayashi, Takashi; Yoshimura, Akihiko; Takaesu, Giichi

    2008-01-04

    Human T cell leukemia virus type 1 (HTLV-1) Tax is an oncoprotein that plays a crucial role in the proliferation and transformation of HTLV-1-infected T lymphocytes. It has recently been reported that Tax activates a MAPKKK family, TAK1. However, the molecular mechanism of Tax-mediated TAK1 activation is not well understood. In this report, we investigated the role of TAK1-binding protein 2 (TAB2) in Tax-mediated TAK1 activation. We found that TAB2 physically interacts with Tax and augments Tax-induced NF-{kappa}B activity. Tax and TAB2 cooperatively activate TAK1 when they are coexpressed. Furthermore, TAK1 activation by Tax requires TAB2 binding as well as ubiquitination of Tax. We also found that the overexpression of TRAF2, 5, or 6 strongly induces Tax ubiquitination. These results suggest that TAB2 may be critically involved in Tax-mediated activation of TAK1 and that NF-{kappa}B-activating TRAF family proteins are potential cellular E3 ubiquitin ligases toward Tax.

  10. NLRP3 inflammasome activation is involved in Ang II-induced kidney damage via mitochondrial dysfunction

    PubMed Central

    Wen, Yi; Liu, Yiran; Tang, Taotao; Lv, Linli; Liu, Hong; Ma, Kunling; Liu, Bicheng

    2016-01-01

    Growing evidence has shown that NLRP3 inflammasome activation promotes the development of tubulointerstitial inflammation and progression of renal injury. We previously found that mitochondrial dysfunction is a critical determinant for the activation of NLRP3 inflammasome in albumin-overload rats. Angiotensin (Ang) II plays an important role in mitochondrial homeostasis. Here, we investigated the role of Ang II in NLRP3 inflammasome activation and the involvement of mitochondrial dysfunction in this process. In vitro, Ang II triggered NLRP3 inflammasome activation in a dose- and time-dependent manner, and this effect is mediated by AT1 receptor rather than AT2 receptor. MitoTEMPO, a mitochondrial targeted antioxidant, attenuated Ang II induced mitochondrial reactive oxygen species (mROS) production and NLRP3 inflammation activation. Following chronic Ang II infusion for 28 days, we observed remarkable tubular epithelial cells (TECs) injury, mitochondrial damage, and albuminuria in WT mice. However, these abnormalities were significantly attenuated in AT1 receptor KO mice. Then, we examined the role of mitochondria in Ang II-infused mice with or without mitoTEMPO treatment. As expected, Ang II-induced mitochondrial dysfunction and NLRP3 inflammasome activation was markedly inhibited by mitoTEMPO. Notably, NLRP3 deletion signally protected TECs from Ang II-triggered mitochondrial dysfunction and NLRP3 inflammasome activation. Taken together, these data demonstrate that Ang II induces NLRP3 inflammasome activation in TECs which is mediated by mitochondrial dysfunction. PMID:27509058

  11. Decreasing Ventromedial Prefrontal Cortex Activity During Sequential Risk-Taking: An fMRI Investigation of the Balloon Analog Risk Task

    PubMed Central

    Schonberg, Tom; Fox, Craig R.; Mumford, Jeanette A.; Congdon, Eliza; Trepel, Christopher; Poldrack, Russell A.

    2012-01-01

    Functional imaging studies examining the neural correlates of risk have mainly relied on paradigms involving exposure to simple chance gambles and an economic definition of risk as variance in the probability distribution over possible outcomes. However, there is little evidence that choices made during gambling tasks predict naturalistic risk-taking behaviors such as drug use, extreme sports, or even equity investing. To better understand the neural basis of naturalistic risk-taking, we scanned participants using fMRI while they completed the Balloon Analog Risk Task, an experimental measure that includes an active decision/choice component and that has been found to correlate with a number of naturalistic risk-taking behaviors. In the task, as in many naturalistic settings, escalating risk-taking occurs under uncertainty and might be experienced either as the accumulation of greater potential rewards, or as exposure to increasing possible losses (and decreasing expected value). We found that areas previously linked to risk and risk-taking (bilateral anterior insula, anterior cingulate cortex, and right dorsolateral prefrontal cortex) were activated as participants continued to inflate balloons. Interestingly, we found that ventromedial prefrontal cortex (vmPFC) activity decreased as participants further expanded balloons. In light of previous findings implicating the vmPFC in value calculation, this result suggests that escalating risk-taking in the task might be perceived as exposure to increasing possible losses (and decreasing expected value) rather than the increasing potential total reward relative to the starting point of the trial. A better understanding of how neural activity changes with risk-taking behavior in the task offers insight into the potential neural mechanisms driving naturalistic risk-taking. PMID:22675289

  12. Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts.

    PubMed

    Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

    2017-02-07

    Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P < 0.05). Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P < 0.05), an indication of reduced microvessel density in tumor xenografts. Moreover, high-dose icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study.

  13. Beyond participation: the association between school extracurricular activities and involvement in violence across generations of immigration.

    PubMed

    Jiang, Xin; Peterson, Ruth D

    2012-03-01

    Participation in extracurricular activities is purported to protect the broad spectrum of youth from a host of behavioral risks. Yet, empirical research on the extent to which this assumption holds for involvement in violence by immigrant youth is limited. Thus, using data for 13,236 (51.8% female) adolescents from the National Longitudinal Study of Adolescent Health, this study explores how the relationship between extracurricular activities and youth violence varies by type of extracurricular activity profile (sports alone, non-sports alone, and a combination of sports and non-sports) and by generations of immigration (first, second, and third-plus). The sample is composed of 9.3% (n = 1,233) first-generation youth, 15.7% (n = 2,080) second generation, and 74.9% (n = 9,923) third-plus generation. The results reveal that adolescents from the third-plus generation (i.e., non-immigrant youth) who participate in non-sports alone or sports plus non-sports have lower odds of involvement in violence than adolescents from the same generation who do not participate in extracurricular activities. However, for first- and second-generation adolescents, participation in extracurricular activities is associated with higher rather than lower odds of violence compared to their non-participating counterparts. These findings challenge the viewpoint that participation in mainstream extracurricular activities as afforded by US schools is equally beneficial for all youth. They also call for additional research that explores why immigrant youth are less likely than non-immigrant youth to gain violence-reducing benefits when they participate in extracurricular activities.

  14. Multi-Attribute Sequential Search

    ERIC Educational Resources Information Center

    Bearden, J. Neil; Connolly, Terry

    2007-01-01

    This article describes empirical and theoretical results from two multi-attribute sequential search tasks. In both tasks, the DM sequentially encounters options described by two attributes and must pay to learn the values of the attributes. In the "continuous" version of the task the DM learns the precise numerical value of an attribute when she…

  15. Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

    PubMed Central

    Sani, M. H. Mohd.; Zakaria, Z. A.; Balan, T.; Teh, L. K.; Salleh, M. Z.

    2012-01-01

    Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway. PMID:22611437

  16. An Initial Investigation of Sexual Minority Youth Involvement in School-Based Extracurricular Activities.

    PubMed

    Toomey, Russell B; Russell, Stephen T

    2013-06-01

    Sexual minority youth are at risk for negative school-based experiences and poor academic outcomes. Yet, little is known about their experiences in positive school-based contexts. Using the National Longitudinal Study of Adolescent Health (1,214 sexual minority and 11,427 heterosexual participants), this study compared participation rates in, predictors of, and outcomes associated with three types of school-based extracurricular activities - sports, arts, and school clubs - by sexual orientation and gender. Findings revealed several significant sexual orientation and gender differences in participation rates in school-based sports, clubs, and arts activities. Further, findings suggested that the outcomes associated with extracurricular activity involvement do not differ by sexual orientation and gender; however, predictors of participation in these domains varied across groups.

  17. An Initial Investigation of Sexual Minority Youth Involvement in School-Based Extracurricular Activities

    PubMed Central

    Russell, Stephen T.

    2012-01-01

    Sexual minority youth are at risk for negative school-based experiences and poor academic outcomes. Yet, little is known about their experiences in positive school-based contexts. Using the National Longitudinal Study of Adolescent Health (1,214 sexual minority and 11,427 heterosexual participants), this study compared participation rates in, predictors of, and outcomes associated with three types of school-based extracurricular activities - sports, arts, and school clubs - by sexual orientation and gender. Findings revealed several significant sexual orientation and gender differences in participation rates in school-based sports, clubs, and arts activities. Further, findings suggested that the outcomes associated with extracurricular activity involvement do not differ by sexual orientation and gender; however, predictors of participation in these domains varied across groups. PMID:24187476

  18. Amyloidosis involving the respiratory system: 5-year's experience of a multi-disciplinary group's activity.

    PubMed

    Scala, Raffaele; Maccari, Uberto; Madioni, Chiara; Venezia, Duccio; La Magra, Lidia Calogera

    2015-01-01

    Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients' clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma). It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.

  19. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure.

    PubMed

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo; Rydbirk, Rasmus; Olesen, Mikkel Vestergaard; Hay-Schmidt, Anders; Pakkenberg, Bente; Aznar, Susana

    2017-03-02

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT2AR activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT2AR blockade does not seem to affect the amygdala-striatal projection.

  20. Evidence that intramolecular interactions are involved in masking the activation domain of transcriptional activator Leu3p.

    PubMed

    Wang, D; Hu, Y; Zheng, F; Zhou, K; Kohlhaw, G B

    1997-08-01

    The Leu3 protein of Saccharomyces cerevisiae regulates the expression of genes involved in branched chain amino acid biosynthesis and in ammonia assimilation. It is modulated by alpha-isopropylmalate, an intermediate in leucine biosynthesis. In the presence of alpha-isopropylmalate, Leu3p is a transcriptional activator. In the absence of the signal molecule, the activation domain is masked, and Leu3p acts as a repressor. The recent discovery that Leu3p retains its regulatory properties when expressed in mammalian cells (Guo, H., and Kohlhaw, G. B. (1996) FEBS Lett. 390, 191-195) suggests that masking and unmasking of the activation domain occur without the participation of auxiliary proteins. Here we present experimental support for this notion and address the mechanism of masking. We show that modulation of Leu3p is exceedingly sensitive to mutations in the activation domain. An activation domain double mutant (D872N/D874N; designated Leu3-dd) was constructed that has the characteristics of a permanently masked activator. Using separately expressed segments containing either the DNA binding domain-middle region or the activation domain of wild type Leu3p (or Leu3-dd) in a modified yeast two-hybrid system, we provide direct evidence for alpha-isopropylmalate-dependent interaction between these segments. Finally, we use the phenotype of Leu3-dd-containing cells (slow growth in the absence of added leucine) to select for suppressor mutations that map to the middle region of Leu3-dd. The properties of nine such suppressors further support the idea that masking is an intramolecular process and suggest a means for mapping the surface involved in masking.

  1. TAB3 involves in hepatic insulin resistance through activation of MAPK pathway.

    PubMed

    Zhao, Yun; Tang, Zhuqi; Zhu, Xiaohui; Wang, Xueqin; Wang, Cuifang; Zhang, Wanlu; Xia, Nana; Wang, Suxin; Huang, Jieru; Cui, Shiwei

    2015-12-01

    Insulin resistance is often accompanied by chronic inflammatory responses. The mitogen-activated protein kinase (MAPK) pathway is rapidly activated in response to many inflammatory cytokines. But the functional role of MAPKs in palmitate-induced insulin resistance has yet to be clarified. In this study, we found that transforming growth factor β-activated kinase binding protein-3 (TAB3) was up-regulated in insulin resistance. Considering the relationship between transforming growth factor β-activated kinase (TAK1) and MAPK pathway, we assumed TAB3 involved in insulin resistance through activation of MAPK pathway. To certify this hypothesis, we knocked down TAB3 in palmitate treated HepG2 cells and detected subsequent biological responses. Importantly, TAB3 siRNA directly reversed insulin sensitivity by improving insulin signal transduction. Moreover, silencing of TAB3 could facilitate hepatic glucose uptake, reverse gluconeogenesis and improve ectopic fat accumulation. Meanwhile, we found that the positive effect of knocking down TAB3 was more significant when insulin resistance occurred. All these results indicate that TAB3 acts as a negative regulator in insulin resistance through activation of MAPK pathway.

  2. Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

    PubMed Central

    Martínez-Martínez, S; Gómez del Arco, P; Armesilla, A L; Aramburu, J; Luo, C; Rao, A; Redondo, J M

    1997-01-01

    Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants. PMID:9343406

  3. Involvement of TREK-1 activity in astrocyte function and neuroprotection under simulated ischemia conditions.

    PubMed

    Wu, Xiao; Liu, Yang; Chen, Xiaojing; Sun, Qian; Tang, Ronghua; Wang, Wei; Yu, Zhiyuan; Xie, Minjie

    2013-03-01

    Astrocytes play a fundamental role in the pathogenesis of ischemic neuronal death. The optimal operation of electrogenic astrocytic transporters and exchangers for some well-defined astrocyte brain homeostatic functions depends on the presence of K(+) channels in the cell membranes and the hyperpolarized membrane potential. Our previous study showed that astrocytes functionally express two-pore domain K(+) channel TREK-1, which helps to set the negative resting membrane potential. However, the roles of TREK-1 on astrocytic function under normal and ischemic conditions remain unclear. In this study, we investigated the expression of TREK-1 protein on cultured astrocytes and the effect of TREK-1 activity on astrocytic glutamate clearance capacity and release of s100β after simulated ischemic insult. TREK-1 immunoreactivity was up-regulated after hypoxia. Suppression of TREK-1 activity inhibited the glutamate clearance capability, enhanced the inflammatory secretion of astrocytes derived s100β and led to increased neuronal apoptosis after ischemic insult. Our results suggest that TREK-1 activity is involved in astrocytic function and neuronal survival. This would provide evidence showing astrocytic TREK-1 involvement in ischemia pathology which may serve as a potential therapeutic target in stroke.

  4. Multiple allosteric sites are involved in the modulation of insulin-degrading-enzyme activity by somatostatin.

    PubMed

    Tundo, Grazia R; Di Muzio, Elena; Ciaccio, Chiara; Sbardella, Diego; Di Pierro, Donato; Polticelli, Fabio; Coletta, Massimo; Marini, Stefano

    2016-10-01

    Somatostatin is a cyclic peptide, released in the gastrointestinal system and the central nervous system, where it is involved in the regulation of cognitive and sensory functions, motor activity and sleep. It is a substrate of insulin-degrading enzyme (IDE), as well as a modulator of its activity and expression. In the present study, we have investigated the modulatory role of somatostatin on IDE activity at 37 °C and pH 7.3 for various substrates [i.e. insulin, β-amyloid (Aβ)1-40 and bradykinin], aiming to quantitatively characterize the correlation between the specific features of the substrates and the regulatory mechanism. Functional data indicate that somatostatin, in addition to the catalytic site of IDE (being a substrate), is also able to bind to two additional exosites, which play different roles according to the size of the substrate and its binding mode to the IDE catalytic cleft. In particular, one exosite, which displays high affinity for somatostatin, regulates only the interaction of IDE with larger substrates (such as insulin and Aβ1-40 ) in a differing fashion according to their various modes of binding to the enzyme. A second exosite, which is involved in the regulation of enzymatic processing by IDE of all substrates investigated (including a 10-25 amino acid long amyloid-like peptide, bradykinin and somatostatin itself, which had been studied previously), probably acts through the alteration of an 'open-closed' equilibrium.

  5. Sequential binary collision ionization mechanisms

    NASA Astrophysics Data System (ADS)

    van Boeyen, R. W.; Watanabe, N.; Doering, J. P.; Moore, J. H.; Coplan, M. A.; Cooper, J. W.

    2004-03-01

    Fully differential cross sections for the electron-impact ionization of the magnesium 3s orbital have been measured in a high-momentum-transfer regime wherein the ionization mechanisms can be accurately described by simple binary collision models. Measurements where performed at incident-electron energies from 400 to 3000 eV, ejected-electron energies of 62 eV, scattering angle of 20 °, and momentum transfers of 2 to 5 a.u. In the out-of-plane geometry of the experiment the cross section is observed far off the Bethe ridge. Both first- and second-order processes can be clearly distinguished as previously observed by Murray et al [Ref. 1] and Schulz et al [Ref. 2]. Owing to the relatively large momentum of the ejected electron, the second order processes can be modeled as sequential binary collisions involving a binary elastic collision between the incident electron and ionic core and a binary knock-out collision between the incident electron and target electron. At low incident-electron energies the cross section for both first and second order processes are comparable, while at high incident energies second-order processes dominate. *Supported by NSF under grant PHY-99-87870. [1] A. J. Murray, M. B. J. Woolf, and F. H. Read J. Phys. B 25, 3021 (1992). [2] M. Schulz, R. Moshammer, D. Fischer, H. Kollmus, D. H. Madison. S. Jones and J. Ullrich, Nature 422, 48 (2003).

  6. Involvement of TACE in colon inflammation: a novel mechanism of regulation via SIRT-1 activation.

    PubMed

    Sharma, Manoranjan; Mohapatra, Jogeswar; Wagh, Akshaya; Patel, Hiren M; Pandey, Dheerendra; Kadam, Shekhar; Argade, Anil; Deshpande, Shrikalp S; Shah, Gourang B; Chatterjee, Abhijit; Jain, Mukul R

    2014-03-01

    TNF-α converting enzyme (TACE) processes the membrane TNF-α to release the bioactive soluble TNF-α. Several evidences suggest the involvement of TNF-α and TACE in inflammatory bowel disease (IBD). Tissue inhibitor of metalloproteinase (TIMP)-3, an endogenous inhibitor of TACE, is positively associated with silent information regulator (SIRT)-1. We aimed to study the expression of TACE, TIMP-3 and SIRT-1 at different stages of colitis and how TACE is regulated in response to SIRT-1 activation. Acute colitis was induced by 3.5% dextran sulfate sodium (DSS) in drinking water for 5days and levels of cytokines and mRNA expression of TACE, TIMP-3 and SIRT-1 were measured in colon at different time intervals. Next, the effect of SIRT-1 activator (resveratrol) or a selective TACE inhibitor (compound 11p) treatment was evaluated. Elevated levels of TNF-α, interleukin (IL)-6, IL-1β, interferon (IFN)-γ and IL-17 were observed during DSS exposure phase which restored to the normal level after DSS removal. A significant increase in TACE and suppression in TIMP-3 and SIRT-1 mRNA level was observed during DSS exposure phase which reverts back to normal towards the remission phase. Treatment with resveratrol significantly elevated SIRT-1 and TIMP-3 and suppressed TACE mRNA expression and was associated with amelioration of disease. Furthermore, treatment with selective TACE inhibitor significantly suppressed body weight loss, disease activity index, colonic myeloperoxidase activity and the elevated levels of cytokines after DSS challenge. These results strongly emphasize the involvement of TACE in colon inflammation and inhibition of TACE directly or indirectly via SIRT-1 activation ameliorates colitis.

  7. Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19.

    PubMed

    Miyata, Masaaki; Hata, Tatsuya; Yamakawa, Hiroki; Kagawa, Tatehiro; Yoshinari, Kouichi; Yamazoe, Yasushi

    2012-10-01

    The intestinal endocrine hormone human fibroblast growth factor 19 (FGF19) is involved in the regulation of not only hepatic bile acid metabolism but also carbohydrate and lipid metabolism. In the present study, bile acid/farnesoid X receptor (FXR) responsiveness in the FGF19 promoter region was investigated by a reporter assay using the human colon carcinoma cell line LS174T. The assay revealed the presence of bile acid/FXR-responsive elements in the 5'-flanking region up to 8.8 kb of FGF19. Deletion analysis indicated that regions from -1866 to -1833, from -1427 to -1353, and from -75 to +262 were involved in FXR responsiveness. Four, four, and two consecutive half-sites of nuclear receptors were observed in the three regions, respectively. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed FXR/retinoid X receptor α (RXRα) heterodimer binding in these three regions. EMSA and reporter assays using mutated constructs indicated that the nuclear receptor IR1, ER2, and DR8 motifs in the 5'-flanking region were involved in FXR responsiveness of FGF19. Lithocholic acid (LCA) (10 μM), chenodeoxycholic acid (CDCA) (10 μM), or GW4064 (0.1 μM) treatment increased reporter activity in a construct including the three motifs under FXR-expressing conditions whereas LCA and not CDCA or GW4064 treatment increased the reporter activity under pregnane X receptor (PXR)-expressing conditions. These results suggest that FGF19 is transcriptionally activated through multiple FXR-responsive elements in the promoter region.

  8. Sequential Logic Model Deciphers Dynamic Transcriptional Control of Gene Expressions

    PubMed Central

    Yeo, Zhen Xuan; Wong, Sum Thai; Arjunan, Satya Nanda Vel; Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar; Giuliani, Alessandro; Tsuchiya, Masa

    2007-01-01

    Background Cellular signaling involves a sequence of events from ligand binding to membrane receptors through transcription factors activation and the induction of mRNA expression. The transcriptional-regulatory system plays a pivotal role in the control of gene expression. A novel computational approach to the study of gene regulation circuits is presented here. Methodology Based on the concept of finite state machine, which provides a discrete view of gene regulation, a novel sequential logic model (SLM) is developed to decipher control mechanisms of dynamic transcriptional regulation of gene expressions. The SLM technique is also used to systematically analyze the dynamic function of transcriptional inputs, the dependency and cooperativity, such as synergy effect, among the binding sites with respect to when, how much and how fast the gene of interest is expressed. Principal Findings SLM is verified by a set of well studied expression data on endo16 of Strongylocentrotus purpuratus (sea urchin) during the embryonic midgut development. A dynamic regulatory mechanism for endo16 expression controlled by three binding sites, UI, R and Otx is identified and demonstrated to be consistent with experimental findings. Furthermore, we show that during transition from specification to differentiation in wild type endo16 expression profile, SLM reveals three binary activities are not sufficient to explain the transcriptional regulation of endo16 expression and additional activities of binding sites are required. Further analyses suggest detailed mechanism of R switch activity where indirect dependency occurs in between UI activity and R switch during specification to differentiation stage. Conclusions/Significance The sequential logic formalism allows for a simplification of regulation network dynamics going from a continuous to a discrete representation of gene activation in time. In effect our SLM is non-parametric and model-independent, yet providing rich biological

  9. Ileocaecal Intussusception with a Lead Point: Unusual MDCT Findings of Active Crohn's Disease Involving the Appendix

    PubMed Central

    Ozan, Ebru; Atac, Gokce Kaan; Akincioglu, Egemen; Keskin, Mete; Gulpinar, Kamil

    2015-01-01

    Adult intussusception is a rare entity accounting for 1% of all bowel obstructions. Unlike intussusceptions in children, which are idiopathic in 90% of cases, adult intussusceptions have an identifiable cause (lead point) in the majority of cases. Crohn's disease (CD) may affect any part of the gastrointestinal tract, including the appendix. It was shown to be a predisposing factor for intussusception. Here, we report a rare case of adult intussusception with a lead point, emphasizing diagnostic input of multidetector computed tomography (MDCT) in a patient with active CD that involves the appendix. PMID:26558130

  10. Sequential biases in accumulating evidence

    PubMed Central

    Huggins, Richard; Dogo, Samson Henry

    2015-01-01

    Whilst it is common in clinical trials to use the results of tests at one phase to decide whether to continue to the next phase and to subsequently design the next phase, we show that this can lead to biased results in evidence synthesis. Two new kinds of bias associated with accumulating evidence, termed ‘sequential decision bias’ and ‘sequential design bias’, are identified. Both kinds of bias are the result of making decisions on the usefulness of a new study, or its design, based on the previous studies. Sequential decision bias is determined by the correlation between the value of the current estimated effect and the probability of conducting an additional study. Sequential design bias arises from using the estimated value instead of the clinically relevant value of an effect in sample size calculations. We considered both the fixed‐effect and the random‐effects models of meta‐analysis and demonstrated analytically and by simulations that in both settings the problems due to sequential biases are apparent. According to our simulations, the sequential biases increase with increased heterogeneity. Minimisation of sequential biases arises as a new and important research area necessary for successful evidence‐based approaches to the development of science. © 2015 The Authors. Research Synthesis Methods Published by John Wiley & Sons Ltd. PMID:26626562

  11. The benefits of in-group contact through physical activity involvement for health and well-being among Korean immigrants

    PubMed Central

    Kim, Junhyoung; Heo, Jinmoo; Kim, Jun

    2014-01-01

    This qualitative study is designed to examine the benefits of physical activity involvement with members of the same ethnic group. For this study, Korean immigrants who were members of Korean physical activity clubs such as badminton and tennis were selected as participants. Using a constructive grounded theory methodology, three themes were identified as benefits of physical activity involvement: (1) the experience of psychological well-being, (2) the creation of a unique cultural world, and (3) the facilitation of physical activity involvement. The findings of this study suggest that Korean immigrant participants gained various social, cultural, and psychological benefits by engaging in activities with other Korean immigrants. PMID:24875239

  12. Tyrosine phosphorylation and protein degradation control the transcriptional activity of WRKY involved in benzylisoquinoline alkaloid biosynthesis

    PubMed Central

    Yamada, Yasuyuki; Sato, Fumihiko

    2016-01-01

    Benzylisoquinoline alkaloids (BIQ) are among the most structurally diverse and pharmaceutically valuable secondary metabolites. A plant-specific WRKY-type transcription factor, CjWRKY1, was isolated from Coptis japonica and identified as a transcriptional activator of BIQ biosynthesis. However, the expression of CjWRKY1 gene alone was not sufficient for the activation of genes encoding biosynthetic enzymes. Here, we report the importance of post-translational regulation of CjWRKY1 in BIQ biosynthesis. First, we detected the differential accumulation of CjWRKY1 protein in two cell lines with similar CjWRKY1 gene expression but different levels of accumulated alkaloids. Further investigation of the WRKY protein identified the phosphorylation of the WRKYGQK core domain at Y115. The CjWRKYY115E phosphorylation-mimic mutant showed loss of nuclear localization, DNA-binding activity, and transactivation activity compared to wild-type CjWRKY1. Rapid degradation of the CjWRKY1 protein was also confirmed following treatment with inhibitors of the 26S proteasome and protease inhibitors. The existence of two independent degradation pathways as well as protein phosphorylation suggests the fine-tuning of CjWRKY1 activities is involved in the regulation of biosynthesis of BIQs. PMID:27552928

  13. Inhibition of Fast Axonal Transport by Pathogenic SOD1 Involves Activation of p38 MAP Kinase

    PubMed Central

    Morfini, Gerardo A.; Bosco, Daryl A.; Brown, Hannah; Gatto, Rodolfo; Kaminska, Agnieszka; Song, Yuyu; Molla, Linda; Baker, Lisa; Marangoni, M. Natalia; Berth, Sarah; Tavassoli, Ehsan; Bagnato, Carolina; Tiwari, Ashutosh; Hayward, Lawrence J.; Pigino, Gustavo F.; Watterson, D. Martin; Huang, Chun-Fang; Banker, Gary; Brown, Robert H.; Brady, Scott T.

    2013-01-01

    Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS) associated with superoxide dismutase 1 (SOD1) mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT) deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS. PMID:23776455

  14. Histamine and spontaneous motor activity: biphasic changes, receptors involved and participation of the striatal dopamine system.

    PubMed

    Chiavegatto, S; Nasello, A G; Bernardi, M M

    1998-01-01

    The time- and dose-related effects of exogenous histamine on spontaneous motor activity and receptors involved were evaluated in male rats. Intracerebroventricular administration of histamine (5.4 and 54.3 nmol) produced a biphasic effect with initial transitory hypoactivity and later hyperactivity expressed by locomotion frequency in an open-field. The rearing frequencies were only reduced by all doses of histamine used. The histamine-induced hypoactivity was inhibited by the H3-antagonist thioperamide and was also induced by the H3-agonist N-alpha-methylhistamine. The histamine-induced hyperactivity phase was blocked by the H1-antagonist mepyramine. The H2-antagonist ranitidine increased locomotion and rearing frequencies. The participation of other neurotransmitters in the persistent hypokinetic effect induced by 135.8 nmol of histamine was determined by HPLC in the striatum and hypothalamus as counter-proof. A decreased DOPAC/DA ratio was observed only in the striatum. In the hypothalamus, low levels of 5HT were detected, probably not correlated with motor activity. In conclusion, the present results suggest that the exogenous histamine-induced hypoactivity response is probably due to activation of H3-receptors as heteroreceptors reducing the activity of the striatal dopaminergic system. This effect can partially overlap with the expression of the hyperactivity induced by H1-receptor activation. The participation of H2-receptors requires further investigation.

  15. Calpain activation is involved in acute manganese neurotoxicity in the rat striatum in vivo.

    PubMed

    Quintanar, Liliana; Montiel, Teresa; Márquez, Maripaz; González, Alejandra; Massieu, Lourdes

    2012-01-01

    Manganese is essential for life, yet chronic exposure to this metal can cause a neurodegenerative disease named manganism that affects motor function. In the present study we have evaluated Mn neurotoxicity after its administration in the rat striatum. The participation of the calcium-dependent protease calpain and the apoptosis-related protease caspase-3, in Mn-induced cell death was monitored in the striatum and globus pallidus. Mn induced the activation of both proteases, although calpain activation seems to be an earlier event. Moreover, while the broad-spectrum caspase inhibitor QVD did not significantly prevent Mn-induced cell death, the specific calpain inhibitor MDL-28170 did. The role of NMDA glutamate receptors on calpain activity was also investigated; blockage of these receptors by MK-801 and memantine did not prevent calpain activation, nor Mn-induced cell death. Finally, studies in striatal homogenates suggest a direct activation of calpain by Mn ions. Altogether the present study suggests that additional mechanisms to excitotoxicity are involved in Mn-induced cell death, placing calpain as an important mediator of acute Mn neurotoxicity in vivo.

  16. Involvement of phosphoinositide 3-kinases in neutrophil activation and the development of acute lung injury.

    PubMed

    Yum, H K; Arcaroli, J; Kupfner, J; Shenkar, R; Penninger, J M; Sasaki, T; Yang, K Y; Park, J S; Abraham, E

    2001-12-01

    Activated neutrophils contribute to the development and severity of acute lung injury (ALI). Phosphoinositide 3-kinases (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. In the present study, we found that exposure of neutrophils to endotoxin resulted in phosphorylation of Akt, activation of NF-kappaB, and expression of the proinflammatory cytokines IL-1beta and TNF-alpha through PI3-K-dependent pathways. In vivo, endotoxin administration to mice resulted in activation of PI3-K and Akt in neutrophils that accumulated in the lungs. The severity of endotoxemia-induced ALI was significantly diminished in mice lacking the p110gamma catalytic subunit of PI3-K. In PI3-Kgamma(-/-) mice, lung edema, neutrophil recruitment, nuclear translocation of NF-kappaB, and pulmonary levels of IL-1beta and TNF-alpha were significantly lower after endotoxemia as compared with PI3-Kgamma(+/+) controls. Among neutrophils that did accumulate in the lungs of the PI3-Kgamma(-/-) mice after endotoxin administration, activation of NF-kappaB and expression of proinflammatory cytokines was diminished compared with levels present in lung neutrophils from PI3-Kgamma(+/+) mice. These results show that PI3-K, and particularly PI3-Kgamma, occupies a central position in regulating endotoxin-induced neutrophil activation, including that involved in ALI.

  17. Characterization of senescence-associated protease activities involved in the efficient protein remobilization during leaf senescence of winter oilseed rape.

    PubMed

    Poret, Marine; Chandrasekar, Balakumaran; van der Hoorn, Renier A L; Avice, Jean-Christophe

    2016-05-01

    Oilseed rape (Brassica napus L.) is a crop plant characterized by a poor nitrogen (N) use efficiency that is mainly due to low N remobilization efficiency during the sequential leaf senescence of the vegetative stage. As a high leaf N remobilization efficiency was strongly linked to a high remobilization of proteins during leaf senescence of rapeseed, our objective was to identify senescence-associated protease activities implicated in the protein degradation. To reach this goal, leaf senescence processes and protease activities were investigated in a mature leaf becoming senescent in plants subjected to ample or low nitrate supply. The characterization of protease activities was performed by using in vitro analysis of RuBisCO degradation with or without inhibitors of specific protease classes followed by a protease activity profiling using activity-dependent probes. As expected, the mature leaf became senescent regardless of the nitrate treatment, and nitrate limitation enhanced the senescence processes associated with an enhanced degradation of soluble proteins. The characterization of protease activities revealed that: (i) aspartic proteases and the proteasome were active during senescence regardless of nitrate supply, and (ii) the activities of serine proteases and particularly cysteine proteases (Papain-like Cys proteases and vacuolar processing enzymes) increased when protein remobilization associated with senescence was accelerated by nitrate limitation. Short statement: Serine and particularly cysteine proteases (both PLCPs and VPEs) seem to play a crucial role in the efficient protein remobilization when leaf senescence of oilseed rape was accelerated by nitrate limitation.

  18. Transmembrane myosin chitin synthase involved in mollusc shell formation produced in Dictyostelium is active.

    PubMed

    Schönitzer, Veronika; Eichner, Norbert; Clausen-Schaumann, Hauke; Weiss, Ingrid M

    2011-12-02

    Several mollusc shells contain chitin, which is formed by a transmembrane myosin motor enzyme. This protein could be involved in sensing mechanical and structural changes of the forming, mineralizing extracellular matrix. Here we report the heterologous expression of the transmembrane myosin chitin synthase Ar-CS1 of the bivalve mollusc Atrina rigida (2286 amino acid residues, M.W. 264 kDa/monomer) in Dictyostelium discoideum, a model organism for myosin motor proteins. Confocal laser scanning immunofluorescence microscopy (CLSM), chitin binding GFP detection of chitin on cells and released to the cell culture medium, and a radiochemical activity assay of membrane extracts revealed expression and enzymatic activity of the mollusc chitin synthase in transgenic slime mold cells. First high-resolution atomic force microscopy (AFM) images of Ar-CS1 transformed cellulose synthase deficient D. discoideumdcsA(-) cell lines are shown.

  19. Sequential Testing: Basics and Benefits

    DTIC Science & Technology

    1978-03-01

    103-109 44. A. Wald , Sequential Analysis, John Wiley and Sons, 1947 45. A Wald and J. Wolfowitz , "Optimum Character of The Sequential Probability Ratio...work done by A. Wald [44].. Wald’s work on sequential analysis can be used virtually’without modification in a situation where decisions are made... Wald can be used. The decision to accept, reject, or continue the test depends on: 8 < (8 0/el)r exp [-(1/01 - 1/0 0 )V(t)] < A (1) where 0 and A are

  20. NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

    SciTech Connect

    Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

    2013-02-15

    During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment.

  1. Transmitting Sport Values: The Importance of Parental Involvement in Children’s Sport Activity

    PubMed Central

    Danioni, Francesca; Barni, Daniela; Rosnati, Rosa

    2017-01-01

    The transmission of positive values between parents and children is generally considered to be the hallmark of successful socialization. As this issue has been widely discussed but surprisingly little researched - especially with reference to core sport values - in this study we aimed to: 1) analyze adolescent athletes’ acceptance of the sport values their parents want to transmit to them (i.e., parental socialization values) and 2) examine the relationship between parental involvement in children’s sportive activity and adolescents’ acceptance of their parents’ socialization values. One hundred and seventy-two Italian adolescents (48.3% male, 51.7% female) who regularly practice team sports were asked to fill out a questionnaire which included the Youth Sport Values Questionnaire – 2 and the Parental Involvement in Sport Questionnaire. The dyadic correlations revealed that young athletes are in general willing to accept their parents’ socialization values in regards to sport. Moreover, from the relative weight analysis (a relatively new data analysis strategy), it emerged that parental involvement characterized by praise and understanding is the most important predictor of adolescents’ willingness to accept their parents’ sport values. Implications of these results and further expansion of the study are discussed. PMID:28344676

  2. Transmitting Sport Values: The Importance of Parental Involvement in Children's Sport Activity.

    PubMed

    Danioni, Francesca; Barni, Daniela; Rosnati, Rosa

    2017-03-01

    The transmission of positive values between parents and children is generally considered to be the hallmark of successful socialization. As this issue has been widely discussed but surprisingly little researched - especially with reference to core sport values - in this study we aimed to: 1) analyze adolescent athletes' acceptance of the sport values their parents want to transmit to them (i.e., parental socialization values) and 2) examine the relationship between parental involvement in children's sportive activity and adolescents' acceptance of their parents' socialization values. One hundred and seventy-two Italian adolescents (48.3% male, 51.7% female) who regularly practice team sports were asked to fill out a questionnaire which included the Youth Sport Values Questionnaire - 2 and the Parental Involvement in Sport Questionnaire. The dyadic correlations revealed that young athletes are in general willing to accept their parents' socialization values in regards to sport. Moreover, from the relative weight analysis (a relatively new data analysis strategy), it emerged that parental involvement characterized by praise and understanding is the most important predictor of adolescents' willingness to accept their parents' sport values. Implications of these results and further expansion of the study are discussed.

  3. Cissus sicyoides: Pharmacological Mechanisms Involved in the Anti-Inflammatory and Antidiarrheal Activities

    PubMed Central

    Beserra, Fernando Pereira; de Cássia Santos, Raquel; Périco, Larissa Lucena; Rodrigues, Vinicius Peixoto; de Almeida Kiguti, Luiz Ricardo; Saldanha, Luiz Leonardo; Pupo, André Sampaio; da Rocha, Lúcia Regina Machado; Dokkedal, Anne Lígia; Vilegas, Wagner; Hiruma-Lima, Clélia Akiko

    2016-01-01

    The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smooth muscle and/or intestinal transit. PMID:26805827

  4. Polyamines and transglutaminase activity are involved in compatible and self-incompatible pollination of Citrus grandis.

    PubMed

    Gentile, Alessandra; Antognoni, Fabiana; Iorio, Rosa Anna; Distefano, Gaetano; Las Casas, Giuseppina; La Malfa, Stefano; Serafini-Fracassini, Donatella; Del Duca, Stefano

    2012-02-01

    Pollination of pummelo (Citrus grandis L. Osbeck) pistils has been studied in planta by adding compatible and self-incompatible (SI) pollen to the stigma surface. The pollen germination has been monitored inside the pistil by fluorescent microscopy showing SI altered morphologies with irregular depositions of callose in the tube walls, and heavy callose depositions in enlarged tips. The polyamine (PA) content as free, perchloric acid (PCA)-soluble and -insoluble fractions and transglutaminase (TGase) activity have been analyzed in order to deepen their possible involvement in the progamic phase of plant reproduction. The conjugated PAs in PCA-soluble fraction were definitely higher than the free and the PCA-insoluble forms, in both compatible and SI pollinated pistils. In pistils, pollination caused an early decrease of free PAs and increase of the bound forms. The SI pollination, showed highest values of PCA-soluble and -insoluble PAs with a maximum in concomitance with the pollen tube arrest. As TGase mediates some of the effects of PAs by covalently binding them to proteins, its activity, never checked before in Citrus, was examined with two different assays. In addition, the presence of glutamyl-PAs confirmed the enzyme assay data and excluded the possibility of a misinterpretation. The SI pollination caused an increase in TGase activity, whereas the compatible pollination caused its decrease. Similarly to bound PAs, the glutamyl-PAs and the enzyme activity peaked in the SI pollinated pistils in concomitance with the observed block of the pollen tube growth, suggesting an involvement of TGase in SI response.

  5. Fine mapping of sequential neutralization epitopes on the subunit protein VP8 of human rotavirus.

    PubMed Central

    Kovacs-Nolan, Jennifer; Yoo, Dongwan; Mine, Yoshinori

    2003-01-01

    The epitopes of the HRV (human rotavirus), especially those involved in virus neutralization, have not been determined in their entirety, and would have significant implications for HRV vaccine development. In the present study, we report on the epitope mapping and identification of sequential neutralization epitopes, on the Wa strain HRV subunit protein VP8, using synthetic overlapping peptides. Polyclonal antibodies against recombinant Wa VP8 were produced previously in chicken, and purified from egg yolk, which showed neutralizing activity against HRV in vitro. Overlapping VP8 peptide fragments were synthesized and probed with the anti-VP8 antibodies, revealing five sequential epitopes on VP8. Further analysis suggested that three of the five epitopes detected, M1-L10, I55-D66 and L223-P234, were involved in virus neutralization, indicating that sequential epitopes may also be important for the HRV neutralization. The interactions of the antibodies with the five epitopes were characterized by an examination of the critical amino acids involved in antibody binding. Epitopes comprised primarily of hydrophobic amino acid residues, followed by polar and charged residues. The more critical amino acids appeared to be located near the centre of the epitopes, with proline, isoleucine, serine, glutamine and arginine playing an important role in the binding of antibody to the VP8 epitopes. PMID:12901721

  6. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  7. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  8. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  9. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  10. 15 CFR 712.1 - Round to zero rule that applies to activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... activities involving Schedule 1 chemicals. 712.1 Section 712.1 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.1 Round to...

  11. Differences between Depressed and Non-Depressed Residents of Nursing Homes on Measures of Daily Activity Involvement and Affect.

    ERIC Educational Resources Information Center

    Voelkl, Judith E.; Mathieu, Mary A.

    1993-01-01

    This study examined how depressed and nondepressed nursing home residents differed on measures of frequency of daily activity involvement and accompanying affect. Interviews indicated the groups differed significantly on frequency of activity involvement and affect. Depressed subjects spent large portions of time watching television. Nondepressed…

  12. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  13. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  14. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  15. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  16. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  17. Identification of an ovarian voltage-activated Na+-channel type: hints to involvement in luteolysis.

    PubMed

    Bulling, A; Berg, F D; Berg, U; Duffy, D M; Stouffer, R L; Ojeda, S R; Gratzl, M; Mayerhofer, A

    2000-07-01

    An endocrine type of voltage-activated sodium channel (eNaCh) was identified in the human ovary and human luteinized granulosa cells (GC). Whole-cell patch-clamp studies showed that the eNaCh in GC is functional and tetrodotoxin (TTX) sensitive. The luteotrophic hormone human CG (hCG) was found to decrease the peak amplitude of the sodium current within seconds. Treatment with hCG for 24-48 h suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and resting membrane potentials. An unexpected role for eNaChs in regulating cell morphology and function was indicated after pharmacological modulation of presumed eNaCh steady-state activity in GC cultures for 24-48 h using TTX (NaCh blocker) and veratridine (NaCh activator). TTX preserved a highly differentiated cellular phenotype. Veratridine not only increased the number of secondary lysosomes but also led to a significantly reduced progesterone production. Importantly, endocrine cells of the nonhuman primate corpus luteum (CL), which represent in vivo counterparts of luteinized GC, also contain eNaCh mRNA. Although the mechanism of channel activity under physiological conditions is not clear, it may include persistent Na+ currents. As observed in GC in culture, abundant secondary lysosomes were particularly evident in the regressing CL, suggesting a functional link between eNaCh activity and this form of cellular regression in vivo. Our results identify eNaCh in ovarian endocrine cells and demonstrate that their expression is under the inhibitory control of hCG. Activation of eNaChs in luteal cells, due to loss of gonadotropin support, may initiate a cascade of events leading to decreased CL function, a process that involves lysosomal activation and autophagy. These results imply that ovarian eNaChs are involved in the physiological demise of the temporary endocrine organ CL in the primate ovary during the menstrual cycle. Because commonly used drugs, including phenytoin, target NaChs, these results

  18. Developmental changes in brain activation involved in the production of novel speech sounds in children.

    PubMed

    Hashizume, Hiroshi; Taki, Yasuyuki; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Asano, Kohei; Takeuchi, Hikaru; Nouchi, Rui; Kotozaki, Yuka; Jeong, Hyeonjeong; Sugiura, Motoaki; Kawashima, Ryuta

    2014-08-01

    Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech.

  19. CIPK23 is involved in iron acquisition of Arabidopsis by affecting ferric chelate reductase activity.

    PubMed

    Tian, Qiuying; Zhang, Xinxin; Yang, An; Wang, Tianzuo; Zhang, Wen-Hao

    2016-05-01

    Iron deficiency is one of the major limiting factors affecting quality and production of crops in calcareous soils. Numerous signaling molecules and transcription factors have been demonstrated to play a regulatory role in adaptation of plants to iron deficiency. However, the mechanisms underlying the iron deficiency-induced physiological processes remain to be fully dissected. Here, we demonstrated that the protein kinase CIPK23 was involved in iron acquisition. Lesion of CIPK23 rendered Arabidopsis mutants hypersensitive to iron deficiency, as evidenced by stronger chlorosis in young leaves and lower iron concentration than wild-type plants under iron-deficient conditions by down-regulating ferric chelate reductase activity. We found that iron deficiency evoked an increase in cytosolic Ca(2+) concentration and the elevated Ca(2+) would bind to CBL1/CBL9, leading to activation of CIPK23. These novel findings highlight the involvement of calcium-dependent CBL-CIPK23 complexes in the regulation of iron acquisition. Moreover, mutation of CIPK23 led to changes in contents of mineral elements, suggesting that CBL-CIPK23 complexes could be as "nutritional sensors" to sense and regulate the mineral homeostasis in Arabisopsis.

  20. The hypotriglyceridemic effect of biotin supplementation involves increased levels of cGMP and AMPK activation.

    PubMed

    Aguilera-Méndez, Asdrúbal; Fernández-Mejía, Cristina

    2012-01-01

    In addition to its role as a carboxylase cofactor, biotin modifies gene expression and has manifold effects on systemic processes. Several studies have shown that biotin supplementation reduces hypertriglyceridemia. We have previously reported that this effect is related to decreased expression of lipogenic genes. In the present work, we analyzed signaling pathways and posttranscriptional mechanisms involved in the hypotriglyceridemic effects of biotin. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg of free biotin/kg diet, respectively for 8 weeks after weaning. The abundance of mature sterol regulatory element-binding protein (SREBP-1c), fatty-acid synthase (FAS), total acetyl-CoA carboxylase-1 (ACC-1) and its phosphorylated form, and AMP-activated protein kinase (AMPK) were evaluated in the liver. We also determined the serum triglyceride concentrations and the hepatic levels of triglycerides and cyclic GMP (cGMP). Compared to the control group, biotin-supplemented mice had lower serum and hepatic triglyceride concentrations. Biotin supplementation increased the levels of cGMP and the phosphorylated forms of AMPK and ACC-1 and decreased the abundance of the mature form of SREBP-1c and FAS. These data provide evidence that the mechanisms by which biotin supplementation reduces lipogenesis involve increased cGMP content and AMPK activation. In turn, these changes lead to augmented ACC-1 phosphorylation and decreased expression of both the mature form of SREBP-1c and FAS. Our results demonstrate for the first time that AMPK is involved in the effects of biotin supplementation and offer new insights into the mechanisms of biotin-mediated hypotriglyceridemic effects.

  1. Mitochondrial Dysfunction Is Involved in the Toxic Activity of Boric Acid against Saprolegnia

    PubMed Central

    Ali, Shimaa E.; Thoen, Even; Evensen, Øystein; Wiik-Nielsen, Jannicke; Gamil, Amr A. A.; Skaar, Ida

    2014-01-01

    There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4–24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp. PMID:25354209

  2. Effects of negative air ions on activity of neural substrates involved in autonomic regulation in rats

    NASA Astrophysics Data System (ADS)

    Suzuki, Satoko; Yanagita, Shinya; Amemiya, Seiichiro; Kato, Yumi; Kubota, Natsuko; Ryushi, Tomoo; Kita, Ichiro

    2008-07-01

    The neural mechanism by which negative air ions (NAI) mediate the regulation of autonomic nervous system activity is still unknown. We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats. In addition, we performed cervical vagotomy to reveal the afferent pathway involved in mediating the effects of NAI on autonomic regulation. NAI significantly decreased BP and HR, and increased HF power of the HRV spectrum. Significant decreases in c-Fos positive nuclei in the PVN and LC, and enhancement of c-Fos expression in the NA and NTS were induced by NAI. After vagotomy, these physiological and neuronal responses to NAI were not observed. These findings suggest that NAI can modulate autonomic regulation through inhibition of neuronal activity in PVN and LC as well as activation of NA neurons, and that these effects of NAI might be mediated via the vagus nerves.

  3. Mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia.

    PubMed

    Ali, Shimaa E; Thoen, Even; Evensen, Øystein; Wiik-Nielsen, Jannicke; Gamil, Amr A A; Skaar, Ida

    2014-01-01

    There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4-24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp.

  4. Anticonvulsant activity of Dorema ammoniacum gum: evidence for the involvement of benzodiazepines and opioid receptors

    PubMed Central

    Motevalian, Manijeh; Mehrzadi, Saeed; Ahadi, Samira; Shojaii, Asie

    2017-01-01

    This study investigated the anticonvulsant activity and possible mechanism of action of an aqueous solution of Dorema ammoniacum gum (DAG) which has been used traditionally in the treatment of convulsions. In this study, the anticonvulsant activity of DAG was examined using the pentylentetrazole (PTZ) model in mice. Thirty male albino mice were divided randomly and equally to 5 groups, and pretreated with normal saline, diazepam, or various doses of DAG (500, 700, and 1000 mg/kg, i.p.), prior to the injection of PTZ (60 mg/kg, i.p.). The latency and duration of seizures were recorded 30 min after PTZ injection. Pretreatments with naloxone and flumazenil in different groups were studied to further clarify the mechanisms of the anticonvulsant action. Phytochemical screening and thin layer chromatography (TLC) fingerprinting of ammoniacum gum was also determined. DAG showed significant anticonvulsant activity at all doses used. The gum delayed both the onset and the duration of seizures induced by PTZ. Treatment with flumazenil before DAG (700 mg/kg) inhibited the effect of gum on seizure duration and latency to some extent and administration of naloxone before DAG also significantly inhibited changes in latency and duration of seizure produced by DAG. The percentage inhibition was greater with naloxone than with flumazenil. This study showed that DAG had significant anticonvulsant activity in PTZ-induced seizures, and GABAergic and opioid systems may be involved. More studies are needed to further investigate its detailed mechanism. PMID:28255314

  5. Joint Associations of Residential Density and Neighborhood Involvement with Physical Activity among a Multiethnic Sample of Urban Adults

    ERIC Educational Resources Information Center

    Johnson-Lawrence, Vicki; Schulz, Amy J.; Zenk, Shannon N.; Israel, Barbara A.; Wineman, Jean; Marans, Robert W.; Rowe, Zachary

    2015-01-01

    Regular physical activity is associated with improvements in overall health. Although resident involvement in neighborhood social activities is positively associated with physical activity, neighborhood design features, including residential density, have varied associations with physical activity. Using data from a multiethnic sample of 696…

  6. Studies on Bronchodilator Activity of Salvia officinalis (Sage): Possible Involvement of K(+) Channel Activation and Phosphodiesterase Inhibition.

    PubMed

    Gilani, Anwarul-Hassan; Rehman, Najeeb-Ur; Khan, Aslam; Alkharfy, Khalid M

    2015-06-01

    The aqueous methanolic extract of the aerial parts of Salvia officinalis (So.Cr) was studied to provide possible underlying mechanism(s) for its medicinal use in asthma using the in vivo bronchodilatory assay and isolated tracheal preparations. S. officinalis (1-10 mg/kg) dose-dependently inhibited carbachol (CCh)-induced bronchospasm in anesthetized rats with three-fold greater potency than the positive control, aminophylline. In tracheal preparations, So.Cr inhibited the low K(+) (25 mM)-induced contractions. Pretreatment of the tissues with 4-aminopyridine reversed the inhibitory effect of the plant extract against low K(+) , whereas glibenclamide did not show any effect, thus showing the involvement of voltage-sensitive K(+) channels. When tested against the CCh-induced pre-contractions for the involvement of any additional mechanism, interestingly, the extract showed a dose-dependent (0.03-0.1 mg/mL) inhibitory effect and shifted the inhibitory concentration response curves of isoprenaline to the left, thus showing phosphodiesterase enzyme inhibitory-like action, similar to that of papaverine. These results indicate that the crude extract of S. officinalis possesses bronchodilatory activity mediated predominantly via activation of voltage-dependent K(+) channels and inhibition of phosphodiesterase enzyme; thus, this study provides sound pharmacological basis for its medicinal use in hyperactive airways disorders such as asthma and cough. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Evolution of phosphorus complexation and mineralogy during (hydro)thermal treatments of activated and anaerobically digested sludge: Insights from sequential extraction and P K-edge XANES.

    PubMed

    Huang, Rixiang; Tang, Yuanzhi

    2016-09-01

    (Hydro)thermal treatments of sewage sludge is a promising option that can simultaneously target safe waste disposal, energy recovery, and nutrient recovery/recycling. The speciation of phosphorus (P) in sludge is of great relevance to P reclamation/recycling and soil application of sludge-derived products, thus it is critical to understand the effects of different treatment techniques and conditions on P speciation. This study systematically characterized P speciation (i.e. complexation and mineral forms) in chars derived from pyrolysis and hydrothermal carbonization (HTC) of municipal sewage sludges. Combined sequential extraction and P K-edge X-ray absorption near edge structure (XANES) spectroscopy analysis revealed the dependence of P transformation on treatment conditions and metal composition in the feedstocks. Pyrolysis of sludges decreased the relative abundance of phytic acid while increased the abundance of Al-associated P. HTC thoroughly homogenized and exposed P for interaction with various metals/minerals, with the final P speciation closely related to the composition/speciation of metals and their affinities to P. Results from this study revealed the mechanisms of P transformation during (hydro)thermal treatments of sewage sludges, and might be applicable to other biosolids. It also provided fundamental knowledge basis for the design and selection of waste management strategies for better P (re)cycling and reclamation.

  8. Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation.

    PubMed

    Hoshino, Katsuaki; Kaisho, Tsuneyasu; Iwabe, Tomio; Takeuchi, Osamu; Akira, Shizuo

    2002-10-01

    Toll-like receptor (TLR) can activate dendritic cells (DC) through common signaling pathways requiring a cytoplasmic adapter, MyD88. However, the signaling is differentially regulated among TLR family members. TLR4 can activate MyD88-deficient bone marrow-derived DC (BMDC), and lead to induction of IFN-inducible genes and up-regulation of co-stimulatory molecules such as CD40, implying that the MyD88-independent signaling pathway functions downstream of TLR4. Because these effects can also be induced by type I IFN, we have analyzed whether type I IFN is involved in TLR4-induced responses. In response to lipopolysaccharide (LPS), IFN-beta gene expression was augmented in both wild-type and MyD88-deficient BMDC. Expression of all IFN-inducible genes except immune-responsive gene 1 (IRG1) was abolished and CD40 up-regulation was decreased in LPS-stimulated BMDC lacking either IFN-alpha/beta receptor (IFN-alpha/betaR) or signal transducer and activator of transcription 1 (STAT-1). Similar to the LPS response, TLR9 signaling can also induce expression of IFN-beta and IFN-inducible genes, and up-regulation of CD40. However, all these effects were MyD88 dependent. Thus, in TLR4 signaling, IFN-beta expression can be induced either by the MyD88-dependent or -independent pathway, whereas, in TLR9 signaling, it is dependent on MyD88. In CpG DNA-stimulated DC, expression of IFN-inducible genes except IRG1 was dependent on type I IFN signaling as in LPS-stimulated DC. However, in contrast to TLR4 signaling, TLR9 signaling requires type I IFN signaling for CD40 up-regulation. Taken together, this study demonstrates differential involvement of type I IFN in TLR4- and TLR9-induced effects on DC.

  9. Augment railgun and sequential discharge

    NASA Astrophysics Data System (ADS)

    Kobayashi, K.

    1993-01-01

    Proprietary R&D efforts toward the creation of tactical weapon systems-applicable railguns are presented. Attention is given to measures taken for projectile velocity maximization and sequential-discharge operation, and to an augmenting railgun which has demonstrated a 66-percent efficiency improvement over the two-rail baseline railgun system. This device is characterized by strong interaction between capacitor bank submodules during sequential discharge.

  10. Sequentially pulsed traveling wave accelerator

    DOEpatents

    Caporaso, George J.; Nelson, Scott D.; Poole, Brian R.

    2009-08-18

    A sequentially pulsed traveling wave compact accelerator having two or more pulse forming lines each with a switch for producing a short acceleration pulse along a short length of a beam tube, and a trigger mechanism for sequentially triggering the switches so that a traveling axial electric field is produced along the beam tube in synchronism with an axially traversing pulsed beam of charged particles to serially impart energy to the particle beam.

  11. Determination of Dehydrogenase Activities Involved in D-Glucose Oxidation in Gluconobacter and Acetobacter Strains

    PubMed Central

    Sainz, Florencia; Jesús Torija, María; Matsutani, Minenosuke; Kataoka, Naoya; Yakushi, Toshiharu; Matsushita, Kazunobu; Mas, Albert

    2016-01-01

    Acetic acid bacteria (AAB) are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane-bound dehydrogenases. In the present study, the enzyme activity of the membrane-bound dehydrogenases [membrane-bound PQQ-glucose dehydrogenase (mGDH), D-gluconate dehydrogenase (GADH) and membrane-bound glycerol dehydrogenase (GLDH)] involved in the oxidation of D-glucose and D-gluconic acid (GA) was determined in six strains of three different species of AAB (three natural and three type strains). Moreover, the effect of these activities on the production of related metabolites [GA, 2-keto-D-gluconic acid (2KGA) and 5-keto-D-gluconic acid (5KGA)] was analyzed. The natural strains belonging to Gluconobacter showed a high mGDH activity and low activity in GADH and GLDH, whereas the Acetobacter malorum strain presented low activity in the three enzymes. Nevertheless, no correlation was observed between the activity of these enzymes and the concentration of the corresponding metabolites. In fact, all the tested strains were able to oxidize D-glucose to GA, being maximal at the late exponential phase of the AAB growth (24 h), which coincided with D-glucose exhaustion and the maximum mGDH activity. Instead, only some of the tested strains were capable of producing 2KGA and/or 5KGA. In the case of Gluconobacter oxydans strains, no 2KGA production was detected which is related to the absence of GADH activity after 24 h, while in the remaining strains, detection of GADH activity after 24 h resulted in a high accumulation of 2KGA. Therefore, it is possible to choose the best strain depending on the desired product composition. Moreover, the sequences of these genes were used to construct phylogenetic trees. According to the sequence of gcd, gene coding for mGDH, Acetobacter and Komagataeibacter

  12. Multienzyme kinetics and sequential metabolism.

    PubMed

    Wienkers, Larry C; Rock, Brooke

    2014-01-01

    Enzymes are the catalysts of biological systems and are extremely efficient. A typical enzyme accelerates the rate of a reaction by factors of at least a million compared to the rate of the same reaction in the absence of the enzyme. In contrast to traditional catalytic enzymes, the family of cytochrome P450 (CYP) enzymes are catalytically promiscuous, and thus they possess remarkable versatility in substrates. The great diversity of reactions catalyzed by CYP enzymes appears to be based on two unique properties of these heme proteins, the ability of their iron to exist under multiple oxidation states with different reactivities and a flexible active site that can accommodate a wide variety of substrates. Herein is a discussion of two distinct types of kinetics observed with CYP enzymes. The first example is of CYP complex kinetic profiles when multiple CYP enzymes form the sample product. The second is sequential metabolism, in other words, the formation of multiple products from one CYP enzyme. Given the degree of CYP enzyme promiscuity, it is hardly surprising that there is also a high degree of complex kinetic profiles generated during the catalytic cycle.

  13. Molecular Genetic Analysis of Activation-tagged Transcription Factors Thought to be Involved in Photomorphogenesis

    SciTech Connect

    Neff, Michael

    2011-06-23

    Plants utilize light as a source of information via families of photoreceptors such as the red/far-red absorbing phytochromes (PHY) and the blue/UVA absorbing cryptochromes (CRY). The main goal of the Neff lab is to use molecular-genetic mutant screens to elucidate signaling components downstream of these photoreceptors. Activation-tagging mutagenesis led to the identification of two putative transcription factors that may be involved in both photomorphogenesis and hormone signaling pathways. sob1-D (suppressor of phyB-dominant) mutant phenotypes are caused by the over-expression of a Dof transcription factor previously named OBP3. Our previous studies indicate that OBP3 is a negative regulator of light-mediated cotyledon expansion and may be involved in modulating responsiveness to the growth-regulating hormone auxin. The sob2-D mutant uncovers a role for LEP, a putative AP2/EREBP-like transcription factor, in seed germination, hypocotyl elongation and responsiveness to the hormone abscisic acid. Based on photobiological and genetic analysis of OBP3-knockdown and LEP-null mutations, we hypothesize that these transcription factors are involved in both light-mediated seedling development and hormone signaling. To examine the role that these genes play in photomorphogenesis we will: 1) Further explore the genetic role of OBP3 in cotyledon/leaf expansion and other photomorphogenic processes as well as examine potential physical interactions between OBP3 and CRY1 or other signaling components that genetically interact with this transcription factor 2) Test the hypothesis that OBP3 is genetically involved in auxin signaling and root development as well as examine the affects of this hormone and light on OBP3 protein accumulation. 3) Test the hypothesis that LEP is involved in seed germination, seedling photomorphogenesis and hormone signaling. Together these experiments will lead to a greater understanding of the complexity of interactions between photoreceptors and DNA

  14. Improving the active involvement of stakeholders and the public in flood risk management - tools of an involvement strategy and case study results from Austria, Germany and Italy

    NASA Astrophysics Data System (ADS)

    Fleischhauer, M.; Greiving, S.; Flex, F.; Scheibel, M.; Stickler, T.; Sereinig, N.; Koboltschnig, G.; Malvati, P.; Vitale, V.; Grifoni, P.; Firus, K.

    2012-09-01

    The EU Flood Risk Management Directive 2007/60/EC aims at an active involvement of interested parties in the setting up of flood risk management plans and thus calls for more governance-related decision-making. This requirement has two perspectives. On the one hand, there is (1) the question of how decision-makers can improve the quality of their governance process. On the other hand, there is (2) the question of how the public shall be appropriately informed and involved. These questions were the centre of the ERA-Net CRUE-funded project IMRA (integrative flood risk governance approach for improvement of risk awareness) that aimed at an optimisation of the flood risk management process by increasing procedural efficiency with an explicit involvement strategy. To reach this goal, the IMRA project partners developed two new approaches that were implemented in three case study areas for the first time in flood risk management: 1. risk governance assessment tool: An indicator-based benchmarking and monitoring tool was used to evaluate the performance of a flood risk management system in regard to ideal risk governance principles; 2. social milieu approach: The concept of social milieus was used to gain a picture of the people living in the case study regions to learn more about their lifestyles, attitudes and values and to use this knowledge to plan custom-made information and participation activities for the broad public. This paper presents basic elements and the application of two innovative approaches as a part of an "involvement strategy" that aims at the active involvement of all interested parties (stakeholders) for assessing, reviewing and updating flood risk management plans, as formulated in the EU Flood Risk Management Directive 2007/60/EC.

  15. Involvement of BLT1 endocytosis and Yes kinase activation in leukotriene B4-induced neutrophil degranulation.

    PubMed

    Gaudreault, Eric; Thompson, Charles; Stankova, Jana; Rola-Pleszczynski, Marek

    2005-03-15

    One of the important biological activities of human neutrophils is degranulation, which can be induced by leukotriene B4 (LTB4). Here we investigated the intracellular signaling events involved in neutrophil degranulation mediated by the high affinity LTB4 receptor, BLT1. Peripheral blood neutrophils as well as the promyeloid PLB-985 cell line, stably transfected with BLT1 cDNA and differentiated into a neutrophil-like cell phenotype, were used throughout this study. LTB4-induced enzyme release was inhibited by 50-80% when cells were pretreated with the pharmacological inhibitors of endocytosis sucrose, Con A and NH4Cl. In addition, transient transfection with a dominant negative form of dynamin (K44A) resulted in approximately 70% inhibition of ligand-induced degranulation. Pretreating neutrophils or BLT1-expressing PLB-985 cells with the Src family kinase inhibitor PP1 resulted in a 30-60% inhibition in BLT1-mediated degranulation. Yes kinase, but not c-Src, Fgr, Hck, or Lyn, was found to exhibit up-regulated kinase activity after LTB4 stimulation. Moreover, BLT1 endocytosis was found to be necessary for Yes kinase activation in neutrophils. LTB4-induced degranulation was also sensitive to inhibition of PI3K. In contrast, it was not affected by inhibition of the mitogen-activated protein kinase MEK kinase, the Janus kinases, or the receptor tyrosine kinase epidermal growth factor receptor or platelet-derived growth factor receptor. Taken together, our results suggest an essential role for BLT1 endocytosis and Yes kinase activation in LTB4-mediated degranulation of human neutrophils.

  16. Transmembrane myosin chitin synthase involved in mollusc shell formation produced in Dictyostelium is active

    SciTech Connect

    Schoenitzer, Veronika; Eichner, Norbert; Clausen-Schaumann, Hauke; Weiss, Ingrid M.

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Dictyostelium produces the 264 kDa myosin chitin synthase of bivalve mollusc Atrina. Black-Right-Pointing-Pointer Chitin synthase activity releases chitin, partly associated with the cell surface. Black-Right-Pointing-Pointer Membrane extracts of transgenic slime molds produce radiolabeled chitin in vitro. Black-Right-Pointing-Pointer Chitin producing Dictyostelium cells can be characterized by atomic force microscopy. Black-Right-Pointing-Pointer This model system enables us to study initial processes of chitin biomineralization. -- Abstract: Several mollusc shells contain chitin, which is formed by a transmembrane myosin motor enzyme. This protein could be involved in sensing mechanical and structural changes of the forming, mineralizing extracellular matrix. Here we report the heterologous expression of the transmembrane myosin chitin synthase Ar-CS1 of the bivalve mollusc Atrina rigida (2286 amino acid residues, M.W. 264 kDa/monomer) in Dictyostelium discoideum, a model organism for myosin motor proteins. Confocal laser scanning immunofluorescence microscopy (CLSM), chitin binding GFP detection of chitin on cells and released to the cell culture medium, and a radiochemical activity assay of membrane extracts revealed expression and enzymatic activity of the mollusc chitin synthase in transgenic slime mold cells. First high-resolution atomic force microscopy (AFM) images of Ar-CS1 transformed cellulose synthase deficient D. discoideumdcsA{sup -} cell lines are shown.

  17. Transient neural activation in human amygdala involved in aversive conditioning of face and voice.

    PubMed

    Iidaka, Tetsuya; Saito, Daisuke N; Komeda, Hidetsugu; Mano, Yoko; Kanayama, Noriaki; Osumi, Takahiro; Ozaki, Norio; Sadato, Norihiro

    2010-09-01

    Elucidating the neural mechanisms involved in aversive conditioning helps find effective treatments for psychiatric disorders such as anxiety disorder and phobia. Previous studies using fMRI and human subjects have reported that the amygdala plays a role in this phenomenon. However, the noxious stimuli that were used as unconditioned stimuli in previous studies (e.g., electric shock) might have been ecologically invalid because we seldom encounter such stimuli in daily life. Therefore, we investigated whether a face stimulus could be conditioned by using a voice that had negative emotional valence and was collected from a real-life environment. A skin conductance response showed that healthy subjects were conditioned by using these stimuli. In an fMRI study, there was greater amygdala activation in response to the faces that had been paired with the voice than to those that had not. The right amygdala showed transient activity in the early stage of acquisition. A psychophysiological interaction analysis indicated that the subcortical pathway from the medial geniculate body to the amygdala played a role in conditioning. Modulation of the subcortical pathway by voice stimuli preceded the transient activity in the amygdala. The finding that an ecologically valid stimulus elicited the conditioning and amygdala response suggests that our brain is automatically processing unpleasant stimuli in daily life.

  18. Protein receptor for activated C kinase 1 is involved in morphine reward in mice.

    PubMed

    Wan, L; Su, L; Xie, Y; Liu, Y; Wang, Y; Wang, Z

    2009-07-07

    Opiate addiction is associated with upregulation of cAMP signaling in the brain. cAMP-responsive element binding protein (CREB), a nuclear transcription factor, is a downstream component of the extracellular signal-regulated protein kinase (ERK) pathway, which has been shown to regulate different physiological and psychological responses of drug addiction. RACK1, the protein receptor for activated C kinase 1, is a multifunctional scaffolding protein known to be a key regulator of various signaling cascades in the CNS. RACK1 functions specifically in integrin mediated activation of ERK cascade and targets active ERK. We examined if RACK1 is involved in the mechanism of drug addiction by regulating CREB in mouse hippocampus and prefrontal cortex. Several expressions were observed. Chronic administration of morphine made the expression of RACK1 and CREB mRNA increase in hippocampus and prefrontal cortex. The expression of RACK1 and CREB protein was strongly positive in CA1, CA3 and dentate gyrus (DG) of the hippocampus of morphine-treated mice brain, especially the pyramidal neurons in the DG of the hippocampus. Using the small interfering RNA technology, we determined that the expression of CREB mRNA was decreased in hippocampus and prefrontal cortex of morphine-treated mice. The expression of RACK1 and CREB protein was negative in CA1, CA3 and DG of hippocampus. These findings suggest that morphine reward can influence the expression of RACK1 in mouse hippocampus and prefrontal cortex through regulating CREB transcription.

  19. Astragaloside IV enhances diabetic wound healing involving upregulation of alternatively activated macrophages.

    PubMed

    Luo, Xiaochun; Huang, Ping; Yuan, Baohong; Liu, Tao; Lan, Fang; Lu, Xiaoyan; Dai, Liangcheng; Liu, Yunjun; Yin, Hui

    2016-06-01

    Astragaloside IV (AS-IV), one of the major active compounds extracted from Astragali Radix, has been used experimentally for its potent antiinflammatory and immunoregulatory activities. In this study, we further investigate the potential efficacy of AS-IV on impaired wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was produced on the back of diabetic mice and treated with AS-IV or vehicle topically. Our results showed that AS-IV application promoted diabetic wound repair with wounds gaping narrower and exhibiting augmented reepithelialization. AS-IV enhanced the collagen deposition and the expression of extracellular matrix (ECM)-related genes such as fibronectin and collagen IIIa, which implies a direct effect of AS-IV on matrix synthesis. AS-IV also improved the new blood vessel formation in wound tissue with increased numbers of endothelial cells and enhanced expression of VEGF and vWF. Moreover, the beneficial effect of AS-IV was related to the development of polarized alternatively activated macrophages, which involved in resolution of inflammation and facilitation of wound repair. All together, these findings suggest that AS-IV may play a potential effect on maintenance of cutaneous homeostasis and acceleration of diabetic wound healing.

  20. Cyclooxygenase-1 and -2 in spinally projecting neurons are involved in CRF-induced sympathetic activation.

    PubMed

    Yamaguchi, Naoko; Okada, Shoshiro

    2009-12-03

    Corticotropin-releasing factor (CRF) in the brain has been shown to stimulate sympathetic activity, leading to elevations of blood pressure, heart rate and plasma catecholamine levels and neuronal activation of the sympathetic ganglia and adrenal medulla. We previously reported that brain cyclooxygenase (COX), the rate-limiting enzyme in the synthesis of prostanoids, is involved in centrally administered CRF-induced sympathetic activation in rats. Therefore, the present study was designed to reveal the effect of centrally administered CRF (1.5 nmol/animal) on the expression of COX isozymes, COX-1 and COX-2, in spinally projecting neurons until 6h after the administration, using rats microinjected with a monosynaptic retrograde tracer into the intermediolateral cell column of the thoracic spinal cord. Retrogradely labeled neurons were detected in the paraventricular hypothalamic nucleus (PVN), locus coeruleus (LC), raphe pallidus nucleus and rostral ventrolateral medulla. Centrally administered CRF significantly increased the number of spinally projecting PVN neurons expressing COX-1 throughout the experimental period and those expressing COX-2 during only the late phase. CRF also increased the number of spinally projecting LC neurons expressing COX-2 throughout the experimental period. In other regions, the CRF administration had no effect on COXs expression in spinally projecting neurons. These results suggest that COX-1 and COX-2 in the PVN and COX-2 in the LC play roles in the CRF-induced sympathetic regulation in rats.

  1. Inhibition of proteasome activity is involved in cobalt-induced apoptosis of human alveolar macrophages.

    PubMed

    Araya, Jun; Maruyama, Muneharu; Inoue, Akira; Fujita, Tadashi; Kawahara, Junko; Sassa, Kazuhiko; Hayashi, Ryuji; Kawagishi, Yukio; Yamashita, Naohiro; Sugiyama, Eiji; Kobayashi, Masashi

    2002-10-01

    Inhalation of particulate cobalt has been known to induce interstitial lung disease. There is growing evidence that apoptosis plays a crucial role in physiological and pathological settings and that the ubiquitin-proteasome system is involved in the regulation of apoptosis. Cadmium, the same transitional heavy metal as cobalt, has been reported to accumulate ubiquitinated proteins in neuronal cells. On the basis of these findings, we hypothesized that cobalt would induce apoptosis in the lung by disturbance of the ubiquitin-proteasome pathway. To evaluate this, we exposed U-937 cells and human alveolar macrophages (AMs) to cobalt chloride (CoCl(2)) and examined their apoptosis by DNA fragmentation assay, 4',6-diamidino-2'-phenylindol dihydrochloride staining, and Western blot analysis. CoCl(2) induced apoptosis and accumulated ubiquitinated proteins. Exposure to CoCl(2) inhibited proteasome activity in U-937 cells. Cobalt-induced apoptosis was mediated via mitochondrial pathway because CoCl(2) released cytochrome c from mitochondria. These results suggest that cobalt-induced apoptosis of AMs may be one of the mechanisms for cobalt-induced lung injury and that the accumulation of ubiquitinated proteins might be involved in this apoptotic process.

  2. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    PubMed Central

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells. PMID:24281104

  3. Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation

    PubMed Central

    Blondel, Marc; Soubigou, Flavie; Evrard, Justine; Nguyen, Phu hai; Hasin, Naushaba; Chédin, Stéphane; Gillet, Reynald; Contesse, Marie-Astrid; Friocourt, Gaëlle; Stahl, Guillaume; Jones, Gary W.; Voisset, Cécile

    2016-01-01

    6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI+] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI+]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI+] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases. PMID:27633137

  4. [Perception of fathers as for their involvement in activities with their children].

    PubMed

    da Silva, Mara Regina Santos; Bueno, Maria Emilia Nunes; Ribeiro, Juliane Portella

    2014-03-01

    This is an exploratory, descriptive study with a quantitative approach and the aim to identzfy the perception of fathers regarding their children's needs; strategies used by fathers to get closer to their children as well as to analyze the influence of household chores and children's education in their fathers' lives. Study subjects were 92 men with six-year-old children, residing in the city of Rio Grande, state of Rio Grande do Sul (RS). The results revealed fathers who are more engaged in activities with their children, valuing confidence, safety, as well as proximity to family as children's main needs, having prioritized the progress children make as well as attention to listening and conversation. Children's education does not aggregate more problems than they imagined, managing to plan life the way they seek to. These findings show that, in the sample studied, fathers have been able to develop more affectionate actions aimed at being more involved with their children.

  5. Carbon Nanotubes as Electrically Active Nanoreactors for Multi-Step Inorganic Synthesis: Sequential Transformations of Molecules to Nanoclusters and Nanoclusters to Nanoribbons.

    PubMed

    Botos, Akos; Biskupek, Johannes; Chamberlain, Thomas W; Rance, Graham A; Stoppiello, Craig T; Sloan, Jeremy; Liu, Zheng; Suenaga, Kazutomo; Kaiser, Ute; Khlobystov, Andrei N

    2016-07-06

    In organic synthesis, the composition and structure of products are predetermined by the reaction conditions; however, the synthesis of well-defined inorganic nanostructures often presents a significant challenge yielding nonstoichiometric or polymorphic products. In this study, confinement in the nanoscale cavities of single-walled carbon nanotubes (SWNTs) provides a new approach for multistep inorganic synthesis where sequential chemical transformations take place within the same nanotube. In the first step, SWNTs donate electrons to reactant iodine molecules (I2), transforming them to iodide anions (I(-)). These then react with metal hexacarbonyls (M(CO)6, M = Mo or W) in the next step, yielding anionic nanoclusters [M6I14](2-), the size and composition of which are strictly dictated by the nanotube cavity, as demonstrated by aberration-corrected high resolution transmission electron microscopy, scanning transmission electron microscopy, and energy dispersive X-ray spectroscopy. Atoms in the nanoclusters [M6I14](2-) are arranged in a perfect octahedral geometry and can engage in further chemical reactions within the nanotube, either reacting with each other leading to a new polymeric phase of molybdenum iodide [Mo6I12]n or with hydrogen sulfide gas giving rise to nanoribbons of molybdenum/tungsten disulfide [MS2]n in the third step of the synthesis. Electron microscopy measurements demonstrate that the products of the multistep inorganic transformations are precisely controlled by the SWNT nanoreactor with complementary Raman spectroscopy revealing the remarkable property of SWNTs to act as a reservoir of electrons during the chemical transformation. The electron transfer from the host nanotube to the reacting guest molecules is essential for stabilizing the anionic metal iodide nanoclusters and for their further transformation to metal disulfide nanoribbons synthesized in the nanotubes in high yield.

  6. A novel carotenoid cleavage activity involved in the biosynthesis of Citrus fruit-specific apocarotenoid pigments

    PubMed Central

    Rodrigo, María J.; Alquézar, Berta; Al-Babili, Salim

    2013-01-01

    Citrus is the first tree crop in terms of fruit production. The colour of Citrus fruit is one of the main quality attributes, caused by the accumulation of carotenoids and their derivative C30 apocarotenoids, mainly β-citraurin (3-hydroxy-β-apo-8′-carotenal), which provide an attractive orange-reddish tint to the peel of oranges and mandarins. Though carotenoid biosynthesis and its regulation have been extensively studied in Citrus fruits, little is known about the formation of C30 apocarotenoids. The aim of this study was to the identify carotenoid cleavage enzyme(s) [CCD(s)] involved in the peel-specific C30 apocarotenoids. In silico data mining revealed a new family of five CCD4-type genes in Citrus. One gene of this family, CCD4b1, was expressed in reproductive and vegetative tissues of different Citrus species in a pattern correlating with the accumulation of C30 apocarotenoids. Moreover, developmental processes and treatments which alter Citrus fruit peel pigmentation led to changes of β-citraurin content and CCD4b1 transcript levels. These results point to the involvement of CCD4b1 in β-citraurin formation and indicate that the accumulation of this compound is determined by the availability of the presumed precursors zeaxanthin and β-cryptoxanthin. Functional analysis of CCD4b1 by in vitro assays unequivocally demonstrated the asymmetric cleavage activity at the 7′,8′ double bond in zeaxanthin and β-cryptoxanthin, confirming its role in C30 apocarotenoid biosynthesis. Thus, a novel plant carotenoid cleavage activity targeting the 7′,8′ double bond of cyclic C40 carotenoids has been identified. These results suggest that the presented enzyme is responsible for the biosynthesis of C30 apocarotenoids in Citrus which are key pigments in fruit coloration. PMID:24006419

  7. A novel carotenoid cleavage activity involved in the biosynthesis of Citrus fruit-specific apocarotenoid pigments.

    PubMed

    Rodrigo, María J; Alquézar, Berta; Alós, Enriqueta; Medina, Víctor; Carmona, Lourdes; Bruno, Mark; Al-Babili, Salim; Zacarías, Lorenzo

    2013-11-01

    Citrus is the first tree crop in terms of fruit production. The colour of Citrus fruit is one of the main quality attributes, caused by the accumulation of carotenoids and their derivative C30 apocarotenoids, mainly β-citraurin (3-hydroxy-β-apo-8'-carotenal), which provide an attractive orange-reddish tint to the peel of oranges and Mandarins. Though carotenoid biosynthesis and its regulation have been extensively studied in Citrus fruits, little is known about the formation of C30 apocarotenoids. The aim of this study was to the identify carotenoid cleavage enzyme(s) [CCD(s)] involved in the peel-specific C30 apocarotenoids. In silico data mining revealed a new family of five CCD4-type genes in Citrus. One gene of this family, CCD4b1, was expressed in reproductive and vegetative tissues of different Citrus species in a pattern correlating with the accumulation of C30 apocarotenoids. Moreover, developmental processes and treatments which alter Citrus fruit peel pigmentation led to changes of β-citraurin content and CCD4b1 transcript levels. These results point to the involvement of CCD4b1 in β-citraurin formation and indicate that the accumulation of this compound is determined by the availability of the presumed precursors zeaxanthin and β-cryptoxanthin. Functional analysis of CCD4b1 by in vitro assays unequivocally demonstrated the asymmetric cleavage activity at the 7',8' double bond in zeaxanthin and β-cryptoxanthin, confirming its role in C30 apocarotenoid biosynthesis. Thus, a novel plant carotenoid cleavage activity targeting the 7',8' double bond of cyclic C40 carotenoids has been identified. These results suggest that the presented enzyme is responsible for the biosynthesis of C30 apocarotenoids in Citrus which are key pigments in fruit coloration.

  8. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

    PubMed

    Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

  9. Dark-induced senescence of barley leaves involves activation of plastid transglutaminases.

    PubMed

    Sobieszczuk-Nowicka, E; Zmienko, A; Samelak-Czajka, A; Łuczak, M; Pietrowska-Borek, M; Iorio, R; Del Duca, S; Figlerowicz, M; Legocka, J

    2015-04-01

    Transglutaminases (E.C. 2.3.2.13) catalyze the post-translational modification of proteins by establishing ε-(γ-glutamyl) lysine isopeptide bonds and by the covalent conjugation of polyamines to endo-glutamyl residues of proteins. In light of the confirmed role of transglutaminases in animal cell apoptosis and only limited information on the role of these enzymes in plant senescence, we decided to investigate the activity of chloroplast transglutaminases (ChlTGases) and the fate of chloroplast-associated polyamines in Hordeum vulgare L. 'Nagrad' leaves, where the senescence process was induced by darkness (day 0) and continued until chloroplast degradation (day 12). Using an anti-TGase antibody, we detected on a subcellular level, the ChlTGases that were associated with destacked/degraded thylakoid membranes, and beginning on day 5, were also found in the stroma. Colorimetric and radiometric assays revealed during senescence an increase in ChlTGases enzymatic activity. The MS/MS identification of plastid proteins conjugated with exogenous polyamines had shown that the ChlTGases are engaged in the post-translational modification of proteins involved in photosystem organization, stress response, and oxidation processes. We also computationally identified the cDNA of Hv-Png1-like, a barley homologue of the Arabidopsis AtPng1 gene. Its mRNA level was raised from days 3 to 10, indicating that transcriptional regulation controls the activity of barley ChlTGases. Together, the presented results deepen our knowledge of the mechanisms of the events happened in dark-induced senescence of barley leaves that might be activation of plastid transglutaminases.

  10. Kinetic analysis of a general model of activation of aspartic proteinase zymogens involving a reversible inhibitor. I. Kinetic analysis.

    PubMed

    Muñoz-López, A; Sotos-Lomas, A; Arribas, E; Masia-Perez, J; Garcia-Molina, F; García-Moreno, M; Varon, R

    2007-04-01

    Starting from a simple general reaction mechanism of activation of aspartic proteinases zymogens involving a uni- and a bimolecular simultaneous activation route and a reversible inhibition step, the time course equation of the zymogen, inhibitor and activated enzyme concentrations have been derived. Likewise, expressions for the time required for any reaction progress and the corresponding mean activation rates as well as the half-life of the global zymogen activation have been derived. An experimental design and kinetic data analysis is suggested to estimate the kinetic parameters involved in the reaction mechanism proposed.

  11. Sequential Syndrome Decoding of Convolutional Codes

    NASA Technical Reports Server (NTRS)

    Reed, I. S.; Truong, T. K.

    1984-01-01

    The algebraic structure of convolutional codes are reviewed and sequential syndrome decoding is applied to those codes. These concepts are then used to realize by example actual sequential decoding, using the stack algorithm. The Fano metric for use in sequential decoding is modified so that it can be utilized to sequentially find the minimum weight error sequence.

  12. A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

    PubMed

    Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

    2016-03-01

    Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge.

  13. Are serotonergic neurons involved in the control of anxiety and in the anxiolytic activity of benzodiazepines?

    PubMed

    Thiebot, M H

    1986-05-01

    Several studies have shown that, like benzodiazepines (BZP), treatments able to reduce or block the activity of CNS serotonergic (5-HT) neurons released punished behavior. Therefore, 5-HT mechanisms have been tentatively implicated in the anti-punishment (anxiolytic?) activity of BZP. Numerous data, however, are not in keeping with this hypothesis. Since not responding enables the animals to avoid punishment but also delays the receipt of food-reward, one of these factors could be an alteration of waiting capacities. Indeed, we have shown that diazepam released behavioral suppression in conflict schedules only when the duration of the punished periods exceeded 1 minute. Moreover, in rats allowed to choose in a T-maze between immediate-but-small vs. delayed-but-large reward, BZP significantly decreased the frequency with which the delayed reward was chosen, with 5-HT uptake blockers producing opposite effects. Therefore, one can hypothesize that BZP render the animals less prone than controls to tolerate delay of reward and that 5-HT mechanisms may be involved in this phenomenon. An altered tolerance to delay of reward should be taken into account when interpreting the BZP-induced release of behavioral inhibition in classical conflict procedures.

  14. Genes Involved in Interleukin-1 Receptor Type II Activities Are Associated With Asthmatic Phenotypes

    PubMed Central

    Madore, Anne-Marie; Vaillancourt, Vanessa T.; Bouzigon, Emmanuelle; Sarnowski, Chloé; Monier, Florent; Dizier, Marie-Hélène; Demenais, Florence

    2016-01-01

    Purpose Interleukin-1 (IL-1) plays a key role in inflammation and immunity and its decoy receptor, IL-1R2, has been implicated in transcriptomic and genetic studies of asthma. Methods Two large asthma family collections, the French-Canadian Saguenay—Lac-St-Jean (SLSJ) study and the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA), were used to investigate the association of SNPs in 10 genes that modulate IL-1R2 activities with asthma, allergic asthma, and atopy. Gene-gene interactions were also tested. Results One SNP in BACE2 was associated with allergic asthma in the SLSJ study and replicated in the EGEA study before statistical correction for multiple testing. Additionally, two SNPs in the MMP2 gene were replicated in both studies prior to statistical correction and reached significance in the combined analysis. Moreover, three gene-gene interactions also survived statistical correction in the combined analyses (BACE1-IL1RAP in asthma and allergic asthma and IL1R1-IL1RAP in atopy). Conclusions Our results highlight the relevance of genes involved in the IL-1R2 activity in the context of asthma and asthma-related traits. PMID:27334786

  15. Involvement of autophagy in antitumor activity of folate-appended methyl-β-cyclodextrin.

    PubMed

    Onodera, Risako; Motoyama, Keiichi; Tanaka, Nao; Ohyama, Ayumu; Okamatsu, Ayaka; Higashi, Taishi; Kariya, Ryusho; Okada, Seiji; Arima, Hidetoshi

    2014-03-20

    Autophagy, the major lysosomal pathway for recycling intracellular components including organelles, is emerging as a key process regulating tumorigenesis and cancer therapy. Most recently, we newly synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD), and demonstrated the potential of FA-M-β-CyD as a new antitumor drug. In this study, we investigated whether anticancer activity of FA-M-β-CyD in folate receptor-α (FR-α)-positive tumor cells is involved in autophagy. In contrast to methyl-β-cyclodextrin (M-β-CyD), FA-M-β-CyD entered KB cells (FR-α (+)) through CLIC/GEEC endocytosis. No significant depression in the DNA content was observed in KB cells after treatment with FA-M-β-CyD. Additionally, the transmembrane potential of mitochondria after treatment with FA-M-β-CyD was drastically elevated. Meanwhile, FA-M-β-CyD induced the formation of autophagic vacuoles, which were partially colocalized with mitochondria, in KB cells. Taken together, these results suggest that FR-α-expressing cell-selective cytotoxic activity of FA-M-β-CyD could be mediated by the regulation of autophagy, rather than the induction of apoptosis.

  16. Mechanisms involved in Escherichia coli and Serratia marcescens removal during activated sludge wastewater treatment

    PubMed Central

    Orruño, Maite; Garaizabal, Idoia; Bravo, Zaloa; Parada, Claudia; Barcina, Isabel; Arana, Inés

    2014-01-01

    Wastewater treatment reduces environmental contamination by removing gross solids and mitigating the effects of pollution. Treatment also reduces the number of indicator organisms and pathogens. In this work, the fates of two coliform bacteria, Escherichia coli and Serratia marcescens, were analyzed in an activated sludge process to determine the main mechanisms involved in the reduction of pathogenic microorganisms during wastewater treatment. These bacteria, modified to express green fluorescent protein, were inoculated in an activated sludge unit and in batch systems containing wastewater. The results suggested that, among the different biological factors implied in bacterial removal, bacterivorous protozoa play a key role. Moreover, a representative number of bacteria persisted in the system as free-living or embedded cells, but their distribution into liquid or solid fractions varied depending on the bacterium tested, questioning the real value of bacterial indicators for the control of wastewater treatment process. Additionally, viable but nonculturable cells constituted an important part of the bacterial population adhered to solid fractions, what can be derived from the competition relationships with native bacteria, present in high densities in this environment. These facts, taken together, emphasize the need for reliable quantitative and qualitative analysis tools for the evaluation of pathogenic microbial composition in sludge, which could represent an undefined risk to public health and ecosystem functions when considering its recycling. PMID:25044599

  17. Plasminogen Activator Inhibitor-1 Is Involved in Streptozotocin-Induced Bone Loss in Female Mice

    PubMed Central

    Tamura, Yukinori; Kawao, Naoyuki; Okada, Kiyotaka; Yano, Masato; Okumoto, Katsumi; Matsuo, Osamu; Kaji, Hiroshi

    2013-01-01

    In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1–deficient mice. Quantitative computed tomography analysis showed that PAI-1 deficiency protected against streptozotocin-induced bone loss in female mice but not in male mice. PAI-1 deficiency blunted the changes in the levels of Runx2, osterix, and alkaline phosphatase in tibia as well as serum osteocalcin levels suppressed by the diabetic state in female mice only. Furthermore, the osteoclast levels in tibia, suppressed in diabetes, were also blunted by PAI-1 deficiency in female mice. Streptozotocin markedly elevated the levels of PAI-1 mRNA in liver in female mice only. In vitro study demonstrated that treatment with active PAI-1 suppressed the levels of osteogenic genes and mineralization in primary osteoblasts from female mouse calvaria. In conclusion, the current study indicates that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in females. The expression of PAI-1 in the liver and the sensitivity of bone cells to PAI-1 may be an underlying mechanism. PMID:23715621

  18. TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity

    PubMed Central

    Andrade, Yaniré N.; Fernandes, Jacqueline; Vázquez, Esther; Fernández-Fernández, José M.; Arniges, Maite; Sánchez, Trinidad M.; Villalón, Manuel; Valverde, Miguel A.

    2005-01-01

    Autoregulation of the ciliary beat frequency (CBF) has been proposed as the mechanism used by epithelial ciliated cells to maintain the CBF and prevent the collapse of mucociliary transport under conditions of varying mucus viscosity. Despite the relevance of this regulatory response to the pathophysiology of airways and reproductive tract, the underlying cellular and molecular aspects remain unknown. Hamster oviductal ciliated cells express the transient receptor potential vanilloid 4 (TRPV4) channel, which is activated by increased viscous load involving a phospholipase A2–dependent pathway. TRPV4-transfected HeLa cells also increased their cationic currents in response to high viscous load. This mechanical activation is prevented in native ciliated cells loaded with a TRPV4 antibody. Application of the TRPV4 synthetic ligand 4α-phorbol 12,13-didecanoate increased cationic currents, intracellular Ca2+, and the CBF in the absence of a viscous load. Therefore, TRPV4 emerges as a candidate to participate in the coupling of fluid viscosity changes to the generation of the Ca2+ signal required for the autoregulation of CBF. PMID:15753126

  19. Involvement of both PKS and NRPS in antibacterial activity in Lysobacter enzymogenes OH11

    PubMed Central

    Zhang, Juan; Du, Liangcheng; Liu, Fengquan; Xu, Feifei; Hu, Baishi; Venturi, Vittorio; Qian, Guoliang

    2014-01-01

    Polyketides and nonribosomal peptides represent two large families of natural products (NPs) with diverse structures and important functions. They are synthesized by polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS), respectively. Lysobacter enzymogenes is emerging as a novel biocontrol agent against pathogens of crop plants and a new source of bioactive NPs, such as antibacterial antibiotic WAP-8294A2 and antifungal antibiotic HSAF. Genome survey of strain OH11, a Chinese L. enzymogenes isolate, detected four novel PKS, NRPS or hybrid gene clusters, designed as cluster A to D. We further individually mutated five genes (PKS or NRPS) located in these four gene clusters, and showed that a PKS gene in cluster A and an NRPS gene in cluster D were involved in the antibacterial activity via a WAP-8294A2 dependent way. The data also showed that none of the five genes was associated with antifungal activity and the regulation of HSAF biosynthesis. Our results reveal the unusual regulatory role of these PKS and NRPS genes that were discovered from genome mining in L. enzymogenes. PMID:24801439

  20. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

    PubMed Central

    Cao, Zhengyu; Li, Xichun; Zou, Xiaohan; Greenwood, Michael; Gerwick, William H.; Murray, Thomas F.

    2015-01-01

    The frequent occurrence of Moorea producens (formerly Lyngbya majuscula) blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH) efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria. PMID:25675001

  1. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis

    PubMed Central

    Chiba, Ko; Tsuchiya, Masahiro; Koide, Masashi; Hagiwara, Yoshihiro; Sasaki, Keiichi; Hattori, Yoshinori; Watanabe, Makoto; Sugawara, Shunji; Kanzaki, Makoto; Endo, Yasuo

    2015-01-01

    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis. PMID:26599867

  2. Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved.

    PubMed

    Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika; Gamba, Gerardo

    2014-06-15

    Modulation of Na(+)-Cl(-) cotransporter (NCC) activity is essential to adjust K(+) excretion in the face of changes in dietary K(+) intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K(+) diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K(+)-citrate diets for 4 days. The low-K(+) diet decreased and high-K(+) diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr(44)/Thr(48)/Thr(53)) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser(383)/Ser(325)). The effect of the low-K(+) diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K(+) diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K(+) diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K(+)-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K(+) increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K(+) diet.

  3. Modulation of NCC activity by low and high K+ intake: insights into the signaling pathways involved

    PubMed Central

    Castañeda-Bueno, María; Cervantes-Perez, Luz Graciela; Rojas-Vega, Lorena; Arroyo-Garza, Isidora; Vázquez, Norma; Moreno, Erika

    2014-01-01

    Modulation of Na+-Cl− cotransporter (NCC) activity is essential to adjust K+ excretion in the face of changes in dietary K+ intake. We used previously characterized genetic mouse models to assess the role of Ste20-related proline-alanine-rich kinase (SPAK) and with-no-lysine kinase (WNK)4 in the modulation of NCC by K+ diets. SPAK knockin and WNK4 knockout mice were placed on normal-, low-, or high-K+-citrate diets for 4 days. The low-K+ diet decreased and high-K+ diet increased plasma aldosterone levels, but both diets were associated with increased phosphorylation of NCC (phospho-NCC, Thr44/Thr48/Thr53) and phosphorylation of SPAK/oxidative stress responsive kinase 1 (phospho-SPAK/OSR1, Ser383/Ser325). The effect of the low-K+ diet on SPAK phosphorylation persisted in WNK4 knockout and SPAK knockin mice, whereas the effects of ANG II on NCC and SPAK were lost in both mouse colonies. This suggests that for NCC activation by ANG II, integrity of the WNK4/SPAK pathway is required, whereas for the low-K+ diet, SPAK phosphorylation occurred despite the absence of WNK4, suggesting the involvement of another WNK (WNK1 or WNK3). Additionally, because NCC activation also occurred in SPAK knockin mice, it is possible that loss of SPAK was compensated by OSR1. The positive effect of the high-K+ diet was observed when the accompanying anion was citrate, whereas the high-KCl diet reduced NCC phosphorylation. However, the effect of the high-K+-citrate diet was aldosterone dependent, and neither metabolic alkalosis induced by bicarbonate, nor citrate administration in the absence of K+ increased NCC phosphorylation, suggesting that it was not due to citrate-induced metabolic alkalosis. Thus, the accompanying anion might modulate the NCC response to the high-K+ diet. PMID:24761002

  4. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis.

    PubMed

    Chiba, Ko; Tsuchiya, Masahiro; Koide, Masashi; Hagiwara, Yoshihiro; Sasaki, Keiichi; Hattori, Yoshinori; Watanabe, Makoto; Sugawara, Shunji; Kanzaki, Makoto; Endo, Yasuo

    2015-01-01

    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis.

  5. Mothers' and Fathers' Involvement in Home Activities with Their Children: Psychosocial Factors and the Role of Parental Self-Efficacy

    ERIC Educational Resources Information Center

    Giallo, Rebecca; Treyvaud, Karli; Cooklin, Amanda; Wade, Catherine

    2013-01-01

    Parent involvement in play, learning, and everyday home activities is important for promoting children's cognitive and language development. The aims of the study were to (a) examine differences between mothers' and fathers' self-reported involvement with their children, (b) explore the relationship between child, parent and family factors, and…

  6. Parent Involvement Activities in School Improvement Plans in the Northwest Region. Summary. Issues & Answers. REL 2008-No. 064

    ERIC Educational Resources Information Center

    Speth, Timothy; Saifer, Steffen; Forehand, Gregory

    2008-01-01

    This document presents a summary of the larger report, "Parent Involvement Activities in School Improvement Plans in the Northwest Region." Although the No Child Left Behind Act of 2001 (NCLB) spells out parent involvement requirements for schools in need of improvement, the majority of the Northwest Region school improvement plans…

  7. Blocking for Sequential Political Experiments.

    PubMed

    Moore, Ryan T; Moore, Sally A

    2013-10-01

    In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects "trickle in" to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion.

  8. A bit serial sequential circuit

    NASA Technical Reports Server (NTRS)

    Hu, S.; Whitaker, S.

    1990-01-01

    Normally a sequential circuit with n state variables consists of n unique hardware realizations, one for each state variable. All variables are processed in parallel. This paper introduces a new sequential circuit architecture that allows the state variables to be realized in a serial manner using only one next state logic circuit. The action of processing the state variables in a serial manner has never been addressed before. This paper presents a general design procedure for circuit construction and initialization. Utilizing pass transistors to form the combinational next state forming logic in synchronous sequential machines, a bit serial state machine can be realized with a single NMOS pass transistor network connected to shift registers. The bit serial state machine occupies less area than other realizations which perform parallel operations. Moreover, the logical circuit of the bit serial state machine can be modified by simply changing the circuit input matrix to develop an adaptive state machine.

  9. Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking.

    PubMed

    Sandoval, Angel; Fraisl, Peter; Arias-Barrau, Elsa; Dirusso, Concetta C; Singer, Diane; Sealls, Whitney; Black, Paul N

    2008-09-15

    These studies defined the expression patterns of genes involved in fatty acid transport, activation and trafficking using quantitative PCR (qPCR) and established the kinetic constants of fatty acid transport in an effort to define whether vectorial acylation represents a common mechanism in different cell types (3T3-L1 fibroblasts and adipocytes, Caco-2 and HepG2 cells and three endothelial cell lines (b-END3, HAEC, and HMEC)). As expected, fatty acid transport protein (FATP)1 and long-chain acyl CoA synthetase (Acsl)1 were the predominant isoforms expressed in adipocytes consistent with their roles in the transport and activation of exogenous fatty acids destined for storage in the form of triglycerides. In cells involved in fatty acid processing including Caco-2 (intestinal-like) and HepG2 (liver-like), FATP2 was the predominant isoform. The patterns of Acsl expression were distinct between these two cell types with Acsl3 and Acsl5 being predominant in Caco-2 cells and Acsl4 in HepG2 cells. In the endothelial lines, FATP1 and FATP4 were the most highly expressed isoforms; the expression patterns for the different Acsl isoforms were highly variable between the different endothelial cell lines. The transport of the fluorescent long-chain fatty acid C(1)-BODIPY-C(12) in 3T3-L1 fibroblasts and 3T3-L1 adipocytes followed typical Michaelis-Menten kinetics; the apparent efficiency (k(cat)/K(T)) of this process increases over 2-fold (2.1 x 10(6)-4.5 x 10(6)s(-1)M(-1)) upon adipocyte differentiation. The V(max) values for fatty acid transport in Caco-2 and HepG2 cells were essentially the same, yet the efficiency was 55% higher in Caco-2 cells (2.3 x 10(6)s(-1)M(-1) versus 1.5 x 10(6)s(-1)M(-1)). The kinetic parameters for fatty acid transport in three endothelial cell types demonstrated they were the least efficient cell types for this process giving V(max) values that were nearly 4-fold lower than those defined form 3T3-L1 adipocytes, Caco-2 cells and HepG2 cells. The

  10. Complementary sequential measurements generate entanglement

    NASA Astrophysics Data System (ADS)

    Coles, Patrick J.; Piani, Marco

    2014-01-01

    We present a paradigm for capturing the complementarity of two observables. It is based on the entanglement created by the interaction between the system observed and the two measurement devices used to measure the observables sequentially. Our main result is a lower bound on this entanglement and resembles well-known entropic uncertainty relations. Besides its fundamental interest, this result directly bounds the effectiveness of sequential bipartite operations—corresponding to the measurement interactions—for entanglement generation. We further discuss the intimate connection of our result with two primitives of information processing, namely, decoupling and coherent teleportation.

  11. Language Non-Selective Activation of Orthography during Spoken Word Processing in Hindi-English Sequential Bilinguals: An Eye Tracking Visual World Study

    ERIC Educational Resources Information Center

    Mishra, Ramesh Kumar; Singh, Niharika

    2014-01-01

    Previous psycholinguistic studies have shown that bilinguals activate lexical items of both the languages during auditory and visual word processing. In this study we examined if Hindi-English bilinguals activate the orthographic forms of phonological neighbors of translation equivalents of the non target language while listening to words either…

  12. Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes.

    PubMed Central

    Coulanges, V; Andre, P; Ziegler, O; Buchheit, L; Vidon, D J

    1997-01-01

    Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity. PMID:9199450

  13. Cocaine-mediated microglial activation involves the ER stress-autophagy axis

    PubMed Central

    Guo, Ming-Lei; Liao, Ke; Periyasamy, Palsamy; Yang, Lu; Cai, Yu; Callen, Shannon E; Buch, Shilpa

    2015-01-01

    Cocaine abuse leads to neuroinflammation, which, in turn, contributes to the pathogenesis of neurodegeneration associated with advanced HIV-1 infection. Autophagy plays important roles in both innate and adaptive immune responses. However, the possible functional link between cocaine and autophagy has not been explored before. Herein, we demonstrate that cocaine exposure induced autophagy in both BV-2 and primary rat microglial cells as demonstrated by a dose- and time-dependent induction of autophagy-signature proteins such as BECN1/Beclin 1, ATG5, and MAP1LC3B. These findings were validated wherein cocaine treatment of BV-2 cells resulted in increased formation of puncta in cells expressing either endogenous MAP1LC3B or overexpressing GFP-MAP1LC3B. Specificity of cocaine-induced autophagy was confirmed by treating cells with inhibitors of autophagy (3-MA and wortmannin). Intriguingly, cocaine-mediated induction of autophagy involved upstream activation of 2 ER stress pathways (EIF2AK3- and ERN1-dependent), as evidenced by the ability of the ER stress inhibitor salubrinal to ameliorate cocaine-induced autophagy. In vivo validation of these findings demonstrated increased expression of BECN1, ATG5, and MAP1LC3B-II proteins in cocaine-treated mouse brains compared to untreated animals. Increased autophagy contributes to cocaine-mediated activation of microglia since pretreatment of cells with wortmannin resulted in decreased expression and release of inflammatory factors (TNF, IL1B, IL6, and CCL2) in microglial cells. Taken together, our findings suggest that cocaine exposure results in induction of autophagy that is closely linked with neuroinflammation. Targeting autophagic proteins could thus be considered as a therapeutic strategy for the treatment of cocaine-related neuroinflammation diseases. PMID:26043790

  14. Evidence for the Involvement of p38 MAPK Activation in Barnacle Larval Settlement

    PubMed Central

    He, Li-Sheng; Xu, Ying; Matsumura, Kiyotaka; Zhang, Yu; Zhang, Gen; Qi, Shu-Hua; Qian, Pei-Yuan

    2012-01-01

    The barnacle Balanus ( = Amphibalanus) amphitrite is a major marine fouling animal. Understanding the molecular mechanism of larval settlement in this species is critical for anti-fouling research. In this study, we cloned one isoform of p38 MAPK (Bar-p38 MAPK) from this species, which shares the significant characteristic of containing a TGY motif with other species such as yeast, Drosophila and humans. The activation of p38 MAPK was detected by an antibody that recognizes the conserved dual phosphorylation sites of TGY. The results showed that phospho-p38 MAPK (pp38 MAPK) was more highly expressed at the cyprid stage, particularly in aged cyprids, in comparison to other stages, including the nauplius and juvenile stages. Immunostaining showed that Bar-p38 MAPK and pp38 MAPK were mainly located at the cyprid antennules, and especially the third and fourth segments, which are responsible for substratum exploration during settlement. The expression and localization patterns of Bar-p38 MAPK suggest its involvement in larval settlement. This postulation was also supported by the larval settlement bioassay with the p38 MAPK inhibitor SB203580. Behavioral analysis by live imaging revealed that the larvae were still capable of exploring the surface of the substratum after SB203580 treatment. This shows that the effect of p38 MAPK on larval settlement might be by regulating the secretion of permanent proteinaceous substances. Furthermore, the level of pp38 MAPK dramatically decreased after full settlement, suggesting that Bar-p38 MAPK maybe plays a role in larval settlement rather than metamorphosis. Finally, we found that Bar-p38 MAPK was highly activated when larvae confronted extracts of adult barnacle containing settlement cues, whereas larvae pre-treated with SB203580 failed to respond to the crude adult extracts. PMID:23115639

  15. Cocaine-mediated microglial activation involves the ER stress-autophagy axis.

    PubMed

    Guo, Ming-Lei; Liao, Ke; Periyasamy, Palsamy; Yang, Lu; Cai, Yu; Callen, Shannon E; Buch, Shilpa

    2015-01-01

    Cocaine abuse leads to neuroinflammation, which, in turn, contributes to the pathogenesis of neurodegeneration associated with advanced HIV-1 infection. Autophagy plays important roles in both innate and adaptive immune responses. However, the possible functional link between cocaine and autophagy has not been explored before. Herein, we demonstrate that cocaine exposure induced autophagy in both BV-2 and primary rat microglial cells as demonstrated by a dose- and time-dependent induction of autophagy-signature proteins such as BECN1/Beclin 1, ATG5, and MAP1LC3B. These findings were validated wherein cocaine treatment of BV-2 cells resulted in increased formation of puncta in cells expressing either endogenous MAP1LC3B or overexpressing GFP-MAP1LC3B. Specificity of cocaine-induced autophagy was confirmed by treating cells with inhibitors of autophagy (3-MA and wortmannin). Intriguingly, cocaine-mediated induction of autophagy involved upstream activation of 2 ER stress pathways (EIF2AK3- and ERN1-dependent), as evidenced by the ability of the ER stress inhibitor salubrinal to ameliorate cocaine-induced autophagy. In vivo validation of these findings demonstrated increased expression of BECN1, ATG5, and MAP1LC3B-II proteins in cocaine-treated mouse brains compared to untreated animals. Increased autophagy contributes to cocaine-mediated activation of microglia since pretreatment of cells with wortmannin resulted in decreased expression and release of inflammatory factors (TNF, IL1B, IL6, and CCL2) in microglial cells. Taken together, our findings suggest that cocaine exposure results in induction of autophagy that is closely linked with neuroinflammation. Targeting autophagic proteins could thus be considered as a therapeutic strategy for the treatment of cocaine-related neuroinflammation diseases.

  16. PRESS40: a project for involving students in active seismic risk mitigation

    NASA Astrophysics Data System (ADS)

    Barnaba, Carla; Contessi, Elisa; Rosa Girardi, Maria

    2016-04-01

    To memorialize the anniversary of the 1976 Friuli earthquake, the Istituto Statale di Istruzione Superiore "Magrini Marchetti" in Gemona del Friuli (NE Italy), with the collaboration of the Istituto Nazionale di Oceanografia e di Geofisica Sperimentale (OGS), has promoted the PRESS40 Project (Prevenzione Sismica nella Scuola a 40 anni dal terremoto del Friuli, that in English sounds like "Seismic Prevention at School 40 years later the Friuli earthquake"). The project has developed in the 2015-2016 school year, starting from the 40th anniversary of the Friuli earthquake, and it aims to disseminate historical memory, seismic culture and awareness of seismic safety in the young generations, too often unconscious of past experiences, as recent seismic hazard perception tests have demonstrated. The basic idea of the PRESS40 Project is to involve the students in experimental activities to be active part of the seismic mitigation process. The Project is divided into two main parts, the first one in which students learn-receive knowledge from researchers, and the second one in which they teach-bring knowledge to younger students. In the first part of the project, 75 students of the "Magrini Marchetti" school acquired new geophysical data, covering the 23 municipalities from which they come from. These municipalities represent a wide area affected by the 1976 Friuli earthquake. In each locality a significant site was examined, represented by a school area. At least, 127 measurements of ambient noise have been acquired. Data processing and interpretation of all the results are still going on, under the supervision of OGS researchers.The second part of the project is planned for the early spring, when the students will present the results of geophysical survey to the younger ones of the monitored schools and to the citizens in occasion of events to commemorate the 40th anniversary of the Friuli earthquake.

  17. Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

    PubMed Central

    Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.

    2014-01-01

    Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733

  18. Postnatal changes of local neuronal circuits involved in activation of jaw-closing muscles.

    PubMed

    Inoue, Tomio; Nakamura, Shiro; Takamatsu, Junichi; Tokita, Kenichi; Gemba, Akiko; Nakayama, Kiyomi

    2007-04-01

    Feeding behaviour in mammals changes from suckling to mastication during postnatal development and the neuronal circuits controlling feeding behaviour should change in parallel to the development of orofacial structures. In this review we discuss the location of excitatory premotor neurons for jaw-closing motoneurons (JCMNs) and postnatal changes of excitatory synaptic transmission from the supratrigeminal region (SupV) to JCMNs. We show that neurons located in SupV and the reticular formation dorsal to the facial nucleus most likely excite JCMNs. Excitatory inputs from SupV to JCMNs are mediated by activation of glutamate and glycine receptors in neonatal rats, whereas glycinergic inputs from SupV to JCMNs become inhibitory with age. We also show that the incidence of post-spike afterdepolarization increases during postnatal development, whereas the amplitude and half-duration of the medium-duration afterhyperpolarization decrease with age. Such postnatal changes in synaptic transmission from SupV to JCMNs and membrane properties of JCMNs might be involved in the transition from suckling to mastication.

  19. Tachykinins activate guinea-pig alveolar macrophages: involvement of NK2 and NK1 receptors.

    PubMed Central

    Brunelleschi, S.; Vanni, L.; Ledda, F.; Giotti, A.; Maggi, C. A.; Fantozzi, R.

    1990-01-01

    1. The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion (O2-.) production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED50 = 0.7 nM) evoked O2-. production from guinea-pig AM; the N-terminal heptapeptide, SP(1-7), was ineffective. In the presence of thiorphan (10(-5) M), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and NKB were both able to induce O2-. production from guinea-pig AM, ED50 values being 0.1 and 1.3 nM, respectively. Therefore, the rank order of activity of natural tachykinins was NKA greater than SP greater than NKB. Tachykinin-evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF-acether and less than those induced by the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). 3. The NK2 receptor agonist [beta-Ala8]-NKA (4-10) dose-dependently evoked O2-. production from guinea-pig AM; the NK1 receptor agonist [Pro9]-SP sulphone acted only at high concentrations, while the NK3 receptor agonist [Me,Phe7]-NKB was ineffective. 4. These findings indicate that guinea-pig AM possess NK2 and possibly some NK1 tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology. PMID:1697194

  20. Activation of Holliday junction recognizing protein involved in the chromosomal stability and immortality of cancer cells.

    PubMed

    Kato, Tatsuya; Sato, Nagato; Hayama, Satoshi; Yamabuki, Takumi; Ito, Tomoo; Miyamoto, Masaki; Kondo, Satoshi; Nakamura, Yusuke; Daigo, Yataro

    2007-09-15

    We identified a novel gene HJURP (Holliday junction-recognizing protein) whose activation seemed to play a pivotal role in the immortality of cancer cells. HJURP was considered a possible downstream target for ataxia telangiectasia mutated signaling, and its expression was increased by DNA double-strand breaks (DSB). HJURP was involved in the homologous recombination pathway in the DSB repair process through interaction with hMSH5 and NBS1, which is a part of the MRN protein complex. HJURP formed nuclear foci in cells at S phase and those subjected to DNA damage. In vitro assays implied that HJURP bound directly to the Holliday junction and rDNA arrays. Treatment of cancer cells with small interfering RNA (siRNA) against HJURP caused abnormal chromosomal fusions and led to genomic instability and senescence. In addition, HJURP overexpression was observed in a majority of lung cancers and was associated with poor prognosis as well. We suggest that HJURP is an indispensable factor for chromosomal stability in immortalized cancer cells and is a potential novel therapeutic target for the development of anticancer drugs.

  1. Involvement of Trichoderma Trichothecenes in the Biocontrol Activity and Induction of Plant Defense-Related Genes

    PubMed Central

    Malmierca, M. G.; Cardoza, R. E.; Alexander, N. J.; McCormick, S. P.; Hermosa, R.; Monte, E.

    2012-01-01

    Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studied. PMID:22562989

  2. Water-soluble chlorophyll protein is involved in herbivore resistance activation during greening of Arabidopsis thaliana

    PubMed Central

    Boex-Fontvieille, Edouard; Rustgi, Sachin; von Wettstein, Diter; Reinbothe, Steffen; Reinbothe, Christiane

    2015-01-01

    Water-soluble chlorophyll proteins (WSCPs) constitute a small family of unusual chlorophyll (Chl)-binding proteins that possess a Kunitz-type protease inhibitor domain. In Arabidopsis thaliana, a WSCP has been identified, named AtWSCP, that forms complexes with Chl and the Chl precursor chlorophyllide (Chlide) in vitro. AtWSCP exhibits a quite unexpected expression pattern for a Chl binding protein and accumulated to high levels in the apical hook of etiolated plants. AtWSCP expression was negatively light-regulated. Transgenic expression of AtWSCP fused to green fluorescent protein (GFP) revealed that AtWSCP is localized to cell walls/apoplastic spaces. Biochemical assays identified AtWSCP as interacting with RD21 (RESPONSIVE TO DESICCATION 21), a granulin domain-containing cysteine protease implicated in stress responses and defense. Reconstitution experiments showed tight interactions between RD21 and WSCP that were relieved upon Chlide binding. Laboratory feeding experiments with two herbivorous isopod crustaceans, Porcellio scaber (woodlouse) and Armadillidium vulgare (pillbug), identified the apical hook as Achilles’ heel of etiolated plants and that this was protected by RD21 during greening. Because Chlide is formed in the apical hook during seedling emergence from the soil, our data suggest an unprecedented mechanism of herbivore resistance activation that is triggered by light and involves AtWSCP. PMID:26016527

  3. β3 subunit of Na,K ATPase regulates T cell activation with no involvement of Na,K ATPase activity.

    PubMed

    Chruewkamlow, Nuttapol; Pata, Supansa; Mahasongkram, Kodchakorn; Laopajon, Witida; Kasinrerk, Watchara; Chiampanichayakul, Sawitree

    2015-05-01

    Na,K ATPase plays an important role in the regulation of Na(+) and K(+) ions that are required for normal resting membrane potential and various cellular functions. Na,K ATPase is composed of two subunits, α and β subunits. Engagement of the β subunit by an agonistic monoclonal antibody (mAb) P-3E10 inhibited T cell activation and induced the G0/G1 cell cycle arrest. In addition, mAb P-3E10 decreased CD25 expression. The mAb P-3E10, however, did not inhibit the proliferation of cell lines and the phagocytosis activity of phagocytes, and did not interfere with the Na,K ATPase activity. These results indicate that mAb P-3E10 reacts to the β subunit and, as a consequence, brings about the regulation of the T cell activation without disturbing the Na,K pump activity. By sequential immunoprecipitation, we demonstrated the expression of the β3 subunit free form apart from the α subunit. In this study, we propose that the β3 subunits of Na,K ATPase are expressed separately from the α subunit, and play a role in regulation of the immune response.

  4. Collagen-induced platelet activation mainly involves the protein kinase C pathway.

    PubMed Central

    Karniguian, A; Grelac, F; Levy-Toledano, S; Legrand, Y J; Rendu, F

    1990-01-01

    This study analyses early biochemical events in collagen-induced platelet activation. An early metabolic event occurring during the lag phase was the activation of PtdIns(4,5)P2-specific phospholipase C. Phosphatidic acid (PtdOH) formation, phosphorylation of P43 and P20, thromboxane B2 (TXB2) synthesis and platelet secretion began after the lag phase, and were similarly time-dependent, except for TXB2 synthesis, which was delayed. Collagen induced extensive P43 phosphorylation, whereas P20 phosphorylation was weak and always lower than with thrombin. The dose-response curves of P43 phosphorylation and granule secretion were similar, and both reached a peak at 7.5 micrograms of collagen/ml, a dose which induced half-maximal PtdOH and TXB2 formation. Sphingosine, assumed to inhibit protein kinase C, inhibited P43 phosphorylation and secretion in parallel. However, sphingosine was not specific for protein kinase C, since a 15 microM concentration, which did not inhibit P43 phosphorylation, blocked TXB2 synthesis by 50%. Sphingosine did not affect PtdOH formation at all, even at 100 microM, suggesting that collagen itself induced this PtdOH formation, independently of TXB2 generation. The absence of external Ca2+ allowed the cleavage of polyphosphoinositides and the accumulation of InsP3 to occur, but impaired P43 phosphorylation, PtdOH and TXB2 formation, and secretion; these were only restored by adding 0.11 microM-Ca2+. In conclusion, stimulation of platelet membrane receptors for collagen initiates a PtdInsP2-specific phospholipase C activation, which is independent of external Ca2+, and might be the immediate receptor-linked response. A Ca2+ influx is indispensable to the triggering of subsequent platelet responses. This stimulation predominantly involves the protein kinase C pathway associated with secretion, and appears not to be mediated by TXB2, at least during its initial stage. Images Fig. 6. PMID:2163606

  5. Signalling pathways involved in the activation of dendritic cells by layered double hydroxide nanoparticles.

    PubMed

    Li, Ang; Qin, Lili; Zhu, Di; Zhu, Rongrong; Sun, Jing; Wang, Shilong

    2010-02-01

    Layered double hydroxide (LDH) nanoparticles are attractive as potential drug vectors for the targeting not only of tissues, but also of intracellular organelles, and particularly the acidic endolysosomes created after cell endocytosis. The purpose of this study was to investigate the ability of LDH nanoparticles designed as vectors to activate dendritic cells (DCs), as measured by various cellular functions. The study also explored the possible signaling pathway through which the LDH nanoparticles exerted their effects on the cellular functions of DCs. First, LDH nanoparticles with different ratios of Mg(OH)(2) to Al(OH)(3) (1:1, 2:1 and 3:1, called R1, R2 and R3 respectively) were optimized and had a hydrodynamic diameter of 57 nm with a zeta potential of +35 mV. Then, the efficient endocytosis of the optimized LDH nanoparticles by bone marrow-derived dendritic cells (MDDCs) was monitored by fluorescence-activated cell sorting. The effect of R1, R2 and R3 on the expression of the pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, and IL-12) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) in MDDCs was examined. The exposure of R1 caused a dose-dependent increase in the expression of TNF-alpha, IL-12, CD86 and CD40, while R2 and R3 did not up-regulate these cytokines and co-stimulatory molecules. Migration assays showed that R1 could increase the migration capacity of DCs to CCL21 and up-regulate the expression of CCR7. Furthermore, we found that R1 significantly increased the NF-kappaB expression in the nucleus (in a dose-dependent manner) and promoted the degradation of total IkappaBalpha levels, indicating that the NF-kappaB signaling pathway might involve in an R1-induced DC activation. Our results suggested that LDH nanoparticles, in the future, may function as a useful vector for ex vivo engineering to promote vaccine delivery in immune cells.

  6. Residues involved in the pore-forming activity of the Clostridium perfringens iota toxin.

    PubMed

    Knapp, Oliver; Maier, Elke; Waltenberger, Eva; Mazuet, Christelle; Benz, Roland; Popoff, Michel R

    2015-02-01

    Clostridium perfringens iota toxin is a binary toxin that is organized into enzyme (Ia) and binding (Ib) components. Ib forms channels in lipid bilayers and mediates the transport of Ia into the target cells. Here we show that Ib residues 334-359 contain a conserved pattern of alternating hydrophobic and hydrophilic residues forming two amphipathic β-strands involved in membrane insertion and channel formation. This stretch of amino acids shows remarkable structural and functional analogies with the β-pore-forming domain of C. perfringens epsilon toxin. Several mutations within the two amphipathic β-strands affected pore formation, single-channel conductance and ion selectivity (S339E-S341E, Q345H N346E) confirming their involvement in channel formation. F454 of Ib corresponds to the Φ-clamp F427 of anthrax protective antigen and F428 of C2II binary toxins. The mutation F454A resulted in a loss of cytotoxicity and strong increase in single-channel conductance (500 pS as compared with 85 pS in 1 M KCl) with a slight decrease in cation selectivity, indicating that the Φ-clamp is highly conserved and crucial for binary toxin activity. In contrast, the mutants Q367D, N430D, L443E had no or only minor effects on Ib properties, while T360I, T360A and T360W caused a dramatic effect on ion selectivity and single-channel conductance, indicating gross disturbance of the oligomer structure. This suggests that, at least in the iota toxin family, T360 has a structural role in the pore organization. Moreover, introduction of charged residues within the channel (S339E-S341E) or in the vestibule (Q367D, N430D and L443E) had virtually no effect on chloroquine or Ia binding, whereas F454A, T360I, T360A and T360W strongly decreased the chloroquine and Ia affinity to Ib. These results support that distinct residues within the vestibule interact with chloroquine and Ia or are responsible for channel structure, while the channel lining amino acids play a less important role.

  7. Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements

    PubMed Central

    Bednark, Jeffery G.; Campbell, Megan E. J.; Cunnington, Ross

    2015-01-01

    Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g., rhythm) and ordinal motor processes. Using high-resolution functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA), we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the supplementary motor area (SMA) and basal-ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia. PMID:26283945

  8. Evaluation Using Sequential Trials Methods.

    ERIC Educational Resources Information Center

    Cohen, Mark E.; Ralls, Stephen A.

    1986-01-01

    Although dental school faculty as well as practitioners are interested in evaluating products and procedures used in clinical practice, research design and statistical analysis can sometimes pose problems. Sequential trials methods provide an analytical structure that is both easy to use and statistically valid. (Author/MLW)

  9. Sequential Effects in Essay Ratings

    ERIC Educational Resources Information Center

    Attali, Yigal

    2011-01-01

    Contrary to previous research on sequential ratings of student performance, this study found that professional essay raters of a large-scale standardized testing program produced ratings that were drawn toward previous ratings, creating an assimilation effect. Longer intervals between the two adjacent ratings and higher degree of agreement with…

  10. Understanding the Meaning African-American Men Give to Their Student Leadership Involvement and Engagement Activities in College

    ERIC Educational Resources Information Center

    Brooks, Karl A.

    2012-01-01

    The purpose of this qualitative, phenomenological study was to explore and gain a deeper understanding of the lived experiences and perceptions of African-American (A-A) men who are persisting in college and who demonstrate participation in co-curricular activities defined as student leadership involvement and engagement activities (SLIEA). The…

  11. Rural Schooling in Georgia: The Experiences of a Minority Community Service Organization Involved in Local School Decision-Making Activities

    ERIC Educational Resources Information Center

    Lowe, Cynthia Louise Altman

    2010-01-01

    This dissertation study was a descriptive case study of a minority community service organization whose members were actively involved in local school decision-making and activities in a rural Northeast Georgia community. Rural schools face unique challenges in light of current educational trends. To address the challenges, rural schools must…

  12. Applications of Bayesian Decision Theory to Sequential Mastery Testing.

    ERIC Educational Resources Information Center

    Vos, Hans J.

    The purpose of this paper is to formulate optimal sequential rules for mastery tests. The framework for this approach is derived from empirical Bayesian decision theory. Both a threshold and linear loss structure are considered. The binomial probability distribution is adopted as the psychometric model involved. Conditions sufficient for…

  13. Mothers' and fathers' involvement with school-age children's care and academic activities in Navajo Indian families.

    PubMed

    Hossain, Ziarat; Anziano, Michael C

    2008-04-01

    This exploratory study examined mothers' and fathers' reports of time involvement in their school-age children's care and academic activities. The study also explored the relationship between parents' socioeconomic status (SES) variables (age, education, income, work hours, and length of marriage) and their relative involvement with children. Mother and father dyads from 34 two-parent Navajo (Diné) Indian families with a second- or third-grade child participated in the study. Repeated measures analysis of variance showed that mothers invested significantly more time in children's care on demand and academic activities than fathers, but the differences in maternal and paternal perceptions of time involvement in routine care were not significant. The gender of the child did not influence the amount of time parents invested in children's care and academic activities. Mothers' involvement with children was not related to any of the SES variables. Fathers' involvement was significantly associated with work hours and length of marriage, and work hours produced significant interaction with fathers' involvement with children. Findings are discussed in light of gender role differences in parental involvement with children within Navajo families.

  14. Family involvement in music impacts participation of children with cochlear implants in music education and music activities.

    PubMed

    Driscoll, Virginia; Gfeller, Kate; Tan, Xueli; See, Rachel L; Cheng, Hsin-Yi; Kanemitsu, Mikiko

    2015-05-01

    Objective Children with cochlear implants (CIs) participate in musical activities in school and daily lives. Considerable variability exists regarding the amount of music involvement and enjoyment. Using the Music Engagement Questionnaire-Preschool/Elementary (MEQ-P/E), we wanted to determine patterns of musical participation and the impact of familial factors on engagement. Methods Parents of 32 children with CIs (16 preschool and 16 elementary) completed a questionnaire regarding the musical involvement of their child with an implant and a normal-hearing (NH) sibling (if one existed). We compared CI children's involvement to that of their NH siblings as well as across groups of children with and without CIs. Correlations between parent ratings of music importance, demographic factors, and involvement of CI and NH children were conducted within and across groups. Results No significant differences were found between children with CIs and NH siblings, meaning children from the same family showed similar levels of musical involvement. When compared at the same developmental stage, no significant differences were found between preschool children with and without CIs. Parents who rated the importance of music as 'low' or 'middle' had children (NH and CI) who were less involved in music activities. Children whose parents rated music importance as 'high' were involved in monthly to weekly music activities with 81.25% reporting daily music listening. Conclusion Despite a less-than-ideal auditory signal for music, preschool and school-aged CI children enjoy and are involved in musical experiences. Families who enjoy and spend a greater amount of time involved in music tend to have children who also engage more actively in music.

  15. Family involvement in music impacts participation of children with cochlear implants in music education and music activities

    PubMed Central

    Driscoll, Virginia; Gfeller, Kate; Tan, Xueli; See, Rachel L.; Cheng, Hsin-Yi; Kanemitsu, Mikiko

    2014-01-01

    Objective Children with cochlear implants (CIs) participate in musical activities in school and daily lives. Considerable variability exists regarding the amount of music involvement and enjoyment. Using the Music Engagement Questionnaire-Preschool/Elementary (MEQ-P/E), we wanted to determine patterns of musical participation and the impact of familial factors on engagement. Methods Parents of 32 children with CIs (16 preschool, 16 elementary) completed a questionnaire regarding the musical involvement of their child with an implant and a normal-hearing (NH) sibling (if one existed). We compared CI children's involvement to that of their NH siblings as well as across groups of children with and without CIs. Correlations between parent ratings of music importance, demographic factors, and involvement of CI and NH children were conducted within and across groups. Results No significant differences were found between children with CIs and NH siblings, meaning children from the same family showed similar levels of musical involvement. When compared at the same developmental stage, no significant differences were found between preschool children with and without CIs. Parents who rated the importance of music as “low” or “middle” had children (NH and CI) who were less involved in music activities. Children whose parents rated music importance as “high” were involved in monthly to weekly music activities with 81.25% reporting daily music listening. Conclusion Despite a less-than-ideal auditory signal for music, preschool and school-aged CI children enjoy and are involved in musical experiences. Families who enjoy and spend a greater amount of time involved in music tend to have children who also engage more actively in music. PMID:25431978

  16. Active involvement of people with intellectual disabilities in health research - A structured literature review.

    PubMed

    Frankena, Tessa Kim; Naaldenberg, Jenneken; Cardol, Mieke; Linehan, Christine; van Schrojenstein Lantman-de Valk, Henny

    2015-01-01

    Actively involving people with intellectual disabilities (ID) in health research, also known as inclusive health research, is increasingly popular. Currently, insight into experiences of this type of research is scarce. To gain insight into this topic, a structured literature review was conducted focussing on (1) existing theories, (2) inclusive methods, (3) added value and (4) barriers and facilitators. Literature published between January 2000 and January 2014 was included covering keywords related to ID and inclusive health research. Searches were performed in Pubmed, CINAHL, PsycINFO, EMBASE and MEDLINE databases, resulting in 26 included papers. Papers were quality assessed and analysed using qualitative data analysis software. Four theories were often simultaneously addressed: participatory research, emancipatory research, inclusive research and Arnstein's ladder. Barriers and facilitators could be divided into preparing, undertaking and finalising phases of research. Authors indicated that their motivation to conduct inclusive health research was based on demands by policy and funding bodies or was based on ethical considerations (i.e., ethical notions and giving people with ID a voice). Upon completion, authors perceived increased quality and validity of their research and several benefits for stakeholders (i.e., people with ID, researchers and healthcare professionals). Overall, there was consistency in their perception of the most important aspects of inclusive health research. Based on the analysis of included papers, four recommendations of inclusive health research with people with ID were found. Inclusive health research should be: (1) tailoring to the specific study; (2) anticipating all stakeholders; (3) considering its added value; and (4) providing insight into its process.

  17. Enzyme activity alteration by cadmium administration to rats: the possibility of iron involvement in lipid peroxidation.

    PubMed

    Casalino, E; Sblano, C; Landriscina, C

    1997-10-15

    The specific activities of D-3-hydroxybutyrate dehydrogenase (BDH) and glutamate dehydrogenase (GDH) are reduced in the liver and kidney of rats intoxicated with 2.5 mg Cd/kg body wt and sacrificed after 24 h; conversely ketone-body concentration is strongly increased in both of these organs and blood. In the same animals a great stimulation of antioxidant enzymes glutathione reductase and glutathione peroxidase occurs. The prooxidant state induced by cadmium in liver mitochondria and microsomes is unaffected by superoxide dismutase, catalase, or mannitol, whereas it is completely blocked by vitamin E thus excluding the involvement of reactive oxygen species in this process. The mechanism by which cadmium induces lipid peroxidation has been investigated by measuring the effect of this metal on liposomes. Ninety-minute treatment of liposomes with CdCl2 does not induce any lipid peroxidation. In contrast, Fe2+ ions under the same conditions cause strong liposome peroxidation. It has also been observed that cadmium promotes a time-dependent iron release from biological membranes. When lipid peroxidation is induced by a low concentration (5 microM) of FeCl2, in place of CdCl2, the characteristics of this process and the sensitivity to the various antioxidants used are similar to those observed with Cd. From these results we conclude that the prooxidative effect of cadmium is an indirect one since it is mediated by iron. With regard to the inhibitory effect on BDH and GDH following cadmium intoxication, it does not appear to be imputable to lipid peroxidation since in vitro investigations indicate that the presence of vitamin E does not remove the inhibition at all.

  18. Plasminogen Activator Inhibitor-1 Is Involved in Impaired Bone Repair Associated with Diabetes in Female Mice

    PubMed Central

    Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

    2014-01-01

    Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1−/−) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1−/− mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1−/− mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1−/− mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1−/− mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells. PMID:24651693

  19. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity.

    PubMed

    de Laat, M A; Kyaw-Tanner, M T; Nourian, A R; McGowan, C M; Sillence, M N; Pollitt, C C

    2011-04-15

    Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n=4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n=4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6h (n=4), 12h (n=4), 24h (n=4) and 48 h (n=4), and in normal control horses (n=4). The only change in gene expression observed was an upregulation of MMP-9 (p<0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p<0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.

  20. Mechanisms involved in the antiplatelet activity of magnesium in human platelets.

    PubMed

    Sheu, Joen-Rong; Hsiao, George; Shen, Ming-Yi; Fong, Tsorng-Harn; Chen, Yi-Win; Lin, Chien-Huang; Chou, Duen-Suey

    2002-12-01

    In this study, magnesium sulphate dose-dependently (0.6-3.0 mmol/l) inhibited platelet aggregation in human platelets stimulated by agonists. Furthermore, magnesium sulphate (3.0 mmol/l) markedly interfered with the binding of fluorescein isothiocanate-triflavin to the glycoprotein (GP)IIb/IIIa complex in platelets stimulated by collagen. Magnesium sulphate (1.5 and 3.0 mmol/l) also inhibited phosphoinositide breakdown and intracellular Ca+2 mobilization in human platelets stimulated by collagen. Magnesium sulphate (3.0 mmol/l) significantly inhibited thromboxane A2 formation stimulated by collagen in platelets. Moreover, magnesium sulphate (1.5 and 3.0 mmol/l) obviously increased the fluorescence of platelet membranes tagged with diphenylhexatriene. In addition, magnesium sulphate (1.5 and 3.0 mmol/l) increased the formation of cyclic adenosine monophosphate (AMP) in platelets. Phosphorylation of a protein of Mr 47 000 (P47) was markedly inhibited by magnesium sulphate (1.5 mmol/l). In conclusion, the antiplatelet activity of magnesium sulphate may involve the following two pathways. (1) Magnesium sulphate may initially induce membrane fluidity changes with resulting interference of fibrinogen binding to the GPIIb/IIIa complex, followed by inhibition of phosphoinositide breakdown and thromboxane A2 formation, thereby leading to inhibition of both intracellular Ca2+ mobilization and phosphorylation of P47. (2) Magnesium sulphate might also trigger the formation of cyclic AM, ultimately resulting in inhibition of the phosphorylation of P47 and intracellular Ca+2 mobilization.

  1. Plasminogen activator inhibitor-1 is involved in impaired bone repair associated with diabetes in female mice.

    PubMed

    Mao, Li; Kawao, Naoyuki; Tamura, Yukinori; Okumoto, Katsumi; Okada, Kiyotaka; Yano, Masato; Matsuo, Osamu; Kaji, Hiroshi

    2014-01-01

    Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1-/-) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1-/- mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1-/- mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1-/- mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1-/- mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells.

  2. Modafinil disrupts prepulse inhibition in mice: strain differences and involvement of dopaminergic and serotonergic activation.

    PubMed

    Kwek, Perrin; van den Buuse, Maarten

    2013-01-15

    Modafinil is a wakefulness-promoting agent with possible beneficial effects for the management of addiction and in psychiatric conditions, but also with abuse potential of its own. The mechanism of action of modafinil remains unclear. We studied pharmacological mechanisms in the effect of modafinil on prepulse inhibition (PPI), a model of sensorimotor gating. Mice were tested in automated startle boxes after administration of modafinil and antagonist drugs. Oral administration of 100mg/kg of modafinil, but not lower doses, caused a significant reduction of PPI in C57Bl/6 mice, but not Balb/c mice. This effect of modafinil could be blocked by co-treatment with the dopamine D(2) receptor antagonist, haloperidol, and the serotonin (5-HT) 2A receptor antagonist, ketanserin, but not the 5-HT(1A) receptor antagonist, WAY100,635. At 30mg/kg, which did not influence PPI, modafinil inhibited PPI disruption caused by the dopamine transporter inhibitor, GBR12909. There was no interaction between modafinil and the serotonin transporter inhibitor, fluoxetine. There were no consistent effects of modafinil on startle amplitude. These results show that oral modafinil treatment may cause disruption of PPI in mice. This effect was strain-dependent, involving dopamine D(2) and 5-HT(2A) receptor activation, and was likely mediated by an interaction with the dopamine transporter. These results extend our insight into the behavioral effects of modafinil and could be of importance for the clinical use of this agent as they may indicate an increased risk of side-effects in conditions where PPI is already reduced, such as in schizophrenia and bipolar disorder.

  3. Massive calcium-activated endocytosis without involvement of classical endocytic proteins.

    PubMed

    Lariccia, Vincenzo; Fine, Michael; Magi, Simona; Lin, Mei-Jung; Yaradanakul, Alp; Llaguno, Marc C; Hilgemann, Donald W

    2011-01-01

    We describe rapid massive endocytosis (MEND) of >50% of the plasmalemma in baby hamster kidney (BHK) and HEK293 cells in response to large Ca transients. Constitutively expressed Na/Ca exchangers (NCX1) are used to generate Ca transients, whereas capacitance recording and a membrane tracer dye, FM 4-64, are used to monitor endocytosis. With high cytoplasmic adenosine triphosphate (ATP; >5 mM), Ca influx causes exocytosis followed by MEND. Without ATP, Ca transients cause only exocytosis. MEND can then be initiated by pipette perfusion of ATP, and multiple results indicate that ATP acts via phosphatidylinositol-bis 4,5-phosphate (PIP(2)) synthesis: PIP(2) substitutes for ATP to induce MEND. ATP-activated MEND is blocked by an inositol 5-phosphatase and by guanosine 5'-[γ-thio]triphosphate (GTPγS). Block by GTPγS is overcome by the phospholipase C inhibitor, U73122, and PIP(2) induces MEND in the presence of GTPγS. MEND can occur in the absence of ATP and PIP(2) when cytoplasmic free Ca is clamped to 10 µM or more by Ca-buffered solutions. ATP-independent MEND occurs within seconds during Ca transients when cytoplasmic solutions contain polyamines (e.g., spermidine) or the membrane is enriched in cholesterol. Although PIP(2) and cholesterol can induce MEND minutes after Ca transients have subsided, polyamines must be present during Ca transients. MEND can reverse over minutes in an ATP-dependent fashion. It is blocked by brief β-methylcyclodextrin treatments, and tests for involvement of clathrin, dynamins, calcineurin, and actin cytoskeleton were negative. Therefore, we turned to the roles of lipids. Bacterial sphingomyelinases (SMases) cause similar MEND responses within seconds, suggesting that ceramide may be important. However, Ca-activated MEND is not blocked by reagents that inhibit SMases. MEND is abolished by the alkylating phospholipase A(2) inhibitor, bromoenol lactone, whereas exocytosis remains robust, and Ca influx causes MEND in cardiac myocytes

  4. Effects of Anodal High-Definition Transcranial Direct Current Stimulation on Bilateral Sensorimotor Cortex Activation During Sequential Finger Movements: An fNIRS Study.

    PubMed

    Muthalib, Makii; Besson, Pierre; Rothwell, John; Ward, Tomas; Perrey, Stephane

    2016-01-01

    Transcranial direct current stimulation (tDCS) is a non-invasive electrical brain stimulation technique that can modulate cortical neuronal excitability and activity. This study utilized functional near infrared spectroscopy (fNIRS) neuroimaging to determine the effects of anodal high-definition (HD)-tDCS on bilateral sensorimotor cortex (SMC) activation. Before (Pre), during (Online), and after (Offline) anodal HD-tDCS (2 mA, 20 min) targeting the left SMC, eight healthy subjects performed a simple finger sequence (SFS) task with their right or left hand in an alternating blocked design (30-s rest and 30-s SFS task, repeated five times). In order to determine the level of bilateral SMC activation during the SFS task, an Oxymon MkIII fNIRS system was used to measure from the left and right SMC, changes in oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin concentration values. The fNIRS data suggests a finding that compared to the Pre condition both the "Online" and "Offline" anodal HD-tDCS conditions induced a significant reduction in bilateral SMC activation (i.e., smaller decrease in HHb) for a similar motor output (i.e., SFS tap rate). These findings could be related to anodal HD-tDCS inducing a greater efficiency of neuronal transmission in the bilateral SMC to perform the same SFS task.

  5. The Role of Family and Community Involvement in the Development and Implementation of School Nutrition and Physical Activity Policy

    PubMed Central

    Kehm, Rebecca; Davey, Cynthia S.; Nanney, Marilyn S.

    2016-01-01

    BACKGROUND Although there are several evidence-based recommendations directed at improving nutrition and physical activity standards in schools, these guidelines have not been uniformly adopted throughout the United States. Consequently, research is needed to identify facilitators promoting schools to implement these recommendations. Therefore, this study analyzed the 2008 School Health Profiles Principal Survey (Profiles) to explore the role of family and community involvement in school nutrition and physical activity standards. METHODS Survey data on nutrition and physical activity policies, as well as family and community involvement, were available for 28 states, representing 6732 secondary schools. One-factor analysis of variance (ANOVA), 2-sample t-tests, Pearson’s chi-square tests, and multiple logistic and linear regression models were employed in this analysis. RESULTS Family and community involvement were associated with schools more frequently utilizing healthy eating strategies and offering students healthier food options. Further, involvement was associated with greater support for physical education staff and more intramural sports opportunities for students. CONCLUSIONS Though family and community involvement have the potential to have a positive influence on school nutrition and physical activity policies and practices, involvement remains low in schools. Increased efforts are needed to encourage collaboration among schools, families, and communities to ensure the highest health standards for all students. PMID:25564977

  6. Application of a FRET probe for Caspase-3 activation in living HeLa cells by sequentially treated cisplatin and TRAIL

    NASA Astrophysics Data System (ADS)

    Lin, Juqiang; Zhang, Zhihong; Yi, Qiushi; Zeng, Shaoqun; Luo, Qingming

    2006-02-01

    Caspase-3 is a kind of cysteine proteases that plays an important role in cell apoptosis. We have constructed a FRET (fluorescence resonance energy transfer) probe fused with ECFP (enhanced cyan fluorescence protein) and DsRed (Discosoma red fluorescent protein) with a linker containing a caspase-3 cleavage sequence (CCS, DEVD).It could be observed much change in fluorescence emission ratio when the probe was cleaved by caspase-3. Therefore, application of this probe we can real-time detected the activation of caspase-3. It was already confirmed that caspase-3 was activated in HeLa cells treated by cisplatin or TRAIL (Tumor necrosis factor (TNF)-related apoptosis-inducing ligand). In the present study, we detected the activation of caspase-3 during cisplatin or TRAIL induced apoptosis in living HeLa cells, and also observed the activation of caspase-3 caused by both cisplatin and TRAIL combined treatment. Our results demonstrated a synergistic effect between cisplatin and TRAIL. Cisplatin is one of the most broadly used drugs in the Clinical applications of cancer chemotherapy, and TRAIL, which belongs to the TNF family proteins, can selectively induce apoptosis in many transformed cells but not in normal cells. Therefore, TRAIL is a very valuably prospective utility as its potential tumor-specific cancer therapeutic. Most of anticancer drugs can induce apoptosis which mediated by the activation of caspase pathway. We can select the best synergistic effect group by our FRET probe. This finding would be useful in the design of treatment modalities for patients.

  7. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

    ERIC Educational Resources Information Center

    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  8. The Theory of Active Involvement: Processes Underlying Interventions that Engage Adolescents in Message Planning and/or Production

    PubMed Central

    Greene, Kathryn

    2013-01-01

    Adolescence is a time of increased risk-taking and recent intervention strategies have included adolescents planning or producing anti-risk messages for their peers. Although these projects may generate enthusiasm, we know little about message planning or production as a strategy for changing adolescent decision-making and behavior. The paper articulates the Theory of Active Involvement (TAI) to describe and explain the processes through which these active involvement interventions influence adolescents. TAI is based on social cognitive theory’s notion of self-regulation and examines multiple perspective-taking and activating the self-reflection processes. The theory specifically describes the process of cognitive changes experienced by participants in active involvement interventions. The sequence is conceptualized as starting when engagement with the intervention (arousal and involvement) produces skill and knowledge gains (immediate outcomes) that lead to reflection (perceived discrepancy) and then other cognitions (expectancies, norms, intentions), with the ultimate outcome being behavior change. Engaging the target audience in a process of self-reflection is conceptualized as the crucial ingredient for meaningful and sustainable change in cognitions and behavior. This paper provides valuable insight into how active involvement strategies function and how to best design these interventions, particularly those targeting adolescents. PMID:23980581

  9. Flavonoid interactions during digestion, absorption, distribution and metabolism: a sequential structure-activity/property relationship-based approach in the study of bioavailability and bioactivity.

    PubMed

    Gonzales, Gerard Bryan; Smagghe, Guy; Grootaert, Charlotte; Zotti, Moises; Raes, Katleen; Van Camp, John

    2015-05-01

    Flavonoids are a group of polyphenols that provide health-promoting benefits upon consumption. However, poor bioavailability has been a major hurdle in their use as drugs or nutraceuticals. Low bioavailability has been associated with flavonoid interactions at various stages of the digestion, absorption and distribution process, which is strongly affected by their molecular structure. In this review, we use structure-activity/property relationship to discuss various flavonoid interactions with food matrices, digestive enzymes, intestinal transporters and blood proteins. This approach reveals specific bioactive properties of flavonoids in the gastrointestinal tract as well as various barriers for their bioavailability. In the last part of this review, we use these insights to determine the effect of different structural characteristics on the overall bioavailability of flavonoids. Such information is crucial when flavonoid or flavonoid derivatives are used as active ingredients in foods or drugs.

  10. Cystic acne improved by photodynamic therapy with short-contact 5-aminolevulinic acid and sequential combination of intense pulsed light and blue light activation.

    PubMed

    Melnick, Stuart

    2005-01-01

    Photodynamic therapy with short-contact 5-aminolevulinic acid (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) and activation by intense pulsed light in an initial treatment and blue light in 3 subsequent treatments has resulted in significant improvement in severity of acne, reduction in the number of lesions, improvement in skin texture, and smoothing of scar edges in an Asian patient with severe (class 4) facial cystic acne and scarring.

  11. Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling

    PubMed Central

    Pavo, Noemi; Lukovic, Dominika; Zlabinger, Katrin; Zimba, Abelina; Lorant, David; Goliasch, Georg; Winkler, Johannes; Pils, Dietmar; Auer, Katharina; Jan Ankersmit, Hendrik; Giricz, Zoltán; Baranyai, Tamas; Sárközy, Márta; Jakab, András; Garamvölgyi, Rita; Emmert, Maximilian Y.; Hoerstrup, Simon P.; Hausenloy, Derek J.; Ferdinandy, Péter; Maurer, Gerald; Gyöngyösi, Mariann

    2017-01-01

    We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls. Hearts were explanted at 5 h (n = 6) and 24 h (n = 6), and transcriptomic profiling of the distal (ischemia-affected) and proximal (non-affected) anterior myocardial regions were analyzed by next generation sequencing (NGS) and post-processing with signaling pathway impact and pathway network analyses. In ischemic region, r-I/R induced early activation of Ca-, adipocytokine and insulin signaling pathways with key regulator STAT3, which was also upregulated in the remote areas together with clusterin (CLU) and TNF-alpha. During the late phase of cardioprotection, antigen immunomodulatory pathways were activated with upregulation of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intrinsic remote conditioning. The temporo-spatially differently activated pathways revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intrinsic remote conditioning for prevention of adverse remodeling. PMID:28266659

  12. The Human Mixed Lineage Leukemia 5 (MLL5), a Sequentially and Structurally Divergent SET Domain-Containing Protein with No Intrinsic Catalytic Activity

    PubMed Central

    Teyssier, Catherine; Déméné, Hélène; Carvalho, João E.; Bird, Louise E.; Lebedev, Andrey; Fattori, Juliana; Schubert, Michael; Dumas, Christian; Bourguet, William; le Maire, Albane

    2016-01-01

    Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through a direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains a Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain, a protein module that usually displays histone lysine methyltransferase activity. We report here the crystal structure of the unliganded SET domain of human MLL5 at 2.1 Å resolution. Although it shows most of the canonical features of other SET domains, both the lack of key residues and the presence in the SET-I subdomain of an unusually large loop preclude the interaction of MLL5 SET with its cofactor and substrate. Accordingly, we show that MLL5 is devoid of any in vitro methyltransferase activity on full-length histones and histone H3 peptides. Hence, the three dimensional structure of MLL5 SET domain unveils the structural basis for its lack of methyltransferase activity and suggests a new regulatory mechanism. PMID:27812132

  13. Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

    PubMed Central

    Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

    2015-01-01

    Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

  14. Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles.

    PubMed

    Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

    2015-01-01

    Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

  15. Character Development within Youth Development Programs: Exploring Multiple Dimensions of Activity Involvement.

    PubMed

    Lynch, Alicia Doyle; Ferris, Kaitlyn A; Burkhard, Brian; Wang, Jun; Hershberg, Rachel M; Lerner, Richard M

    2016-03-01

    We examined links among three dimensions of youth involvement (intensity, duration, and engagement) in Boy Scouts of America (BSA), an international out-of-school time (OST) youth development program designed to promote moral and performance character in boys. Using data from 737 youth and their parents who participated in one of 40 BSA program sites (commonly referred to as "packs"), we first considered how individual- and pack-level measures of program involvement were differentially linked with character development. Next, we examined whether pack-level involvement characteristics moderate individual-level involvement characteristics, hypothesizing that highly involved packs would serve to further enhance the positive effects of high levels of individual involvement. Results indicated engagement was the strongest, most frequent predictor of increases in both moral and performance character. Although there were no direct effects of pack-level intensity, duration, or engagement, the effects of individual-level engagement were moderated by pack-level engagement, suggesting that the largest increases in moral and performance character occurred among highly engaged youth who were enrolled in highly engaged packs. These results highlight the need to examine multiple dimensions of OST program involvement simultaneously, and suggest that strengthening youth engagement in programming may provide a means for enhancing the positive effects of high-quality youth programming.

  16. Personal involvement is related to increased search motivation and associated with activity in left BA44-a pilot study.

    PubMed

    Schaefer, Michael; Rumpel, Franziska; Sadrieh, Abdolkarim; Reimann, Martin; Denke, Claudia

    2015-01-01

    Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI). We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. fMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product.

  17. Sequential processing during noun phrase production.

    PubMed

    Bürki, Audrey; Sadat, Jasmin; Dubarry, Anne-Sophie; Alario, F-Xavier

    2016-01-01

    This study examined whether the brain operations involved during the processing of successive words in multi word noun phrase production take place sequentially or simultaneously. German speakers named pictures while ignoring a written distractor superimposed on the picture (picture-word interference paradigm) using the definite determiner and corresponding German noun. The gender congruency and the phonological congruency (i.e., overlap in first phonemes) between target and distractor were manipulated. Naming responses and EEG were recorded. The behavioural performance replicated both the phonology and the gender congruency effects (i.e., shorter naming latencies for gender congruent than incongruent and for phonologically congruent than incongruent trials). The phonological and gender manipulations also influenced the EEG data. Crucially, the two effects occurred in different time windows and over different sets of electrodes. The phonological effect was observed substantially earlier than the gender congruency effect. This finding suggests that the processing of determiners and nouns during determiner noun phrase production occurs at least partly sequentially.

  18. Sequential effects in Olympic synchronized diving scores

    PubMed Central

    2017-01-01

    When judging performances in a sequence, the current score is often influenced by the preceding score. Where athletes are perceived to be similar, a judgement is assimilated towards the previous one. However, if judges focus on the differences between the two athletes, this will result in a contrasting influence on their scores. Here, I investigate sequential effects during synchronized diving events at the 2012 and 2016 Olympic Games. Although previous research found assimilation in scores of gymnasts, the current data showed contrast effects—current scores benefited from following a poor performance but were at a disadvantage if they followed a high-scoring performance. One explanation may be that the processes involved in judging synchronized pairs results in a focus on the differences between athletes, producing a contrast effect across dives. That the specific direction of this sequential bias may depend on the particular sport has implications for how judges might approach their roles in a context-dependent manner, as well as how such biases should be addressed. PMID:28280583

  19. Caffeine in hot drinks elicits cephalic phase responses involving cardiac activity.

    PubMed

    McMullen, Michael K; Whitehouse, Julie M; Shine, Gillian; Whitton, Peter A; Towell, Anthony

    2012-09-01

    Caffeine stimulates both oropharyngeal and gut bitter taste receptors (hTAS2Rs) and so has the potential to elicit reflex autonomic responses. Coffee containing 130 mg caffeine has been reported to increase heart rate for 30 min post-ingestion. Whereas added-caffeine, in doses of 25 to 200 mg, ingested with decaffeinated coffee/tea decreases heart rate 10 to 30 min post-ingestion. This study aimed to clarify caffeine's chemosensory impact. Double-espresso coffees were compared to a placebo-control capsule in a double-blind between-measures design. Coffees tested were regular coffee (130 mg caffeine) and decaffeinated coffee with added-caffeine (0, 67 and 134 mg). Cardiovascular measures from three post-ingestion phases: 1) 0 to 5; 2) 10 to 15; and 3) 25 to 30 min; were compared to pre-ingestion measures. Participants comprised 11 women in the control group and 10 women in the test group. Decaffeinated coffee elicited no changes. Decaffeinated coffee with 67 mg caffeine: decreased dp/dt in Phase 1. Decaffeinated coffee with 134 mg caffeine: increased heart rate in Phases 1 and 2; decreased spontaneous baroreflex sensitivity in Phase 1; and increased diastolic pressure in Phases 2 and 3. Regular coffee: increased heart rate in Phases 1 and 2; decreased dp/dt in all phases; and decreased systolic pressure in Phase 1. Caffeine is the substance in regular coffee which elicits chemosensory autonomic reflex responses, which involves heart activity and the baroreflex. Compared to the caffeine in regular coffee, added-caffeine elicits somewhat different chemosensory responses including a more pronounced pressor effect and resetting of the baroreflex. Caffeine in commonly consumed amounts, as well as modulating body processes by blocking adenosine receptors, can elicit reflex autonomic responses during the ingestion of caffeinated drinks. It is plausible that caffeine stimulates hTAS2Rs, during the ingestion of coffee, eliciting cephalic phase responses. These cephalic phase

  20. Melanosis in Penaeus monodon: Involvement of the Laccase-like Activity of Hemocyanin.

    PubMed

    Bris, Cédric Le; Cudennec, Benoit; Dhulster, Pascal; Drider, Djamel; Duflos, Guillaume; Grard, Thierry

    2016-01-27

    In shrimp, the development of postmortem melanosis resulting from phenoloxidase activities leads to important economic losses. Phenoloxidase enzymes include catechol oxidases, laccases, and tyrosinases, but hemocyanin is also capable of phenoloxidase activities. These activities have been explored in Penaeus monodon, using different substrates. Results highlighted that tyrosinase-specific substrates were little oxidized, whereas hydroquinone (laccase-specific substrate) was more highly oxidized than l-DOPA (nonspecific substrate) in the pereopods and pleopods. Global phenoloxidase activity, assayed with l-DOPA, did not appear thermally stable over time and probably resulted from phenoloxidase enzymes. Conversely, the laccase-like activity assayed with hydroquinone was thermally stable over time, reflecting the thermal stability of hemocyanin. Independently of the anatomical compartment, the temperature, or the substrate, the highest activities were assayed in the cuticular compartments. This study demonstrates the complexity of phenoloxidase activities in P. monodon, and the importance of considering all the activities, including laccase-like activities such as that of hemocyanin.

  1. Astrocytes inhibit nitric oxide-dependent Ca(2+) dynamics in activated microglia: involvement of ATP released via pannexin 1 channels.

    PubMed

    Orellana, Juan A; Montero, Trinidad D; von Bernhardi, Rommy

    2013-12-01

    Under inflammatory conditions, microglia exhibit increased levels of free intracellular Ca(2+) and produce high amounts of nitric oxide (NO). However, whether NO, Ca(2+) dynamics, and gliotransmitter release are reciprocally modulated is not fully understood. More importantly, the effect of astrocytes in the potentiation or suppression of such signaling is unknown. Our aim was to address if astrocytes could regulate NO-dependent Ca(2+) dynamics and ATP release in LPS-stimulated microglia. Griess assays and Fura-2AM time-lapse fluorescence images of microglia revealed that LPS produced an increased basal [Ca(2+) ]i that depended on the sequential activation of iNOS, COXs, and EP1 receptor. TGFβ1 released by astrocytes inhibited the abovementioned responses and also abolished LPS-induced ATP release by microglia. Luciferin/luciferase assays and dye uptake experiments showed that release of ATP from LPS-stimulated microglia occurred via pannexin 1 (Panx1) channels, but not connexin 43 hemichannels. Moreover, in LPS-stimulated microglia, exogenous ATP triggered activation of purinergic P2Y1 receptors resulting in Ca(2+) release from intracellular stores. Interestingly, TGFβ1 released by astrocytes inhibited ATP-induced Ca(2+) response in LPS-stimulated microglia to that observed in control microglia. Finally, COX/EP1 receptor signaling and activation of P2 receptors via ATP released through Panx1 channels were critical for the increased NO production in LPS-stimulated microglia. Thus, Ca(2+) dynamics depended on the inflammatory profile of microglia and could be modulated by astrocytes. The understanding of mechanisms underlying glial cell regulatory crosstalk could contribute to the development of new treatments to reduce inflammatory cytotoxicity in several brain pathologies.

  2. On Disturbed Sequential Hypothesis Testing

    DTIC Science & Technology

    1991-06-01

    procedures over the classical single sensor schemes. 14. SUBJECT TERMS iS NUMBER OF PAGES Sensor Fusion, Signal Processing, Detection Comunication 150...matrix. Proakis [28] described the random walk formulation approach and derived the exact distribution of the test length T and the ASN for quantized...Trans. Inform. Theory vol. IT-26, No. 2, pp. 255-259, March 1980. 141 [28] J. G. Proakis , "Exact distribution functions of test length for sequential

  3. Video Games and Children: Effects on Leisure Activities, Schoolwork, and Peer Involvement.

    ERIC Educational Resources Information Center

    Creasey, Gary L; Myers, Barbara J

    1986-01-01

    Measures the indirect effect a home video system has on children's leisure activities, school work, and peer contacts. Concludes that owning a video game does not greatly alter a child's activities. (HOD)

  4. Involvement in Extracurricular Activities: Identifying Differences in Perceptions of School Climate

    ERIC Educational Resources Information Center

    Martinez, Andrew; Coker, Crystal; McMahon, Susan D.; Cohen, Jonathan; Thapa, Amrit

    2016-01-01

    Many youth participate in extracurricular activities, and research has linked activity participation with school engagement and academic success. Social-ecological theory suggests that the social contexts of different types of extracurricular activities may differentially affect student outcomes. Yet, there is scant research examining the relation…

  5. Parental Involvement in Active Transport to School Initiatives: A Multi-Site Case Study

    ERIC Educational Resources Information Center

    Eyler, Amy; Baldwin, Julie; Carnoske, Cheryl; Nickelson, Jan; Troped, Philip; Steinman, Lesley; Pluto, Delores; Litt, Jill; Evenson, Kelly; Terpstra, Jennifer; Brownson, Ross; Schmid, Thomas

    2008-01-01

    Background: Increasing physical activity in youth is a recommended approach to curbing the childhood obesity epidemic. One way to help increase children's daily activity is to promote active transportation to and from school (ATS). Purpose: The purpose of this case study was to explore parental perception of, and participation in, ATS initiatives.…

  6. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases.

    PubMed

    González, Hugo; Elgueta, Daniela; Montoya, Andro; Pacheco, Rodrigo

    2014-09-15

    Neuroinflammation constitutes a fundamental process involved in the progression of several neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. Microglial cells play a central role in neuroinflammation, promoting neuroprotective or neurotoxic microenvironments, thus controlling neuronal fate. Acquisition of different microglial functions is regulated by intercellular interactions with neurons, astrocytes, the blood-brain barrier, and T-cells infiltrating the central nervous system. In this study, an overview of the regulation of microglial function mediated by different intercellular communications is summarised and discussed. Afterward, we focus in T-cell-mediated regulation of neuroinflammation involved in neurodegenerative disorders.

  7. Parent Advocacy: Now More Than Ever Active Involvement in Educational Decisions.

    ERIC Educational Resources Information Center

    Ammer, Jerome J.; Littleton, Barbara Rhein

    Questionnaires were completed by 217 parents of handicapped children to determine their present level of involvement and their desired participation in the education process. The sample (a rural population in central West Virginia, a suburban population in affluent school districts on Long Island, New York, and a city population from a mixed set…

  8. Examining Parent Involvement Activities in Two Immigrant-Impacted Schools: A Comparative Case Study

    ERIC Educational Resources Information Center

    Marquez, Amalia

    2012-01-01

    K-12 schools with large immigrant populations face a myriad of challenges, including low academic achievement and high dropout rates of Latino students. Parental involvement is a practical strategy in positively influencing student outcomes along the K-12 continuum. To this end, it is essential that immigrant impacted schools work together with…

  9. Undergraduate Involvement in Extracurricular Activities and Leadership Development in College of Agriculture and Life Sciences Students

    ERIC Educational Resources Information Center

    Foreman, Elizabeth A.; Retallick, Michael S.

    2012-01-01

    The purpose of this study was to identify and describe experiences of undergraduate extracurricular involvement that result in increased leadership development. Senior students in the College of Agriculture and Life Sciences at Iowa State University completed an online questionnaire about their extracurricular experiences. Leadership development…

  10. 16 CFR 1031.5 - Criteria for Commission involvement in voluntary standards activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... COMMISSION GENERAL COMMISSION PARTICIPATION AND COMMISSION EMPLOYEE INVOLVEMENT IN VOLUNTARY STANDARDS... voluntary standard once it is issued, and the means of ascertaining such compliance based on overall market..., small business, public interests and other individuals having knowledge or expertise in the areas...

  11. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... children, the exemption at 34 CFR 97.101(b)(2) (i.e., research involving the use of educational tests....101(b)(2) continues to apply, unmodified by 34 CFR 97.401(b), to— (i) Educational tests; and (ii... (physical, psychological, social, financial, legal, or other) and assess their likelihood and...

  12. 48 CFR 3452.224-71 - Notice about research activities involving human subjects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... children, the exemption at 34 CFR 97.101(b)(2) (i.e., research involving the use of educational tests....101(b)(2) continues to apply, unmodified by 34 CFR 97.401(b), to— (i) Educational tests; and (ii... (physical, psychological, social, financial, legal, or other) and assess their likelihood and...

  13. Strategies for Effective Faculty Involvement in Online Activities Aimed at Promoting Critical Thinking and Deep Learning

    ERIC Educational Resources Information Center

    Abdul Razzak, Nina

    2016-01-01

    Highly-traditional education systems that mainly offer what is known as "direct instruction" usually result in graduates with a surface approach to learning rather than a deep one. What is meant by deep-learning is learning that involves critical analysis, the linking of ideas and concepts, creative problem solving, and application…

  14. Behavioral activation by CRF: evidence for the involvement of the ventral forebrain.

    PubMed

    Tazi, A; Swerdlow, N R; LeMoal, M; Rivier, J; Vale, W; Koob, G F

    1987-07-06

    Rats injected intracerebroventricularly with corticotropin releasing factor (CRF) at the level of the lateral ventricle or cisterna magna showed a dose-dependent increase in locomotor activity. The increase in locomotor activity from injections of CRF into the cisterna magna was blocked by a cold cream plug in the cerebral aqueduct. An identical plug failed to block the increase in locomotor activity produced by CRF injected into the lateral ventricle. Intracerebral injections of CRF produced a site specific increase in locomotor activity with the largest increases observed from CRF injected into the substantia innominata/lateral preoptic area. Results suggest that the locomotor activating effects of CRF may be due to an activation of CRF receptors in the ventral forebrain, a region rich in CRF cell bodies and projections.

  15. Optimisation and molecular signalling of apoptosis in sequential cryotherapy and chemotherapy combination in human A549 lung cancer xenografts in SCID mice

    PubMed Central

    Forest, V; Hadjeres, R; Bertrand, R; Jean-François, R

    2009-01-01

    We define the optimal parameters for combination of cryotherapy (nitrous oxide) with chemotherapy (vinorelbine ditartrate, VNB) treatment and characterise some of the signals involved for apoptosis activation. No advantage appeared when cryotherapy and VNB were combined simultaneously compared to cryosurgery alone. In contrast, tumour volumes were reduced after a sequential treatment schedule, where each individual treatment was separated by 48 h. No significant benefit appeared when the sequential treatment was separated by 24 h, although some individual mice showed a good response. The sequence of treatment had no impact on the observed tumour growth inhibition in mice. The number of apoptotic cells was significantly augmented in the sequential treatment schedule where VNB was administered 48 h before cryotherapy. In this sequential treatment, the number of apoptotic cells correlated with heightened expression of the BH3-only Puma, Noxa and Bim-EL, at both the mRNA and protein levels. No significant change in Bax, Bcl-xL and Bcl-2 mRNA expression was apparent, whereas Mcl-1 expression increased only slightly to a much lower level than BH3-only mRNAs. Our data indicate that 48 h sequential rather than simultaneous cryotherapy with VNB in future cancer cryochemotherapy schedules will enhance the tumour response, and argue that VNB administration, 48 h before cryotherapy, will provoke apoptosis more efficiently. PMID:19455143

  16. 75 FR 10526 - In the Matter of Mr. Lawrence E. Grimm; Order Prohibiting Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION In the Matter of Mr. Lawrence E. Grimm; Order Prohibiting Involvement in NRC-Licensed Activities I Mr. Lawrence E. Grimm was employed as a radiation safety officer at the U.S. Department of...

  17. 77 FR 31045 - Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Jaime Sánchez

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... [Federal Register Volume 77, Number 101 (Thursday, May 24, 2012)] [Notices] [Pages 31045-31047] [FR Doc No: 2012-12621] NUCLEAR REGULATORY COMMISSION [NRC-2012-0115; IA-11-036] Order Prohibiting Involvement in NRC-Licensed Activities; In the Matter of Jaime S[aacute]nchez I Jaime S[aacute]nchez (Mr....

  18. 78 FR 66968 - In the Matter of Landon E. Brittain; Order Prohibiting Involvement In NRC-Licensed Activities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION In the Matter of Landon E. Brittain; Order Prohibiting Involvement In NRC-Licensed Activities (Effective Immediately) I Landon E. Brittain was formerly employed as a senior reactor operator (SRO) at...

  19. 77 FR 3010 - In the Matter of Mr. Francis Guilbeau; Order Prohibiting Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-20

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION In the Matter of Mr. Francis Guilbeau; Order Prohibiting Involvement in NRC-Licensed Activities I Mr. Francis Guilbeau was employed as a Radiographer at Accurate NDE & Inspection, LLC, (Accurate NDE or Licensee) located in Broussard, Louisiana,...

  20. Expectations of Rock Music Consumption for Entertainment and Information Relative to the Active Involvement of the User.

    ERIC Educational Resources Information Center

    Rouner, Donna; Noyes, Amy

    Before examining potentially negative effects of rock music on adolescents, it is necessary to demonstrate links between adolescent motivations for consuming rock music and active involvement relative to that use and also to consider how much rock listeners rely on rock music as a source for information about values, beliefs, and social…

  1. Children's Well-Being and Involvement in Physically Active Outdoors Play in a Norwegian Kindergarten: Playful Sharing of Physical Experiences

    ERIC Educational Resources Information Center

    Bjørgen, Kathrine

    2015-01-01

    This qualitative study explores the conditions of children's level of well-being and their involvement in physically active play during kindergarten outdoors time. Observations of three to five year olds from one kindergarten in central Norway were conducted. The researcher followed the children around the kindergarten's outdoors playground and…

  2. Predicting Adolescents' Organized Activity Involvement: The Role of Maternal Depression History, Family Relationship Quality, and Adolescent Cognitions

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Martin, Nina C.; Garber, Judy

    2007-01-01

    Although the potential benefits of organized activity involvement during high school have been documented, little is known about what familial and individual characteristics are associated with higher levels of participation. Using structural equation modeling, this longitudinal study examined the extent to which maternal depression history (i.e.,…

  3. Parental Involvement in School Activities and Reading Literacy: Findings and Implications from PIRLS 2011 Data. Policy Brief No. 3

    ERIC Educational Resources Information Center

    Mirazchiyski, Plamen; Klemencic, Eva

    2014-01-01

    This policy brief presents evidence demonstrating a positive association between parental involvement in school activities and student performance in the Progress in International Reading Literacy Study (PIRLS) 2011. This association, which was evident in most of the 54 education systems analyzed, indicates that students enrolled in schools with…

  4. 76 FR 11529 - Gregory Desobry, Ph.D.; Order Requiring Notification of Involvement in NRC-Licensed Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Gregory Desobry, Ph.D.; Order Requiring Notification of Involvement in NRC-Licensed Activities I... Mr. Desobry, Ph.D., requests a hearing, that person shall set forth with particularity the manner...

  5. 75 FR 55366 - In the Matter of Mark M. Ficek; Order Prohibiting Involvement in NRC-Licensed Activities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    .... Ficek; Order Prohibiting Involvement in NRC-Licensed Activities (Effective Immediately) Mr. Mark M. Ficek is the President, owner, and former radiation safety officer (RSO) of Mattingly Testing Services... issued to Mr. Ficek, the NRC is also issuing Mattingly an Order Revoking License (Effective...

  6. Ideas Exchange: Should Students Be Granted a Waiver from Physical Education if They Are Involved in Other Activities?

    ERIC Educational Resources Information Center

    Sipe, Roberta; Belka, David; Kamla, Jim; Christenson, Robert S.; Magnotta, John; Lorenzi, David G.

    2009-01-01

    This article presents the opinions/ideas of professionals who were asked this question: "Should students be granted a waiver from physical education if they are involved in other activities?" These professionals share the pros and cons of the waiver question.

  7. High Inorganic Triphosphatase Activities in Bacteria and Mammalian Cells: Identification of the Enzymes Involved

    PubMed Central

    Lakaye, Bernard; Servais, Anne-Catherine; Scholer, Georges; Fillet, Marianne; Elias, Benjamin; Derochette, Jean-Michel; Crommen, Jacques; Wins, Pierre; Bettendorff, Lucien

    2012-01-01

    Background We recently characterized a specific inorganic triphosphatase (PPPase) from Nitrosomonas europaea. This enzyme belongs to the CYTH superfamily of proteins. Many bacterial members of this family are annotated as predicted adenylate cyclases, because one of the founding members is CyaB adenylate cyclase from A. hydrophila. The aim of the present study is to determine whether other members of the CYTH protein family also have a PPPase activity, if there are PPPase activities in animal tissues and what enzymes are responsible for these activities. Methodology/Principal Findings Recombinant enzymes were expressed and purified as GST- or His-tagged fusion proteins and the enzyme activities were determined by measuring the release of inorganic phosphate. We show that the hitherto uncharacterized E. coli CYTH protein ygiF is a specific PPPase, but it contributes only marginally to the total PPPase activity in this organism, where the main enzyme responsible for hydrolysis of inorganic triphosphate (PPPi) is inorganic pyrophosphatase. We further show that CyaB hydrolyzes PPPi but this activity is low compared to its adenylate cyclase activity. Finally we demonstrate a high PPPase activity in mammalian and quail tissue, particularly in the brain. We show that this activity is mainly due to Prune, an exopolyphosphatase overexpressed in metastatic tumors where it promotes cell motility. Conclusions and General Significance We show for the first time that PPPase activities are widespread in bacteria and animals. We identified the enzymes responsible for these activities but we were unable to detect significant amounts of PPPi in E. coli or brain extracts using ion chromatography and capillary electrophoresis. The role of these enzymes may be to hydrolyze PPPi, which could be cytotoxic because of its high affinity for Ca2+, thereby interfering with Ca2+ signaling. PMID:22984449

  8. A qualitative study of the activities performed by people involved in clinical decision support: recommended practices for success

    PubMed Central

    Wright, Adam; Ash, Joan S; Erickson, Jessica L; Wasserman, Joe; Bunce, Arwen; Stanescu, Ana; St Hilaire, Daniel; Panzenhagen, Morgan; Gebhardt, Eric; McMullen, Carmit; Middleton, Blackford; Sittig, Dean F

    2014-01-01

    Objective To describe the activities performed by people involved in clinical decision support (CDS) at leading sites. Materials and methods We conducted ethnographic observations at seven diverse sites with a history of excellence in CDS using the Rapid Assessment Process and analyzed the data using a series of card sorts, informed by Linstone's Multiple Perspectives Model. Results We identified 18 activities and grouped them into four areas. Area 1: Fostering relationships across the organization, with activities (a) training and support, (b) visibility/presence on the floor, (c) liaising between people, (d) administration and leadership, (e) project management, (f) cheerleading/buy-in/sponsorship, (g) preparing for CDS implementation. Area 2: Assembling the system with activities (a) providing technical support, (b) CDS content development, (c) purchasing products from vendors (d) knowledge management, (e) system integration. Area 3: Using CDS to achieve the organization's goals with activities (a) reporting, (b) requirements-gathering/specifications, (c) monitoring CDS, (d) linking CDS to goals, (e) managing data. Area 4: Participation in external policy and standards activities (this area consists of only a single activity). We also identified a set of recommendations associated with these 18 activities. Discussion All 18 activities we identified were performed at all sites, although the way they were organized into roles differed substantially. We consider these activities critical to the success of a CDS program. Conclusions A series of activities are performed by sites strong in CDS, and sites adopting CDS should ensure they incorporate these activities into their efforts. PMID:23999670

  9. Noncommutative Biology: Sequential Regulation of Complex Networks

    PubMed Central

    Letsou, William; Cai, Long

    2016-01-01

    Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome. We showed that with noncommutative control, it is possible to independently control targets that would otherwise be activated simultaneously using combinatorial logic. Consequently, sequential logic overcomes the information bottleneck inherent in complex networks. We derived scaling laws for two noncommutative models of regulation, motivated by phosphorylation/neural networks and chromosome folding, respectively, and showed that they scale super-exponentially in the number of regulators. We also showed that specificity in control is robust to the loss of a regulator. Lastly, we connected these theoretical results to real biological networks that demonstrate specificity in the context of promiscuity. These results show that achieving a desired outcome often necessitates roundabout steps. PMID:27560383

  10. Optical Topography of Evoked Brain Activity during Mental Tasks Involving Whole Number Operations

    ERIC Educational Resources Information Center

    Ortiz, Enrique

    2014-01-01

    Students start to memorize arithmetic facts from early elementary school mathematics activities. Their fluency or lack of fluency with these facts could affect their efforts as they carry out mental calculations as adults. This study investigated participants' levels of brain activation and possible reasons for these levels as they solved…

  11. Involvement of Cot activity in the proliferation of ALCL lymphoma cells

    SciTech Connect

    Fernandez, Margarita; Manso, Rebeca; Bernaldez, Flavia; Lopez, Pilar; Martin-Duce, Antonio; Alemany, Susana

    2011-08-12

    Highlights: {yields} We show here that ALCL lymphoma cell lines present high levels of Cot (MAP3K8). {yields} We show that Cot mediates the constitutive Erk1/2 activation in SUDHL-1 cells. {yields} Inhibition of Cot activity reduces the number of cell divisions in SUDHL-1 cells. {yields} Cot controls the activation state of p70 S6K and JunB expression in SUDHL-1 cells. -- Abstract: Anaplastic large-cell lymphoma (ALCL) cells overexpress CD30 on their cell surface, show increased levels of activated Erk1/2 and of JunB; participating JunB in the proliferative capacity of these lymphomas. Here, we show that ALCL lymphoma cells also present high expression levels of the proto-oncogenic Cot (MAP3K8). Using pharmacological drugs as well as the RNA interference technique we show that Cot protein is responsible for the constitutive Erk1/2 activation in the ALCL lymphoma cells, SUDHL-1. Besides, inhibition of Cot activity reduces the number of cell divisions which is achieved, at least in part, by the control that Cot exercises on the activation state of p70 S6K and on the expression levels of JunB. Since Cot represents an alternative mode, independently of RAF, to activate Erk1/2, all these data strongly suggest that molecular targeting of Cot may be a potential new specific strategy for ALCL lymphomas therapy, without the fully disturbance of the Erk1/2 function.

  12. Student Involvement in Extracurricular Activities and Post-Secondary Education Placement

    ERIC Educational Resources Information Center

    Martin, Courtney J.

    2015-01-01

    Extracurricular activities have been an important part of adolescents' lives for generations (Kremer-Sadlik, Izquierdo, & Fatigante, 2010). Extracurricular activities take place outside of the classroom and result in several benefits to students (National Federation of State High School Associations [NFHS], 2010). With the recent recession in…

  13. Discovering the Thermodynamics of Simultaneous Equilibria: An Entropy Analysis Activity Involving Consecutive Equilibria

    ERIC Educational Resources Information Center

    Bindel, Thomas H.

    2007-01-01

    An activity is presented in which the thermodynamics of simultaneous, consecutive equilibria are explored. The activity is appropriate for second-year high school or AP chemistry. Students discover that a reactant-favored (entropy-diminishing or endergonic) reaction can be caused to happen if it is coupled with a product-favored reaction of…

  14. Involvement of Hevea latex organelle membrane proteins in the rubber biosynthesis activity and regulatory function.

    PubMed

    Wititsuwaannakul, Dhirayos; Rattanapittayaporn, Atiya; Koyama, Tanetoshi; Wititsuwaannakul, Rapepun

    2004-03-15

    Centrifugation of fresh Hevea rubber latex yields three distinct fractions. The sediment bottom fraction (BF) content of membrane-bound organelles is ca. 20 vol.-% of latex. Prolonged storage or delayed use of fresh latex will result in disintegration and loss of the bottom fraction. This is due to the osmotically sensitive BF rupture and its membrane debris being tightly bound to the top rubber particles (RP) phase. The BF membrane was found to be highly active for rubber biosynthesis (RB), in contrast to previous reports that describe RB only occurring on the RP surface. It was clearly shown that washed BF membrane (WBM) was much more active than fresh RP for RB activity. WBM was highly activated by SDS for RB in a biphasic manner, but SDS strongly inhibited the RP. Probably WBM micelle formation resulted in a highly increased active surface area for RB. C55-PP (UPP) was a very active allylic for WBM in RB function, but inactive for RP. Serial acetone extraction of WBM proteins showed a distinct profile of the fractions with different RB activity. WBM isolated proteins suspended in 2% sodium dodecyl sulfate (SDS) with an RB activity equal to that of intact WBM was with the 20% acetone protein fraction. The 60 and 80% fractions were inactive. Combining the 20 with 80% fractions showed a complete inhibition of RB activity. Complete RB loss was also found when WBM was mixed with the 80% fraction, indicating that WBM has both an enzyme system and a factor for regulation of the RB activity in a well controlled metabolic function for the latex RB process.

  15. Activation of Hepatic Lipase Expression by Oleic Acid: Possible Involvement of USF1

    PubMed Central

    van Deursen, Diederik; van Leeuwen, Marije; Akdogan, Deniz; Adams, Hadie; Jansen, Hans; Verhoeven, Adrie J.M.

    2009-01-01

    Polyunsaturated fatty acids affect gene expression mainly through peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element binding proteins (SREBPs), but how monounsaturated fatty acids affect gene expression is poorly understood. In HepG2 cells, oleate supplementation has been shown to increase secretion of hepatic lipase (HL). We hypothesized that oleate affects HL gene expression at the transcriptional level. To test this, we studied the effect of oleate on HL promoter activity using HepG2 cells and the proximal HL promoter region (700 bp). Oleate increased HL expression and promoter activity 1.3–2.1 fold and reduced SREBP activity by 50%. Downregulation of SREBP activity by incubation with cholesterol+25-hydroxycholesterol had no effect on HL promoter activity. Overexpression of SREBP2, but not SREBP1, reduced HL promoter activity, which was effected mainly through the USF1 binding site at -307/-312. Oleate increased the nuclear abundance of USF1 protein 2.7 ± 0.6 fold, while USF1 levels were reduced by SREBP2 overexpression. We conclude that oleate increases HL gene expression via USF1. USF1 may be an additional fatty acid sensor in liver cells. PMID:22253973

  16. Measuring the Activity of Leucine-Rich Repeat Kinase 2: A Kinase Involved in Parkinson's Disease

    PubMed Central

    Lee, Byoung Dae; Li, Xiaojie; Dawson, Ted M.; Dawson, Valina L.

    2015-01-01

    Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common cause of autosomal dominant Parkinson's disease. LRRK2 has multiple functional domains including a kinase domain. The kinase activity of LRRK2 is implicated in the pathogenesis of Parkinson's disease. Developing an assay to understand the mechanisms of LRRK2 kinase activity is important for the development of pharmacologic and therapeutic applications. Here, we describe how to measure in vitro LRRK2 kinase activity and its inhibition. PMID:21960214

  17. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

    SciTech Connect

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru; Niwa, Koichi; Hattori, Yuichi; Kondo, Takashi; Inanami, Osamu

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced by treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.

  18. Involvement of cytochrome P-450 enzyme activity in the selectivity and safening action of pyrazosulfuron-ethyl.

    PubMed

    Yun, M S; Shim, I S; Usui, K

    2001-03-01

    To investigate the selectivity and safening action of the sulfonylurea herbicide pyrazosulfuron-ethyl (PSE), pyrazosulfuron-ethyl O-demethylase (PSEOD) activity involving oxidative metabolism by cytochrome P-450 was studied in rice (Oryza sativa L cv Nipponbare) and Cyperus serotinus Rottb. Cytochrome P-450-dependent activity was demonstrated by the use of the inducers 1,8-naphthalic anhydride and ethanol, the herbicides PSE, bensulfuron-methyl, dimepiperate and dymron, or the inhibitor piperonyl butoxide (PBO). Growth inhibition in C serotinus seedlings was more severe than that in rice seedlings. O-Dealkylation activities of PSE were induced differently in rice and in C serotinus, with distinctly higher activity in rice seedlings. The induced PSEOD activities were slightly inhibited by PBO in rice seedlings, whereas they were strongly inhibited in C serotinus seedlings. Dimepiperate and dymron were effective safeners of rice against PSE treatment. Treatments with herbicide alone resulted in less induction of PSEOD activity compared with combined treatments of the herbicide and safener. PSEOD activity in rice seedlings induced with herbicide alone was strongly inhibited by PBO, whereas it was weakly inhibited in rice seedlings induced with combinations of PSE and two safeners. These results suggest that O-demethylation by cytochrome P-450 enzymes may be involved in the metabolism of PSE and may contribute to its selectivity and safening action. Furthermore, these results suggest the existence of a multiple form of cytochrome P-450 in plants.

  19. [The involvement of prostaglandins in the inhibiting effect of endotoxin on the myoelectric activity of the gastrointestinal system in pigs].

    PubMed

    Wechsung, E

    1996-01-01

    The probable involvement of prostaglandins in the myoelectrical response of the antrum pylori and small intestine to endotoxin (LPS) was studied in the piglet. In these experiments the influence of I.V. infusion of PGF2 alpha and PGE2 and of I.V. injection of LPS, without and with indomethacin (INDO) pretreatment, on myoelectrical activity of the antrum pylori, duodenum, jejunum and ileum as well as on some clinical and haematological parameters was studied. Infusion of the 2 PG's, especially PGE2, inhibited myoelectrical activity of the antrum pylori. PGE2 also reduced duodenal activity. PGF2 alpha was without effect on duodenal and jejunal activity, but stimulated ileal activity. Both PG's induced fever, nausea, vomiting and sedation or excitation. With the higher dose of PGE2 diarrhoea was also observed. Injection of LPS induced identical myoelectrical and clinical changes, as described for PGE2. However, endotoxin did not induce diarrhoea. Depending on the dose, administration of LPS resulted in a leukocytosis or a leukopenia together with an increase in band neutrophils. Following pretreatment with INDO the effects of LPS on gastrointestinal electrical activity were reduced and its clinical symptoms were nearly completely inhibited. The haematological changes induced by LPS, however, were not influenced by INDO. These experiments suggest a possible involvement of the PG's in the clinical symptoms and in the initial inhibitory effect of LPS on myoelectrical activity especially of the antrum. However, the induced haematological changes are probably not mediated by the arachidonic acid pathway.

  20. Histochemical location of key enzyme activities involved in receptivity and self-incompatibility in the olive tree (Olea europaea L.).

    PubMed

    Serrano, Irene; Olmedilla, Adela

    2012-12-01

    Stigma-surface and style enzymes are important for pollen reception, selection and germination. This report deals with the histochemical location of the activity of four basic types of enzyme involved in these processes in the olive (Olea europaea L.). The detection of peroxidase, esterase and acid-phosphatase activities at the surface of the stigma provided evidence of early receptivity in olive pistils. The stigma maintained its receptivity until the arrival of pollen. Acid-phosphatase activity appeared in the style at the moment of anthesis and continued until the fertilization of the ovule. RNase activity was detected in the extracellular matrix of the styles of flowers just before pollination and became especially evident in pistils after self-pollination. This activity gradually decreased until it practically disappeared in more advanced stages. RNase activity was also detected in pollen tubes growing in pollinated pistils and appeared after in vitro germination in the presence of self-incompatible pistils. These findings suggest that RNases may well be involved in intraspecific pollen rejection in olive flowers. To the best of our knowledge this is the first time that evidence of enzyme activity in stigma receptivity and pollen selection has been described in this species.

  1. Aesthetic activities and aesthetic attitudes: influences of education, background and personality on interest and involvement in the arts.

    PubMed

    McManus, I C; Furnham, A

    2006-11-01

    There have been few studies of why some people are frequently involved in aesthetic activities such as going to the theatre, reading or playing musical instruments, whereas others are less involved. This study assesses the broad roles of education, personality and demographic factors such as social class, age and sex. More aesthetic activity was associated with music and art education, whereas science education had a substantial negative relationship with aesthetic activity, both directly and also indirectly via reduced art education. More aesthetic activity was particularly related to higher scores on the personality factor of openness, and also to lower scores on agreeableness and conscientiousness. Higher parental social class was also associated with more aesthetic activity, as also was lower age. Sex had no relationship to aesthetic activity, as neither did masculinity-femininity. Positive aesthetic attitudes were also related moderately to aesthetic activity, but were particularly strongly related to openness to experience, and somewhat less to extraversion. Class, age and sex had no direct relationship to aesthetic attitudes.

  2. Directory of DOE and contractor personnel involved in non-government standards activities

    SciTech Connect

    1995-08-01

    This document contains a listing of DOE employees and DOE contractors who have submitted form DOE F 1300.2, Record of Non-Government Standards Activity. Additional names were added from rosters supplied by non-Government standards bodies.

  3. 78 FR 57818 - Commission Participation and Commission Employee Involvement in Voluntary Standards Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... From the Federal Register Online via the Government Publishing Office CONSUMER PRODUCT SAFETY... Standards Activities AGENCY: Consumer Product Safety Commission. ACTION: Notice of proposed rulemaking. SUMMARY: The United States Consumer Product Safety Commission (Commission or CPSC) is issuing a...

  4. Random sequential adsorption on fractals.

    PubMed

    Ciesla, Michal; Barbasz, Jakub

    2012-07-28

    Irreversible adsorption of spheres on flat collectors having dimension d < 2 is studied. Molecules are adsorbed on Sierpinski's triangle and carpet-like fractals (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled numerically using random sequential adsorption (RSA) algorithm. The paper concentrates on measurement of fundamental properties of coverages, i.e., maximal random coverage ratio and density autocorrelation function, as well as RSA kinetics. Obtained results allow to improve phenomenological relation between maximal random coverage ratio and collector dimension. Moreover, simulations show that, in general, most of known dimensional properties of adsorbed monolayers are valid for non-integer dimensions.

  5. Sequential ranging: How it works

    NASA Technical Reports Server (NTRS)

    Baugh, Harold W.

    1993-01-01

    This publication is directed to the users of data from the Sequential Ranging Assembly (SRA), and to others who have a general interest in range measurements. It covers the hardware, the software, and the processes used in acquiring range data; it does not cover analytical aspects such as the theory of modulation, detection, noise spectral density, and other highly technical subjects. In other words, it covers how ranging is done, but not the details of why it works. The publication also includes an appendix that gives a brief discussion of PN ranging, a capability now under development.

  6. A high speed sequential decoder

    NASA Technical Reports Server (NTRS)

    Lum, H., Jr.

    1972-01-01

    The performance and theory of operation for the High Speed Hard Decision Sequential Decoder are delineated. The decoder is a forward error correction system which is capable of accepting data from binary-phase-shift-keyed and quadriphase-shift-keyed modems at input data rates up to 30 megabits per second. Test results show that the decoder is capable of maintaining a composite error rate of 0.00001 at an input E sub b/N sub o of 5.6 db. This performance has been obtained with minimum circuit complexity.

  7. The Sequential Parameter Optimization Toolbox

    NASA Astrophysics Data System (ADS)

    Bartz-Beielstein, Thomas; Lasarczyk, Christian; Preuss, Mike

    The sequential parameter optimization toolbox (SPOT) is one possible implementation of the SPO framework introduced in Chap. 2. It has been successfully applied to numerous heuristics for practical and theoretical optimization problems. We describe the mechanics and interfaces employed by SPOT to enable users to plug in their own algorithms. Furthermore, two case studies are presented to demonstrate how SPOT can be applied in practice, followed by a discussion of alternative metamodels to be plugged into it.We conclude with some general guidelines.

  8. Functionalized sorbent for chemical separations and sequential forming process

    DOEpatents

    Fryxell, Glen E [Kennewick, WA; Zemanian, Thomas S [Richland, WA

    2012-03-20

    A highly functionalized sorbent and sequential process for making are disclosed. The sorbent includes organic short-length amino silanes and organic oligomeric polyfunctional amino silanes that are dispersed within pores of a porous support that form a 3-dimensional structure containing highly functionalized active binding sites for sorption of analytes.

  9. Platelet Activation by Low Concentrations of Intact Oxidized LDL Particles Involves the PAF Receptor

    PubMed Central

    Chen, Rui; Chen, Xi; Salomon, Robert G.; McIntyre, Thomas M.

    2008-01-01

    Objective Mitochondrial depolarization aids platelet activation. Oxidized LDL (oxLDL) contains the medium length oxidatively truncated phospholipid hexadecyl azelaoyl-lysoPAF (HAz-LPAF) that disrupts mitochondrial function in nucleated cells, so oxLDL may augment platelet activation. Methods and Results Flow cytometry showed intact oxLDL particles synergized with sub-threshold amounts of soluble agonists to increase intracellular Ca++, and initiate platelet aggregation and surface expression of activated gpIIb/IIIa and P-selectin. oxLDL also induced aggregation and increased intracellular Ca++ in FURA2-labeled cells by itself at low, although not higher, concentrations. HAz-LPAF, alone and in combination with sub-stimulatory amounts of thrombin, rapidly increased cytoplasmic Ca++ and initiated aggregation. HAz-LPAF depolarized mitochondria in intact platelets, but this required concentrations beyond those that directly activated platelets. An unexpectedly large series of chemically pure truncated phospholipids generated by oxidative fragmentation of arachidonoyl-, docosahexaneoyl-, or linoleoyl alkyl phospholipids were platelet agonists. The PAF receptor, thought to effectively recognize only phospholipids with very short sn-2 residues, was essential for platelet activation because PAF receptor agonists blocked signaling by all these medium length phospholipids and oxLDL. Conclusions Intact oxLDL particles activate platelets through the PAF receptor, and the PAF receptor responds to a far wider range of oxidized phospholipids in oxLDL than anticipated. PMID:19112165

  10. Reactive oxygen species are involved in arsenic trioxide inhibition of pyruvate dehydrogenase activity.

    PubMed

    Samikkannu, Thangavel; Chen, Chien-Hung; Yih, Ling-Huei; Wang, Alexander S S; Lin, Shu-Yu; Chen, Tsen-Chien; Jan, Kun-Yan

    2003-03-01

    Arsenite was shown to inhibit pyruvate dehydrogenase (PDH) activity through binding to vicinal dithiols in pure enzyme and tissue extract. However, no data are available on how arsenite inhibits PDH activity in human cells. The IC(50) values for arsenic trioxide (As(2)O(3)) to inhibit the PDH activity in porcine heart pure enzyme preparation and in human leukemia cell line HL60 cells were estimated to be 182 and 2 microM, respectively. Thus, As(2)O(3) inactivation of PDH activity was about 90 times more potent in HL60 cells than in purified enzyme preparation. The IC(50) values for As(2)O(3) and phenylarsine oxide to reduce the vicinal thiol content in HL60 cells were estimated to be 81.7 and 1.9 microM, respectively. Thus, As(2)O(3) is a potent PDH inhibitor but a weak vicinal thiol reacting agent in HL60 cells. Antioxidants but not dithiol compounds suppressed As(2)O(3) inhibition of PDH activity in HL60 cells. Conversely, dithiol compounds but not antioxidants suppressed the inhibition of PDH activity by phenylarsine oxide. As(2)O(3) increased H(2)O(2) level in HL60 cells, but this was not observed for phenylarsine oxide. Mitochondrial respiration inhibitors suppressed the As(2)O(3)-induced H(2)O(2) production and As(2)O(3) inhibition of PDH activity. Moreover, metal chelators ameliorated whereas Fenton metals aggravated As(2)O(3) inhibition of PDH activity. Treatment with H(2)O(2) plus Fenton metals also decreased the PDH activity in HL60 cells. Therefore, it seems that As(2)O(3) elevates H(2)O(2) production in mitochondria and this may produce hydroxyl through the Fenton reaction and result in oxidative damage to the protein of PDH. The present results suggest that arsenite may cause protein oxidation to inactivate an enzyme and this can occur at a much lower concentration than arsenite binding directly to the critical thiols.

  11. Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation

    PubMed Central

    Karikari, Thomas K.; Yawson, Nat Ato; Quansah, Emmanuel

    2016-01-01

    Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers’ scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public. PMID:27385932

  12. Developing Science Communication in Africa: Undergraduate and Graduate Students should be Trained and Actively Involved in Outreach Activity Development and Implementation.

    PubMed

    Karikari, Thomas K; Yawson, Nat Ato; Quansah, Emmanuel

    2016-01-01

    Despite recent improvements in scientific research output from Africa, public understanding of science in many parts of the continent remains low. Science communication there is faced with challenges such as (i) lack of interest among some scientists, (ii) low availability of training programs for scientists, (iii) low literacy rates among the public, and (iv) multiplicity of languages. To address these challenges, new ways of training and motivating scientists to dialogue with non-scientists are essential. Developing communication skills early in researchers' scientific career would be a good way to enhance their public engagement abilities. Therefore, a potentially effective means to develop science communication in Africa would be to actively involve trainee scientists (i.e., undergraduate and graduate students) in outreach activity development and delivery. These students are often enthusiastic about science, eager to develop their teaching and communication skills, and can be good mentors to younger students. Involving them in all aspects of outreach activity is, therefore, likely to be a productive implementation strategy. However, science communication training specifically for students and the involvement of these students in outreach activity design and delivery are lacking in Africa. Here, we argue that improving the training and involvement of budding scientists in science communication activities would be a good way to bridge the wide gap between scientists and the African public.

  13. Involvement of dopaminergic neuronal cystatin C in neuronal injury-induced microglial activation and neurotoxicity.

    PubMed

    Dutta, Garima; Barber, David S; Zhang, Ping; Doperalski, Nicholas J; Liu, Bin

    2012-08-01

    Factors released from injured dopaminergic (DA) neurons may trigger microglial activation and set in motion a vicious cycle of neuronal injury and inflammation that fuels progressive DA neurodegeneration in Parkinson's disease. In this study, using proteomic and immunoblotting analysis, we detected elevated levels of cystatin C in conditioned media (CM) from 1-methyl-4-phenylpyridinium and dieldrin-injured rat DA neuronal cells. Immunodepletion of cystatin C significantly reduced the ability of DA neuronal CM to induce activation of rat microglial cells as determined by up-regulation of inducible nitric oxide synthase, production of free radicals and release of proinflammatory cytokines as well as activated microglia-mediated DA neurotoxicity. Treatment of the cystatin C-containing CM with enzymes that remove O- and sialic acid-, but not N-linked carbohydrate moieties markedly reduced the ability of the DA neuronal CM to activate microglia. Taken together, these results suggest that DA neuronal cystatin C plays a role in the neuronal injury-induced microglial activation and neurotoxicity. These findings from the rat DA neuron-microglia in vitro model may help guide continued investigation to define the precise role of cystatin C in the complex interplay among neurons and glia in the pathogenesis of Parkinson's disease.

  14. Activity involvement as an ecological asset: profiles of participation and youth outcomes.

    PubMed

    Agans, Jennifer P; Champine, Robey B; DeSouza, Lisette M; Mueller, Megan Kiely; Johnson, Sara Kassie; Lerner, Richard M

    2014-06-01

    Prior research has demonstrated that participation in out-of-school time activities is associated with positive and healthy development among adolescents. However, fewer studies have examined how trajectories of participation across multiple activities can impact developmental outcomes. Using data from Wave 3 (approximately Grade 7) through Wave 8 (approximately Grade 12) of the 4-H Study of Positive Youth Development, this study examined patterns of breadth in out-of-school time participation in activities and associated outcomes in positive youth development (PYD), Contribution to self and community, risk behaviors, and depressive symptoms. We assessed 927 students (on average across waves, 65.4% female) from a relatively racially and ethnically homogeneous sample (about 74% European American, across waves) with a mean age in Wave 3 of 12.98 years (SD = 0.52). The results indicated that high likelihood of participation in activities was consistently associated with fewer negative outcomes and higher scores on PYD and Contribution, as compared to low likelihood of participation in activities. Changes in the breadth of participation (in particular, moving from a high to a low likelihood of participation) were associated with increased substance use, depressive symptoms, and risk behaviors. Limitations of the current study, implications for future research, and applications to youth programs are discussed.

  15. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity.

    PubMed

    Watanabe, Hideki; Gaide, Olivier; Pétrilli, Virginie; Martinon, Fabio; Contassot, Emmanuel; Roques, Stéphanie; Kummer, Jean A; Tschopp, Jürg; French, Lars E

    2007-08-01

    The inflammasome is a cytosolic protein complex regulating the activation of caspase-1, which cleaves the pro-inflammatory cytokines IL-1beta and IL-18 into their active form. The inflammasome is composed of a NACHT-, LRR- and pyrin (NALP) family member that acts as a sensor for danger signals and the adaptor protein apoptosis-associated speck-like protein containing a CARD domain (ASC), which allows the recruitment of caspase-1 in the complex. In the skin, exposure to contact sensitizers (CS) such as trinitro-chlorobenzene causes an immune response called contact hypersensitivity (CHS) or eczema. In this delayed-type hypersensitivity response, efficient priming of the adaptive immunity depends on the concomitant activation of the innate immune system, including IL-1beta/IL-18 activation in the skin. To determine if the inflammasome contributes to CHS, we have analyzed its capacity to react to CS in vitro and in vivo. We show here that key components of the inflammasome are present in human keratinocytes and that CS like trinitro-chlorobenzene induce caspase-1/ASC dependent IL-1beta and IL-18 processing and secretion. We also show that ASC- and NALP3-deficient mice display an impaired response to CS. These findings suggest that CS act as danger signals that activate the inflammasome in the skin, and reveal a new role of NALP3 and ASC as regulators of innate immunity in CHS.

  16. NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells

    SciTech Connect

    Nishina, Takashi; Yamaguchi, Noritaka; Gohda, Jin; Semba, Kentaro; Inoue, Jun-ichiro

    2009-10-09

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  17. IL-37 Confers Protection against Mycobacterial Infection Involving Suppressing Inflammation and Modulating T Cell Activation

    PubMed Central

    Yang, Hua; He, Xin; Ji, Qun; Bai, Wenjuan; Chen, Hao; Chen, Jianxia; Peng, Wenxia; Liu, Siyu; Liu, Zhonghua; Ge, Baoxue

    2017-01-01

    Interleukin-37 (IL-37), a novel member of the IL-1 family, plays fundamental immunosuppressive roles by broadly reducing both innate inflammation and acquired immunity, but whether it is involved in the pathogenesis of tuberculosis (TB) has not been clearly elucidated. In this study, single nucleotide polymorphism (SNP) analysis demonstrated an association of the genetic variant rs3811047 of IL-37 with TB susceptibility. In line with previous report, a significant elevated IL-37 abundance in the sera and increased expression of IL-37 protein in the peripheral blood mononuclear cells (PBMC) were observed in TB patients in comparison to healthy controls. Moreover, release of IL-37 were detected in either macrophages infected with Mycobacterium tuberculosis (Mtb) or the lung of BCG-infected mice, concurrent with reduced production of proinflammatory cytokines including IL-6 and TNF-α. Furthermore, in contrast to wild-type mice, BCG-infected IL-37-Tg mice manifested with reduced mycobacterial burden and tissue damage in the lung, accompanied by higher frequency of Th1 cell and less frequencies of regulatory T cells and Th17 cells in the spleen. Taken together, our findings demonstrated that IL-37 conferred resistance to Mtb infection possibly involving suppressing detrimental inflammation and modulating T cell responses. These findings implicated that IL-37 may be employed as a new molecular target for the therapy and diagnosis of TB. PMID:28076390

  18. Involvement of active oxygen in lipid peroxide radical reaction of epidermal homogenate following ultraviolet light exposure

    SciTech Connect

    Nishi, J.; Ogura, R.; Sugiyama, M.; Hidaka, T.; Kohno, M. )

    1991-07-01

    To elucidate the radical mechanism of lipid peroxidation induced by ultraviolet light (UV) irradiation, an electron spin resonance (ESR) study was made on epidermal homogenate prepared from albino rat skin. The exposure of the homogenate to UV light resulted in an increase in lipid peroxide content, which was proportional to the time of UV exposure. Using ESR spin trapping (dimethyl-1-pyrroline-N-oxide, DMPO), the DMPO spin adduct spectrum of lipid radicals (L.) was measured following UV exposure (DMPO-L.:aN = 15.5 G, aH = 22.7 G), as was the spectrum of DMPO-hydroxyl radical (DMPO-OH, aN = aH = 15.5 G). In the presence of superoxide dismutase, the DMPO spin adduct spectrum of lipid radicals was found to be reduced remarkably. Therefore, it was shown that the generation of the lipid radicals partially involves superoxide anion radicals, in addition to hydroxyl radicals. In the ESR free-radical experiment, an ESR signal appeared at g = 2.0064 when the ESR tube filled with homogenate was exposed to UV light at -150 degrees C. The temperature-dependent change in the ESR free radical signal of homogenate exposed to UV light was observed at temperatures varying from -150 degrees C to room temperature. By using degassed samples, it was confirmed that oxygen is involved in the formation of the lipid peroxide radicals (LOO.) from the lipid radicals (L.).

  19. Teacher management behaviors and pupil task involvement during small group laboratory activities

    NASA Astrophysics Data System (ADS)

    Beasley, Warren

    A major concern of many beginning and experienced teachers is that of classroom management and control. This article describes recent research into defining classroom management procedures that are used by high school science teachers and their relationship to pupil ontaskness. The classroom is conceptualized as a manipulable behavioral system. This construct arises directly from Barker's (1968) ecological psychology, the classroom and its occupants being conceptualized as a behavior setting. The behaviors of the teacher and the pupils are an integral part of the unit (behavior setting), which in turn coerces certain behaviors from its participants. Thus settings, and, in particular, subsettings, are seen as more important determiners of social behavior than the personality of individual teacher or pupil. The methodology employed in this research has involved the extensive use of video in naturalistic science classrooms. Tapes of both teacher and pupil behaviors were continuously and independently recorded. Intensive analysis using electronic recording instruments interfaced with the computer has allowed the collection and sophisticated analysis of the observational data. Data relating to teacher management behavior in small group settings have been analyzed and the relationships to pupil task involvement have been explored.

  20. Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation.

    PubMed

    Mohamad, Saharuddin B; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

    2002-05-01

    Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation.

  1. Phospholipase A{sub 2} is involved in the mechanism of activation of neutrophils by polychlorinated biphenyls

    SciTech Connect

    Tithof, P.K.; Schiamberg, E.; Ganey, P.E.; Peters-Golden, M.

    1996-01-01

    Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), activates neutrophils to produce superoxide anion (O{sub 2}{sup {minus}}) by a mechanism that involves phospholipase C-dependent hydrolysis of membrane phosphoinositides; however, subsequent signal transduction mechanisms are unknown. This study determines whether phospholipase A{sub 2}-dependent release of arachidonic acid is involved in PCB-induced O{sub 2}{sup {minus}} production. O{sub 2}{sup {minus}} production was measured in vitro in glycogen-elicited, rat neutrophils in the presence and absence of the inhibitors of phospholipase A{sub 2}: quinacrine, 4-bromophenacyl bromide (BPB), and manoalide. All three agents significantly decreased the amount of O{sub 2}{sup {minus}} detected during stimulation of neutrophils with Aroclor 1242. Similar inhibition occurred when neutrophils were activated with the classical stimuli, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate. The effects of BPB and manoalide were not a result of cytotoxicity or other nonspecific effects. Significant release of {sup 3}H-arachidonic acid preceded O{sub 2}{sup {minus}} production in neutrophils stimulated with Aroclor 1242 or fMLP. Manoalide, at a concentration that abolished O{sub 2}{sup {minus}} production, also inhibited the release of {sup 3}H-arachidonate. Aspirin, zileuton, or WEB 2086 did not affect Aroclor 1242-induced O{sub 2}{sup {minus}} production, suggesting that eicosanoids and platelet-activating factor are not needed for neutrophil activation by PCBs. Activation of phos-pholipase A{sub 2} and O{sub 2}{sup {minus}} production do not appear to involve the Ah receptor. These data suggest that Aroclor 1242 stimulates neutrophils to produce O{sub 2}{sup {minus}} by a mechanism that involves phospholipase A{sub 2}-dependent release of arachiodonic acid. 49 refs., 6 figs., 2 tabs.

  2. Involvement of a membrane potassium channel in heparan sulphate-induced activation of macrophages.

    PubMed

    Ren, Jian-Dong; Fan, Li; Tian, Fu-Zhou; Fan, Kai-Hua; Yu, Bo-Tao; Jin, Wei-Hua; Tan, Yong-Hong; Cheng, Long

    2014-03-01

    Increasing evidence has demonstrated that Toll-like receptor 4 (TLR4) -mediated systemic inflammatory response syndrome accompanied by multiple organ failure, is one of the most common causes of death in patients with severe acute pancreatitis. Recent reports have revealed that heparan sulphate (HS) proteoglycan, a component of extracellular matrices, potentiates the activation of intracellular pro-inflammatory responses via TLR4, contributing to the aggravation of acute pancreatitis. However, little is known about the participants in the HS/TLR4-mediated inflammatory cascades. Our previous work provided a clue that a membrane potassium channel (MaxiK) is responsible for HS-induced production of inflammatory cytokines. Therefore, in this report we attempted to reveal the roles of MaxiK in the activation of macrophages stimulated by HS. Our results showed that incubation of RAW264.7 cells with HS up-regulated MaxiK and TLR4 expression levels. HS could also activate MaxiK channels to promote the efflux of potassium ions from cells, as measured by the elevated activity of caspase-1, whereas this was significantly abolished by treatment with paxilline, a specific blocker of the MaxiK channel. Moreover, it was found that paxilline substantially inhibited HS-induced activation of several different transcription factors in macrophages, including nuclear factor-κB, p38 and interferon regulatory factor-3, followed by decreased production of tumour necrosis factor-α and interferon-β. Taken together, our investigation provides evidence that the HS/TLR4-mediated intracellular inflammatory cascade depends on the activation of MaxiK, which may offer an important opportunity for a new approach in therapeutic strategies of severe acute pancreatitis.

  3. Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

    PubMed Central

    2014-01-01

    Background In neuroinflammatory diseases, macrophages can play a dual role in the process of tissue damage, depending on their activation status (M1 / M2). M1 macrophages are considered to exert damaging effects to neurons, whereas M2 macrophages are reported to aid regeneration and repair of neurons. Their migration within the central nervous system may be of critical importance in the final outcome of neurodegeneration in neuroinflammatory diseases e.g. multiple sclerosis (MS). To provide insight into this process, we examined the migratory capacity of human monocyte-derived M1 and M2 polarised macrophages towards chemoattractants, relevant for neuroinflammatory diseases like MS. Methods Primary cultures of human monocyte-derived macrophages were exposed to interferon gamma and lipopolysaccharide (LPS) to evoke proinflammatory (M1) activation or IL-4 to evoke anti-inflammatory (M2) activation. In a TAXIScan assay, migration of M0, M1 and M2 towards chemoattractants was measured and quantified. Furthermore the adhesion capacity and the expression levels of integrins as well as chemokine receptors of M0, M1 and M2 were assessed. Alterations in cell morphology were analysed using fluorescent labelling of the cytoskeleton. Results Significant differences were observed between M1 and M2 macrophages in the migration towards chemoattractants. We show that M2 macrophages migrated over longer distances towards CCL2, CCL5, CXCL10, CXCL12 and C1q compared to non-activated (M0) and M1 macrophages. No differences were observed in the adhesion of M0, M1 and M2 macrophages to multiple matrix components, nor in the expression of integrins and chemokine receptors. Significant changes were observed in the cytoskeleton organization upon stimulation with CCL2, M0, M1 and M2 macrophages adopt a spherical morphology and the cytoskeleton is rapidly rearranged. M0 and M2 macrophages are able to form filopodia, whereas M1 macrophages only adapt a spherical morphology. Conclusions

  4. Sodium tungstate activates glycogen synthesis through a non-canonical mechanism involving G-proteins.

    PubMed

    Zafra, Delia; Nocito, Laura; Domínguez, Jorge; Guinovart, Joan J

    2013-01-31

    Tungstate treatment ameliorates experimental diabetes by increasing liver glycogen deposition through an as yet unidentified mechanism. The signalling mechanism of tungstate was studied in CHOIR cells and primary cultured hepatocytes. This compound exerted its pro-glycogenic effects through a new G-protein-dependent and Tyr-Kinase Receptor-independent mechanism. Chemical or genetic disruption of G-protein signalling prevented the activation of the Ras/ERK cascade and the downstream induction of glycogen synthesis caused by tungstate. Thus, these findings unveil a novel non-canonical signalling pathway that leads to the activation of glycogen synthesis and that could be exploited as an approach to treat diabetes.

  5. Rundown of the hyperpolarization-activated KAT1 channel involves slowing of the opening transitions regulated by phosphorylation.

    PubMed Central

    Tang, X D; Hoshi, T

    1999-01-01

    Disappearance of the functional activity or rundown of ion channels upon patch excision in many cells involves a decrease in the number of channels available to open. A variety of cellular and biophysical mechanisms have been shown to be involved in the rundown of different ion channels. We examined the rundown process of the plant hyperpolarization-activated KAT1 K+ channel expressed in Xenopus oocytes. The decrease in the KAT1 channel activity on patch excision was accompanied by progressive slowing of the activation time course, and it was caused by a shift in the voltage dependence of the channel without any change in the single-channel amplitude. The single-channel analysis showed that patch excision alters only the transitions leading up to the burst states of the channel. Patch cramming or concurrent application of protein kinase A (PKA) and ATP restored the channel activity. In contrast, nonspecific alkaline phosphatase (ALP) accelerated the rundown time course. Low internal pH, which inhibits ALP activity, slowed the KAT1 rundown time course. The results show that the opening transitions of the KAT1 channel are enhanced not only by hyperpolarization but also by PKA-mediated phosphorylation. PMID:10354434

  6. Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity.

    PubMed

    Baba, Shiro; Onga, Kazuko; Kakizawa, Sho; Ohyama, Kyoji; Yasuda, Kunihiko; Otsubo, Hiroshi; Scott, Brian W; Burnham, W McIntyre; Matsuo, Takayuki; Nagata, Izumi; Mori, Nozomu

    2016-06-08

    BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy.

  7. Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity

    PubMed Central

    Baba, Shiro; Onga, Kazuko; Kakizawa, Sho; Ohyama, Kyoji; Yasuda, Kunihiko; Otsubo, Hiroshi; Scott, Brian W.; Burnham, W. McIntyre; Matsuo, Takayuki; Nagata, Izumi; Mori, Nozomu

    2016-01-01

    BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy. PMID:27273072

  8. An efficient and economical treatment for batik textile wastewater containing high levels of silicate and organic pollutants using a sequential process of acidification, magnesium oxide, and palm shell-based activated carbon application.

    PubMed

    Birgani, Payam Moradi; Ranjbar, Navid; Abdullah, Rosniah Che; Wong, Kien Tiek; Lee, Gooyong; Ibrahim, Shaliza; Park, Chulhwan; Yoon, Yeomin; Jang, Min

    2016-12-15

    Considering the chemical properties of batik effluents, an efficient and economical treatment process was established to treat batik wastewater containing not only high levels of Si and chemical oxygen demand (COD), but also toxic heavy metals. After mixing the effluents obtained from the boiling and soaking steps in the batik process, acidification using concentrated hydrochloric acid (conc. HCl) was conducted to polymerize the silicate under acidic conditions. Consequently, sludge was produced and floated. XRD and FT-IR analyses showed that wax molecules were coordinated by hydrogen bonding with silica (SiO2). The acidification process removed ∼78-95% of COD and ∼45-50% of Si, depending on the pH. In the next stage, magnesium oxide (MgO) was applied to remove heavy metals completely and almost 90% of the Si in the liquid phase. During this step, about 70% of COD was removed in the hydrogel that arose as a consequence of the crosslinking characteristics of the formed nano-composite, such as magnesium silicate or montmorillonite. The hydrogel was composed mainly of waxes with polymeric properties. Then, the remaining Si (∼300 mg/L) in the wastewater combined with the effluents from the rinsing steps was further treated using 50 mg/L MgO. As a final step, palm-shell activated carbon (PSAC) was used to remove the remaining COD to < 50 mg/L at pH 3. Overall, the sequential process of acidification and MgO/PSAC application developed could serve as an economical and effective treatment option for treating heavily polluted batik effluents.

  9. Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis

    PubMed Central

    Jackson, Joseph W.; Singh, Meera V.; Singh, Vir B.; Jones, Letitia D.; Davidson, Gregory A.; Ture, Sara; Morrell, Craig N.; Schifitto, Giovanni; Maggirwar, Sanjay B.

    2016-01-01

    Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet-associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies. PMID:27270236

  10. Fantasy Activity and the Televiewing Event: Considerations for an Information Processing Construct of Involvement.

    ERIC Educational Resources Information Center

    Lindlof, Thomas R.

    The similarities between television viewing and fantasy activity (daydreaming, reverie, mind-wandering, internal dialogue) more than warrant the building of a theoretical construct, especially in the context of recent empirical research on television viewing consequences. A construct of the television viewing process, based on cognitive theories…

  11. Peroxiredoxin-3 Is Involved in Bactericidal Activity through the Regulation of Mitochondrial Reactive Oxygen Species

    PubMed Central

    Lee, Sena; Wi, Sae Mi; Min, Yoon

    2016-01-01

    Peroxiredoxin-3 (Prdx3) is a mitochondrial protein of the thioredoxin family of antioxidant peroxidases and is the principal peroxidase responsible for metabolizing mitochondrial hydrogen peroxide. Recent reports have shown that mitochondrial reactive oxygen species (mROS) contribute to macrophage-mediated bactericidal activity in response to Toll-like receptors. Herein, we investigated the functional effect of Prdx3 in bactericidal activity. The mitochondrial localization of Prdx3 in HEK293T cells was confirmed by cell fractionation and confocal microscopy analyses. To investigate the functional role of Prdx3 in bactericidal activity, Prdx3-knockdown (Prdx3KD) THP-1 cells were generated. The mROS levels in Prdx3KD THP-1 cells were significantly higher than those in control THP-1 cells. Moreover, the mROS levels were markedly increased in response to lipopolysaccharide. Notably, the Salmonella enterica serovar Typhimurium infection assay revealed that the Prdx3KD THP-1 cells were significantly resistant to S. Typhimurium infection, as compared with control THP-1 cells. Taken together, these results indicate that Prdx3 is functionally important in bactericidal activity through the regulation of mROS. PMID:28035213

  12. School-based extracurricular activity involvement and adolescent self-esteem: a growth-curve analysis.

    PubMed

    Kort-Butler, Lisa A; Hagewen, Kellie J

    2011-05-01

    Research on adolescent self-esteem indicates that adolescence is a time in which individuals experience important changes in their physical, cognitive, and social identities. Prior research suggests that there is a positive relationship between an adolescent's participation in structured extracurricular activities and well-being in a variety of domains, and some research indicates that these relationships may be dependent on the type of activities in which adolescents participate. Building on previous research, a growth-curve analysis was utilized to examine self-esteem trajectories from adolescence (age 14) to young adulthood (age 26). Using 3 waves of data from National Longitudinal Study of Adolescent Health (n = 5,399; 47.8% male), the analysis estimated a hierarchical growth-curve model emphasizing the effects of age and type of school-based extracurricular activity portfolio, including sports and school clubs, on self-esteem. The results indicated that age had a linear relationship with self-esteem over time. Changes in both the initial level of self-esteem and the growth of self-esteem over time were significantly influenced by the type of extracurricular activity portfolio. The findings were consistent across race and sex. The results support the utility of examining the longitudinal impact of portfolio type on well-being outcomes.

  13. Mechanism of activation of methyltransferases involved in translation by the Trm112 ‘hub’ protein

    PubMed Central

    Liger, Dominique; Mora, Liliana; Lazar, Noureddine; Figaro, Sabine; Henri, Julien; Scrima, Nathalie; Buckingham, Richard H.; van Tilbeurgh, Herman; Heurgué-Hamard, Valérie; Graille, Marc

    2011-01-01

    Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases. PMID:21478168

  14. Sustainability and Science Learning: Perceptions from 8th Grade Students Involved with a Role Playing Activity

    ERIC Educational Resources Information Center

    Freire, Sofia; Baptista, Mónica; Freire, Ana

    2016-01-01

    Raising awareness about sustainability is an urgent need and as such education for sustainability has gained relevancy for the last decades. It is acknowledged that science education can work as an important context for educating for sustainability. The goal of the present paper is to describe a role-playing activity about the construction of a…

  15. Enjoyment Fosters Engagement: The Key to Involving Middle School Students in Physical Education and Physical Activity

    ERIC Educational Resources Information Center

    Pharez, Emily S.

    2016-01-01

    This article describes the challenges faced by a middle school teacher who inherited a recreation-based physical education program in which students had been accustomed to choosing what they wanted to do. Stressing the importance of implementing a standards-based program in which students of all skill levels and activity preferences were able to…

  16. A Multi-Institutional Examination of the Relationships between High School Activity Involvement and Leadership Characteristics

    ERIC Educational Resources Information Center

    Simonsen, Jon C.; Velez, Jonathan J.; Foor, Ryan M.; Birkenholz, Robert J.; Foster, Daniel D.; Wolf, Kattlyn J.; Epps, Rebekah B.

    2014-01-01

    Developing leaders is vital to the future of our nation. As institutions of higher education address the need for leadership through courses and experiences, there is a need to recognize and acknowledge the potential impact of high school activity participation on leadership development. This descriptive-correlational study surveyed first-time…

  17. Marketing Informal Education Institutions in Israel: The Centrality of Customers' Active Involvement in Service Development

    ERIC Educational Resources Information Center

    Oplatka, Izhar

    2004-01-01

    The current paper outlines a unique marketing perspective that prevails in some informal education institutions in Israel parallel with "traditional modes of marketing", such as promotion, public relations and the like. Based on a case study research in five community centres, a service development based on active participation of the…

  18. Ethanol Effects Involve Non-canonical Unfolded Protein Response Activation in Yeast Cells

    PubMed Central

    Navarro-Tapia, Elisabet; Pérez-Torrado, Roberto; Querol, Amparo

    2017-01-01

    The unfolded protein response (UPR) is a conserved intracellular signaling pathway that controls transcription of endoplasmic reticulum (ER) homeostasis related genes. Ethanol stress has been recently described as an activator of the UPR response in yeast Saccharomyces cerevisiae, but very little is known about the causes of this activation. Although some authors ensure that the UPR is triggered by the unfolded proteins generated by ethanol in the cell, there are studies which demonstrate that protein denaturation occurs at higher ethanol concentrations than those used to trigger the UPR. Here, we studied UPR after ethanol stress by three different approaches and we concluded that unfolded proteins do not accumulate in the ER under. We also ruled out inositol depletion as an alternative mechanism to activate the UPR under ethanol stress discarding that ethanol effects on the cell decreased inositol levels by different methods. All these data suggest that ethanol, at relatively low concentrations, does not cause unfolded proteins in the yeasts and UPR activation is likely due to other unknown mechanism related with a restructuring of ER membrane due to the effect of ethanol. PMID:28326077

  19. Involvement of sensor kinase gene (skrp 1122) for biocontrol activity by Pseudomonas synxantha BG33R

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research identified Pseudomonas synxantha BG33R as potential carrier for a nematode egg-kill factor. Further research indicated that BG33R exhibits a broad-spectrum of antagonistic activity against oomycetes, fungi, nematodes and insects. Earlier screening for negative egg-kill factor indi...

  20. The Development of Spatial Skills through Interventions Involving Block Building Activities

    ERIC Educational Resources Information Center

    Casey, Beth M.; Andrews, Nicole; Schindler, Holly; Kersh, Joanne E.; Samper, Alexandra; Copley, Juanita

    2008-01-01

    This study investigated the use of block-building interventions to develop spatial-reasoning skills in kindergartners. Two intervention conditions and a control condition were included to determine, first, whether the block building activities themselves benefited children's spatial skills, and secondly, whether a story context further improved…

  1. Regrouping: Organized Activity Involvement and Social Adjustment across the Transition to High School

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Aikins, Julie Wargo; Arola, Nicole T.

    2013-01-01

    Although organized activities (OAs) have been established as important contexts of development, limited work has examined the role of OAs across the high school transition in buffering adolescents' social adjustment by providing opportunities for visibility and peer affiliation. The transition to high school is characterized by numerous changes…

  2. The Effect of the New Copyright Law on the Interlibrary Loan Activity Involving Periodicals.

    ERIC Educational Resources Information Center

    Steuben, John

    Since 1954 when Congress authorized the Copyright Office to prepare a series of studies to serve as background for revision hearings, copyright has been one of the major issues in librarianship. Although the impact that the New Copyright Law will have on interlibrary loan activity is yet to be determined, there is a need to know whether present…

  3. Department of Energy interest and involvement in nuclear plant license renewal activities

    SciTech Connect

    Bustard, L.D. ); Harrison, D.L. . Office of LWR Safety and Technology)

    1991-01-01

    Recognizing the importance of nuclear license renewal to the nation's energy strategy, the Department of Energy (DOE) initiated a plant lifetime improvement program during 1985 to determine the feasibility of the license renewal option for US nuclear plants. Initial activities of the DOE program focused on determining whether there were technical and economic obstacles that might preclude or limit the successful implementation of the license renewal option. To make this determination, DOE cosponsored with the Electric Power Research Institute (EPRI) pilot-plant efforts by Virginia Electric Power and Northern States Power. Both pilot-plant efforts concluded that life extension is technically and economically feasible. In parallel with the pilot-plant activities, DOE performed national economic studies that demonstrated the economic desirability of life extension. Having demonstrated the feasibility of life extension, DOE, in conjunction with EPRI, selected two lead plants to demonstrate the license renewal process. These lead plants are Yankee Atomic's Yankee Rowe facility and Northern States Power's Monticello facility. DOE also initiated activities to develop the technical and regulatory bases to support the license renewal process in the United States. DOE has recently identified nuclear plant license renewal to be an important element of its National Energy Strategy. This paper summarizes the significant results, conclusions, and ongoing activities of the DOE effort. 18 refs.

  4. School-Based Extracurricular Activity Involvement and Adolescent Self-Esteem: A Growth-Curve Analysis

    ERIC Educational Resources Information Center

    Kort-Butler, Lisa A.; Hagewen, Kellie J.

    2011-01-01

    Research on adolescent self-esteem indicates that adolescence is a time in which individuals experience important changes in their physical, cognitive, and social identities. Prior research suggests that there is a positive relationship between an adolescent's participation in structured extracurricular activities and well-being in a variety of…

  5. Involvement of SOX proteins in lens-specific activation of crystallin genes.

    PubMed Central

    Kamachi, Y; Sockanathan, S; Liu, Q; Breitman, M; Lovell-Badge, R; Kondoh, H

    1995-01-01

    We have studied the mechanism of delta 1-crystallin gene activation, which occurs early in lens cell differentiation, and have previously shown that an essential element of the delta 1-crystallin enhancer is bound by a group of nuclear factors, delta EF2, among which delta EF2a is highly enriched in lens cells. In this report we show that the cDNA of delta EF2a codes for the chicken SOX-2 protein (cSOX-2), which is structurally related to the sex-determining factor SRY. Sox-2 is expressed at high levels in the early developing lens in both chicken and mouse embryos. Overexpression of delta EF2a/cSOX-2 increased delta 1-crystallin enhancer activity to a plateau in lens cells, but not in fibroblasts, consistent with the previously drawn conclusion that delta EF2a activates transcription only in concert with another factor present in the lens. This result supports the model that SOX proteins act as architectural components in the activating complex formed on an enhancer, as indicated for another HMG domain protein, lymphoid enhancer binding factor 1 (LEF-1). We also show that SOX protein binding is essential for lens-specific promoter activity of the mouse gamma F-crystallin gene. This work is the first to show delta- and gamma-crystallin genes as examples of direct regulatory targets of SOX proteins and provides evidence that diversified crystallin genes are regulated, at least partly, by a common mechanism. Images PMID:7628452

  6. Prevalence of disabled people involved in Spanish Civil Guard's police activity.

    PubMed

    González, José L; Cendra, Jacobo; Manzanero, Antonio L

    2013-11-01

    Improving interventions with victims and offenders with disabilities requires analysis of the degree of prevalence of crimes in which these people are involved. For this purpose, data regarding interventions made by the Spanish Civil Guard between 2008 and 2010, in which 2099 people had some kind of disability, have been collected and analyzed, with particular regard to criminal offenses (felonies and/or misdemeanors). In this study, the relationship between the types of disability a person has and other variables like their connection to the incident, their gender, age, the relationship between victim and perpetrator, and the time and place of the events were all taken into consideration. The results show that most of the victims with disabilities served by the Spanish Civil Guard were male. The interventions were mainly aid and rescues. Criminal offenses were only 20% of the events.

  7. Involvement of mitochondrial activity in mediating ELF-EMF stimulatory effect on human sperm motility.

    PubMed

    Iorio, Roberto; Delle Monache, Simona; Bennato, Francesca; Di Bartolomeo, Claudia; Scrimaglio, Renato; Cinque, Benedetta; Colonna, Rosella Cardigno

    2011-01-01

    It has recently been reported that the exposure of human spermatozoa to an extremely low frequency (ELF) electromagnetic field (EMF) with a square waveform of 5 mT amplitude and frequency of 50 Hz improves sperm motility. The functional relationship between the energy metabolism and the enhancement of human sperm motility induced by ELF-EMF was investigated. Sperm exposure to ELF-EMF resulted in a progressive and significant increase of mitochondrial membrane potential and levels of ATP, ADP and NAD(+) that was associated with a progressive and significant increase in the sperm kinematic parameters. No significant effects were detected on other parameters such as ATP/ADP ratio and energy charge. When carbamoyl cyanide m-chlorophenylhydrazone (CICCP) was applied to inhibit the oxidative phosphorylation in the mitochondria, the values of energy parameters and motility in the sperm incubated in the presence of glucose and exposed to ELF-EMF did not change, thus indicating that the glycolysis was not involved in mediating ELF-EMF stimulatory effect on motility. By contrast, when pyruvate and lactate were provided instead of glucose, the energy status and motility increased significantly in ELF-EMF-treated sperm. Under these culture conditions, the inhibition of glycolitic metabolism by 2-deoxy-D-glucose (DOG) again resulted in increased values of energy and kinematic parameters, indicating that gluconeogenesis was not involved in producing glucose for use in glycolysis. We concluded that the key role in mediating the stimulatory effects exerted by ELF-EMF on human sperm motility is played by mitochondrial oxidative phosphorylation rather than glycolysis.

  8. Mechanosensitive channels are activated by stress in the actin stress fibres, and could be involved in gravity sensing in plants.

    PubMed

    Tatsumi, H; Furuichi, T; Nakano, M; Toyota, M; Hayakawa, K; Sokabe, M; Iida, H

    2014-01-01

    Mechanosensitive (MS) channels are expressed in a variety of cells. The molecular and biophysical mechanism involved in the regulation of MS channel activities is a central interest in basic biology. MS channels are thought to play crucial roles in gravity sensing in plant cells. To date, two mechanisms have been proposed for MS channel activation. One is that tension development in the lipid bilayer directly activates MS channels. The second mechanism proposes that the cytoskeleton is involved in the channel activation, because MS channel activities are modulated by pharmacological treatments that affect the cytoskeleton. We tested whether tension in the cytoskeleton activates MS channels. Mammalian endothelial cells were microinjected with phalloidin-conjugated beads, which bound to stress fibres, and a traction force to the actin cytoskeleton was applied by dragging the beads with optical tweezers. MS channels were activated when the force was applied, demonstrating that a sub-pN force to the actin filaments activates a single MS channel. Plants may use a similar molecular mechanism in gravity sensing, since the cytoplasmic Ca(2+) concentration increase induced by changes in the gravity vector was attenuated by potential MS channel inhibitors, and by actin-disrupting drugs. These results support the idea that the tension increase in actin filaments by gravity-dependent sedimentation of amyloplasts activates MS Ca(2+) -permeable channels, which can be the molecular mechanism of a Ca(2+) concentration increase through gravistimulation. We review recent progress in the study of tension sensing by actin filaments and MS channels using advanced biophysical methods, and discuss their possible roles in gravisensing.

  9. The effect of sequential therapy for postmenopausal women with osteoporosis

    PubMed Central

    Lou, Shenghan; Lv, Houchen; Wang, Guoqi; Li, Zhirui; Li, Ming; Zhang, Licheng; Tang, Peifu

    2016-01-01

    Abstract Background: Osteoporosis, more likely to occur in postmenopausal women, is a chronic condition that usually requires a long-term treatment strategy, but the use of either antiresorptive or anabolic drugs should be limited to 18 to 24 months. Discontinuing antiosteoporosis drugs may result in rapidly declining bone mineral density (BMD). Therefore, many patients are treated with the sequential use of 2 or more drugs. However, whether switching treatment from anabolic to antiresorptive drugs or the reverse could maintain or further increase BMD; and whether the sequential therapy could outperform the monotherapy under the same treatment duration still remains unclear. Nowadays, no firm conclusions were drawn. Methods: We searched Medline, Embase, and Cochrane Library from January 1, 1974 until February 1, 2016 to identify all randomized controlled trials for evaluating the effectiveness of sequential therapy of antiresorptive and anabolic drugs in postmenopausal osteoporosis women with the BMD changes of lumbar spine, femoral neck, and total hip as the outcomes. We evaluated the methodological quality and abstracted relevant data according to the Cochrane Handbook. Results: Eight trials involving 1509 patients were included. The pooled data showed that after switching treatment, the alternative drugs maintained the BMD and significantly increased the percentage change in BMD at the lumbar spine (MD, 3.59; 95% CI, 2.26–4.93), femoral neck (MD, 1.44; 95% CI, 0.60–2.27), and total hip (MD, 1.24; 95% CI, −0.12 to 2.60), although change in BMD was not significantly increased at the total hip. The sequential therapy significantly increased BMD from baseline at the lumbar spine (SMD, 0.59; 95% CI, 0.26–0.91), femoral neck (SMD, 0.22; 95% CI, 0.06–0.37), and total hip (SMD, 0.28; 95% CI, 0.01–0.56). Conclusions: After switching treatment, sequential therapy further increased BMD. The sequential therapy showed a more significant improvement in BMD

  10. Sequentially triggered star formation in OB associations

    NASA Astrophysics Data System (ADS)

    Preibisch, Thomas; Zinnecker, Hans

    We discuss observational evidence for sequential and triggered star formation in galactic and extragalactic OB associations. We will first review in detail the star formation process in the Scorpius-Centaurus OB association, the nearest OB association to the Sun, where several recent extensive studies have provided comprehensive information on the stellar content and the ages of the different OB subgroups. These data have allowed us to reconstruct the star formation history of the association in some detail and provided important insight into the activity in the rho Oph and Lupus dark clouds, and with the origin of several young stellar groups in the southern sky. After discussing evidence for triggered star formation in and around various other Galactic OB associations (e.g. Ori OB1, Per OB2) we will compare the observational results with recent models of rapid star formation in the turbulent interstellar medium (cf. Briceno et al. chapter in Protostars and Planets V, in press).

  11. Sequential state generation by model neural networks.

    PubMed Central

    Kleinfeld, D

    1986-01-01

    Sequential patterns of neural output activity form the basis of many biological processes, such as the cyclic pattern of outputs that control locomotion. I show how such sequences can be generated by a class of model neural networks that make defined sets of transitions between selected memory states. Sequence-generating networks depend upon the interplay between two sets of synaptic connections. One set acts to stabilize the network in its current memory state, while the second set, whose action is delayed in time, causes the network to make specified transitions between the memories. The dynamic properties of these networks are described in terms of motion along an energy surface. The performance of the networks, both with intact connections and with noisy or missing connections, is illustrated by numerical examples. In addition, I present a scheme for the recognition of externally generated sequences by these networks. PMID:3467316

  12. Mechanistic studies on a sequential PDT protocol

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2016-03-01

    A low (~LD15) PDT dose resulting in selective lysosomal photodamage can markedly promote photokilling by subsequent photodamage targeted to mitochondria. Experimental data are consistent with the proposal that cleavage of the autophagyassociated protein ATG5 to a pro-apoptotic fragment is responsible for this effect. This process is known to be dependent on the proteolytic activity of calpain. We have proposed that Ca2+ released from photodamaged lysosomes is the trigger for ATG5 cleavage. We can now document the conversion of ATG5 to the truncated form after lysosomal photodamage. Photofrin, a photosensitizer that targets both mitochondria and lysosomes, can be used for either phase of the sequential PDT process. The ability of Photofrin to target both loci may explain the well-documented efficacy of this agent.

  13. Signal-transducing mechanisms involved in activation of the platelet collagen receptor integrin alpha(2)beta(1).

    PubMed

    Jung, S M; Moroi, M

    2000-03-17

    Evidence was obtained about the mechanism responsible for platelet integrin alpha(2)beta activation by determining effects of various inhibitors on soluble collagen binding, a parameter to assess integrin alpha(2)beta(1) activation, in stimulated platelets. Agonists that can also activate platelet glycoprotein IIb/IIIa are able to activate integrin alpha(2)beta(1), but those operating via glycoprotein Ib cannot. Activation of alpha(2)beta(1) induced by low thrombin or collagen-related peptide concentrations was almost completely inhibited by apyrase, and the inhibitors wortmannin, 4-amino-5-(chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, bisindolylmaleimide I, and SQ29548 significantly inhibited it. Activation induced by high thrombin or collagen-related peptide concentrations was far less sensitive to these inhibitors. However, only wortmannin markedly inhibited ADP-induced integrin alpha(2)beta(1) activation, and this was not ADP concentration-dependent. These results suggest that at the low agonist concentrations, the released ADP would be a primary inducer of integrin alpha(2)beta(1) activation, while at the high agonist concentrations, there would be several pathways through which integrin alpha(2)beta(1) activation can be induced. Kinetic analyses revealed that ADP-induced platelets had about the same number of binding sites (B(max)) as thrombin-induced platelets, but their affinity (K(d)) for soluble collagen was 3.7-12.7-fold lower, suggesting that activated integrin alpha(2)beta(1) induced by ADP is different from that induced by thrombin. The data are consistent with an activation mechanism involving released ADP and in which there exists two different states of activated integrin alpha(2)beta(1); these activated forms of integrin alpha(2)beta(1) would have different conformations that determine their ligand affinity.

  14. Factors Involved in Iranian Women Heads of Household’s Health Promotion Activities: A Grounded Theory Study

    PubMed Central

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh

    2013-01-01

    We aimed to explore and describe the factors involved in Iranian women heads of household’s health promotion activities. Grounded theory was used as the method. Sixteen women heads of household were recruited. Data were generated by semi structured interviews. Our findings indicated that remainder of resources (money, time and energy) alongside perceived severity of health risk were two main factors whereas women’s personal and socio-economic characteristics were two contextual factors involved in these women's health promotion activities. To help these women improve their health status, we recommended that the government, non-governmental organizations and health care professionals provide them with required resources and increase their knowledge by holding training sessions. PMID:24039645

  15. C1q complement component and -antibodies reflect SLE activity and kidney involvement.

    PubMed

    Horák, P; Hermanová, Z; Zadrazil, J; Ciferská, H; Ordeltová, M; Kusá, L; Zurek, M; Tichý, T

    2006-07-01

    The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAMactive and nonactive SLE (154.6+/-115 IU/ml vs. 50.6+/-73, p=0.001). C1q complement component was statistically lower in patients with lupus nephritis (144+/-30 mg/l vs. 175+/-50 mg/ml, p=0.002) and in active patients (138+/-40 mg/l vs. 202+/-20 mg/l, p=0.001). If the two parameters are measured together, they seem to have a mirror-like pattern of serum concentration, and they are potential markers of SLE activity and of the presence of lupus nephritis.

  16. Involvement of activation of NADPH oxidase and extracellular signal-regulated kinase (ERK) in renal cell injury induced by zinc.

    PubMed

    Matsunaga, Yoshiko; Kawai, Yoshiko; Kohda, Yuka; Gemba, Munekazu

    2005-05-01

    Zinc is employed as a supplement; however, zinc-related nephropathy is not generally known. In this study, we investigated zinc-induced renal cell injury using a pig kidney-derived cultured renal epithelial cell line, LLC-PK(1), with proximal kidney tubule-like features, and examined the involvement of free radicals and extracellular signal-regulated kinase (ERK) in the cell injury. The LLC-PK(1) cells showed early uptake of zinc (30 microM), and the release of lactate dehydrogenase (LDH), an index of cell injury, was observed 24 hr after uptake. Three hours after zinc exposure, generation of reactive oxygen species (ROS) was increased. An antioxidant, N, N'-diphenyl-p-phenylenediamine (DPPD), inhibited a zinc-related increase in ROS generation and zinc-induced renal cell injury. An NADPH oxidase inhibitor, diphenyleneiodonium (DPI), inhibited a zinc-related increase in ROS generation and cell injury. We investigated translocation from the cytosol fraction of the p67(phox) subunit, which is involved in the activation of NADPH oxidase, to the membrane fraction, and translocation was induced 3 hr after zinc exposure. We examined the involvement of ERK1/2 in the deterioration of zinc-induced renal cell injury, and the association between ERK1/2 and an increase in ROS generation. Six hours after zinc exposure, the activation (phosphorylation) of ERK1/2 was observed. An antioxidant, DPPD, inhibited the zinc-related activation of ERK1/2. An MAPK/ERK kinase (MEK1/2) inhibitor, U0126, almost completely inhibited zinc-related cell injury (the release of LDH), but did not influence ROS generation. These results suggest that early intracellular uptake of zinc by LLC-PK(1) cells causes the activation of NADPH oxidase, and that ROS generation by the activation of the enzyme leads to the deterioration of renal cell injury via the activation of ERK1/2.

  17. Facilitation handlings induce increase in electromyographic activity of muscles involved in head control of cerebral palsy children.

    PubMed

    Simon, Anelise de Saldanha; do Pinho, Alexandre Severo; Grazziotin Dos Santos, Camila; Pagnussat, Aline de Souza

    2014-10-01

    This study aimed to investigate the electromyographic (EMG) activation of the main cervical muscles involved in the head control during two postures widely used for the facilitation of head control in children with Cerebral Palsy (CP). A crossover trial involving 31 children with clinical diagnosis of CP and spastic quadriplegia was conducted. Electromyography was used to measure muscular activity in randomized postures. Three positions were at rest: (a) lateral decubitus, (b) ventral decubitus on the floor and (c) ventral decubitus on the wedge. Handlings for facilitating the head control were performed using the hip joint as key point of control in two postures: (a) lateral decubitus and (b) ventral decubitus on wedge. All children underwent standardized handlings, performed by the same researcher with experience in the neurodevelopmental treatment. EMG signal was recorded from muscles involved in the head control (paraspinal and sternocleidomastoid muscles) in sagittal, frontal and transverse planes, at the fourth cervical vertebra (C4), tenth thoracic vertebra (T10) and sternocleidomastoid muscle (SCM) levels. The results showed a significant increase in muscle activation when handling was performed in the lateral decubitus at C4 (P<0.001), T10 (P<0.001) and SCM (P=0.02) levels. A significant higher muscle activation was observed when handling was performed in lateral decubitus when compared to ventral decubitus at C4 level (P<0.001). Handling in ventral decubitus also induced an increase in EMG activation at T10 (P=0.018) and SCM (P=0.004) levels but not at C4 level (P=0.38). In conclusion, handlings performed in both positions may induce the facilitation of head control, as evaluated by the activity of cervical and upper trunk muscles. Handling performed in lateral decubitus may induce a slightly better facilitation of head control. These findings contribute to evidence-based physiotherapy practice for the rehabilitation of severely spastic quadriplegic CP

  18. Involvement of Activated Cdc42 Kinase1 in Colitis and Colorectal Neoplasms

    PubMed Central

    Lv, Chaolan; Gu, Hongxiang; Zhao, Xinmei; Huang, Liyun; Zhou, Sanxi; Zhi, Fachao

    2016-01-01

    Background Activated Cdc42 kinase1 (ACK1) is a non-receptor tyrosine kinase which is critical for cell survival, proliferation, and migration. Genomic amplification of ACK1 has been reported in multiple human cancers. We aimed to investigate ACK1 protein expression in colorectal mucosa with inflammation and neoplasm, and to evaluate its correlation with disease activity and severity. Material/Methods A total of 250 individuals who underwent total colonoscopy were collected randomly from January 2007 to May 2013 in Nanfang Hospital, Guangzhou, China. Colorectal mucosal biopsy specimens were obtained by endoscopy from 78 patients with ulcerative colitis (UC), 22 with Crohn’s disease (CD), 20 with infectious colitis, 26 with non-IBD and noninfectious colitis, 16 with sporadic adenomas, 4 with dysplasia-associated lesions or masses, 10 with sporadic colorectal cancer (CRC), 4 with UC-related CRC, 10 with hyperplastic polyps, and 60 without colonic abnormalities. ACK1 protein levels were determined immunohistochemically. The correlations of ACK1 expression with disease activity and severity were also evaluated. Results Significantly increased ACK1 expression was observed in epithelial cells of colorectal mucosa with inflammation and dysplasia compared to controls (P<0.05). ACK1 expression correlated with clinical activity in IBD (χ2=4.57, P=0.033 for UC; χ2=5.68, P=0.017 for CD), as well as grade of dysplasia in preneoplastic lesions (P<0.05). No significant differences in ACK1 expression were found between UC and CD, or between IBD and non-IBD conditions (P>0.05). Conclusions ACK1 protein is increased extensively in colitis and colorectal dysplasia. ACK1 overexpression may play a role in colorectal inflammation and neoplasms. PMID:27926694

  19. Involvement of Activated Cdc42 Kinase1 in Colitis and Colorectal Neoplasms.

    PubMed

    Lv, Chaolan; Zhao, Xinmei; Gu, Hongxiang; Huang, Liyun; Zhou, Sanxi; Zhi, Fachao

    2016-12-07

    BACKGROUND Activated Cdc42 kinase1 (ACK1) is a non-receptor tyrosine kinase which is critical for cell survival, proliferation, and migration. Genomic amplification of ACK1 has been reported in multiple human cancers. We aimed to investigate ACK1 protein expression in colorectal mucosa with inflammation and neoplasm, and to evaluate its correlation with disease activity and severity. MATERIAL AND METHODS A total of 250 individuals who underwent total colonoscopy were collected randomly from January 2007 to May 2013 in Nanfang Hospital, Guangzhou, China. Colorectal mucosal biopsy specimens were obtained by endoscopy from 78 patients with ulcerative colitis (UC), 22 with Crohn's disease (CD), 20 with infectious colitis, 26 with non-IBD and noninfectious colitis, 16 with sporadic adenomas, 4 with dysplasia-associated lesions or masses, 10 with sporadic colorectal cancer (CRC), 4 with UC-related CRC, 10 with hyperplastic polyps, and 60 without colonic abnormalities. ACK1 protein levels were determined immunohistochemically. The correlations of ACK1 expression with disease activity and severity were also evaluated. RESULTS Significantly increased ACK1 expression was observed in epithelial cells of colorectal mucosa with inflammation and dysplasia compared to controls (P<0.05). ACK1 expression correlated with clinical activity in IBD (χ²=4.57, P=0.033 for UC; χ²=5.68, P=0.017 for CD), as well as grade of dysplasia in preneoplastic lesions (P<0.05). No significant differences in ACK1 expression were found between UC and CD, or between IBD and non-IBD conditions (P>0.05). CONCLUSIONS ACK1 protein is increased extensively in colitis and colorectal dysplasia. ACK1 overexpression may play a role in colorectal inflammation and neoplasms.

  20. Prevention of cannabinoid withdrawal syndrome by lithium: involvement of oxytocinergic neuronal activation.

    PubMed

    Cui, S S; Bowen, R C; Gu, G B; Hannesson, D K; Yu, P H; Zhang, X

    2001-12-15

    Cannabis (i.e., marijuana and cannabinoids) is the most commonly used illicit drug in developed countries, and the lifetime prevalence of marijuana dependence is the highest of all illicit drugs in the United States. To provide clues for finding effective pharmacological treatment for cannabis-dependent patients, we examined the effects and possible mechanism of lithium administration on the cannabinoid withdrawal syndrome in rats. A systemic injection of the mood stabilizer lithium, at serum levels that were clinically relevant, prevented the cannabinoid withdrawal syndrome. The effects of lithium were accompanied by expression of the cellular activation marker Fos proteins within most oxytocin-immunoreactive neurons and a significant increase in oxytocin mRNA expression in the hypothalamic paraventricular and supraoptic nuclei. Lithium also produced a significant elevation of oxytocin levels in the peripheral blood. We suggest that the effects of lithium against the cannabinoid withdrawal syndrome are mediated by oxytocinergic neuronal activation and subsequent release and action of oxytocin within the CNS. In support of our hypothesis, we found that the effects of lithium against the cannabinoid withdrawal syndrome were antagonized by systemic preapplication of an oxytocin antagonist and mimicked by systemic or intracerebroventricular injection of oxytocin. These results demonstrate that oxytocinergic neuronal activation plays a critical role in the action of lithium against the cannabinoid withdrawal syndrome in rats, thus providing a potentially novel strategy for the treatment of cannabis dependence in humans.

  1. Involvement of urokinase-type plasminogen activator system in cancer: an overview.

    PubMed

    Mekkawy, Ahmed H; Pourgholami, Mohammad H; Morris, David L

    2014-09-01

    Currently, there are several studies supporting the role of urokinase-type plasminogen activator (uPA) system in cancer. The association of uPA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the uPA inhibitors (PAI-1 and PAI-2). Plasmin promotes degradation of basement membrane and extracellular matrix (ECM) components as well as activation of ECM latent matrix metalloproteases. Degradation and remodeling of the surrounding tissues is crucial in the early steps of tumor progression by facilitating expansion of the tumor mass, release of tumor growth factors, activation of cytokines as well as induction of tumor cell proliferation, migration, and invasion. Hence, many tumors showed a correlation between uPA system component levels and tumor aggressiveness and survival. Therefore, this review summarizes the structure of the uPA system, its contribution to cancer progression, and the clinical relevance of uPA family members in cancer diagnosis. In addition, the review evaluates the significance of uPA system in the development of cancer-targeted therapies.

  2. Involvement of Fungal Pectin Methylesterase Activity in the Interaction Between Fusarium graminearum and Wheat.

    PubMed

    Sella, Luca; Castiglioni, Carla; Paccanaro, Maria Chiara; Janni, Michela; Schäfer, Wilhelm; D'Ovidio, Renato; Favaron, Francesco

    2016-04-01

    The genome of Fusarium graminearum, the causal agent of Fusarium head blight of wheat, contains two putative pectin methylesterase (PME)-encoding genes. However, when grown in liquid culture containing pectin, F. graminearum produces only a single PME, which was purified and identified. Its encoding gene, expressed during wheat spike infection, was disrupted by targeted homologous recombination. Two Δpme mutant strains lacked PME activity but were still able to grow on highly methyl-esterified pectin even though their polygalacturonase (PG) activity showed a reduced capacity to depolymerize this substrate. The enzymatic assays performed with purified F. graminearum PG and PME demonstrated an increase in PG activity in the presence of PME on highly methyl-esterified pectin. The virulence of the mutant strains was tested on Triticum aestivum and Triticum durum spikes, and a significant reduction in the percentage of symptomatic spikelets was observed between 7 and 12 days postinfection compared with wild type, demonstrating that the F. graminearum PME contributes to fungal virulence on wheat by promoting spike colonization in the initial and middle stages of infection. In contrast, transgenic wheat plants with increased levels of pectin methyl esterification did not show any increase in resistance to the Δpme mutant, indicating that the infectivity of the fungus relies only to a certain degree on pectin degradation.

  3. Endogenous nitric oxide accumulation is involved in the antifungal activity of Shikonin against Candida albicans

    PubMed Central

    Liao, Zebin; Yan, Yu; Dong, Huaihuai; Zhu, Zhenyu; Jiang, Yuanying; Cao, Yingying

    2016-01-01

    The aim of the present study was to investigate the role of nitric oxide (NO) in the antifungal activity of Shikonin (SK) against Candida albicans (C. albicans) and to clarify the underlying mechanism. The results showed that the NO donors S-nitrosoglutathione (GSNO) and L-arginine could enhance the antifungal activity of SK, whereas the NO production inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) attenuated antifungal action. Using the fluorescent dye 3-amino,4-aminomethyl-2′, 7-difluorescein, diacetate (DAF-FM DA), we found that the accumulation of NO in C. albicans was increased markedly by SK in a time- and dose-dependent manner. In addition, the results of real-time reverse transcription-PCR (RT-PCR) demonstrated that the transcription level of YHB1 in C. albicans was greatly increased upon incubation of SK. Consistently, the YHB1-null mutant (yhb1Δ/Δ) exhibited a higher susceptibility to SK than wild-type cells. In addition, although the transcription level of CTA4 in C. albicans was not significantly changed when exposed to SK, the CTA4-null mutant (cta4Δ/Δ) was more susceptible to SK. Collectively, SK is the agent found to execute its antifungal activity directly via endogenous NO accumulation, and NO-mediated damage is related to the suppression of YHB1 and the function of CTA4. PMID:27530748

  4. Involvement of nitric oxide donor compounds in the bactericidal activity of human neutrophils in vitro.

    PubMed

    Klink, Magdalena; Cedzyński, Maciej; St Swierzko, Anna; Tchórzewski, Henryk; Sulowska, Zofia

    2003-04-01

    The bactericidal activity of human neutrophils against extracellular and facultatively intracellular bacteria was studied in the presence of the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), a molsidomine metabolite. SNP and molsidomine are drugs commonly used as nitrovasodilators in coronary heart disease. It is demonstrated here that the NO donor compounds themselves did not affect the viability and survival of the bacterial strains tested. Neither SNP nor SIN-1 had any effect on the process of bacteria ingestion. In contrast, NO donors enhanced the ability of neutrophils to kill Escherichia coli, Proteus vulgaris and Salmonella Anatum. However, strains differed in their susceptibility to SNP- and SIN-1-mediated killing by neutrophils. Removal of the superoxide anion reduced the bactericidal activity of SNP- and SIN-1-treated neutrophils against E. coli and S. Anatum. This suggests that the NO derivatives formed in the reaction of NO generated from donors with the reactive oxygen species released by phagocytosed neutrophils potentiate the bactericidal activity of human neutrophils in vitro. The above original observation discussed here suggests clinical significance for the treatment of patients with nitrovasodilators in the course of coronary heart disease therapy.

  5. Novel DNA mismatch-repair activity involving YB-1 in human mitochondria.

    PubMed

    de Souza-Pinto, Nadja C; Mason, Penelope A; Hashiguchi, Kazunari; Weissman, Lior; Tian, Jingyan; Guay, David; Lebel, Michel; Stevnsner, Tinna V; Rasmussen, Lene Juel; Bohr, Vilhelm A

    2009-06-04

    Maintenance of the mitochondrial genome (mtDNA) is essential for proper cellular function. The accumulation of damage and mutations in the mtDNA leads to diseases, cancer, and aging. Mammalian mitochondria have proficient base excision repair, but the existence of other DNA repair pathways is still unclear. Deficiencies in DNA mismatch repair (MMR), which corrects base mismatches and small loops, are associated with DNA microsatellite instability, accumulation of mutations, and cancer. MMR proteins have been identified in yeast and coral mitochondria; however, MMR proteins and function have not yet been detected in human mitochondria. Here we show that human mitochondria have a robust mismatch-repair activity, which is distinct from nuclear MMR. Key nuclear MMR factors were not detected in mitochondria, and similar mismatch-binding activity was observed in mitochondrial extracts from cells lacking MSH2, suggesting distinctive pathways for nuclear and mitochondrial MMR. We identified the repair factor YB-1 as a key candidate for a mitochondrial mismatch-binding protein. This protein localizes to mitochondria in human cells, and contributes significantly to the mismatch-binding and mismatch-repair activity detected in HeLa mitochondrial extracts, which are significantly decreased when the intracellular levels of YB-1 are diminished. Moreover, YB-1 depletion in cells increases mitochondrial DNA mutagenesis. Our results show that human mitochondria contain a functional MMR repair pathway in which YB-1 participates, likely in the mismatch-binding and recognition steps.

  6. BAP31 is involved in T cell activation through TCR signal pathways

    PubMed Central

    Niu, Kunwei; Xu, Jialin; Cao, Yuhua; Hou, Yue; Shan, Mu; Wang, Yanqing; Xu, Yang; Sun, Mingyi; Wang, Bing

    2017-01-01

    BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice. The BAP31 knockout T cells decreased the proliferation activated by TCR signal pathways. Further studies clarified that BAP31 affects the phosphorylation levels of both Zap70/Lck/Lat of the upstream members and Akt/GSK/Jnk/Erk of the downstream members of TCR signal pathways. Furthermore, BAP31 can regulate the expression of some markers such as CD3/TCRα/TCRβ and some cytokines like IL-2/IFN-γ/IL-6/TNF-α which are important for T cell activation. Taken together, these results demonstrate that BAP31 may play an important role in T cell activation by regulating TCR signaling. PMID:28333124

  7. Identification of serum component involved in generation of neo-lectin with agglutinating and phenoloxidase activities in human serum.

    PubMed

    Manikandan, Beulaja; Ramar, Manikandan; Munusamy, Arumugam

    2014-01-01

    Human serum albumin (HSA) was identified as the component involved in generation of neo-lectin molecules with both lectin and phenoloxidase activities. Pronase treated HSA was able to agglutinate hen RBC and oxidize hydroquinone. Sodium dodecyl sulphate (SDS) treated HSA agglutinated both hen and sheep RBC as well as oxidized dopamine. The hemagglutinating activities of pronase/SDS treated HSA observed against hen RBC were dosimetric. The oxidation of pronase/SDS treated HSA with hydroquinone/dopamine, respectively, was inhibitable by inhibitors of phenoloxidase, namely, phenylthiourea and tropolone. Very low concentrations of HSA could generate these humoral neo-lectin molecules.

  8. Workers' active involvement in the improvement of occupational safety and health in a textile enterprise--a case study.

    PubMed

    Milczarek, Małgorzata; Szczecińska, Katarzyna

    2006-01-01

    Part of the Polish-Swedish OSHMAN project was carried out in a textile company. It aimed at implementing and improving effective health and safety management with workers' active involvement at all levels of the enterprise. The two main problems to be solved during the project were decreasing occupational risk and improving workers' poor knowledge on occupational risk. Training courses, workshops and practical activities were undertaken. As expected, there were changes in work organisation and improvement in the way workstations were looked after, which led to a decrease in occupational risk. Workers were highly committed during the project. Nevertheless it seems that more training should be directed at middle management.

  9. Activism and Leadership Development: Examining the Relationship between College Student Activism Involvement and Socially Responsible Leadership Capacity

    ERIC Educational Resources Information Center

    Page, Jeremy Dale

    2010-01-01

    The purpose of this study was to examine the relationship between participation in student activism and leadership development among college students. This study applied the social change model of leadership development (SCM) as the theoretical model used to measure socially responsible leadership capacity in students. The study utilized data…

  10. Aeromonas hydrophila induced head kidney macrophage apoptosis in Clarias batrachus involves the activation of calpain and is caspase-3 mediated.

    PubMed

    Banerjee, Chaitali; Goswami, Ramansu; Verma, Gaurav; Datta, Malabika; Mazumder, Shibnath

    2012-07-01

    The mechanism of macrophage cytotoxicity induced by Aeromonas hydrophila is yet unresolved. We observed A. hydrophila induces Head Kidney Macrophage (HKM) apoptosis in Clarias batrachus, as evident from Hoechst 33342 and AnnexinV-Propidium Iodide staining and presence of oligonucleosomal DNA ladder. Initiation of apoptosis required the bacteria to be alive, be actively phagocytosed into HKM and was dependent on host proteins. Elevated cytosolic calcium and consequent calpain activity that declined following pre-incubation with EGTA, verapamil and nifedipine implicates the role of calcium influx through voltage gated calcium channels and calpain in A. hydrophila-induced HKM apoptosis. Though, calpain-1 and -2 were involved, calpain-2 appeared to be more important in the process. EGTA, verapamil, nifedipine and calpain-2 inhibitor reduced caspase-3 activity and apoptosis. We conclude that A. hydrophila alters cytosolic calcium homeostasis initiating the activation of calpains, more specifically calpain-2, which leads to caspase-3 mediated HKM apoptosis in C. batrachus.

  11. Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis.

    PubMed

    Cieslar, S R L; Madsen, T G; Purdie, N G; Trout, D R; Osborne, V R; Cant, J P

    2014-01-01

    To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (KATP) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that KATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial

  12. Protein phosphatase and kinase activities possibly involved in exocytosis regulation in Paramecium tetraurelia.

    PubMed

    Kissmehl, R; Treptau, T; Hofer, H W; Plattner, H

    1996-07-01

    In Paramecium tetraurelia cells synchronous exocytosis induced by aminoethyldextran (AED) is accompanied by an equally rapid dephosphorylation of a 63 kDa phosphoprotein (PP63) within 80 ms. In vivo, rephosphorylation occurs within a few seconds after AED triggering. In homogenates (P)P63 can be solubilized in all three phosphorylation states (phosphorylated, dephosphorylated and rephosphorylated) and thus tested in vitro. By using chelators of different divalent cations, de- and rephosphorylation of PP63 and P63 respectively can be achieved by an endogenous protein phosphatase/kinase system. Dephosphorylation occurs in the presence of EDTA, whereas in the presence of EGTA this was concealed by phosphorylation by endogenous kinase(s), thus indicating that phosphorylation of P63 is calcium-independent. Results obtained with protein phosphatase inhibitors (okadaic acid, calyculin A) allowed us to exclude a protein serine/threonine phosphatase of type I (with selective sensitivity in Paramecium). Protein phosphatase 2C is also less likely to be a candidate because of its requirement for high Mg2+ concentrations. According to previous evidence a protein serine/threonine phosphatase of type 2B (calcineurin; CaN) is possibly involved. We have now found that bovine brain CaN dephosphorylates PP63 in vitro. Taking into account the specific requirements of this phosphatase in vitro, with p-nitrophenyl phosphate as a substrate, we have isolated a cytosolic phosphatase of similar characteristics by combined preparative gel electrophoresis and affinity-column chromatography. In Paramecium this phosphatase also dephosphorylates PP63 in vitro (after 32P labelling in vivo). Using various combinations of ion exchange, affinity and hydrophobic interaction chromatography we have also isolated three different protein kinases from the soluble fraction, i.e. a cAMP-dependent protein kinase (PKA), a cGMP-dependent protein kinase (PKG) and a casein kinase. Among the kinases tested, PKA

  13. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    SciTech Connect

    Wang, Bing Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-07-19

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

  14. Possible involvement of galectin-3 in microglial activation in the hippocampus with trimethyltin treatment.

    PubMed

    Yang, Miyoung; Kim, Juhwan; Kim, Taehyub; Kim, Sung-Ho; Kim, Jong-Choon; Kim, Jeongtae; Takayama, Chitoshi; Hayashi, Akinobu; Joo, Hong-Gu; Shin, Taekyun; Moon, Changjong

    2012-12-01

    Trimethyltin (TMT) is an organotin neurotoxicant with effects that are selectively localized to the limbic system (especially the hippocampus), which produces memory deficits and temporal lobe seizures. Galectin-3 (Gal-3) is a beta-galactoside-binding lectin that is important in cell proliferation and regulation of apoptosis. The present study evaluated the temporal expression of Gal-3 in the hippocampus of adult BALB/c mice after TMT treatment (i.p., 2.5mg/kg). Western blotting analyses showed that Gal-3 immunoreactivity began to increase days after treatment; the immunoreactivity peaked significantly within days after treatment but significantly declined between days 4 and 8. Immunohistochemical analysis indicated that Gal-3 expression was very rare in the hippocampi of vehicle-treated controls. However, Gal-3 immunoreactivity appeared between 2 and 8 days after TMT treatment and was primarily localized to the hippocampal dentate gyrus (DG), in which neuronal degeneration occurred. The immunoreactivity was detected predominantly in most of the Iba1-positive microglia and in some GFAP-positive astrocytes of the hippocampal DG. Furthermore, Gal-3 expression co-localized with the pro-inflammatory enzymes cyclooxygenase-2 and inducible nitric oxide synthase in the hippocampal DG. Therefore, we suggest that Gal-3 is involved in the inflammatory process of neurodegenerative disorder induced by organotin intoxication.

  15. Involvement of PRMT1 in hnRNPQ activation and internalization of insulin receptor

    SciTech Connect

    Iwasaki, Hiroaki

    2008-07-25

    Insulin signaling in skeletal L6 myotubes is known to be affected by arginine methylation catalyzed by protein N-arginine methyltransferase 1 (PRMT1), however, the mechanism by which this occurs has not yet been defined. This study aimed to determine the exact substrate involved in the methylation and regulating insulin signaling in cells. Insulin enhanced arginine methylation of a 66-kDa protein (p66) concomitant with translocation of PRMT1 to the membrane fraction. Peptide mass fingerprinting identified p66 as a heterogeneous nuclear ribonucleoprotein, hnRNPQ that was bound to and methylated by PRMT1. Pharmacological inhibition of methylation (MTA) and small interfering RNA against PRMT1 (PRMT1-siRNA) attenuated insulin-stimulated tyrosine phosphorylation of hnRNPQ and insulin receptor (IR), and the interaction between hnRNPQ and IR. MTA, PRMT1-siRNA, and hnRNPQ-siRNA inhibited internalization of IR in the same manner. These data suggest that the PRMT1-mediated methylation of hnRNPQ is implicated in IR trafficking and insulin signaling in skeletal L6 myotubes.

  16. Involvement of glutamate 97 in ion influx through photo-activated channelrhodopsin-2.

    PubMed

    Tanimoto, Saki; Sugiyama, Yuka; Takahashi, Tetsuo; Ishizuka, Toru; Yawo, Hiromu

    2013-01-01

    The light absorption of a channelrhodopsin-2 (ChR2) is followed by conformational changes to the molecule, which allows the channel structure to become permeable to cations. Previously, a single point mutation in ChR2, which replaces glutamate residue 97 with a nonpolar alanine (E97A), was found to attenuate the photocurrent, suggesting that the E97 residue is involved in ion flux regulation. Here, the significance of E97 and its counterpart ChR1 (E136) were extensively studied by mutagenesis, whereby we replaced these glutamates with aspartate (D), glutamine (Q) or arginine (R). We found that the charge at this position strongly influences ion permeation and that the photocurrents were attenuated in the order of ChR2>E97D≈E97Q>E97R. We observed similar results with our chimeric/synthetic/artificial construct, ChR-wide receiver (ChRWR), which contains the first to fifth transmembrane helices of ChR1. The E-to-Q or E-to-R mutations, but not the E-to-D mutation, strongly retarded the sensitivity to the Gd(3+)-dependent blocking of the ChR1 or ChR2 channels. Our results suggest that the glutamate residue at this position lies in the outer pore, where it interacts with a cation to facilitate dehydration, and that this residue is the primary binding target of Gd(3+).

  17. Phage Orf Family Recombinases: Conservation of Activities and Involvement of the Central Channel in DNA Binding

    PubMed Central

    Curtis, Fiona A.; Malay, Ali D.; Trotter, Alexander J.; Wilson, Lindsay A.; Barradell-Black, Michael M. H.; Bowers, Laura Y.; Reed, Patricia; Hillyar, Christopher R. T.; Yeo, Robert P.; Sanderson, John M.; Heddle, Jonathan G.; Sharples, Gary J.

    2014-01-01

    Genetic and biochemical evidence suggests that λ Orf is a recombination mediator, promoting nucleation of either bacterial RecA or phage Redβ recombinases onto single-stranded DNA (ssDNA) bound by SSB protein. We have identified a diverse family of Orf proteins that includes representatives implicated in DNA base flipping and those fused to an HNH endonuclease domain. To confirm a functional relationship with the Orf family, a distantly-related homolog, YbcN, from Escherichia coli cryptic prophage DLP12 was purified and characterized. As with its λ relative, YbcN showed a preference for binding ssDNA over duplex. Neither Orf nor YbcN displayed a significant preference for duplex DNA containing mismatches or 1-3 nucleotide bulges. YbcN also bound E. coli SSB, although unlike Orf, it failed to associate with an SSB mutant lacking the flexible C-terminal tail involved in coordinating heterologous protein-protein interactions. Residues conserved in the Orf family that flank the central cavity in the λ Orf crystal structure were targeted for mutagenesis to help determine the mode of DNA binding. Several of these mutant proteins showed significant defects in DNA binding consistent with the central aperture being important for substrate recognition. The widespread conservation of Orf-like proteins highlights the importance of targeting SSB coated ssDNA during lambdoid phage recombination. PMID:25083707

  18. Paxillin-dependent paxillin kinase linker and p21-activated kinase localization to focal adhesions involves a multistep activation pathway.

    PubMed

    Brown, Michael C; West, Kip A; Turner, Christopher E

    2002-05-01

    The precise temporal-spatial regulation of the p21-activated serine-threonine kinase PAK at the plasma membrane is required for proper cytoskeletal reorganization and cell motility. However, the mechanism by which PAK localizes to focal adhesions has not yet been elucidated. Indirect binding of PAK to the focal adhesion protein paxillin via the Arf-GAP protein paxillin kinase linker (PKL) and PIX/Cool suggested a mechanism. In this report, we demonstrate an essential role for a paxillin-PKL interaction in the recruitment of activated PAK to focal adhesions. Similar to PAK, expression of activated Cdc42 and Rac1, but not RhoA, stimulated the translocation of PKL from a generally diffuse localization to focal adhesions. Expression of the PAK regulatory domain (PAK1-329) or the autoinhibitory domain (AID 83-149) induced PKL, PIX, and PAK localization to focal adhesions, indicating a role for PAK scaffold activation. We show PIX, but not NCK, binding to PAK is necessary for efficient focal adhesion localization of PAK and PKL, consistent with a PAK-PIX-PKL linkage. Although PAK activation is required, it is not sufficient for localization. The PKL amino terminus, containing the PIX-binding site, but lacking paxillin-binding subdomain 2 (PBS2), was unable to localize to focal adhesions and also abrogated PAK localization. An identical result was obtained after PKLDeltaPBS2 expression. Finally, neither PAK nor PKL was capable of localizing to focal adhesions in cells overexpressing paxillinDeltaLD4, confirming a requirement for this motif in recruitment of the PAK-PIX-PKL complex to focal adhesions. These results suggest a GTP-Cdc42/GTP-Rac triggered multistep activation cascade leading to the stimulation of the adaptor function of PAK, which through interaction with PIX provokes a functional PKL PBS2-paxillin LD4 association and consequent recruitment to focal adhesions. This mechanism is probably critical for the correct subcellular positioning of PAK, thereby

  19. Pb-inhibited mitotic activity in onion roots involves DNA damage and disruption of oxidative metabolism.

    PubMed

    Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2014-09-01

    Plant responses to abiotic stress significantly affect the development of cells, tissues and organs. However, no studies correlating Pb-induced mitotic inhibition and DNA damage and the alterations in redox homeostasis during root division per se were found in the literature. Therefore, an experiment was conducted to evaluate the impact of Pb on mitotic activity and the associated changes in the oxidative metabolism in onion roots. The cytotoxic effect of Pb on cell division was assessed in the root meristems of Allium cepa (onion). The mitotic index (MI) was calculated and chromosomal abnormalities were sought. Pb-treatment induced a dose-dependent decrease in MI in the onion root tips and caused mitotic abnormalities such as distorted metaphase, fragments, sticky chromosomes, laggards, vagrant chromosomes and bridges. Single Cell Gel Electrophoresis was also performed to evaluate Pb induced genotoxicity. It was accompanied by altered oxidative metabolism in the onion root tips suggesting the interference of Pb with the redox homeostasis during cell division. There was a higher accumulation of malondialdehyde, conjugated dienes and hydrogen peroxide, and a significant increase in the activities of superoxide dismutases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases in Pb-treated onion roots, whereas catalases activity exhibited a decreasing pattern upon Pb exposure. The study concludes that Pb-induced cytotoxicity and genotoxicity in the onion roots is mediated through ROS and is also tightly linked to the cell cycle. The exposure to higher concentrations arrested cell cycle leading to cell death, whereas different repair responses are generated at lower concentrations, thereby allowing the cell to complete the cell cycle.

  20. Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCɛ pathway

    PubMed Central

    Mousseaux, Delphine; Le Gallic, Lionel; Ryan, Joanne; Oiry, Catherine; Gagne, Didier; Fehrentz, Jean-Alain; Galleyrand, Jean-Claude; Martinez, Jean

    2006-01-01

    The growth hormone secretagogue receptor 1a (GHSR-1a) is a G-protein coupled receptor, involved in the biological actions of ghrelin by triggering inositol phosphates and calcium intracellular second messengers. It has also been reported that ghrelin could activate the 44- and 42-kDa extracellular signal-regulated protein kinases (ERK1/2) in different cell lines, but it is not clear whether this regulation is GHSR-1a dependent or not. To provide direct evidence for the coupling of GHSR-1a to ERK1/2 activation, this pathway has been studied in a heterologous expression system. Thus, in Chinese hamster ovary (CHO) cells we showed that ghrelin induced, via the human GHSR-1a, a transient and dose-dep endent activation of ERK1/2 leading to activation of the transcriptional factor Elk1. We then investigated the precise mechanisms involved in GHSR-1a-mediated ERK1/2 activation using various specific inhibitors and dominant-negative mutants and found that internalization of GHSR-1a was not necessary. Our results also indicate that phospholipase C (PLC) was involved in GHSR-1a-mediated ERK1/2 activation, however, pathways like tyrosine kinases, including Src, and phosphoinositide 3-kinases were not found to be involved. GHSR-1a-mediated ERK1/2 activation was abolished both by a general protein kinase C (PKC) inhibitor, Gö6983, and by PKC depletion using overnight pretreatment with phorbol ester. Moreover, the calcium chelator, BAPTA-AM, and the inhibitor of conventional PKCs, Gö6976, had no effect on the GHSR-1a-mediated ERK1/2 activation, suggesting the involvement of novel PKC isoforms (ɛ, δ), but not conventional or atypical PKCs. Further analyses suggest that PKCɛ is required for the activation of ERK1/2. Taken together, these data suggest that ghrelin, through GHSR-1a, activates the Elk1 transcriptional factor and ERK1/2 by a PLC- and PKCɛ-dependent pathway. PMID:16582936

  1. Regulation of ERK1/2 activity by ghrelin-activated growth hormone secretagogue receptor 1A involves a PLC/PKCvarepsilon pathway.

    PubMed

    Mousseaux, Delphine; Le Gallic, Lionel; Ryan, Joanne; Oiry, Catherine; Gagne, Didier; Fehrentz, Jean-Alain; Galleyrand, Jean-Claude; Martinez, Jean

    2006-06-01

    1. The growth hormone secretagogue receptor 1a (GHSR-1a) is a G-protein coupled receptor, involved in the biological actions of ghrelin by triggering inositol phosphates and calcium intracellular second messengers. It has also been reported that ghrelin could activate the 44- and 42-kDa extracellular signal-regulated protein kinases (ERK1/2) in different cell lines, but it is not clear whether this regulation is GHSR-1a dependent or not. 2. To provide direct evidence for the coupling of GHSR-1a to ERK1/2 activation, this pathway has been studied in a heterologous expression system. 3. Thus, in Chinese hamster ovary (CHO) cells we showed that ghrelin induced, via the human GHSR-1a, a transient and dose-dependent activation of ERK1/2 leading to activation of the transcriptional factor Elk1. 4. We then investigated the precise mechanisms involved in GHSR-1a-mediated ERK1/2 activation using various specific inhibitors and dominant-negative mutants and found that internalization of GHSR-1a was not necessary. Our results also indicate that phospholipase C (PLC) was involved in GHSR-1a-mediated ERK1/2 activation, however, pathways like tyrosine kinases, including Src, and phosphoinositide 3-kinases were not found to be involved. GHSR-1a-mediated ERK1/2 activation was abolished both by a general protein kinase C (PKC) inhibitor, Gö6983, and by PKC depletion using overnight pretreatment with phorbol ester. Moreover, the calcium chelator, BAPTA-AM, and the inhibitor of conventional PKCs, Gö6976, had no effect on the GHSR-1a-mediated ERK1/2 activation, suggesting the involvement of novel PKC isoforms (epsilon, delta), but not conventional or atypical PKCs. Further analyses suggest that PKCepsilon is required for the activation of ERK1/2. 5. Taken together, these data suggest that ghrelin, through GHSR-1a, activates the Elk1 transcriptional factor and ERK1/2 by a PLC- and PKCepsilon-dependent pathway.

  2. Regulatory elements involved in the bidirectional activity of an immunoglobulin promoter.

    PubMed Central

    Doyen, N; Dreyfus, M; Rougeon, F

    1989-01-01

    We show that the promoter from the mouse VH441 heavy-chain immunoglobulin gene, when present on plasmids transiently introduced into myeloma cells, promotes transcription bidirectionally, due to the presence on both strands of TATA-like sequences bracketing the highly conserved decanucleotide element. The two divergent promoters compete for the transcriptional machinery, their relative strength ultimately reflecting the likeness of the two TATA boxes to the consensus sequence. Moreover, their relative activity is also strongly influenced by certain point mutations within the distally located heavy-chain enhancer. The bearing of these results on current concepts of promoter function is discussed. Images PMID:2494644

  3. Autolysis of bovine enteropeptidase heavy chain: evidence of fragment 118-465 involvement in trypsinogen activation.

    PubMed

    Mikhailova, A G; Rumsh, L D

    1999-01-15

    Variations in bovine enteropeptidase (EP) activity were shown to result from autolysis caused by the loss of calcium ions; the cleavage sites were determined. The native enzyme preferred its natural substrate, trypsinogen (KM=2.4 microM), to the peptide and fusion protein substrates (KM=200 and 125 microM, respectively). On the other hand, the truncated enzyme composed of the C-terminal fragment 466-800 of EP heavy chain and intact light chain did not distinguish these substrates. The results suggest that the N-terminal fragment 118-465 of the enteropeptidase heavy chain contains a secondary substrate-binding site that interacts directly with trypsinogen.

  4. Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression.

    PubMed

    Zeng, Zhifeng; Yang, Haiyuan; Wang, Ying; Ren, Jiafa; Dai, Yifan; Dai, Chunsun

    2017-04-10

    Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cells, a rat kidney interstitial fibroblast cell line, were stimulated with TGFβ1. A Caenorhabditis elegans fat-1 transgenic mouse model in which n-3 PUFAs are endogenously produced from n-6 PUFAs owing to the expression of n-3 fatty acid desaturase were deployed. Docosahexaenoic acid (DHA), one member of n-3 PUFAs family, could suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally, DHA could largely inhibit TGFβ1-stimulated Akt but not S6 or Smad3 phosphorylation at a time dependent manner. To decipher the role for n-3 PUFAs in protecting against kidney fibrosis, fat-1 transgenic mice were operated with unilateral ureter obstruction (UUO). Compared to the wild types, fat-1 transgenics developed much less kidney fibrosis and inflammatory cell accumulation accompanied by less p-Akt (Ser473), p-Akt (Thr308), p-S6 and p-Smad3 in kidney tissues at day 7 after UUO. Thus, n-3 PUFAs can attenuate fibroblast activation and kidney fibrosis, which may be associated with the inhibition of mTORC2 signaling.

  5. Constitutive opioid receptor activation: a prerequisite mechanism involved in acute opioid withdrawal.

    PubMed

    Freye, E; Levy, Jv

    2005-06-01

    The opioid receptor antagonist naltrexone, which is used in detoxification and rehabilitation programmes in opioid addicts, can precipitate opioid withdrawal symptoms even in patients who have no opioid present. We tested the hypothesis that in order to precipitate withdrawal, opioids need to convert the inactive opioid receptor site via protein kinase C into a constitutively active form on which the antagonist precipitates withdrawal. Acute microg/kg), given for 6 days, which was followed by the antagonist naltrexone (20 microg/kg i.v.) in the awake trained canine (n = 10). Abrupt displacement of opioid binding resulted in acute withdrawal symptoms: increase in blood pressure, heart rate, increase in amplitude height of somatosensory evoked potential, reduced tolerance to colon distention and a significant increase in grading of vegetative variables (restlessness, panting, thrashing of the head, whining, yawning, gnawing, salivation and/or rhinorrhoea, mydriasis, stepping of extremities and vomiting). Following a washout period of 14 days, the same animals were given the highly specific protein kinase C inhibitor H7 (250 microg/kg) prior to the same dosages of sufentanil and naltrexone. Such pretreatment was able to either attenuate or completely abolish the acute withdrawal symptoms. The data suggest that for precipitation of withdrawal, intracellular phosphorylation is a prerequisite in order to activate the opioid mu-receptor. In such a setting, naltrexone acts like an 'inverse agonist' relative to the action of the antagonist on a non-preoccupied receptor site not being exposed previously to a potent opioid agonist.

  6. Molecular Changes Involving MEK3-p38 MAPK Activation in Chronic Masticatory Myalgia.

    PubMed

    Meng, H; Gao, Y; Kang, Y F; Zhao, Y P; Yang, G J; Wang, Y; Cao, Y; Gan, Y H; Xie, Q F

    2016-09-01

    The exact mechanism underlying chronic masticatory myalgia (CMM), a conspicuous symptom in temporomandibular disorders, remains unclear. This investigation compared gene expression profiles between CMM patients and healthy subjects. Peripheral blood leukocytes were collected in 8 cases and 8 controls and subjected to whole genome microarray analyses. Data were analyzed with Gene Ontology and interactive pathways analyses. According to Gene Ontology analysis, categories such as ion transport, response to stimuli, and metabolic process were upregulated. The pathway analysis suggested overexpression of the mitogen-activated protein kinase (MAPK) pathway in CMM patients and to a higher degree in a pathway network. Overexpression of representative members of the MAPK pathway-including MAPK kinase 3 (MEK3), calcium voltage-gated channel auxiliary subunit gamma 2 (CACNG2), and growth arrest and DNA damage-inducible gamma (GADD45G)-was validated with real-time polymerase chain reaction. The upregulation of MEK3 was negatively correlated with the age of the CMM group. In the next step, the authors focused on MEK3, the gene that exhibited the greatest degree of differential expression, and its downstream target protein p38 MAPK. The results revealed upregulation of MEK3, as well as phosphorylated MEK3 and phosphorylated p38 MAPK, in CMM patients. These results provide a "fingerprint" for mechanistic studies of CMM in the future and highlight the importance of MEK3-p38 MAPK activation in CMM.

  7. Tryptophan overloading activates brain regions involved with cognition, mood and anxiety.

    PubMed

    Silva, Luana C A; Viana, Milena B; Andrade, José S; Souza, Melyssa A; Céspedes, Isabel C; D'Almeida, Vânia

    2017-02-16

    Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

  8. Antifungal activity of Brazilian medicinal plants involved in popular treatment of mycoses.

    PubMed

    Cruz, M C S; Santos, P O; Barbosa, A M; de Mélo, D L F M; Alviano, C S; Antoniolli, A R; Alviano, D S; Trindade, R C

    2007-05-04

    A survey of medicinal plants used to treat common mycoses was done in the Curituba district, Sergipe State, Brazil. One hundred inhabitants were interviewed by health agents and traditional healers. Four different plants were the most cited (more than 50% of the citations): Ziziphus joazeiro, Caesalpinia pyramidalis, Bumelia sartorum and Hymenea courbaril. The aqueous extracts obtained following traditional methods and using different parts of these plants, were submitted to drop agar diffusion tests for primary antimicrobial screening. Only the water infusion extract of Ziziphus joazeiro and Caesalpinea pyramidalis presented a significant antifungal activity against Trichophyton rubrum, Candida guilliermondii, Candida albicans, Cryptococcus neoformans and Fonsecaea pedrosoi, when compared to the antifungal agent amphotericin B. The minimal inhibitory concentration (MIC) of the bioactive extracts was evaluated by the microdilution method. Best activity with a MIC of 6.5 microg/ml for both extracts was observed against Trichophyton rubrum and Candida guilliermondii. Ziziphus joazeiro and Caesalpinea pyramidalis extracts presented also low acute toxicity in murine models. The present study validates the folk use of these plant extracts and indicates that they can be effective potential candidates for the development of new strategies to treat fungal infections.

  9. Breast cancer survivors involved in vigorous team physical activity: psychosocial correlates of maintenance participation.

    PubMed

    Culos-Reed, S Nicole; Shields, Christopher; Brawley, Lawrence R

    2005-07-01

    Physical activity is increasingly being promoted as a means to achieve both physical and psychological benefits for cancer survivors. For women with breast cancer, one sport growing in popularity is dragon boating. The purpose of the present investigation was to examine the psychosocial correlates of dragon boat participation over the course of a season. Six crews completed the baseline (early-season) assessment (n = 109) and late-season assessments (n = 56). The self-report questionnaire completed at both time points included an assessment of the theory of planned behaviour variables, quality of life, cohesion, and physical activity levels. A prospective examination of the TPB variables revealed attitude at early season as the only significant predictor of behavioural intentions 12 weeks later at late season (R2 adjusted = 0.27, p < 0.001). Overall, the group environment was cohesive at a level similar to that for female sport teams among the asymptomatic population. As well, participants' health-related quality of life was similar to normal, healthy women of similar age for both mental and physical health.

  10. GM1 ganglioside is involved in epigenetic activation loci of neuronal cells

    PubMed Central

    Tsai, Yi-Tzang; Itokazu, Yutaka; Yu, Robert K.

    2015-01-01

    Gangliosides are sialic acid-containing glycosphingolipids that are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and are mainly regulated through stage-specific expression of glycosyltransferase (ganglioside synthase) genes. We previously demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase) gene promoter resulted in recruitment of trans-activation factors. In addition, we reported that epigenetic activation of the GalNAcT gene was also detected as accompanied by an apparent induction of neuronal differentiation in neural stem cells responding to an exogenous supplement of ganglioside GM1. Here, we present evidence supporting the concept that nuclear GM1 is associated with gene regulation in neuronal cells. We found that nuclear GM1 binds acetylated histones on the promoters of the GalNAcT and NeuroD1 genes in differentiated neurons. Our study demonstrates for the first time that GM1 interacts with chromatin via acetylated histones at the nuclear periphery of neuronal cells. PMID:26498762

  11. Antihistoplasma effect of activated mouse splenic macrophages involves production of reactive nitrogen intermediates.

    PubMed Central

    Lane, T E; Wu-Hsieh, B A; Howard, D H

    1994-01-01

    The mechanism by which recombinant murine gamma interferon (rMuIFN-gamma) and bacterial lipopolysaccharide (LPS) activate mouse resident splenic macrophages to inhibit the intracellular growth of the fungus Histoplasma capsulatum was examined. Growth inhibition depended on L-arginine metabolism. The growth inhibitory state normally induced by rMuIFN-gamma and LPS in resident splenic macrophages did not occur when the macrophages were cultured in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of L-arginine metabolism. Resident splenic macrophages treated with rMuIFN-gamma and LPS produced nitrite (NO2-), an end product of L-arginine metabolism. When macrophages were cultured in the presence of NG-monomethyl-L-arginine together with rMuIFN-gamma and LPS, only baseline levels of NO2- were detected. Spleen cells from H. capsulatum-infected mice produced high levels of NO2- in culture. The production of NO2- correlated with in vitro inhibition of the intracellular growth of H. capsulatum. Anti-tumor necrosis factor alpha antibody did not block NO2- production by the immigrant splenic macrophages and did not abolish the antihistoplasma activity. PMID:8168960

  12. Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression

    PubMed Central

    Zeng, Zhifeng; Yang, Haiyuan; Wang, Ying; Ren, Jiafa; Dai, Yifan; Dai, Chunsun

    2017-01-01

    Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cells, a rat kidney interstitial fibroblast cell line, were stimulated with TGFβ1. A Caenorhabditis elegans fat-1 transgenic mouse model in which n-3 PUFAs are endogenously produced from n-6 PUFAs owing to the expression of n-3 fatty acid desaturase were deployed. Docosahexaenoic acid (DHA), one member of n-3 PUFAs family, could suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally, DHA could largely inhibit TGFβ1-stimulated Akt but not S6 or Smad3 phosphorylation at a time dependent manner. To decipher the role for n-3 PUFAs in protecting against kidney fibrosis, fat-1 transgenic mice were operated with unilateral ureter obstruction (UUO). Compared to the wild types, fat-1 transgenics developed much less kidney fibrosis and inflammatory cell accumulation accompanied by less p-Akt (Ser473), p-Akt (Thr308), p-S6 and p-Smad3 in kidney tissues at day 7 after UUO. Thus, n-3 PUFAs can attenuate fibroblast activation and kidney fibrosis, which may be associated with the inhibition of mTORC2 signaling. PMID:28393852

  13. Microfluidic IEF technique for sequential phosphorylation analysis of protein kinases

    NASA Astrophysics Data System (ADS)

    Choi, Nakchul; Song, Simon; Choi, Hoseok; Lim, Bu-Taek; Kim, Young-Pil

    2015-11-01

    Sequential phosphorylation of protein kinases play the important role in signal transduction, protein regulation, and metabolism in living cells. The analysis of these phosphorylation cascades will provide new insights into their physiological functions in many biological functions. Unfortunately, the existing methods are limited to analyze the cascade activity. Therefore, we suggest a microfluidic isoelectric focusing technique (μIEF) for the analysis of the cascade activity. Using the technique, we show that the sequential phosphorylation of a peptide by two different kinases can be successfully detected on a microfluidic chip. In addition, the inhibition assay for kinase activity and the analysis on a real sample have also been conducted. The results indicate that μIEF is an excellent means for studies on phosphorylation cascade activity.

  14. Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study.

    PubMed

    Tyvaert, L; Hawco, C; Kobayashi, E; LeVan, P; Dubeau, F; Gotman, J

    2008-08-01

    Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD

  15. Sequential visibility-graph motifs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-04-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of sequential visibility-graph motifs, smaller substructures of n consecutive nodes that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated with general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable of distinguishing among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification and description of physical, biological, and financial time series.

  16. Sequential detection of web defects

    DOEpatents

    Eichel, Paul H.; Sleefe, Gerard E.; Stalker, K. Terry; Yee, Amy A.

    2001-01-01

    A system for detecting defects on a moving web having a sequential series of identical frames uses an imaging device to form a real-time camera image of a frame and a comparitor to comparing elements of the camera image with corresponding elements of an image of an exemplar frame. The comparitor provides an acceptable indication if the pair of elements are determined to be statistically identical; and a defective indication if the pair of elements are determined to be statistically not identical. If the pair of elements is neither acceptable nor defective, the comparitor recursively compares the element of said exemplar frame with corresponding elements of other frames on said web until one of the acceptable or defective indications occur.

  17. Sequential power-up circuit

    DOEpatents

    Kronberg, James W.

    1992-01-01

    A sequential power-up circuit for starting several electrical load elements in series to avoid excessive current surge, comprising a voltage ramp generator and a set of voltage comparators, each comparator having a different reference voltage and interfacing with a switch that is capable of turning on one of the load elements. As the voltage rises, it passes the reference voltages one at a time and causes the switch corresponding to that voltage to turn on its load element. The ramp is turned on and off by a single switch or by a logic-level electrical signal. The ramp rate for turning on the load element is relatively slow and the rate for turning the elements off is relatively fast. Optionally, the duration of each interval of time between the turning on of the load elements is programmable.

  18. Sequentially Executed Model Evaluation Framework

    SciTech Connect

    2015-10-20

    Provides a message passing framework between generic input, model and output drivers, and specifies an API for developing such drivers. Also provides batch and real-time controllers which step the model and I/O through the time domain (or other discrete domain), and sample I/O drivers. This is a library framework, and does not, itself, solve any problems or execute any modeling. The SeMe framework aids in development of models which operate on sequential information, such as time-series, where evaluation is based on prior results combined with new data for this iteration. Has applications in quality monitoring, and was developed as part of the CANARY-EDS software, where real-time water quality data is being analyzed for anomalies.

  19. Sequentially Executed Model Evaluation Framework

    SciTech Connect

    2014-02-14

    Provides a message passing framework between generic input, model and output drivers, and specifies an API for developing such drivers. Also provides batch and real-time controllers which step the model and 1/0 through the time domain (or other discrete domain), and sample 1/0 drivers. This is a Framework library framework, and does not, itself, solve any problems or execute any modelling. The SeMe framework aids in development of models which operate on sequential information, such as time-series, where evaluation is based on prior results combined with new data for this iteration. Ha) applications in quality monitoring, and was developed as part of the CANARY-EDS software, where real-time water quality data is being analyzed

  20. Using Long-Distance Scientist Involvement to Enhance NASA Volunteer Network Educational Activities

    NASA Astrophysics Data System (ADS)

    Ferrari, K.

    2012-12-01

    Since 1999, the NASA/JPL Solar System Ambassadors (SSA) and Solar System Educators (SSEP) programs have used specially-trained volunteers to expand education and public outreach beyond the immediate NASA center regions. Integrating nationwide volunteers in these highly effective programs has helped optimize agency funding set aside for education. Since these volunteers were trained by NASA scientists and engineers, they acted as "stand-ins" for the mission team members in communities across the country. Through the efforts of these enthusiastic volunteers, students gained an increased awareness of NASA's space exploration missions through Solar System Ambassador classroom visits, and teachers across the country became familiarized with NASA's STEM (Science, Technology, Engineering and Mathematics) educational materials through Solar System Educator workshops; however the scientist was still distant. In 2003, NASA started the Digital Learning Network (DLN) to bring scientists into the classroom via videoconferencing. The first equipment was expensive and only schools that could afford the expenditure were able to benefit; however, recent advancements in software allow classrooms to connect to the DLN via personal computers and an internet connection. Through collaboration with the DLN at NASA's Jet Propulsion Laboratory and the Goddard Spaceflight Center, Solar System Ambassadors and Solar System Educators in remote parts of the country are able to bring scientists into their classroom visits or workshops as guest speakers. The goals of this collaboration are to provide special elements to the volunteers' event, allow scientists opportunities for education involvement with minimal effort, acquaint teachers with DLN services and enrich student's classroom learning experience.;